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Early, Late, PrEP, PEP |
Covid Analysis (Preprint) (meta analysis) |
meta-analysis v216 |
HCQ for COVID-19: real-time meta analysis of 351 studies |
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• Meta analysis using the most serious outcome reported shows 62% [52‑70%] improvement for the 36 early treatment studies. Results are similar after exclusion based sensitivity analysis and after restriction to peer-reviewed st.. |
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Early, Late, PrEP, PEP
Early, Late, PrEP, PEP
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HCQ for COVID-19: real-time meta analysis of 351 studies |
Covid Analysis (Preprint) (meta analysis) |
• Meta analysis using the most serious outcome reported shows 62% [52‑70%] improvement for the 36 early treatment studies. Results are similar after exclusion based sensitivity analysis and after restriction to peer-reviewed studies. The 15 mortality results shows 72% [57‑81%] lower mortality, and the 15 hospitalization results shows 41% [28‑52%] improvement.• 20 early treatment studies show statistically significant improvements in isolation (14 for the most serious outcome).• Late treatment is less successful, with only 67% of the 235 studies reporting a positive effect. Very late stage treatment is not effective and may be harmful, especially when using excessive dosages.• 77% of Randomized Controlled Trials (RCTs) for early, PrEP, or PEP treatment report positive effects, the probability of results as good or better for an ineffective treatment is 0.0085.• There is evidence of bias towards publishing negative results. 76% of prospective studies report positive effects, compared to 71% of retrospective studies. Studies from North America are 2.5 times more likely to report negative results than studies from the rest of the world combined, p = 0.0000000693.• Negative meta analyses of HCQ generally choose a subset of trials, focusing on late treatment, especially trials with very late treatment and excessive dosages.• While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 4% of HCQ studies show zero events in the treatment arm. Multiple treatments are typically used in combination, which may be significantly more effective.• No treatment, vaccine, or intervention is 100% available and effective for all variants. All practical, effective, and safe means should be used. Denying the efficacy of treatments increases mortality, morbidity, collateral damage, and endemic risk.• All data to reproduce this paper and the sources are in the appendix. See [García-Albéniz, Ladapo, Prodromos, Risch, Risch (B)] for other meta analyses showing efficacy when HCQ is used early or for prophylaxis. Total | 351 studies | 5,717 authors | 461,461 patients | Positive effects | 254 studies | 4,088 authors | 330,781 patients | Early treatment | 62% improvement | RR 0.38 [0.30-0.48] | Late treatment | 19% improvement | RR 0.81 [0.77-0.86] |
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Meta |
García-Albéniz et al., European Journal of Epidemiology, doi:10.1007/s10654-022-00891-4 (preprint 1/25/22) (meta analysis) |
cases, ↓28.0%, p=0.003 |
Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19 |
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Systematic review and meta-analysis of HCQ prophylaxis RCTs showing a statistically significant reduction in cases for pre-exposure prophylaxis. For PEP trials there were very long treatment delays - in one trial about a third of particip.. |
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Meta
Meta
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Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19 |
García-Albéniz et al., European Journal of Epidemiology, doi:10.1007/s10654-022-00891-4 (preprint 1/25/22) (meta analysis) |
Systematic review and meta-analysis of HCQ prophylaxis RCTs showing a statistically significant reduction in cases for pre-exposure prophylaxis.For PEP trials there were very long treatment delays - in one trial about a third of participants were enrolled 4 days after exposure with an additional shipping delay of ~46 hours on average, and in another trial participants were enrolled up to 7 days after exposure, with an unknown additional delay before treatment, and results suggesting that exposure detection was delayed.
risk of case, 28.0% lower, RR 0.72, p = 0.003, PrEP.
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risk of case, 9.0% lower, RR 0.91, p = 0.45, PEP.
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García-Albéniz et al., 8/9/2022, peer-reviewed, 5 authors.
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PrEP |
Polo et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2022.07.006 |
symp. case, ↓51.0%, p=0.79 |
Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo controlled randomized trial in healthcare workers |
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Early terminated healthcare worker prophylaxis RCT in Spain, showing lower risk of symptomatic cases with HCQ prophylaxis, without statistical significance due to the small number of events. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo controlled randomized trial in healthcare workers |
Polo et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2022.07.006 |
Early terminated healthcare worker prophylaxis RCT in Spain, showing lower risk of symptomatic cases with HCQ prophylaxis, without statistical significance due to the small number of events.
risk of symptomatic case, 51.0% lower, RR 0.49, p = 0.79, treatment 3 of 224 (1.3%), control 5 of 211 (2.4%), NNT 97, Kaplan–Meier, primary outcome.
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risk of case, 27.0% lower, RR 0.73, p = 0.31, treatment 21 of 224 (9.4%), control 23 of 211 (10.9%), Kaplan–Meier.
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Polo et al., 8/5/2022, Double Blind Randomized Controlled Trial, placebo-controlled, Spain, peer-reviewed, median age 38.0, 189 authors, trial NCT04334928 (history) (EPICOS).
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Dosing |
Xu et al., Rapid Communications in Mass Spectrometry, doi:10.1002/rcm.9358 (Dosing) |
dosing study |
A study of impurities in the repurposed COVID-19 drug hydroxychloroquine sulfate by UHPLC-Q/TOF-MS and LC-SPE-NMR |
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Analysis of HCQ from two manufacturers showing 9 different impurities, with significantly different concentrations for each manufacturer. |
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Dosing
Dosing
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A study of impurities in the repurposed COVID-19 drug hydroxychloroquine sulfate by UHPLC-Q/TOF-MS and LC-SPE-NMR |
Xu et al., Rapid Communications in Mass Spectrometry, doi:10.1002/rcm.9358 (Dosing) |
Analysis of HCQ from two manufacturers showing 9 different impurities, with significantly different concentrations for each manufacturer.
Xu et al., 7/26/2022, peer-reviewed, 4 authors.
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PrEP |
Patel et al., medRxiv, doi:10.1101/2022.07.13.22277606 (Preprint) |
cases, ↓46.3%, p=0.001 |
Factors Associated with COVID-19 Breakthrough Infection in the Pre-Omicron Era Among Vaccinated Patients with Rheumatic Diseases: A Cohort Study |
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Retrospective 11,468 vaccinated rheumatic disease patients in the USA, showing lower risk of COVID-19 with HCQ/CQ use compared with all other treatments. Adjusted results are only provided with respect to specific other treatments. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Factors Associated with COVID-19 Breakthrough Infection in the Pre-Omicron Era Among Vaccinated Patients with Rheumatic Diseases: A Cohort Study |
Patel et al., medRxiv, doi:10.1101/2022.07.13.22277606 (Preprint) |
Retrospective 11,468 vaccinated rheumatic disease patients in the USA, showing lower risk of COVID-19 with HCQ/CQ use compared with all other treatments. Adjusted results are only provided with respect to specific other treatments.
risk of case, 46.3% lower, RR 0.54, p = 0.001, treatment 28 of 18,358 (0.2%), control 223 of 78,509 (0.3%), cases vs. total person-months, unadjusted.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Patel et al., 7/15/2022, retrospective, USA, preprint, mean age 60.0, 12 authors.
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Late |
Malundo et al., IJID Regions, doi:10.1016/j.ijregi.2022.07.009 |
death, ↑24.4%, p=0.32 |
Predictors of Mortality among inpatients with COVID-19 Infection in a Tertiary Referral Center in the Philippines |
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Retrospective 1,215 hospitalized patients in the Phillipines, showing no significant difference in outcomes with remdesivir or HCQ use in unadjusted results subject to confounding by indication. |
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Late treatment study
Late treatment study
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Predictors of Mortality among inpatients with COVID-19 Infection in a Tertiary Referral Center in the Philippines |
Malundo et al., IJID Regions, doi:10.1016/j.ijregi.2022.07.009 |
Retrospective 1,215 hospitalized patients in the Phillipines, showing no significant difference in outcomes with remdesivir or HCQ use in unadjusted results subject to confounding by indication.
risk of death, 24.4% higher, RR 1.24, p = 0.32, treatment 20 of 90 (22.2%), control 201 of 1,125 (17.9%).
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Malundo et al., 7/14/2022, retrospective, Philippines, peer-reviewed, 16 authors, study period 12 March, 2021 - 9 September, 2021.
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PrEP |
Raabe et al., medRxiv, doi:10.1101/2022.07.01.22277058 (Preprint) |
symp. case, ↓82.2%, p=0.17 |
Hydroxychloroquine pre-exposure prophylaxis to prevent SARS-CoV-2 among health care workers at risk for SARS-CoV-2 exposure: A nonrandomized controlled trial |
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Small prophylaxis study with 130 healthcare workers in the USA, showing lower symptomatic cases with HCQ prophylaxis, without statistical significance. HCQ participants were significantly older. The only symptomatic HCQ patient reported h.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Hydroxychloroquine pre-exposure prophylaxis to prevent SARS-CoV-2 among health care workers at risk for SARS-CoV-2 exposure: A nonrandomized controlled trial |
Raabe et al., medRxiv, doi:10.1101/2022.07.01.22277058 (Preprint) |
Small prophylaxis study with 130 healthcare workers in the USA, showing lower symptomatic cases with HCQ prophylaxis, without statistical significance. HCQ participants were significantly older. The only symptomatic HCQ patient reported headache only as a potential COVID-19 symptom.
risk of symptomatic case, 82.2% lower, RR 0.18, p = 0.17, treatment 1 of 59 (1.7%), control 2 of 21 (9.5%), NNT 13.
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risk of symptomatic case, 88.4% lower, RR 0.12, p = 0.07, treatment 0 of 59 (0.0%), control 2 of 21 (9.5%), NNT 10, relative risk is not 0 because of continuity correction due to zero events, fever.
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risk of case, 28.8% lower, RR 0.71, p = 0.65, treatment 4 of 59 (6.8%), control 2 of 21 (9.5%), NNT 36, seroconversion.
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Early |
Nimitvilai et al., Journal of Global Infectious Diseases, doi:10.4103/jgid.jgid_281_21 |
progression, ↓50.9%, p=0.62 |
A randomized controlled trial of combined ivermectin and zinc sulfate versus combined hydroxychloroquine, darunavir/ritonavir, and zinc sulfate among adult patients with asymptomatic or mild coronavirus-19 infection |
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RCT low-risk patients in Thailand comparing HCQ, darunavir/ritonavir, and zinc, with ivermectin and zinc, showing no significant differences. All patients recovered. 65% of patients were asymptomatic at baseline, 26% were PCR- at baseline.. |
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Early treatment study
Early treatment study
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A randomized controlled trial of combined ivermectin and zinc sulfate versus combined hydroxychloroquine, darunavir/ritonavir, and zinc sulfate among adult patients with asymptomatic or mild coronavirus-19 infection |
Nimitvilai et al., Journal of Global Infectious Diseases, doi:10.4103/jgid.jgid_281_21 |
RCT low-risk patients in Thailand comparing HCQ, darunavir/ritonavir, and zinc, with ivermectin and zinc, showing no significant differences. All patients recovered. 65% of patients were asymptomatic at baseline, 26% were PCR- at baseline, and 84% were culture negative at baseline. The percentage of patients symptomatic at baseline was 15% higher for ivermectin.The reported trial id NCT02045069 is a 2014 dengue trial with a status of recruiting [clinicaltrials.gov]. Authors claim both treatments had no clinical benefit, however all patients were discharged from quarantine as planned between 10-14 days, and there was no control group. Authors claim there was "no clear evidence of antiviral effects for the control arm", however there was no control arm. Authors indicate that all patients were discharged within 14 days, however they report that one patient had Ct 22.11 at day 12.
risk of progression, 50.9% lower, RR 0.49, p = 0.62, treatment 1 of 57 (1.8%), control 2 of 56 (3.6%), NNT 55.
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risk of no viral clearance, 49.7% higher, RR 1.50, p = 0.12, treatment 25 of 56 (44.6%), control 17 of 57 (29.8%), mid-recovery, day 7, modified intention-to-treat.
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risk of no viral clearance, 56.0% higher, RR 1.56, p = 0.048, treatment 24 of 38 (63.2%), control 17 of 42 (40.5%), mid-recovery, day 7, per-protocol.
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time to viral-, 16.7% higher, relative time 1.17, p = 0.42, treatment 57, control 56.
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Nimitvilai et al., 6/29/2022, Randomized Controlled Trial, Thailand, peer-reviewed, 10 authors, study period December 2020 - April 2021, this trial compares with another treatment - results may be better when compared to placebo, this trial uses multiple treatments in the treatment arm (combined with darunavir/ritonavir and zinc sulfate) - results of individual treatments may vary, trial NCT02045069 (history).
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Late |
Silva et al., Frontiers in Cellular and Infection Microbiology, doi:10.3389/fcimb.2022.899702 |
death, ↑46.1%, p=0.21 |
Clinical-Epidemiology Aspect of Inpatients With Moderate or Severe COVID-19 in a Brazilian Macroregion: Disease and Countermeasures |
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Retrospective 395 hospitalized patients in Brazil, showing higher mortality with HCQ treatment, without statistical significance. |
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Late treatment study
Late treatment study
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Clinical-Epidemiology Aspect of Inpatients With Moderate or Severe COVID-19 in a Brazilian Macroregion: Disease and Countermeasures |
Silva et al., Frontiers in Cellular and Infection Microbiology, doi:10.3389/fcimb.2022.899702 |
Retrospective 395 hospitalized patients in Brazil, showing higher mortality with HCQ treatment, without statistical significance.
risk of death, 46.1% higher, RR 1.46, p = 0.21, treatment 21, control 374, adjusted, OR converted to RR, multivariable, control prevalance approximated with overall prevalence.
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Silva et al., 5/20/2022, retrospective, Brazil, peer-reviewed, mean age 58.4, 28 authors, study period 25 March, 2020 - 21 October, 2020.
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Early |
Gkioulekas et al., Authorea, Inc., doi:10.22541/au.164745391.17821933/v2 (Preprint) |
Frequentist and Bayesian analysis methods for case series data and application to early outpatient COVID-19 treatment case series of high risk patients |
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Hybrid statistical framework for evaluating treatment protocols. COVID-19 treatment protocols often use risk stratification, multiple treatments, and customization based on the disease stage and the patient. Authors find strong evidence f.. |
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Early treatment study
Early treatment study
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Frequentist and Bayesian analysis methods for case series data and application to early outpatient COVID-19 treatment case series of high risk patients |
Gkioulekas et al., Authorea, Inc., doi:10.22541/au.164745391.17821933/v2 (Preprint) |
Hybrid statistical framework for evaluating treatment protocols. COVID-19 treatment protocols often use risk stratification, multiple treatments, and customization based on the disease stage and the patient. Authors find strong evidence for the efficacy of the early outpatient treatment protocols considered.
Gkioulekas et al., 5/16/2022, retrospective, preprint, 3 authors.
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Late |
Hong et al., PLOS ONE, doi:10.1371/journal.pone.0267645 |
no recov., ↓24.9%, p=0.45 |
Use of combined treatment of 3rd-generation cephalosporin, azithromycin and antiviral agents on moderate SARs-CoV-2 patients in South Korea: A retrospective cohort study |
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Retrospective 25 hospitalized patients treated with cephalosporin, azithromycin, and HCQ, and 217 SOC patients in South Korea, reporting no significant differences. 5 patients receiving lopinavir/ritonavir and HCQ >5 days were excluded fo.. |
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Late treatment study
Late treatment study
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Use of combined treatment of 3rd-generation cephalosporin, azithromycin and antiviral agents on moderate SARs-CoV-2 patients in South Korea: A retrospective cohort study |
Hong et al., PLOS ONE, doi:10.1371/journal.pone.0267645 |
Retrospective 25 hospitalized patients treated with cephalosporin, azithromycin, and HCQ, and 217 SOC patients in South Korea, reporting no significant differences. 5 patients receiving lopinavir/ritonavir and HCQ >5 days were excluded for unknown reasons. HCQ was typically initiated based on progression or side effects from another treatment. Conflicting results are reported. Table 2 indicates 15 CA/HCQ patients after matching, while Table S2 shows 25, and the Table 3 count is blank. S2 appears to incorrectly show before matching results, and the after matching results are missing in Table 3. 200mg HCQ bid.
recovery time, 24.9% lower, HR 0.75, p = 0.45, treatment 15, control 15, propensity score matching.
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hospitalization time, 12.7% higher, HR 1.13, p = 0.75, treatment 15, control 15, propensity score matching.
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viral clearance time, 0.5% lower, HR 1.00, p = 0.99, treatment 15, control 15, propensity score matching.
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Hong et al., 5/4/2022, retrospective, South Korea, peer-reviewed, 11 authors, study period 28 February, 2020 - 28 April, 2020.
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PrEP |
Satti et al., Cureus, doi:10.7759/cureus.24382 |
cases, ↓61.5%, p=0.04 |
Characteristics and Obstetric Outcomes in Women With Autoimmune Rheumatic Disease During the COVID-19 Pandemic in Qatar |
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Retrospective 80 consecutive pregnant patients with autoimmune rheumatic diseases in Qatar, showing lower risk of COVID-19 cases with HCQ prophylaxis. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Characteristics and Obstetric Outcomes in Women With Autoimmune Rheumatic Disease During the COVID-19 Pandemic in Qatar |
Satti et al., Cureus, doi:10.7759/cureus.24382 |
Retrospective 80 consecutive pregnant patients with autoimmune rheumatic diseases in Qatar, showing lower risk of COVID-19 cases with HCQ prophylaxis.
risk of case, 61.5% lower, RR 0.39, p = 0.04, treatment 10 of 63 (15.9%), control 7 of 17 (41.2%), NNT 4.0.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Satti et al., 4/22/2022, retrospective, Qatar, peer-reviewed, 6 authors.
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In Vitro |
Faísca et al., Pharmaceutics, doi:10.3390/pharmaceutics14040877 (In Vitro) |
In Vitro |
Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2 |
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In Vitro study showing improved antiviral activity with ionic formulations of HCQ. |
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In Vitro
In Vitro
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Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2 |
Faísca et al., Pharmaceutics, doi:10.3390/pharmaceutics14040877 (In Vitro) |
In Vitro study showing improved antiviral activity with ionic formulations of HCQ.
Faísca et al., 4/17/2022, peer-reviewed, 6 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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Early |
Roy-García et al., medRxiv, doi:10.1101/2022.04.06.22273531 (Preprint) |
progression, ↑100%, p=1.00 |
Efficacy and Safety of Fixed Combination of Hydroxychloroquine with Azithromycin Versus Hydroxychloroquine and Placebo in Patients with Mild COVID-19: Randomized, double blind, Placebo controlled trial |
Details
Small early terminated RCT in Mexico with 31 HCQ and 31 control patients, showing higher progression with treatment. There were no hospitalizations in the HCQ and control groups. HCQ patients were older, 38 vs. 32. There were no differenc.. |
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Early treatment study
Early treatment study
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Efficacy and Safety of Fixed Combination of Hydroxychloroquine with Azithromycin Versus Hydroxychloroquine and Placebo in Patients with Mild COVID-19: Randomized, double blind, Placebo controlled trial |
Roy-García et al., medRxiv, doi:10.1101/2022.04.06.22273531 (Preprint) |
Small early terminated RCT in Mexico with 31 HCQ and 31 control patients, showing higher progression with treatment. There were no hospitalizations in the HCQ and control groups. HCQ patients were older, 38 vs. 32. There were no differences in QT segment duration and no cardiovascular complications.The analysis presented includes data from participants that withdrew consent or received incorrect medication (5 patients for HCQ+AZ, 1 HCQ, 0 control). The HCQ+AZ arm was not blind due to the use of a different pill regimen. Results for the individual components of the progression outcome are not provided.The dosing regimen is poor. Dosing studies and HCQ trials show that a loading dose and sufficiently high doses are important to reach therapeutic concentrations quickly [Ali, Ragonnet], and that excessive cumulative doses over time are harmful.With the already late treatment (IQR 4-6 days) and non-weight-specific dosing, it is likely that therapeutic concentrations would not be reached early enough during the viral phase in most patients, and the continued treatment for 10 days suggests harmful tissue concentrations could be reached for some patients.
risk of progression, 100% higher, RR 2.00, p = 1.00, treatment 2 of 31 (6.5%), control 1 of 31 (3.2%), supplemental oxygen.
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risk of progression, 233.3% higher, RR 3.33, p = 0.06, treatment 10 of 31 (32.3%), control 3 of 31 (9.7%), pneumonia.
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risk of progression, 225.0% higher, RR 3.25, p = 0.02, treatment 13 of 31 (41.9%), control 4 of 31 (12.9%), oxygen saturation less than 90%, dyspnea, or pneumonia.
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Roy-García et al., 4/16/2022, Double Blind Randomized Controlled Trial, Mexico, preprint, 11 authors, average treatment delay 5.0 days, dosage 200mg bid days 1-10, trial NCT04964583 (history).
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Late |
Hafez et al., Antibiotics, doi:10.3390/antibiotics11040498 |
viral+, ↓12.3%, p=0.59 |
Antiviral Used among Non-Severe COVID-19 Cases in Relation to Time till Viral Clearance: A Retrospective Cohort Study |
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Retrospective hospitalized patients in the United Arab Emirates, showing no significant difference in viral clearance with different combinations of HCQ, AZ, favipiravir, and lopinavir/ritonavir. |
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Late treatment study
Late treatment study
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Antiviral Used among Non-Severe COVID-19 Cases in Relation to Time till Viral Clearance: A Retrospective Cohort Study |
Hafez et al., Antibiotics, doi:10.3390/antibiotics11040498 |
Retrospective hospitalized patients in the United Arab Emirates, showing no significant difference in viral clearance with different combinations of HCQ, AZ, favipiravir, and lopinavir/ritonavir.
viral clearance time, 12.3% lower, HR 0.88, p = 0.59, treatment 40, control 1,446, Cox proportional hazards.
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viral clearance time, 58.7% lower, HR 0.41, p = 0.09, treatment 4, control 1,446, HCQ + favipiravir + lopinavir/ritonavir, Cox proportional hazards.
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Hafez et al., 4/8/2022, retrospective, United Arab Emirates, peer-reviewed, 6 authors.
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Submit Corrections or Comments
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PrEP |
Walbi et al., Journal of International Medical Research, doi:10.1177/03000605221090363 |
Effect of chronic hydroxychloroquine use on COVID-19 risk in patients with rheumatoid arthritis and systemic lupus erythematosus: a multicenter retrospective cohort |
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Retrospective RA/SLE patients in Saudi Arabia. Numbers in this paper are contradictory. Figure 1 and the introduction to the results indicate 304 HCQ users, while Table 1 and later in the results shows 207 (arms switched). The subsequent .. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Effect of chronic hydroxychloroquine use on COVID-19 risk in patients with rheumatoid arthritis and systemic lupus erythematosus: a multicenter retrospective cohort |
Walbi et al., Journal of International Medical Research, doi:10.1177/03000605221090363 |
Retrospective RA/SLE patients in Saudi Arabia. Numbers in this paper are contradictory. Figure 1 and the introduction to the results indicate 304 HCQ users, while Table 1 and later in the results shows 207 (arms switched). The subsequent text reporting the ICU results (2 non-HCQ-users, zero HCQ users) suggests that the labels are switched in Figure 2, or possibly just specific results.
Excluded in meta analysis:
unresolved data inconsistency.
Walbi et al., 4/6/2022, retrospective, Saudi Arabia, peer-reviewed, 16 authors, study period March 2020 - February 2021.
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In Vitro |
Delandre et al., Pharmaceuticals, doi:10.3390/ph15040445 (In Vitro) |
In Vitro |
Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants |
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In Vitro study with 30 COVID-19 strains from 14 variants, showing stronger efficacy with ivermectin compared to CQ and remdesivir, and relatively homogeneous efficacy with ivermectin regardless of strain/variant, in contrast to results fo.. |
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In Vitro
In Vitro
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Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants |
Delandre et al., Pharmaceuticals, doi:10.3390/ph15040445 (In Vitro) |
In Vitro study with 30 COVID-19 strains from 14 variants, showing stronger efficacy with ivermectin compared to CQ and remdesivir, and relatively homogeneous efficacy with ivermectin regardless of strain/variant, in contrast to results for CQ and remdesivir.CQ showed better efficacy for omicron compared to most other variants.
Delandre et al., 4/2/2022, peer-reviewed, 12 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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Early |
Avezum et al., The Lancet Regional Health - Americas, doi:10.1016/j.lana.2022.100243 |
death, ↓0.7%, p=1.00 |
Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial |
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Authors have not responded to a request for the data. Outpatient RCT with 687 HCQ and 682 control patients in Brazil, showing lower hospitalization with treatment, not reaching statistical significance. Higher efficacy was seen with treat.. |
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Early treatment study
Early treatment study
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Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial |
Avezum et al., The Lancet Regional Health - Americas, doi:10.1016/j.lana.2022.100243 |
Authors have not responded to a request for the data.Outpatient RCT with 687 HCQ and 682 control patients in Brazil, showing lower hospitalization with treatment, not reaching statistical significance. Higher efficacy was seen with treatment <4 days from onset, RR 0.61. The associated meta analysis includes mostly late treatment studies, for example in [Schwartz] the median delay from onset was 7 days. [Omrani] is missing. The values for [Johnston] are incorrect - the study shows 4 hospitalizations in the control arm - RR for this study should be 0.58 instead of 0.78.
risk of death, 0.7% lower, RR 0.99, p = 1.00, treatment 5 of 687 (0.7%), control 5 of 682 (0.7%), NNT 18741, all-cause death.
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risk of death, 56.0% higher, HR 1.56, p = 0.54, treatment 5 of 687 (0.7%), control 5 of 682 (0.7%), adjusted, univariate Firth's penalized likelihood.
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risk of mechanical ventilation, 32.4% higher, RR 1.32, p = 0.79, treatment 8 of 687 (1.2%), control 6 of 682 (0.9%).
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risk of ICU admission, 16.4% lower, RR 0.84, p = 0.61, treatment 16 of 687 (2.3%), control 19 of 682 (2.8%), NNT 219.
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risk of hospitalization, 23.5% lower, RR 0.77, p = 0.18, treatment 44 of 689 (6.4%), control 57 of 683 (8.3%), NNT 51.
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risk of hospitalization, 40.0% lower, RR 0.60, p = 0.15, treatment 267, control 265, <4 days.
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Avezum et al., 3/31/2022, Double Blind Randomized Controlled Trial, Brazil, peer-reviewed, 40 authors, study period 12 May, 2020 - 7 July, 2021, average treatment delay 4.0 days, dosage 400mg bid day 1, 200mg bid days 2-7, trial NCT04466540 (history).
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Submit Corrections or Comments
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PrEP |
MacFadden et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofac156 |
cases, ↓12.0%, p=0.01 |
Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications |
Details
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing lower cases with chronic use of HCQ. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications |
MacFadden et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofac156 |
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing lower cases with chronic use of HCQ.
risk of case, 12.0% lower, OR 0.88, p = 0.01, RR approximated with OR.
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MacFadden et al., 3/29/2022, retrospective, Canada, peer-reviewed, 9 authors, study period 15 January, 2020 - 31 December, 2020.
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Submit Corrections or Comments
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Late |
AlQahtani et al., Scientific Reports, doi:10.1038/s41598-022-08794-w |
ICU, ↓23.5%, p=1.00 |
Randomized controlled trial of favipiravir, hydroxychloroquine, and standard care in patients with mild/moderate COVID-19 disease |
Details
RCT with 54 favipiravir, 51 HCQ, and 52 SOC hospitalized patients in Bahrain, showing no significant differences. Viral clearance improved with both treatments, but did not reach statistical significance with the small sample size. |
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Late treatment study
Late treatment study
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Randomized controlled trial of favipiravir, hydroxychloroquine, and standard care in patients with mild/moderate COVID-19 disease |
AlQahtani et al., Scientific Reports, doi:10.1038/s41598-022-08794-w |
RCT with 54 favipiravir, 51 HCQ, and 52 SOC hospitalized patients in Bahrain, showing no significant differences. Viral clearance improved with both treatments, but did not reach statistical significance with the small sample size.
risk of ICU admission, 23.5% lower, RR 0.76, p = 1.00, treatment 3 of 51 (5.9%), control 4 of 52 (7.7%), NNT 55.
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risk of no recovery, 4.1% lower, RR 0.96, p = 0.94, treatment 5 of 49 (10.2%), control 5 of 47 (10.6%), NNT 230.
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risk of no viral clearance, 47.4% lower, RR 0.53, p = 0.13, treatment 7 of 38 (18.4%), control 14 of 40 (35.0%), NNT 6.0.
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AlQahtani et al., 3/23/2022, Randomized Controlled Trial, Bahrain, peer-reviewed, 13 authors, study period August 2020 - March 2021, trial NCT04387760 (history).
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Submit Corrections or Comments
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PrEP |
Oztas et al., Journal of Medical Virology, doi:10.1002/jmv.27731 |
hosp., ↑215.1%, p=0.36 |
Frequency and Severity of COVID-19 in Patients with Various Rheumatic Diseases Treated Regularly with Colchicine or Hydroxychloroquine |
Details
Retrospective 317 HCQ users and 333 household contacts, showing higher risk with HCQ. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Frequency and Severity of COVID-19 in Patients with Various Rheumatic Diseases Treated Regularly with Colchicine or Hydroxychloroquine |
Oztas et al., Journal of Medical Virology, doi:10.1002/jmv.27731 |
Retrospective 317 HCQ users and 333 household contacts, showing higher risk with HCQ.Authors do not adjust for the very different baseline risk for systemic
autoimmune disease patients. Other research shows that the risk of COVID-19
for systemic autoimmune disease patients is much higher overall, Ferri et al.
show OR 4.42, p<0.001 [Ferri].
risk of hospitalization, 215.1% higher, RR 3.15, p = 0.36, treatment 3 of 317 (0.9%), control 1 of 333 (0.3%).
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risk of symptomatic case, 40.1% higher, RR 1.40, p = 0.44, treatment 16 of 317 (5.0%), control 12 of 333 (3.6%).
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risk of case, 5.0% higher, RR 1.05, p = 0.88, treatment 22 of 317 (6.9%), control 22 of 333 (6.6%).
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Excluded in after exclusion results of meta analysis:
not adjusting for the different baseline risk of systemic autoimmune patients, excessive unadjusted differences between groups.
Oztas et al., 3/21/2022, retrospective, Turkey, peer-reviewed, 15 authors.
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Submit Corrections or Comments
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Dosing |
Ragonnet et al., Future Pharmacology, doi:10.3390/futurepharmacol2010007 (Dosing) |
dosing study |
Drug Repositioning in Intensive Care Patients and Pharmacokinetic Variability: The Illustration of Hydroxychloroquine |
Details
Comparison of two HCQ dosing regimens, showing high inter-individual variability of HCQ concentrations (as in ), and significantly better plasma concentrations for the dosing regimen including a loading dose. |
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Details
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Dosing
Dosing
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Drug Repositioning in Intensive Care Patients and Pharmacokinetic Variability: The Illustration of Hydroxychloroquine |
Ragonnet et al., Future Pharmacology, doi:10.3390/futurepharmacol2010007 (Dosing) |
Comparison of two HCQ dosing regimens, showing high inter-individual variability of HCQ concentrations (as in [Ruiz]), and significantly better plasma concentrations for the dosing regimen including a loading dose.
Ragonnet et al., 3/19/2022, peer-reviewed, 9 authors.
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Submit Corrections or Comments
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Late |
Ebongue et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2022.102292 |
death, ↓43.0%, p=0.04 |
Factors predicting in-hospital all-cause mortality in COVID 19 patients at the Laquintinie Hospital Douala, Cameroon |
Details
Retrospective 580 hospitalized COVID+ patients in Cameroon, showing lower mortality with HCQ+AZ treatment. |
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Details
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Late treatment study
Late treatment study
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Factors predicting in-hospital all-cause mortality in COVID 19 patients at the Laquintinie Hospital Douala, Cameroon |
Ebongue et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2022.102292 |
Retrospective 580 hospitalized COVID+ patients in Cameroon, showing lower mortality with HCQ+AZ treatment.
risk of death, 43.0% lower, HR 0.57, p = 0.04, treatment 93 of 522 (17.8%), control 36 of 58 (62.1%), NNT 2.3, adjusted, multivariable.
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Ebongue et al., 3/18/2022, retrospective, Cameroon, peer-reviewed, 27 authors, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary.
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Submit Corrections or Comments
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Late |
Uyaroğlu et al., Acta Medica, doi:10.32552/2022.ActaMedica.719 |
death, ↑200.0%, p=1.00 |
Comparison of Favipiravir to Hydroxychloroquine Plus Azithromycin in the Treatment of Patients with Non-critical COVID-19: A Single-center, Retrospective, Propensity Score-matched Study |
Details
PSM retrospective 260 late stage hospitalized COVID-19 pneumonia patients in Turkey, showing no significant difference between favipiravir and HCQ. |
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Details
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Late treatment study
Late treatment study
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Comparison of Favipiravir to Hydroxychloroquine Plus Azithromycin in the Treatment of Patients with Non-critical COVID-19: A Single-center, Retrospective, Propensity Score-matched Study |
Uyaroğlu et al., Acta Medica, doi:10.32552/2022.ActaMedica.719 |
PSM retrospective 260 late stage hospitalized COVID-19 pneumonia patients in Turkey, showing no significant difference between favipiravir and HCQ.
risk of death, 200.0% higher, RR 3.00, p = 1.00, treatment 1 of 42 (2.4%), control 0 of 42 (0.0%), continuity correction due to zero event.
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risk of ICU admission, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 42 (0.0%), control 1 of 42 (2.4%), NNT 42, relative risk is not 0 because of continuity correction due to zero events.
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hospitalization time, 9.8% lower, relative time 0.90, p = 0.90, treatment 42, control 42.
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Uyaroğlu et al., 3/17/2022, retrospective, propensity score matching, Turkey, peer-reviewed, 6 authors, study period 20 March, 2020 - 30 September, 2020, this trial compares with another treatment - results may be better when compared to placebo.
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Submit Corrections or Comments
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Late |
Salehi et al., Research Square, doi:10.21203/rs.3.rs-1362678/v1 (Preprint) |
death, ↑14.5%, p=0.44 |
Risk factors of death in mechanically ventilated COVID-19 patients: a retrospective multi-center study |
Details
Retrospective 125 mechanically ventilated ICU patients in Iran, showing no significant difference with HCQ treatment in unadjusted results. |
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Details
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Late treatment study
Late treatment study
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Risk factors of death in mechanically ventilated COVID-19 patients: a retrospective multi-center study |
Salehi et al., Research Square, doi:10.21203/rs.3.rs-1362678/v1 (Preprint) |
Retrospective 125 mechanically ventilated ICU patients in Iran, showing no significant difference with HCQ treatment in unadjusted results.
risk of death, 14.5% higher, RR 1.14, p = 0.44, treatment 53 of 86 (61.6%), control 21 of 39 (53.8%).
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Salehi et al., 3/11/2022, retrospective, Iran, preprint, mean age 62.0, 11 authors, study period April 2021 - September 2021.
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Submit Corrections or Comments
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Late |
Azaña Gómez et al., Medicina Clínica, doi:10.1016/j.medcli.2022.01.008 |
death, ↓35.8%, p<0.0001 |
Mortality risk factors in patients with SARS-CoV-2 infection and atrial fibrillation: Data from the SEMI-COVID-19 registry |
Details
Retrospective 1,816 COVID-19 patients with atrial fibrillation in Spain, showing lower mortality with HCQ treatment. |
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Details
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Late treatment study
Late treatment study
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Mortality risk factors in patients with SARS-CoV-2 infection and atrial fibrillation: Data from the SEMI-COVID-19 registry |
Azaña Gómez et al., Medicina Clínica, doi:10.1016/j.medcli.2022.01.008 |
Retrospective 1,816 COVID-19 patients with atrial fibrillation in Spain, showing lower mortality with HCQ treatment.
risk of death, 35.8% lower, RR 0.64, p < 0.001, treatment 500 of 1,378 (36.3%), control 238 of 421 (56.5%), NNT 4.9.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Azaña Gómez et al., 3/10/2022, retrospective, Spain, peer-reviewed, 10 authors, study period 1 March, 2020 - 1 October, 2020.
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Submit Corrections or Comments
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PrEP |
Del Amo, J., medRxiv, doi:10.1101/2022.03.02.22271710 (Preprint) |
symp. case, ↓51.0%, p=0.79 |
Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo controlled randomized trial in healthcare workers |
Details
PrEP RCT with 231 HCQ, 220 TDF/FTC+HCQ, 233 TDF/FTC, and 223 placebo healthcare workers in Spain, Bolivia, and Venezuela, showing lower risk of symptomatic COVID-19 in all treatment arms, without statistical significance. Only 907 of the .. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo controlled randomized trial in healthcare workers |
Del Amo, J., medRxiv, doi:10.1101/2022.03.02.22271710 (Preprint) |
PrEP RCT with 231 HCQ, 220 TDF/FTC+HCQ, 233 TDF/FTC, and 223 placebo healthcare workers in Spain, Bolivia, and Venezuela, showing lower risk of symptomatic COVID-19 in all treatment arms, without statistical significance. Only 907 of the planned 4,000 participants were recruited. EudraCT number 2020-001385-11.
risk of symptomatic case, 51.0% lower, RR 0.49, p = 0.79, treatment 3 of 231 (1.3%), control 5 of 223 (2.2%), NNT 106, HCQ, Kaplan–Meier.
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risk of symptomatic case, 61.0% lower, RR 0.39, p = 0.72, treatment 3 of 220 (1.4%), control 5 of 223 (2.2%), TDF+HCQ, Kaplan–Meier.
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risk of case, 27.0% lower, RR 0.73, p = 0.31, treatment 21 of 231 (9.1%), control 23 of 223 (10.3%), HCQ, Kaplan–Meier.
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risk of case, 49.0% lower, RR 0.51, p = 0.09, treatment 13 of 220 (5.9%), control 23 of 223 (10.3%), NNT 23, TDF+HCQ, Kaplan–Meier.
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Del Amo et al., 3/4/2022, Double Blind Randomized Controlled Trial, placebo-controlled, multiple countries, preprint, 1 author, study period April 2020 - May 2021, dosage 200mg daily, trial NCT04334928 (history) (EPICOS).
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Submit Corrections or Comments
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Late |
Tsanovska et al., Infectious Disorders - Drug Targets, doi:10.2174/1871526522666220303121209 |
death, ↓57.9%, p=0.03 |
Hydroxychloroquine (HCQ) treatment for hospitalized patients with COVID- 19. |
Details
PSM prospective study of 260 COVID-19 patients in Bulgaria, showing lower mortality, ventilation, and ICU admission with HCQ treatment. |
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Details
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Late treatment study
Late treatment study
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Hydroxychloroquine (HCQ) treatment for hospitalized patients with COVID- 19. |
Tsanovska et al., Infectious Disorders - Drug Targets, doi:10.2174/1871526522666220303121209 |
PSM prospective study of 260 COVID-19 patients in Bulgaria, showing lower mortality, ventilation, and ICU admission with HCQ treatment.
risk of death, 57.9% lower, RR 0.42, p = 0.03, treatment 8 of 70 (11.4%), control 19 of 70 (27.1%), NNT 6.4, propensity score matching.
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risk of mechanical ventilation, 73.9% lower, RR 0.26, p < 0.001, treatment 6 of 70 (8.6%), control 23 of 70 (32.9%), NNT 4.1, propensity score matching.
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risk of ICU admission, 70.4% lower, RR 0.30, p < 0.001, treatment 8 of 70 (11.4%), control 27 of 70 (38.6%), NNT 3.7, propensity score matching.
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Tsanovska et al., 3/3/2022, prospective, Bulgaria, peer-reviewed, 8 authors, study period 6 November, 2020 - 28 December, 2020.
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Submit Corrections or Comments
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Late |
Soto et al., PLOS ONE, doi:10.1371/journal.pone.0264789 |
death, ↑6.0%, p=0.46 |
Mortality and associated risk factors in patients hospitalized due to COVID-19 in a Peruvian reference hospital |
Details
Retrospective 1,418 very late stage (46% mortality) patients in Peru, showing no significant difference with HCQ. There is strong confounding by indication, for example 48% of patients with baseline SpO2 <70% were treated compared with 22.. |
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Details
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Late treatment study
Late treatment study
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Mortality and associated risk factors in patients hospitalized due to COVID-19 in a Peruvian reference hospital |
Soto et al., PLOS ONE, doi:10.1371/journal.pone.0264789 |
Retrospective 1,418 very late stage (46% mortality) patients in Peru, showing no significant difference with HCQ. There is strong confounding by indication, for example 48% of patients with baseline SpO2 <70% were treated compared with 22% for SpO2 >95%. There may also be significant confounding by time with SOC changing substantially over the first few months of the pandemic.
risk of death, 6.0% higher, HR 1.06, p = 0.46, treatment 292 of 590 (49.5%), control 362 of 828 (43.7%), Cox proportional hazards.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details, substantial unadjusted confounding by indication likely, substantial confounding by time possible due to significant changes in SOC and treatment propensity near the start of the pandemic.
Soto et al., 3/2/2022, retrospective, Peru, peer-reviewed, median age 58.0, 10 authors, study period April 2020 - August 2020, dosage not specified.
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Submit Corrections or Comments
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Late |
Rouamba et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2022.02.034 |
death, ↓80.0%, p<0.0001 |
Assessment of Recovery Time, Worsening and Death, among COVID-19 inpatients and outpatients, under treatment with Hydroxychloroquine or Chloroquine plus Azithromycin Combination in Burkina Faso |
Details
Retrospective 863 COVID-19 patients in Burkina Faso, showing lower mortality, lower progression for outpatients, and faster viral clearance with HCQ/CQ treatment. Only the lower mortality was statistically significant. NCT04445441. |
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Details
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Late treatment study
Late treatment study
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Assessment of Recovery Time, Worsening and Death, among COVID-19 inpatients and outpatients, under treatment with Hydroxychloroquine or Chloroquine plus Azithromycin Combination in Burkina Faso |
Rouamba et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2022.02.034 |
Retrospective 863 COVID-19 patients in Burkina Faso, showing lower mortality, lower progression for outpatients, and faster viral clearance with HCQ/CQ treatment. Only the lower mortality was statistically significant. NCT04445441.
risk of death, 80.0% lower, HR 0.20, p < 0.001, treatment 20 of 336 (6.0%), control 24 of 73 (32.9%), NNT 3.7, adjusted, inpatients, multivariable, Cox proportional hazards.
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risk of progression, 20.0% lower, HR 0.80, p = 0.43, treatment 75 of 745 (10.1%), control 19 of 118 (16.1%), adjusted, all patients, multivariable, Cox proportional hazards.
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risk of progression, 73.0% lower, HR 0.27, p = 0.05, treatment 23 of 399 (5.8%), control 4 of 33 (12.1%), adjusted, outpatients, multivariable, Cox proportional hazards, early treatment result.
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risk of progression, 7.0% higher, HR 1.07, p = 0.83, treatment 52 of 347 (15.0%), control 15 of 85 (17.6%), adjusted, inpatients, multivariable, Cox proportional hazards.
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time to viral clearance, 30.6% lower, HR 0.69, p = 0.26, treatment 746, control 118, adjusted, all patients, propensity score matching, multivariable, Cox proportional hazards, primary outcome.
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time to viral clearance, 13.0% lower, HR 0.87, p = 0.29, treatment 746, control 118, adjusted, all patients, without PSM, multivariable, Cox proportional hazards, primary outcome.
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time to viral clearance, 21.3% lower, HR 0.79, p = 0.37, treatment 399, control 33, adjusted, outpatients, multivariable, Cox proportional hazards, primary outcome, early treatment result.
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time to viral clearance, 13.8% lower, HR 0.86, p = 0.37, treatment 345, control 86, adjusted, inpatients, multivariable, Cox proportional hazards, primary outcome.
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Rouamba et al., 2/26/2022, retrospective, Burkina Faso, peer-reviewed, mean age 42.2, 17 authors, study period 9 March, 2020 - 31 October, 2020, dosage 200mg tid days 1-10, HCQ 200mg tid daily or CQ 250mg bid daily, trial NCT04445441 (history).
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Submit Corrections or Comments
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PrEP |
Opdam et al., Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2551 |
hosp., ↓45.0%, p=0.18 |
Identification of Risk Factors for COVID‐19 Hospitalization in Patients with Anti‐Rheumatic Drugs: Results from a Multicenter Nested Case Control Study |
Details
Retrospective 81 cases and 396 controls among rheumatic disease patients in the Netherlands, showing lower risk of hospitalization with HCQ prophylaxis, without statistical significance. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Identification of Risk Factors for COVID‐19 Hospitalization in Patients with Anti‐Rheumatic Drugs: Results from a Multicenter Nested Case Control Study |
Opdam et al., Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2551 |
Retrospective 81 cases and 396 controls among rheumatic disease patients in the Netherlands, showing lower risk of hospitalization with HCQ prophylaxis, without statistical significance.
risk of hospitalization, 45.0% lower, OR 0.55, p = 0.18, treatment 8 of 81 (9.9%) cases,
59 of 396 (14.9%) controls, NNT 17, case control OR.
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Opdam et al., 2/23/2022, retrospective, Netherlands, peer-reviewed, 9 authors.
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Submit Corrections or Comments
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Late |
Hall et al., The Annals of Thoracic Surgery, doi:10.1016/j.athoracsur.2022.01.043 |
death, ↓11.2%, p=0.31 |
Multi-institutional Analysis of 505 COVID-19 Patients Supported with ECMO: Predictors of Survival |
Details
Retrospective 505 ECMO patients showing no significant difference in mortality in unadjusted results. |
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Details
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Late treatment study
Late treatment study
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Multi-institutional Analysis of 505 COVID-19 Patients Supported with ECMO: Predictors of Survival |
Hall et al., The Annals of Thoracic Surgery, doi:10.1016/j.athoracsur.2022.01.043 |
Retrospective 505 ECMO patients showing no significant difference in mortality in unadjusted results.
risk of death, 11.2% lower, RR 0.89, p = 0.31, treatment 31 of 56 (55.4%), control 280 of 449 (62.4%), NNT 14.
|
Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Hall et al., 2/18/2022, retrospective, USA, peer-reviewed, 15 authors.
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Submit Corrections or Comments
|
|
PrEP |
Ugarte-Gil et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2021-221636 |
severe case, ↓44.4%, p=0.007 |
Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance |
Details
Retrospective 1,606 SLE patients showing lower risk of severe COVID-19 outcomes with HCQ/CQ use. |
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Details
Source
PDF
Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance |
Ugarte-Gil et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2021-221636 |
Retrospective 1,606 SLE patients showing lower risk of severe COVID-19 outcomes with HCQ/CQ use.
risk of severe case, 44.4% lower, OR 0.56, p = 0.007, treatment 665, control 230, adjusted, HCQ/CQ only vs. no SLE medication, multivariable, RR approximated with OR.
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Ugarte-Gil et al., 2/16/2022, retrospective, multiple countries, peer-reviewed, 58 authors.
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Submit Corrections or Comments
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Late |
Beaumont et al., Infectious Diseases Now, doi:10.1016/j.idnow.2022.02.001 |
death/int., ↓14.1%, p=0.55 |
Factors associated with hospital admission and adverse outcome for COVID-19: role of social factors and medical care |
Details
Retrospective 296 hospitalized patients in France, showing no significant difference with HCQ treatment. |
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Details
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Late treatment study
Late treatment study
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Factors associated with hospital admission and adverse outcome for COVID-19: role of social factors and medical care |
Beaumont et al., Infectious Diseases Now, doi:10.1016/j.idnow.2022.02.001 |
Retrospective 296 hospitalized patients in France, showing no significant difference with HCQ treatment.
risk of death/intubation, 14.1% lower, HR 0.86, p = 0.55, treatment 7 of 38 (18.4%), control 88 of 258 (34.1%), NNT 6.4, adjusted, OR converted to RR, Cox proportional hazards.
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Beaumont et al., 2/13/2022, retrospective, France, peer-reviewed, 22 authors, average treatment delay 6.0 days.
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Submit Corrections or Comments
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Late |
Albanghali et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2022.02.001 |
death, ↑34.6%, p=0.46 |
Clinical Characteristics and Treatment Outcomes of Mild to Moderate Covid-19 Patients in Saudi Arabia: A Single Centre Study |
Details
Retrospective 811 hospitalized COVID+ patients in Saudi Arabia, showing higher mortality with HCQ treatment in unadjusted results subject to confounding by indication. |
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Details
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Late treatment study
Late treatment study
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Clinical Characteristics and Treatment Outcomes of Mild to Moderate Covid-19 Patients in Saudi Arabia: A Single Centre Study |
Albanghali et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2022.02.001 |
Retrospective 811 hospitalized COVID+ patients in Saudi Arabia, showing higher mortality with HCQ treatment in unadjusted results subject to confounding by indication.
risk of death, 34.6% higher, RR 1.35, p = 0.46, treatment 20 of 466 (4.3%), control 11 of 345 (3.2%).
|
Excluded in after exclusion results of meta analysis:
unadjusted results with no group details, substantial unadjusted confounding by indication likely.
Albanghali et al., 2/3/2022, retrospective, Saudi Arabia, peer-reviewed, 8 authors.
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Submit Corrections or Comments
|
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Late |
Omma et al., The Journal of Infection in Developing Countries, doi:10.3855/jidc.14933 |
death, ↓28.2%, p=0.30 |
Hydroxychloroquine shortened hospital stay and reduced intensive care unit admissions in hospitalized COVID-19 patients |
Details
Retrospective 393 hospitalized COVID-19 patients in Turkey, showing lower ICU admission and shorter hospitalization time with HCQ. There was no significant difference for mortality. Severity was higher in the HCQ group with greater baseli.. |
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Details
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Late treatment study
Late treatment study
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Hydroxychloroquine shortened hospital stay and reduced intensive care unit admissions in hospitalized COVID-19 patients |
Omma et al., The Journal of Infection in Developing Countries, doi:10.3855/jidc.14933 |
Retrospective 393 hospitalized COVID-19 patients in Turkey, showing lower ICU admission and shorter hospitalization time with HCQ. There was no significant difference for mortality. Severity was higher in the HCQ group with greater baseline ventilation, high flow oxygen, fever, and dyspnea.
risk of death, 28.2% lower, RR 0.72, p = 0.30, treatment 17 of 213 (8.0%), control 20 of 180 (11.1%), NNT 32.
|
risk of ICU admission, 50.2% lower, RR 0.50, p = 0.004, treatment 23 of 213 (10.8%), control 39 of 180 (21.7%), NNT 9.2.
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hospitalization time, 16.7% lower, relative time 0.83, p = 0.007, treatment 213, control 180.
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Omma et al., 1/31/2022, retrospective, Turkey, peer-reviewed, 11 authors, study period 1 April, 2020 - 31 December, 2020.
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Submit Corrections or Comments
|
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PrEP |
Strangfeld et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-219498 |
death, ↓48.0%, p<0.0001 |
Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry |
Details
Retrospective 3,729 rheumatic disease patients showing lower risk of mortality with HCQ/CQ use (HCQ/CQ vs. no DMARD therapy). |
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Details
Source
PDF
Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry |
Strangfeld et al., Annals of the Rheumatic Diseases, doi:10.1136/annrheumdis-2020-219498 |
Retrospective 3,729 rheumatic disease patients showing lower risk of mortality with HCQ/CQ use (HCQ/CQ vs. no DMARD therapy).
risk of death, 48.0% lower, RR 0.52, p < 0.001, treatment 27 of 426 (6.3%), control 124 of 739 (16.8%), NNT 9.6, adjusted, OR converted to RR, HCQ/CQ vs. no DMARD therapy, multivariable.
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Strangfeld et al., 1/27/2022, retrospective, multiple countries, peer-reviewed, 37 authors, study period 24 March, 2020 - 1 July, 2020.
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Submit Corrections or Comments
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PrEP |
Erden et al., Bratislava Medical Journal, doi:10.4149/BLL_2022_018 |
death, ↑150.0%, p=1.00 |
COVID-19 outcomes in patients with antiphospholipid syndrome: a retrospective cohort study |
Details
Retrospective 9 COVID-19 patients with antiphospholipid syndrome in Turkey, showing no significant differences based on existing HCQ treatment. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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COVID-19 outcomes in patients with antiphospholipid syndrome: a retrospective cohort study |
Erden et al., Bratislava Medical Journal, doi:10.4149/BLL_2022_018 |
Retrospective 9 COVID-19 patients with antiphospholipid syndrome in Turkey, showing no significant differences based on existing HCQ treatment.
risk of death, 150.0% higher, RR 2.50, p = 1.00, treatment 1 of 6 (16.7%), control 0 of 3 (0.0%), continuity correction due to zero event.
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risk of hospitalization, 75.0% lower, RR 0.25, p = 0.23, treatment 1 of 6 (16.7%), control 2 of 3 (66.7%), NNT 2.0.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Erden et al., 1/23/2022, retrospective, Turkey, peer-reviewed, 11 authors.
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Late |
Lavilla Olleros et al., PLOS ONE, doi:10.1371/journal.pone.0261711 |
death, ↓36.2%, p<0.0001 |
Use of glucocorticoids megadoses in SARS-CoV-2 infection in a spanish registry: SEMI-COVID-19 |
Details
Retrospective 14,921 hospitalized patients in Spain, showing lower mortality with HCQ treatment. |
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Late treatment study
Late treatment study
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Use of glucocorticoids megadoses in SARS-CoV-2 infection in a spanish registry: SEMI-COVID-19 |
Lavilla Olleros et al., PLOS ONE, doi:10.1371/journal.pone.0261711 |
Retrospective 14,921 hospitalized patients in Spain, showing lower mortality with HCQ treatment.
risk of death, 36.2% lower, RR 0.64, p < 0.001, treatment 2,285 of 12,772 (17.9%), control 774 of 2,149 (36.0%), NNT 5.5, adjusted, OR converted to RR, multivariable.
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Lavilla Olleros et al., 1/21/2022, retrospective, Spain, peer-reviewed, 22 authors.
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Late |
Alwafi et al., Cureus, doi:10.7759/cureus.21442 |
viral+, ↓14.7%, p=0.65 |
Negative Nasopharyngeal SARS-CoV-2 PCR Conversion in Response to Different Therapeutic Interventions |
Details
Retrospective 93 hospitalized patients in Saudi Arabia, 45 treated with CQ/HCQ, showing no significant difference in viral clearance. More patients treated with CQ/HCQ had severe cases at baseline (20% vs. 2%). |
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Late treatment study
Late treatment study
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Negative Nasopharyngeal SARS-CoV-2 PCR Conversion in Response to Different Therapeutic Interventions |
Alwafi et al., Cureus, doi:10.7759/cureus.21442 |
Retrospective 93 hospitalized patients in Saudi Arabia, 45 treated with CQ/HCQ, showing no significant difference in viral clearance. More patients treated with CQ/HCQ had severe cases at baseline (20% vs. 2%).
risk of no viral clearance, 14.7% lower, RR 0.85, p = 0.65, treatment 12 of 45 (26.7%), control 15 of 48 (31.2%), NNT 22, day 5, primary outcome.
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risk of no viral clearance, 25.3% lower, RR 0.75, p = 0.60, treatment 7 of 45 (15.6%), control 10 of 48 (20.8%), NNT 19, day 12.
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Excluded in after exclusion results of meta analysis:
excessive unadjusted differences between groups.
Alwafi et al., 1/20/2022, retrospective, Saudi Arabia, peer-reviewed, 6 authors, study period 7 March, 2020 - 15 April, 2020.
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Submit Corrections or Comments
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Late |
Tu et al., Infectious Diseases & Immunity, doi:10.1097/ID9.0000000000000037 |
death, ↓17.2%, p=0.81 |
Risk Factors for Severity and Mortality in Adult Patients Confirmed with COVID-19 in Sierra Leone: A Retrospective Study |
Details
Retrospective 180 hospitalized COVID-19 patients in Sierra Leone, showing no significant difference with HCQ treatment in unadjusted results, however HCQ was significantly more likely to be used for severe patients (33% vs. 12%). |
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Late treatment study
Late treatment study
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Risk Factors for Severity and Mortality in Adult Patients Confirmed with COVID-19 in Sierra Leone: A Retrospective Study |
Tu et al., Infectious Diseases & Immunity, doi:10.1097/ID9.0000000000000037 |
Retrospective 180 hospitalized COVID-19 patients in Sierra Leone, showing no significant difference with HCQ treatment in unadjusted results, however HCQ was significantly more likely to be used for severe patients (33% vs. 12%).
risk of death, 17.2% lower, RR 0.83, p = 0.81, treatment 6 of 37 (16.2%), control 28 of 143 (19.6%), NNT 30.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Tu et al., 1/13/2022, retrospective, Sierraleone, peer-reviewed, 11 authors, study period 31 March, 2020 - 11 August, 2020.
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Early |
Tyson et al., Preprint (Preprint) |
death, ↓99.8%, p<0.0001 |
Low Rates of Hospitalization and Death in 4,376 COVID-19 Patients Given Early Ambulatory Medical and Supportive Care. A Case Series and Observational Study. |
Details
Retrospective 4,376 patients with mild/moderate COVID-19 in the USA treated with multiple medications including HCQ/ivermectin, favipiravir, vitamin C, D, quercetin, zinc, mAbs, budesonide, dexamethasone, prednisone, and colchicine (exact.. |
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Details
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Early treatment study
Early treatment study
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Low Rates of Hospitalization and Death in 4,376 COVID-19 Patients Given Early Ambulatory Medical and Supportive Care. A Case Series and Observational Study. |
Tyson et al., Preprint (Preprint) |
Retrospective 4,376 patients with mild/moderate COVID-19 in the USA treated with multiple medications including HCQ/ivermectin, favipiravir, vitamin C, D, quercetin, zinc, mAbs, budesonide, dexamethasone, prednisone, and colchicine (exact treatments specific to each patient), showing significantly lower hospitalization and mortality compared to the surrounding community.
risk of death, 99.8% lower, RR 0.002, p < 0.001, treatment 0 of 3,962 (0.0%), control 471 of 20,921 (2.3%), NNT 44, relative risk is not 0 because of continuity correction due to zero events, All AVUC mild patients vs. Imperial County (corrected).
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risk of hospitalization, 99.8% lower, RR 0.002, p < 0.001, treatment 2 of 3,962 (0.1%), control 4,343 of 20,921 (20.8%), NNT 4.8, All AVUC mild patients vs. Imperial County (corrected).
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risk of death, 97.0% lower, RR 0.03, p < 0.001, treatment 3 of 4,375 (0.1%), control 471 of 20,921 (2.3%), NNT 46, All AVUC patients vs. Imperial County (corrected).
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risk of hospitalization, 99.0% lower, RR 0.010, p < 0.001, treatment 9 of 4,375 (0.2%), control 4,343 of 20,921 (20.8%), NNT 4.9, All AVUC patients vs. Imperial County (corrected).
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Tyson et al., 1/13/2022, retrospective, USA, preprint, 13 authors.
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Late |
AbdelGhaffar et al., PLOS ONE, doi:10.1371/journal.pone.0262348 |
death, ↓99.9%, p<0.0001 |
Prediction of mortality in hospitalized Egyptian patients with Coronavirus disease-2019: A multicenter retrospective study |
Details
Retrospective 3,712 hospitalized patients in Egypt, showing lower mortality with HCQ treatment in unadjusted results. According to the official treatment protocol, HCQ was recommended with higher risk and/or more serious cases. |
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Late treatment study
Late treatment study
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Prediction of mortality in hospitalized Egyptian patients with Coronavirus disease-2019: A multicenter retrospective study |
AbdelGhaffar et al., PLOS ONE, doi:10.1371/journal.pone.0262348 |
Retrospective 3,712 hospitalized patients in Egypt, showing lower mortality with HCQ treatment in unadjusted results. According to the official treatment protocol, HCQ was recommended with higher risk and/or more serious cases.
risk of death, 99.9% lower, RR 0.001, p < 0.001, treatment 0 of 238 (0.0%), control 900 of 3,474 (25.9%), NNT 3.9, relative risk is not 0 because of continuity correction due to zero events.
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AbdelGhaffar et al., 1/11/2022, retrospective, Egypt, peer-reviewed, 17 authors, study period April 2020 - July 2020.
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Submit Corrections or Comments
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PrEP |
Juneja et al., Journal of Basic and Clinical Physiology and Pharmacology, doi:10.1515/jbcpp-2021-0221 |
severe case, ↑141.8%, p=0.59 |
Hydroxychloroquine pre-exposure prophylaxis provides no protection against COVID-19 among health care workers: a cross-sectional study in a tertiary care hospital in North India |
Details
Retrospective 2,200 healthcare workers in India, 996 taking HCQ prophylaxis, showing no significant differences. There were large differences in the occupation of participants and therefore exposure, and the authors make no adjustments. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Hydroxychloroquine pre-exposure prophylaxis provides no protection against COVID-19 among health care workers: a cross-sectional study in a tertiary care hospital in North India |
Juneja et al., Journal of Basic and Clinical Physiology and Pharmacology, doi:10.1515/jbcpp-2021-0221 |
Retrospective 2,200 healthcare workers in India, 996 taking HCQ prophylaxis, showing no significant differences. There were large differences in the occupation of participants and therefore exposure, and the authors make no adjustments.
risk of severe case, 141.8% higher, RR 2.42, p = 0.59, treatment 2 of 996 (0.2%), control 1 of 1,204 (0.1%).
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risk of case, 6.4% higher, RR 1.06, p = 0.67, treatment 103 of 996 (10.3%), control 117 of 1,204 (9.7%).
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Excluded in after exclusion results of meta analysis:
excessive unadjusted differences between groups.
Juneja et al., 1/7/2022, retrospective, India, peer-reviewed, 9 authors, study period 2 April, 2020 - 3 September, 2020.
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Submit Corrections or Comments
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PEP |
McKinnon et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.12.343 |
symp. case, ↓2.5%, p=1.00 |
Safety and Tolerability of Hydroxychloroquine in healthcare workers and first responders for the prevention of COVID-19: WHIP COVID-19 Study |
Details
HCQ prophylaxis RCT with 201 weekly HCQ patients, 197 daily HCQ patients, and 200 control patients, concluding the prophylaxis is safe. There were no grade 3 or 4 AEs, SAEs, ER visits, or hospitalizations. There was only 4 confirmed cases.. |
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Post Exposure Prophylaxis study
Post Exposure Prophylaxis study
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Safety and Tolerability of Hydroxychloroquine in healthcare workers and first responders for the prevention of COVID-19: WHIP COVID-19 Study |
McKinnon et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.12.343 |
HCQ prophylaxis RCT with 201 weekly HCQ patients, 197 daily HCQ patients, and 200 control patients, concluding the prophylaxis is safe. There were no grade 3 or 4 AEs, SAEs, ER visits, or hospitalizations. There was only 4 confirmed cases, 2 in the placebo arm and one in each HCQ arm. 60% of patients had exposure at baseline.HCQ 400mg weekly or HCQ 200mg daily after a loading dose of 400mg on day 1.
risk of symptomatic case, 2.5% lower, RR 0.98, p = 1.00, treatment 2 of 365 (0.5%), control 1 of 178 (0.6%), NNT 7219, daily and weekly HCQ combined.
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risk of symptomatic case, no change, RR 1.00, p = 1.00, treatment 1 of 178 (0.6%), control 1 of 178 (0.6%), daily HCQ.
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risk of symptomatic case, 4.8% lower, RR 0.95, p = 1.00, treatment 1 of 187 (0.5%), control 1 of 178 (0.6%), NNT 3698, weekly HCQ.
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risk of symptomatic case, 53.3% lower, RR 0.47, p = 1.00, treatment 0 of 25 (0.0%), control 1 of 178 (0.6%), NNT 178, relative risk is not 0 because of continuity correction due to zero events, AD patients.
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risk of case, 51.2% lower, RR 0.49, p = 0.60, treatment 2 of 365 (0.5%), control 2 of 178 (1.1%), NNT 174, daily and weekly HCQ combined.
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risk of case, 50.0% lower, RR 0.50, p = 1.00, treatment 1 of 178 (0.6%), control 2 of 178 (1.1%), NNT 178, daily HCQ.
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risk of case, 52.4% lower, RR 0.48, p = 0.61, treatment 1 of 187 (0.5%), control 2 of 178 (1.1%), NNT 170, weekly HCQ.
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risk of case, 69.5% lower, RR 0.30, p = 1.00, treatment 0 of 25 (0.0%), control 2 of 178 (1.1%), NNT 89, relative risk is not 0 because of continuity correction due to zero events, AD patients.
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McKinnon et al., 12/23/2021, Double Blind Randomized Controlled Trial, USA, peer-reviewed, 10 authors, trial NCT04341441 (history) (WHIP COVID-19).
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Submit Corrections or Comments
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PrEP |
Rao et al., Expert Review of Anti-infective Therapy, doi:10.1080/14787210.2022.2015326 |
cases, ↓11.0%, p=0.68 |
Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 infection among healthcare workers: a prospective cohort study |
Details
Prospective PrEP study with low risk healthcare workers in India showing RR=0.89 [0.53-1.52]. There were no significant adverse effects. Only mean age and gender distribution are provided for baseline characteristics, no severity informat.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 infection among healthcare workers: a prospective cohort study |
Rao et al., Expert Review of Anti-infective Therapy, doi:10.1080/14787210.2022.2015326 |
Prospective PrEP study with low risk healthcare workers in India showing RR=0.89 [0.53-1.52]. There were no significant adverse effects. Only mean age and gender distribution are provided for baseline characteristics, no severity information is provided, and no adjustments were made. Authors analyze HCQ use for <8 vs. ≥8 weeks, noting a lack of statistical significance, but not providing the results.
risk of case, 11.0% lower, RR 0.89, p = 0.68, treatment 16 of 273 (5.9%), control 67 of 1,021 (6.6%), NNT 143.
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Excluded in after exclusion results of meta analysis:
unadjusted results with minimal group details.
Rao et al., 12/4/2021, prospective, India, peer-reviewed, 8 authors.
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Submit Corrections or Comments
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Late |
Ferreira et al., Revista da Associação Médica Brasileira, doi:10.1590/1806-9282.20210661 |
death, ↑151.5%, p=0.03 |
Outcomes associated with Hydroxychloroquine and Ivermectin in hospitalized patients with COVID-19: a single-center experience |
Details
Retrospective 230 hospitalized patients in Brazil showing higher mortality with HCQ treatment. Authors note that the treatments were more likely to be offered to sicker patients. Authors indicate that they do not know when medication was .. |
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Late treatment study
Late treatment study
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Outcomes associated with Hydroxychloroquine and Ivermectin in hospitalized patients with COVID-19: a single-center experience |
Ferreira et al., Revista da Associação Médica Brasileira, doi:10.1590/1806-9282.20210661 |
Retrospective 230 hospitalized patients in Brazil showing higher mortality with HCQ treatment. Authors note that the treatments were more likely to be offered to sicker patients. Authors indicate that they do not know when medication was started, which in some cases could have been after ICU admission or intubation. Dosage is unknown.
risk of death, 151.5% higher, RR 2.51, p = 0.03, treatment 17 of 111 (15.3%), control 11 of 81 (13.6%), OR converted to RR, multivariate.
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risk of death/intubation, 45.9% higher, RR 1.46, p = 0.23, treatment 30 of 111 (27.0%), control 15 of 81 (18.5%).
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risk of death/intubation/ICU, 61.3% higher, RR 1.61, p = 0.04, treatment 42 of 111 (37.8%), control 19 of 81 (23.5%).
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Ferreira et al., 11/26/2021, retrospective, Brazil, peer-reviewed, 5 authors, study period 12 March, 2020 - 8 July, 2020, average treatment delay 7.0 days, dosage not specified.
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Submit Corrections or Comments
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Late |
Calderón et al., PAMJ - Clinical Medicine, doi:10.11604/pamj-cm.2021.7.15.30981 |
death, ↑214.8%, p=0.38 |
Treatment with hydroxychloroquine vs nitazoxanide in patients with COVID-19: brief report |
Details
Planned RCT of HCQ vs. HCQ+nitazoxanide which was aborted due to the retracted Surgisphere paper. Authors retrospectively analyze a small set of HCQ vs. nitazoxanide patients (which were protocol deviations in the planned RCT), showing re.. |
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Late treatment study
Late treatment study
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Treatment with hydroxychloroquine vs nitazoxanide in patients with COVID-19: brief report |
Calderón et al., PAMJ - Clinical Medicine, doi:10.11604/pamj-cm.2021.7.15.30981 |
Planned RCT of HCQ vs. HCQ+nitazoxanide which was aborted due to the retracted Surgisphere paper. Authors retrospectively analyze a small set of HCQ vs. nitazoxanide patients (which were protocol deviations in the planned RCT), showing reduced hospitalization time and ICU admission with nitazoxanide.
risk of death, 214.8% higher, RR 3.15, p = 0.38, treatment 5 of 27 (18.5%), control 1 of 17 (5.9%).
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risk of mechanical ventilation, 651.9% higher, RR 7.52, p = 0.15, treatment 4 of 27 (14.8%), control 0 of 17 (0.0%), continuity correction due to zero event.
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risk of ICU admission, 145.5% higher, RR 2.45, p < 0.001, treatment 16 of 27 (59.3%), control 0 of 17 (0.0%), adjusted.
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hospitalization time, 107.4% higher, relative time 2.07, p = 0.006, treatment 27, control 17.
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Calderón et al., 11/23/2021, retrospective, Mexico, peer-reviewed, 7 authors, dosage 200mg bid days 1-7.
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Submit Corrections or Comments
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PrEP |
Ahmed et al., BioMed Research International, doi:10.1155/2021/1676914 |
cases, ↓99.3%, p=0.08 |
Factors Affecting the Incidence, Progression, and Severity of COVID-19 in Type 1 Diabetes Mellitus |
Details
Retrospective type 1 diabetes patients in Saudi Arabia showing reduced risk of cases with HCQ prophylaxis. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Factors Affecting the Incidence, Progression, and Severity of COVID-19 in Type 1 Diabetes Mellitus |
Ahmed et al., BioMed Research International, doi:10.1155/2021/1676914 |
Retrospective type 1 diabetes patients in Saudi Arabia showing reduced risk of cases with HCQ prophylaxis.
risk of case, 99.3% lower, OR 0.007, p = 0.08, treatment 0 of 50 (0.0%) cases,
13 of 50 (26.0%) controls, NNT 1.7, case control OR.
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Ahmed et al., 11/23/2021, retrospective, Saudi Arabia, peer-reviewed, 7 authors.
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Submit Corrections or Comments
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PrEP |
Samajdar et al., Journal of the Association of Physicians India, 69:11 |
cases, ↓74.5%, p<0.0001 |
Ivermectin and Hydroxychloroquine for Chemo-Prophylaxis of COVID-19: A Questionnaire Survey of Perception and Prescribing Practice of Physicians vis-a-vis Outcomes |
Details
Physician survey in India with 164 ivermectin prophylaxis, 129 HCQ prophylaxis, and 81 control patients, showing significantly lower COVID-19 cases with treatment. Details of the treatment and control groups and the definition of cases ar.. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Ivermectin and Hydroxychloroquine for Chemo-Prophylaxis of COVID-19: A Questionnaire Survey of Perception and Prescribing Practice of Physicians vis-a-vis Outcomes |
Samajdar et al., Journal of the Association of Physicians India, 69:11 |
Physician survey in India with 164 ivermectin prophylaxis, 129 HCQ prophylaxis, and 81 control patients, showing significantly lower COVID-19 cases with treatment. Details of the treatment and control groups and the definition of cases are not provided, and the results are subject to survey bias. Authors also report on community prophylaxis but present only combined ivermectin/HCQ results.
risk of case, 74.5% lower, RR 0.25, p < 0.001, treatment 12 of 129 (9.3%), control 29 of 81 (35.8%), NNT 3.8, OR converted to RR, physician survey.
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risk of case, 48.6% lower, RR 0.51, p = 0.03, treatment 11 of 109 (10.1%), control 39 of 200 (19.5%), NNT 11, OR converted to RR, combined ivermectin or HCQ in community.
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Excluded in after exclusion results of meta analysis:
minimal details provided, unadjusted results with no group details, results may be significantly affected by survey bias.
Samajdar et al., 11/17/2021, retrospective, India, peer-reviewed, 9 authors, study period 1 September, 2020 - 31 December, 2020, dosage not specified.
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Late |
Schmidt et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.34330 |
death, ↑333.0%, p=0.0001 |
Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19 |
Details
Retrospective 1,106 prostate cancer patients, showing higher mortality with HCQ treatment. |
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Late treatment study
Late treatment study
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Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19 |
Schmidt et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.34330 |
Retrospective 1,106 prostate cancer patients, showing higher mortality with HCQ treatment.
risk of death, 333.0% higher, OR 4.33, p < 0.001, treatment 70, control 407, adjusted, propensity score matching, multivariable, RR approximated with OR, excluded in exclusion analyses:
confounding by indication is likely and adjustments do not consider COVID-19 severity at baseline.
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risk of severe case, 613.0% higher, OR 7.13, p < 0.001, treatment 70, control 407, adjusted, propensity score matching, multivariable, RR approximated with OR, excluded in exclusion analyses:
confounding by indication is likely and adjustments do not consider COVID-19 severity at baseline.
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Schmidt et al., 11/12/2021, retrospective, USA, peer-reviewed, 42 authors, study period 17 March, 2020 - 11 February, 2021.
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Submit Corrections or Comments
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Late |
Cortez et al., Western Pacific Surveillance and Response Journal, doi:10.5365/wpsar.2021.12.4.852 |
death, ↓15.0%, p=1.00 |
Clinical characteristics and outcomes of COVID-19 patients in a tertiary hospital in Baguio City, Philippines |
Details
Retrospective 280 hospitalized patients in the Philippines, 25 treated with HCQ, not showing any significant differences in unadjusted results. |
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Late treatment study
Late treatment study
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Clinical characteristics and outcomes of COVID-19 patients in a tertiary hospital in Baguio City, Philippines |
Cortez et al., Western Pacific Surveillance and Response Journal, doi:10.5365/wpsar.2021.12.4.852 |
Retrospective 280 hospitalized patients in the Philippines, 25 treated with HCQ, not showing any significant differences in unadjusted results.
risk of death, 15.0% lower, RR 0.85, p = 1.00, treatment 1 of 25 (4.0%), control 12 of 255 (4.7%), NNT 142.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Cortez et al., 11/11/2021, retrospective, Philippines, peer-reviewed, 29 authors, study period March 2020 - October 2020.
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Submit Corrections or Comments
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Early |
Chechter et al., medRxiv, doi:10.1101/2021.11.05.21265569 (Preprint) |
hosp., ↓94.7%, p=0.004 |
Evaluation of patients treated by telemedicine in the COVID-19 pandemic by a private clinic in Sao Paulo, Brazil: A non-randomized clinical trial preliminary study |
Details
Prospective study of 187 telemedicine patients in Brazil. 74 presenting with moderate symptoms were offered treatment with HCQ+AZ, 12 did not accept HCQ (taking AZ only), forming a control group. There was lower hospitalization and improv.. |
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Early treatment study
Early treatment study
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Evaluation of patients treated by telemedicine in the COVID-19 pandemic by a private clinic in Sao Paulo, Brazil: A non-randomized clinical trial preliminary study |
Chechter et al., medRxiv, doi:10.1101/2021.11.05.21265569 (Preprint) |
Prospective study of 187 telemedicine patients in Brazil. 74 presenting with moderate symptoms were offered treatment with HCQ+AZ, 12 did not accept HCQ (taking AZ only), forming a control group. There was lower hospitalization and improved recovery with treatment. There appears to be different group sizes in the text and tables without explanation (maybe a typo). RBR-658khm.
risk of hospitalization, 94.7% lower, RR 0.05, p = 0.004, treatment 0 of 60 (0.0%), control 3 of 12 (25.0%), NNT 4.0, relative risk is not 0 because of continuity correction due to zero events.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Chechter et al., 11/5/2021, prospective, Brazil, preprint, 13 authors, dosage 800mg day 1, 400mg days 2-5, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary.
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Late |
Sarhan et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2021.10.024 |
death, ↓25.7%, p=0.39 |
Efficacy of the early treatment with tocilizumab-hydroxychloroquine and tocilizumab-remdesivir in severe COVID-19 Patients |
Details
Small 108 patient RCT comparing HCQ vs. remdesivir in very late stage treatment. All patients received tocilizumab. There were significant unadjusted baseline differences in ventilation and ICU admission. NCT04779047. REC-H-PhBSU-21011. |
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Late treatment study
Late treatment study
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Efficacy of the early treatment with tocilizumab-hydroxychloroquine and tocilizumab-remdesivir in severe COVID-19 Patients |
Sarhan et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2021.10.024 |
Small 108 patient RCT comparing HCQ vs. remdesivir in very late stage treatment. All patients received tocilizumab. There were significant unadjusted baseline differences in ventilation and ICU admission. NCT04779047. REC-H-PhBSU-21011.
risk of death, 25.7% lower, RR 0.74, p = 0.39, treatment 12 of 56 (21.4%), control 15 of 52 (28.8%), NNT 13.
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risk of no hospital discharge, 25.7% lower, RR 0.74, p = 0.39, treatment 12 of 56 (21.4%), control 15 of 52 (28.8%), NNT 13.
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hospitalization time, 25.0% higher, relative time 1.25, p = 0.06, treatment 56, control 52.
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Excluded in after exclusion results of meta analysis:
very late stage, >50% on oxygen/ventilation at baseline, significant unadjusted differences between groups.
Sarhan et al., 11/2/2021, Randomized Controlled Trial, Egypt, peer-reviewed, 8 authors, study period 1 October, 2020 - 10 March, 2021, this trial compares with another treatment - results may be better when compared to placebo, trial NCT04779047 (history).
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Submit Corrections or Comments
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Late |
Shousha et al., World Journal of Gastroenterology, doi:10.3748/wjg.v27.i40.6951 |
death, ↓11.5%, p=0.87 |
Hepatic and gastrointestinal disturbances in Egyptian patients infected with coronavirus disease 2019: A multicentre cohort study |
Details
Retrospective 547 hospitalized COVID+ patients in Egypt, showing no significant differences with CQ/HCQ treatment in unadjusted analysis. Treatments were applied according to patient conditions, demographics, and comorbidities as per the .. |
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Late treatment study
Late treatment study
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Hepatic and gastrointestinal disturbances in Egyptian patients infected with coronavirus disease 2019: A multicentre cohort study |
Shousha et al., World Journal of Gastroenterology, doi:10.3748/wjg.v27.i40.6951 |
Retrospective 547 hospitalized COVID+ patients in Egypt, showing no significant differences with CQ/HCQ treatment in unadjusted analysis. Treatments were applied according to patient conditions, demographics, and comorbidities as per the the official guidelines, indicating strong confounding by indication.
risk of death, 11.5% lower, RR 0.88, p = 0.87, treatment 12 of 136 (8.8%), control 41 of 411 (10.0%), NNT 87, unadjusted.
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Excluded in meta analysis:
confounding by indication, unadjusted results and treatment used selectively per official protocol, unadjusted results with no group details.
Shousha et al., 10/28/2021, retrospective, Egypt, peer-reviewed, 18 authors, study period 15 April, 2020 - 29 July, 2020.
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Late |
Guglielmetti et al., Scientific Reports, doi:10.1038/s41598-021-00243-4 |
death, ↓28.0%, p=0.10 |
Treatment for COVID-19—a cohort study from Northern Italy |
Details
Retrospective 600 hospitalized patients in Italy, showing lower mortality with HCQ treatment, without reaching statistical significance (p = 0.1). |
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Details
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Late treatment study
Late treatment study
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Treatment for COVID-19—a cohort study from Northern Italy |
Guglielmetti et al., Scientific Reports, doi:10.1038/s41598-021-00243-4 |
Retrospective 600 hospitalized patients in Italy, showing lower mortality with HCQ treatment, without reaching statistical significance (p = 0.1).
risk of death, 28.0% lower, HR 0.72, p = 0.10, treatment 474, control 126, multivariable Cox proportional hazards.
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Guglielmetti et al., 10/25/2021, retrospective, Italy, peer-reviewed, 19 authors, study period 21 February, 2020 - 15 May, 2020.
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Submit Corrections or Comments
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PrEP |
Belmont et al., ClinicalTrials.gov, NCT04354870 (Preprint) |
symp. case, ↓78.6%, p=0.21 |
COVID-19 PrEP HCW HCQ Study |
Details
Prospective study of HCQ prophylaxis in the USA, with 56 HCQ patients and 24 control patients, showing no significant differences. NCT04354870 |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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COVID-19 PrEP HCW HCQ Study |
Belmont et al., ClinicalTrials.gov, NCT04354870 (Preprint) |
Prospective study of HCQ prophylaxis in the USA, with 56 HCQ patients and 24 control patients, showing no significant differences. NCT04354870
risk of symptomatic case, 78.6% lower, RR 0.21, p = 0.21, treatment 1 of 56 (1.8%), control 2 of 24 (8.3%), NNT 15.
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risk of case, 14.3% lower, RR 0.86, p = 1.00, treatment 4 of 56 (7.1%), control 2 of 24 (8.3%), NNT 84.
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Submit Corrections or Comments
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Late |
Atipornwanich et al., SSRN Electronic Journal, doi:10.2139/ssrn.3936499 |
death, ↓56.2%, p=0.07 |
Various Combinations of Favipiravir, Lopinavir-Ritonavir, Darunavir-Ritonavir, High-Dose Oseltamivir, and Hydroxychloroquine for the Treatment of COVID-19: A Randomized Controlled Trial (FIGHT-COVID-19 Study) |
Details
RCT 320 patients in Thailand, showing significantly lower progression with HCQ for moderate/severe patients, and faster viral clearance with mild patients (statistically significant for 800mg). There are two sets of results - for moderate.. |
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Details
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Late treatment study
Late treatment study
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Various Combinations of Favipiravir, Lopinavir-Ritonavir, Darunavir-Ritonavir, High-Dose Oseltamivir, and Hydroxychloroquine for the Treatment of COVID-19: A Randomized Controlled Trial (FIGHT-COVID-19 Study) |
Atipornwanich et al., SSRN Electronic Journal, doi:10.2139/ssrn.3936499 |
RCT 320 patients in Thailand, showing significantly lower progression with HCQ for moderate/severe patients, and faster viral clearance with mild patients (statistically significant for 800mg). There are two sets of results - for moderate/severe patients, and for mild patients. There was no mortality for mild patients. NCT04303299.
risk of death, 56.2% lower, RR 0.44, p = 0.07, treatment 7 of 100 (7.0%), control 16 of 100 (16.0%), NNT 11, moderate/severe, HCQ arms vs. non-HCQ arms.
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risk of progression, 54.2% lower, RR 0.46, p = 0.02, treatment 11 of 100 (11.0%), control 24 of 100 (24.0%), NNT 7.7, moderate/severe, HCQ arms vs. non-HCQ arms.
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time to viral-, 7.1% lower, relative time 0.93, p = 0.51, treatment mean 10.4 (±6.3) n=50, control mean 11.2 (±5.7) n=50, moderate/severe, oseltamivir arms, primary outcome.
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time to viral-, 6.9% lower, relative time 0.93, p = 0.47, treatment mean 9.5 (±5.0) n=50, control mean 10.2 (±4.6) n=50, moderate/severe, favipiravir arms, primary outcome.
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risk of progression, 150.0% higher, RR 2.50, p = 1.00, treatment 1 of 60 (1.7%), control 0 of 30 (0.0%), continuity correction due to zero event, mild, early treatment result.
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time to viral-, 43.3% lower, relative time 0.57, p = 0.04, treatment mean 8.9 (±6.0) n=30, control mean 15.7 (±16.7) n=30, mild, HCQ 800, primary outcome, early treatment result.
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time to viral-, 36.3% lower, relative time 0.64, p = 0.09, treatment mean 10.0 (±6.9) n=30, control mean 15.7 (±16.7) n=30, mild, HCQ 400, primary outcome, early treatment result.
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Atipornwanich et al., 10/5/2021, Randomized Controlled Trial, Thailand, peer-reviewed, 16 authors, dosage 400mg days 1-14, 800mg/day or 400mg/day, this trial compares with another treatment - results may be better when compared to placebo, this trial uses multiple treatments in the treatment arm (combined with oseltamivir/favipiravir and duranivir/ritonavir for moderate/severe, oseltamivir and duranivir/ritonavir for mild) - results of individual treatments may vary, trial NCT04303299 (history).
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Submit Corrections or Comments
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Late |
Babalola et al., Research Square, doi:10.21203/rs.3.rs-950352/v1 (Preprint) |
no disch., ↑54.5%, p=0.20 |
A Randomized Controlled Trial of Ivermectin Monotherapy Versus Hydroxychloroquine, Ivermectin, and Azithromycin Combination Therapy in Covid-19 Patients in Nigeria |
Details
Small RCT with 61 patients in Nigeria, all patients treated with ivermectin, zinc, and vitamin C, showing no significant improvements in recovery with the addition of HCQ+AZ. PACTR202108891693522. |
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Late treatment study
Late treatment study
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A Randomized Controlled Trial of Ivermectin Monotherapy Versus Hydroxychloroquine, Ivermectin, and Azithromycin Combination Therapy in Covid-19 Patients in Nigeria |
Babalola et al., Research Square, doi:10.21203/rs.3.rs-950352/v1 (Preprint) |
Small RCT with 61 patients in Nigeria, all patients treated with ivermectin, zinc, and vitamin C, showing no significant improvements in recovery with the addition of HCQ+AZ. PACTR202108891693522.
risk of no hospital discharge, 54.5% higher, RR 1.55, p = 0.20, treatment 17 of 30 (56.7%), control 11 of 30 (36.7%), day 7.
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risk of no viral clearance, 9.5% lower, RR 0.90, p = 0.78, treatment 19 of 30 (63.3%), control 21 of 30 (70.0%), NNT 15, day 5 mid-recovery.
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Babalola et al., 10/1/2021, Single Blind Randomized Controlled Trial, Nigeria, preprint, 6 authors, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary.
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Submit Corrections or Comments
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PrEP |
Fung et al., PLoS ONE, doi:10.1371/journal.pone.0266922 (preprint 10/1/2021) |
death, ↓13.0%, p=0.15 |
Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients |
Details
Retrospective database analysis of 374,229 patients in the USA, showing no significant difference with HCQ use, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research sh.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients |
Fung et al., PLoS ONE, doi:10.1371/journal.pone.0266922 (preprint 10/1/2021) |
Retrospective database analysis of 374,229 patients in the USA, showing no significant difference with HCQ use, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].Authors compare with patients that never used HCQ and with patients that previously used HCQ. The comparison with patients previously using HCQ is more relevant because the matching of patients with systemic autoimmune disease is likely to be better.
risk of death, 13.0% lower, HR 0.87, p = 0.15, vs. past use (better match for systemic autoimmune diseases).
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risk of hospitalization, 3.0% lower, HR 0.97, p = 0.63, vs. past use (better match for systemic autoimmune diseases).
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risk of case, 9.0% lower, HR 0.91, p = 0.02, vs. past use (better match for systemic autoimmune diseases).
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risk of death, 8.0% higher, HR 1.08, p = 0.26, vs. never used.
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risk of hospitalization, 6.0% higher, HR 1.06, p = 0.13, vs. never used.
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risk of case, 5.0% lower, HR 0.95, p = 0.03, vs. never used.
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Excluded in after exclusion results of meta analysis:
not fully adjusting for the different baseline risk of systemic autoimmune patients.
Fung et al., 10/1/2021, retrospective, population-based cohort, USA, peer-reviewed, 6 authors.
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Submit Corrections or Comments
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Late |
Menardi et al., PharmAdvances, doi:10.36118/pharmadvances.2021.15 |
death, ↓35.2%, p=0.12 |
A retrospective analysis on pharmacological approaches to COVID-19 patients in an Italian hub hospital during the early phase of the pandemic |
Details
Retrospective 277 hospitalized patients in Italy, showing lower mortality with HCQ treatment, not reaching statistical significance, and subject to confounding by indication. |
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Details
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Late treatment study
Late treatment study
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A retrospective analysis on pharmacological approaches to COVID-19 patients in an Italian hub hospital during the early phase of the pandemic |
Menardi et al., PharmAdvances, doi:10.36118/pharmadvances.2021.15 |
Retrospective 277 hospitalized patients in Italy, showing lower mortality with HCQ treatment, not reaching statistical significance, and subject to confounding by indication.
risk of death, 35.2% lower, RR 0.65, p = 0.12, treatment 32 of 200 (16.0%), control 19 of 77 (24.7%), NNT 12.
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Excluded in after exclusion results of meta analysis:
excessive unadjusted differences between groups, substantial unadjusted confounding by indication likely.
Menardi et al., 9/30/2021, retrospective, Italy, peer-reviewed, 10 authors.
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Submit Corrections or Comments
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Late |
Uygen et al., Northern Clinics of Istanbul, doi:10.14744/nci.2021.65471 |
viral- time, ↓12.2%, p=0.05 |
Effect of Hydroxychloroquine Use on the Length Of Hospital Stay in Children Diagnosed With Covid 19 |
Details
Retrospective 40 pediatric hospitalized patients, 15 treated with HCQ, showing 7.2 vs. 8.2 days until PCR-, not quite reaching statistical significance. |
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Details
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Late treatment study
Late treatment study
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Effect of Hydroxychloroquine Use on the Length Of Hospital Stay in Children Diagnosed With Covid 19 |
Uygen et al., Northern Clinics of Istanbul, doi:10.14744/nci.2021.65471 |
Retrospective 40 pediatric hospitalized patients, 15 treated with HCQ, showing 7.2 vs. 8.2 days until PCR-, not quite reaching statistical significance.
time to viral-, 12.2% lower, relative time 0.88, p = 0.05, treatment 15, control 25.
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Uygen et al., 9/15/2021, retrospective, Turkey, peer-reviewed, 4 authors.
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Submit Corrections or Comments
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Late |
Çivriz Bozdağ et al., Turk. J. Haematol., doi:10.4274/tjh.galenos.2021.2021.0287 |
death, ↑399.2%, p=0.003 |
Clinical Characteristics and Outcome of COVID-19 in Turkish Hematological Malignancy Patients |
Details
Retrospective 340 patients with hematological malignancy in Turkey, showing higher mortality with HCQ treatment. Confounding by time is likely because more HCQ patients were earlier in time when overall treatment protocols were significan.. |
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Late treatment study
Late treatment study
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Clinical Characteristics and Outcome of COVID-19 in Turkish Hematological Malignancy Patients |
Çivriz Bozdağ et al., Turk. J. Haematol., doi:10.4274/tjh.galenos.2021.2021.0287 |
Retrospective 340 patients with hematological malignancy in Turkey, showing higher mortality with HCQ treatment. Confounding by time is likely because more HCQ patients were earlier in time when overall treatment protocols were significantly worse.
risk of death, 399.2% higher, RR 4.99, p = 0.003, treatment 35, control 140.
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Excluded in after exclusion results of meta analysis:
substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
Çivriz Bozdağ et al., 9/15/2021, retrospective, Turkey, peer-reviewed, 62 authors.
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Submit Corrections or Comments
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Late |
Alotaibi et al., International Journal of General Medicine, 2021:14 |
death, ↑133.5%, p=0.05 |
Effectiveness and Safety of Favipiravir Compared to Hydroxychloroquine for Management of Covid-19: A Retrospective Study |
Details
Retrospective hospitalized patients in Saudi Arabia, showing lower mortality with favipiravir compared to HCQ, not quite reaching statistical significance. Authors do not indicate the factors behind which therapy was chosen. May be subjec.. |
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Late treatment study
Late treatment study
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Effectiveness and Safety of Favipiravir Compared to Hydroxychloroquine for Management of Covid-19: A Retrospective Study |
Alotaibi et al., International Journal of General Medicine, 2021:14 |
Retrospective hospitalized patients in Saudi Arabia, showing lower mortality with favipiravir compared to HCQ, not quite reaching statistical significance. Authors do not indicate the factors behind which therapy was chosen. May be subject to significant confounding by indication and confounding by time.
risk of death, 133.5% higher, RR 2.33, p = 0.05, treatment 193, control 244, multivariate.
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Alotaibi et al., 9/14/2021, retrospective, Saudi Arabia, peer-reviewed, 11 authors, this trial compares with another treatment - results may be better when compared to placebo.
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Submit Corrections or Comments
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PrEP |
Agarwal et al., medRxiv, doi:10.1101/2021.09.13.21262971 (Preprint) |
hosp., ↓94.8%, p=0.61 |
Low dose hydroxychloroquine prophylaxis for COVID-19 - a prospective study |
Details
Small prophylaxis trial with 29 low dose HCQ and 455 control healthcare workers in India, showing no statistically significant differences. |
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Details
Source
PDF
Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Low dose hydroxychloroquine prophylaxis for COVID-19 - a prospective study |
Agarwal et al., medRxiv, doi:10.1101/2021.09.13.21262971 (Preprint) |
Small prophylaxis trial with 29 low dose HCQ and 455 control healthcare workers in India, showing no statistically significant differences.
risk of hospitalization, 94.8% lower, RR 0.05, p = 0.61, treatment 0 of 29 (0.0%), control 17 of 455 (3.7%), NNT 27, relative risk is not 0 because of continuity correction due to zero events.
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relative severity, 26.9% better, RR 0.73, p = 0.21, treatment 29, control 455.
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risk of case, 4.6% higher, RR 1.05, p = 0.81, treatment 6 of 29 (20.7%), control 90 of 455 (19.8%).
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Agarwal et al., 9/14/2021, prospective, India, preprint, 1 author.
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Submit Corrections or Comments
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Early |
Accinelli et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2021.102163 |
Hydroxychloroquine / azithromycin in COVID-19: The association between time to treatment and case fatality rate |
Details
Retrospective 1,265 outpatients in Peru treated with HCQ+AZ showing mortality associated with treatment delay. Mortality was six times lower than the national average. |
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Details
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Early treatment study
Early treatment study
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Hydroxychloroquine / azithromycin in COVID-19: The association between time to treatment and case fatality rate |
Accinelli et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2021.102163 |
Retrospective 1,265 outpatients in Peru treated with HCQ+AZ showing mortality associated with treatment delay. Mortality was six times lower than the national average.
Accinelli et al., 9/14/2021, peer-reviewed, 6 authors, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary.
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Submit Corrections or Comments
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Early |
Sawanpanyalert et al., Southeast Asian Journal of Tropical Medicine and Public Health, 52:4 |
progression, ↓42.0%, p=0.37 |
Assessment of outcomes following implementation of antiviral treatment guidelines for COVID-19 during the first wave in Thailand |
Details
Retrospective 744 hospitalized patients in Thailand, showing lower risk of a poor outcome for favipiravir treatment within 4 days of symptom onset. Early treatment with CQ/HCQ and lopinavir/ritonavir or darunavir/ritonavir also showed low.. |
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Details
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Early treatment study
Early treatment study
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Assessment of outcomes following implementation of antiviral treatment guidelines for COVID-19 during the first wave in Thailand |
Sawanpanyalert et al., Southeast Asian Journal of Tropical Medicine and Public Health, 52:4 |
Retrospective 744 hospitalized patients in Thailand, showing lower risk of a poor outcome for favipiravir treatment within 4 days of symptom onset. Early treatment with CQ/HCQ and lopinavir/ritonavir or darunavir/ritonavir also showed lower risk, but without statistical significance. Sample sizes for the number of patients treated within 4 days of symptom onset are not provided.
risk of death, ICU, intubation, or high-flow oxygen, 42.0% lower, OR 0.58, p = 0.37, within 4 days of symptom onset, RR approximated with OR.
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Sawanpanyalert et al., 9/9/2021, retrospective, Thailand, peer-reviewed, 11 authors, dosage varies, this trial uses multiple treatments in the treatment arm (combined with lopinavir/ritonavir or darunavir/ritonavir) - results of individual treatments may vary.
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Submit Corrections or Comments
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Late |
Karruli et al., Microbial Drug Resistance, doi:10.1089/mdr.2020.0489 |
death, ↓4.8%, p=1.00 |
Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience |
Details
Retrospective 32 ICU patients, showing no significant difference with HCQ treatment in unadjusted results. |
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Late treatment study
Late treatment study
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Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience |
Karruli et al., Microbial Drug Resistance, doi:10.1089/mdr.2020.0489 |
Retrospective 32 ICU patients, showing no significant difference with HCQ treatment in unadjusted results.
risk of death, 4.8% lower, RR 0.95, p = 1.00, treatment 20 of 28 (71.4%), control 3 of 4 (75.0%), NNT 28.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Karruli et al., 9/1/2021, retrospective, Italy, peer-reviewed, 13 authors, study period March 2020 - May 2020.
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Submit Corrections or Comments
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PrEP |
Cordtz et al., Journal of Clinical Medicine, doi:10.3390/jcm10173842 |
hosp., ↓40.0%, p=0.39 |
Incidence of COVID-19 Hospitalisation in Patients with Systemic Lupus Erythematosus: A Nationwide Cohort Study from Denmark |
Details
Retrospective 2,533 SLE patients in Denmark showing no significant difference in hospitalization risk for COVID-19 cases with HCQ treatment. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Incidence of COVID-19 Hospitalisation in Patients with Systemic Lupus Erythematosus: A Nationwide Cohort Study from Denmark |
Cordtz et al., Journal of Clinical Medicine, doi:10.3390/jcm10173842 |
Retrospective 2,533 SLE patients in Denmark showing no significant difference in hospitalization risk for COVID-19 cases with HCQ treatment.
risk of hospitalization, 40.0% lower, HR 0.60, p = 0.39, treatment 1,170, control 1,363, adjusted.
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Cordtz et al., 8/27/2021, retrospective, population-based cohort, Denmark, peer-reviewed, 8 authors, study period 1 March, 2020 - 2 February, 2021.
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Submit Corrections or Comments
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Early |
Rodrigues et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2021.106428 |
hosp., ↑200.0%, p=1.00 |
Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance |
Details
RCT 84 low risk patients, 42 treated with HCQ/AZ, showing no significant differences. There was only one hospitalization which was in the treatment arm. |
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Details
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Early treatment study
Early treatment study
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Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance |
Rodrigues et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2021.106428 |
RCT 84 low risk patients, 42 treated with HCQ/AZ, showing no significant differences. There was only one hospitalization which was in the treatment arm.
risk of hospitalization, 200.0% higher, RR 3.00, p = 1.00, treatment 1 of 42 (2.4%), control 0 of 42 (0.0%), continuity correction due to zero event.
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risk of no viral clearance, 14.4% lower, RR 0.86, p = 0.15, treatment 29 of 36 (80.6%), control 32 of 34 (94.1%), NNT 7.4, PP, day 3.
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risk of no viral clearance, 13.1% lower, RR 0.87, p = 0.45, treatment 23 of 36 (63.9%), control 25 of 34 (73.5%), NNT 10, PP, day 6.
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risk of no viral clearance, 23.3% lower, RR 0.77, p = 0.47, treatment 13 of 36 (36.1%), control 16 of 34 (47.1%), NNT 9.1, PP, day 9.
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risk of no viral clearance, 3.1% lower, RR 0.97, p = 1.00, treatment 31 of 42 (73.8%), control 32 of 42 (76.2%), NNT 42, ITT, day 3.
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risk of no viral clearance, no change, RR 1.00, p = 1.00, treatment 25 of 42 (59.5%), control 25 of 42 (59.5%), ITT, day 6.
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risk of no viral clearance, 6.2% lower, RR 0.94, p = 1.00, treatment 15 of 42 (35.7%), control 16 of 42 (38.1%), NNT 42, ITT, day 9.
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time to viral-, 8.8% lower, relative time 0.91, p = 0.26, treatment 36, control 34, PP.
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time to viral-, 1.4% lower, relative time 0.99, p = 0.85, treatment 42, control 42, ITT.
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Rodrigues et al., 8/25/2021, Double Blind Randomized Controlled Trial, Brazil, peer-reviewed, 8 authors, average treatment delay 3.8 days, dosage 400mg bid days 1-7, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary.
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Submit Corrections or Comments
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PrEP |
Naggie et al., medRxiv, doi:10.1101/2021.08.19.21262275 (Preprint) |
symp. case, ↓23.5%, p=0.18 |
Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial (HERO-HCQ) |
Details
RCT 1,360 healthcare workers in the USA showing OR 0.75 [0.49-1.15] for confirmed or suspected COVID-19 clinical infection by day 30. There were no significant safety issues. Authors note that pooling the results with the COVID PREP study.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial (HERO-HCQ) |
Naggie et al., medRxiv, doi:10.1101/2021.08.19.21262275 (Preprint) |
RCT 1,360 healthcare workers in the USA showing OR 0.75 [0.49-1.15] for confirmed or suspected COVID-19 clinical infection by day 30. There were no significant safety issues. Authors note that pooling the results with the COVID PREP study gives OR 0.74 [0.55-1.0] p = 0.046.
risk of symptomatic case, 23.5% lower, RR 0.76, p = 0.18, treatment 41 of 683 (6.0%), control 53 of 676 (7.8%), NNT 54, OR converted to RR, logistic regression.
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risk of symptomatic case, 29.3% lower, RR 0.71, p = 0.18, treatment 41 of 683 (6.0%), control 53 of 676 (7.8%), NNT 54, OR converted to RR, Mantel–Haenszel.
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Naggie et al., 8/25/2021, Randomized Controlled Trial, USA, preprint, 22 authors, trial NCT04334148 (history) (HERO-HCQ).
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Submit Corrections or Comments
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PrEP |
Patil et al., Research Square, doi:10.21203/rs.3.rs-805748/v1 (Preprint) |
death, ↓65.9%, p=0.10 |
A Prospective Longitudinal Study Evaluating The Influence of Immunosuppressives and Other Factors On COVID-19 in Autoimmune Rheumatic Diseases |
Details
Prospective study of 9,212 autoimmune rheumatic disease patients showing lower mortality with HCQ, without reaching statistical significance. Authors incorrectly state "HCQ use did not influence occurrence of COVID-19 (RR = 0.909, CI.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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A Prospective Longitudinal Study Evaluating The Influence of Immunosuppressives and Other Factors On COVID-19 in Autoimmune Rheumatic Diseases |
Patil et al., Research Square, doi:10.21203/rs.3.rs-805748/v1 (Preprint) |
Prospective study of 9,212 autoimmune rheumatic disease patients showing lower mortality with HCQ, without reaching statistical significance. Authors incorrectly state "HCQ use did not influence occurrence of COVID-19 (RR = 0.909, CI (0.715,1.154), p = 0.432) or mortality (p = 0.097)" [nature.com]. CFR for the autoimmune rheumatic disease patients was 4.6 times higher than in the general population from the same area.
risk of death, 65.9% lower, RR 0.34, p = 0.10, treatment 5,266, control 3,946.
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risk of case, 9.1% lower, RR 0.91, p = 0.43, treatment 167 of 5,266 (3.2%), control 147 of 3,946 (3.7%), NNT 181, adjusted.
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Patil et al., 8/24/2021, prospective, India, preprint, 20 authors.
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Submit Corrections or Comments
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Late |
Eldeen et al., Microbes and Infectious Diseases, doi:10.21608/mid.2021.85877.1177 |
Comparative study between the therapeutic effect of remdesivir versus hydroxychloroquine in COVID-19 hospitalized patients |
Details
Small study comparing 25 HCQ and 25 remdesivir hospitalized patients, reporting faster viral clearance with remdesivir. The article proof is missing the results for the HCQ group. Confounding by time is likely - remdesivir patients were a.. |
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Late treatment study
Late treatment study
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Comparative study between the therapeutic effect of remdesivir versus hydroxychloroquine in COVID-19 hospitalized patients |
Eldeen et al., Microbes and Infectious Diseases, doi:10.21608/mid.2021.85877.1177 |
Small study comparing 25 HCQ and 25 remdesivir hospitalized patients, reporting faster viral clearance with remdesivir. The article proof is missing the results for the HCQ group. Confounding by time is likely - remdesivir patients were after HCQ patients in time, and treatment protocols improved over the period of the study.
Eldeen et al., 8/16/2021, peer-reviewed, 5 authors.
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N/A |
Tai et al., Pharmaceutics, doi:10.3390/pharmaceutics13081260 |
Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19 |
Details
Analysis of HCQ solutions suitable for nebulization for COVID-19. |
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N/A
N/A
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Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19 |
Tai et al., Pharmaceutics, doi:10.3390/pharmaceutics13081260 |
Analysis of HCQ solutions suitable for nebulization for COVID-19.
Tai et al., 8/14/2021, peer-reviewed, 8 authors.
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PEP |
Shabani et al., Pulmonary Pharmacology & Therapeutics, doi:10.1016/j.pupt.2021.102069 |
symp. case, ↓19.0%, p=1.00 |
Evaluation of the Prophylactic Effect of Hydroxychloroquine on People in Close-Contact with Patients with Covid-19 |
Details
Small PEP trial with 51 HCQ patients, not showing a significant difference in cases. IRCT20130917014693N10. |
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Post Exposure Prophylaxis study
Post Exposure Prophylaxis study
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Evaluation of the Prophylactic Effect of Hydroxychloroquine on People in Close-Contact with Patients with Covid-19 |
Shabani et al., Pulmonary Pharmacology & Therapeutics, doi:10.1016/j.pupt.2021.102069 |
Small PEP trial with 51 HCQ patients, not showing a significant difference in cases. IRCT20130917014693N10.
risk of symptomatic case, 19.0% lower, RR 0.81, p = 1.00, treatment 2 of 51 (3.9%), control 3 of 62 (4.8%), NNT 109, day 7.
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risk of case, 6.4% higher, RR 1.06, p = 1.00, treatment 7 of 51 (13.7%), control 8 of 62 (12.9%), day 7, PCR+ and symptomatic.
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risk of case, 21.6% higher, RR 1.22, p = 0.78, treatment 7 of 51 (13.7%), control 7 of 62 (11.3%), day 7, PCR+ only.
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Shabani et al., 8/10/2021, prospective, Iran, peer-reviewed, 16 authors.
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PrEP |
Stricker et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2021.08.001 (meta analysis) |
death, ↓75.0%, p<0.0001 |
Hydroxychloroquine Pre-Exposure Prophylaxis for COVID-19 in Healthcare Workers from India: A Meta-Analysis |
Details
Meta analysis of 11 HCQ PrEP studies in India covering 7,616 healthcare workers, showing significantly lower cases with treatment. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Hydroxychloroquine Pre-Exposure Prophylaxis for COVID-19 in Healthcare Workers from India: A Meta-Analysis |
Stricker et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2021.08.001 (meta analysis) |
Meta analysis of 11 HCQ PrEP studies in India covering 7,616 healthcare workers, showing significantly lower cases with treatment.
risk of death, 75.0% lower, RR 0.25, p < 0.001, treatment 1,273, control 4,127, >=6 doses.
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risk of death, 44.0% lower, RR 0.56, p = 0.004, treatment 3,489, control 4,127, any number of doses.
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Stricker et al., 8/5/2021, peer-reviewed, 2 authors.
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Late |
Özuygur Ermiş et al., Turkish Journal of Medical Sciences, doi:10.3906/sag-2009-64 |
The Efficacy of Hydroxychloroquine and Azithromycin Combination Therapy on Hospital Mortality in COVID 19 Pneumonia Patients |
Details
Retrospective 370 hospitalized patients, 222 receiving HCQ+AZ and 148 receiving HCQ, showing mortality OR 0.61 [0.23-1.59], p = 0.31 for the addition of AZ. |
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Late treatment study
Late treatment study
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The Efficacy of Hydroxychloroquine and Azithromycin Combination Therapy on Hospital Mortality in COVID 19 Pneumonia Patients |
Özuygur Ermiş et al., Turkish Journal of Medical Sciences, doi:10.3906/sag-2009-64 |
Retrospective 370 hospitalized patients, 222 receiving HCQ+AZ and 148 receiving HCQ, showing mortality OR 0.61 [0.23-1.59], p = 0.31 for the addition of AZ.
Özuygur Ermiş et al., 8/4/2021, peer-reviewed, 13 authors.
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PrEP |
Bhatt et al., medRxiv, doi:10.1101/2021.08.02.21260750 (Preprint) |
cases, ↑49.3%, p=0.02 |
Hydroxychloroquine Prophylaxis against Coronavirus Disease-19: Practice Outcomes among Health-Care Workers |
Details
Observational study of 927 low-risk healthcare workers in India, 731 volunteering for weekly HCQ prophylaxis, showing higher cases with treatment in unadjusted results. Clinical outcome was in the protocol, however no information on which.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Hydroxychloroquine Prophylaxis against Coronavirus Disease-19: Practice Outcomes among Health-Care Workers |
Bhatt et al., medRxiv, doi:10.1101/2021.08.02.21260750 (Preprint) |
Observational study of 927 low-risk healthcare workers in India, 731 volunteering for weekly HCQ prophylaxis, showing higher cases with treatment in unadjusted results. Clinical outcome was in the protocol, however no information on which patients were symptomatic is provided. There were no adverse events and no hospitalizations or deaths. Adherence was very low, decreasing weekly, with almost all participants discontinuing by week 11. The majority of infections occurred in later weeks when adherence was very low, and there was no per protocol analysis. #ECR/206/Inst/GJ/2013/RR-20.
risk of case, 49.3% higher, RR 1.49, p = 0.02, treatment 167 of 731 (22.8%), control 30 of 196 (15.3%).
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Bhatt et al., 8/4/2021, prospective, India, preprint, 4 authors.
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Late |
Alghamdi et al., Saudi Pharmaceutical Journal, doi:10.1016/j.jsps.2021.08.008 |
death, ↑39.2%, p=0.52 |
Clinical characteristics and treatment outcomes of severe (ICU) COVID-19 patients in Saudi Arabia: A single centre study |
Details
Retrospective 171 ICU patients in Saudi Arabia showing no significant difference for HCQ treatment in unadjusted results. |
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Late treatment study
Late treatment study
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Clinical characteristics and treatment outcomes of severe (ICU) COVID-19 patients in Saudi Arabia: A single centre study |
Alghamdi et al., Saudi Pharmaceutical Journal, doi:10.1016/j.jsps.2021.08.008 |
Retrospective 171 ICU patients in Saudi Arabia showing no significant difference for HCQ treatment in unadjusted results.
risk of death, 39.2% higher, RR 1.39, p = 0.52, treatment 29 of 128 (22.7%), control 7 of 43 (16.3%).
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details, very late stage, ICU patients.
Alghamdi et al., 8/4/2021, retrospective, Saudi Arabia, peer-reviewed, 1 author.
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Submit Corrections or Comments
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Late |
Barra et al., medRxiv, doi:10.1101/2021.07.30.21261220 (Preprint) |
death, ↓10.8%, p=1.00 |
COVID-19 in hospitalized patients in 4 hospitals in San Isidro, Buenos Aires, Argentina |
Details
Retrospective 668 hospitalized patients in Argentina, 18 treated with HCQ, not showing a significant difference in unadjusted results. |
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Late treatment study
Late treatment study
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COVID-19 in hospitalized patients in 4 hospitals in San Isidro, Buenos Aires, Argentina |
Barra et al., medRxiv, doi:10.1101/2021.07.30.21261220 (Preprint) |
Retrospective 668 hospitalized patients in Argentina, 18 treated with HCQ, not showing a significant difference in unadjusted results.
risk of death, 10.8% lower, RR 0.89, p = 1.00, treatment 2 of 18 (11.1%), control 81 of 650 (12.5%), NNT 74, unadjusted.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Barra et al., 7/31/2021, retrospective, Argentina, preprint, 12 authors, average treatment delay 5.0 days.
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Early |
Sobngwi et al., medRxiv, doi:10.1101/2021.07.25.21260838 (Preprint) |
no recov., ↓51.6%, p=0.44 |
Doxycycline is a safe alternative to Hydroxychloroquine + Azithromycin to prevent clinical worsening and hospitalization in mild COVID-19 patients: An open label randomized clinical trial (DOXYCOV) |
Details
RCT 194 mild/asymptomatic low-risk patients in Cameroon, 97 treated with HCQ+AZ and 97 treated with doxycycline, showing 2.1% symptomatic patients at day 10 with HCQ+AZ, versus 4.3% with doxycycline, but without statistical significance. .. |
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Early treatment study
Early treatment study
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Doxycycline is a safe alternative to Hydroxychloroquine + Azithromycin to prevent clinical worsening and hospitalization in mild COVID-19 patients: An open label randomized clinical trial (DOXYCOV) |
Sobngwi et al., medRxiv, doi:10.1101/2021.07.25.21260838 (Preprint) |
RCT 194 mild/asymptomatic low-risk patients in Cameroon, 97 treated with HCQ+AZ and 97 treated with doxycycline, showing 2.1% symptomatic patients at day 10 with HCQ+AZ, versus 4.3% with doxycycline, but without statistical significance. There were only 6 patients with symtoms at day 10. There was no mortality or hospitalization, and no major adverse events.
risk of no recovery, 51.6% lower, RR 0.48, p = 0.44, treatment 2 of 95 (2.1%), control 4 of 92 (4.3%), NNT 45, day 10.
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risk of no recovery, 3.2% lower, RR 0.97, p = 1.00, treatment 18 of 95 (18.9%), control 18 of 92 (19.6%), NNT 162, day 3.
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risk of no viral clearance, 3.2% lower, RR 0.97, p = 0.88, treatment 32 of 95 (33.7%), control 32 of 92 (34.8%), NNT 91, day 10.
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Sobngwi et al., 7/29/2021, Randomized Controlled Trial, Cameroon, preprint, 16 authors, dosage 400mg days 1-5, this trial compares with another treatment - results may be better when compared to placebo.
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PrEP |
Küçükakkaş et al., Research Square, doi:10.21203/rs.3.rs-43812/v1 (Preprint) |
ICU, ↑42.9%, p=1.00 |
The effect of hydroxychloroquine against SARS-CoV-2 infection in rheumatoid arthritis patients |
Details
Retrospective 17 rheumatoid arthritis COVID-19+ patients, 7 on HCQ treatment, showing no significant differences. They study reports only including hospitalized patients, but the results include non-hospitalized patients. Results do not r.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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The effect of hydroxychloroquine against SARS-CoV-2 infection in rheumatoid arthritis patients |
Küçükakkaş et al., Research Square, doi:10.21203/rs.3.rs-43812/v1 (Preprint) |
Retrospective 17 rheumatoid arthritis COVID-19+ patients, 7 on HCQ treatment, showing no significant differences. They study reports only including hospitalized patients, but the results include non-hospitalized patients. Results do not reflect potential difference in the probability that a case is serious enough to have been tested and identified. Few group details are provided (even the age of patients in each group is not specified).
risk of ICU admission, 42.9% higher, RR 1.43, p = 1.00, treatment 1 of 7 (14.3%), control 1 of 10 (10.0%).
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Excluded in after exclusion results of meta analysis:
minimal details of groups provided.
Küçükakkaş et al., 7/20/2021, retrospective, Turkey, preprint, 2 authors.
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Submit Corrections or Comments
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Late |
Alhamlan et al., medRxiv, doi:10.1101/2021.07.13.21260428 (Preprint) |
death, ↑52.0%, p=0.57 |
Epidemiology and Clinical Characteristics in Individuals with Confirmed SARS-CoV-2 Infection During the Early COVID-19 Pandemic in Saudi Arabia |
Details
Retrospective hospitalized patients in Saudi Arabia showing higher mortality with most treatments although not reaching statistical significance. Confounding by indication, time, or other factors is likely (a 19x higher risk with lopinavi.. |
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Late treatment study
Late treatment study
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Epidemiology and Clinical Characteristics in Individuals with Confirmed SARS-CoV-2 Infection During the Early COVID-19 Pandemic in Saudi Arabia |
Alhamlan et al., medRxiv, doi:10.1101/2021.07.13.21260428 (Preprint) |
Retrospective hospitalized patients in Saudi Arabia showing higher mortality with most treatments although not reaching statistical significance. Confounding by indication, time, or other factors is likely (a 19x higher risk with lopinavir/ritonavir and 3.5x higher risk with azithromycin is not supported by other studies for example). The number of patients treated with HCQ is not provided.
risk of death, 52.0% higher, HR 1.52, p = 0.57.
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Excluded in after exclusion results of meta analysis:
substantial unadjusted confounding by indication likely, substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
Alhamlan et al., 7/16/2021, retrospective, database analysis, Saudi Arabia, preprint, 10 authors.
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Late |
Barrat-Due et al., Annals of Internal Medicine, doi:10.7326/M21-0653 |
death, ↑120.0%, p=0.35 |
Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 |
Details
Small RCT in Norway with 52 HCQ and 42 remdesivir patients, showing no significant differences with treatment. Add-on trial to WHO Solidarity. NCT04321616. |
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Late treatment study
Late treatment study
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Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 |
Barrat-Due et al., Annals of Internal Medicine, doi:10.7326/M21-0653 |
Small RCT in Norway with 52 HCQ and 42 remdesivir patients, showing no significant differences with treatment. Add-on trial to WHO Solidarity. NCT04321616.
risk of death, 120.0% higher, RR 2.20, p = 0.35, treatment 4 of 45 (8.9%), control 2 of 48 (4.2%), adjusted.
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Barrat-Due et al., 7/13/2021, Double Blind Randomized Controlled Trial, Norway, peer-reviewed, 41 authors, average treatment delay 8.0 days, trial NCT04321616 (history).
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Submit Corrections or Comments
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Late |
Tamura et al., Diabetology & Metabolic Syndrome, doi:10.1186/s13098-021-00695-8 |
death, ↑299.0%, p=0.04 |
Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies |
Details
Retrospective 188 hospitalized patients in Brazil, showing higher risk of mortality with HCQ. Relatively few patients received HCQ. The results are likely subject to confounding by indication with treatment more likely for severe cases, a.. |
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Late treatment study
Late treatment study
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Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies |
Tamura et al., Diabetology & Metabolic Syndrome, doi:10.1186/s13098-021-00695-8 |
Retrospective 188 hospitalized patients in Brazil, showing higher risk of mortality with HCQ. Relatively few patients received HCQ. The results are likely subject to confounding by indication with treatment more likely for severe cases, and severity was not used in adjustments. Confounding by time is likely, with declining use of HCQ and improving SOC over the study period.
risk of death, 299.0% higher, OR 3.99, p = 0.04, treatment 25, control 163, adjusted, multivariable, RR approximated with OR.
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Excluded in after exclusion results of meta analysis:
substantial unadjusted confounding by indication likely, substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
Tamura et al., 7/13/2021, retrospective, Brazil, peer-reviewed, 4 authors, study period 10 March, 2020 - 13 November, 2020.
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Submit Corrections or Comments
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Late |
Arabi et al., Intensive Care Medicine |
death, ↑44.5%, p=0.01 |
Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial |
Details
Very late stage RCT with 50 ICU patients treated with HCQ, 255 lopinavir-ritonavir patients, and 27 combined therapy patients, showing higher mortality with all treatments. |
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Late treatment study
Late treatment study
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Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial |
Arabi et al., Intensive Care Medicine |
Very late stage RCT with 50 ICU patients treated with HCQ, 255 lopinavir-ritonavir patients, and 27 combined therapy patients, showing higher mortality with all treatments.
risk of death, 44.5% higher, RR 1.44, p = 0.01, treatment 17 of 49 (34.7%), control 106 of 353 (30.0%), adjusted, OR converted to RR, multivariable.
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Arabi et al., 7/12/2021, Randomized Controlled Trial, multiple countries, peer-reviewed, 1 author, trial NCT02735707 (history) (REMAP-CAP).
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Submit Corrections or Comments
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Late |
Roger et al., Anaesthesia Critical Care & Pain Medicine, doi:10.1016/j.accpm.2021.100931 |
death, 0.0%, p=0.94 |
French Multicentre Observational Study on SARS-CoV-2 infections Intensive care initial management: the FRENCH CORONA Study |
Details
Prospective study of 966 ICU patients in France, 289 treated with HCQ, showing no significant difference with treatment. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered, w.. |
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Late treatment study
Late treatment study
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French Multicentre Observational Study on SARS-CoV-2 infections Intensive care initial management: the FRENCH CORONA Study |
Roger et al., Anaesthesia Critical Care & Pain Medicine, doi:10.1016/j.accpm.2021.100931 |
Prospective study of 966 ICU patients in France, 289 treated with HCQ, showing no significant difference with treatment. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered, while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
risk of death, no change, RR 1.00, p = 0.94, treatment 53 of 289 (18.3%), control 120 of 677 (17.7%), OR converted to RR.
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Excluded in after exclusion results of meta analysis:
substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
Roger et al., 7/10/2021, prospective, France, peer-reviewed, 34 authors, average treatment delay 8.0 days.
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Submit Corrections or Comments
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Late |
Jacobs et al., The Annals of Thoracic Surgery, doi:10.1016/j.athoracsur.2021.06.026 |
death, ↓6.6%, p=0.74 |
Multi-institutional Analysis of 200 COVID-19 Patients treated with ECMO:Outcomes and Trends |
Details
Prospective study of 200 ECMO patients showing no significant difference in unadjusted results for HCQ treatment. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered (as shown.. |
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Late treatment study
Late treatment study
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Multi-institutional Analysis of 200 COVID-19 Patients treated with ECMO:Outcomes and Trends |
Jacobs et al., The Annals of Thoracic Surgery, doi:10.1016/j.athoracsur.2021.06.026 |
Prospective study of 200 ECMO patients showing no significant difference in unadjusted results for HCQ treatment. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered (as shown in figure 4), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
risk of death, 6.6% lower, RR 0.93, p = 0.74, treatment 24 of 46 (52.2%), control 86 of 154 (55.8%), NNT 27.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details, substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
Jacobs et al., 7/6/2021, prospective, USA, peer-reviewed, 14 authors.
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Submit Corrections or Comments
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PrEP |
Shaw et al., Journal of Drugs in Dermatology, doi:10.36849/JDD.5843 |
cases, ↓13.0%, p=0.006 |
COVID-19 in Individuals Treated With Long-Term Hydroxychloroquine: A Propensity Score-Matched Analysis of Cicatricial Alopecia Patients |
Details
PSM retrospective 144 alopecia patients in the USA, showing lower risk of COVID-19 with HCQ prophylaxis. The supplemental appendix is not available. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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COVID-19 in Individuals Treated With Long-Term Hydroxychloroquine: A Propensity Score-Matched Analysis of Cicatricial Alopecia Patients |
Shaw et al., Journal of Drugs in Dermatology, doi:10.36849/JDD.5843 |
PSM retrospective 144 alopecia patients in the USA, showing lower risk of COVID-19 with HCQ prophylaxis. The supplemental appendix is not available.
risk of case, 13.0% lower, OR 0.87, p = 0.006, treatment 45, control 99, adjusted, propensity score matching, multivariable, RR approximated with OR.
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Shaw et al., 7/1/2021, retrospective, USA, peer-reviewed, 10 authors, study period 1 March, 2020 - 15 May, 2020.
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Submit Corrections or Comments
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Late |
Taieb et al., J. Clin. Med. 2021, doi:10.3390/jcm10132954 |
no disch., ↓38.7%, p=0.02 |
Hydroxychloroquine and Azithromycin Treatment of Hospitalized Patients Infected with SARS-CoV-2 in Senegal from March to October 2020 |
Details
Retrospective 926 patients in Senegal, 674 treated with HCQ+AZ, showing significantly higher hospital discharge at day 15 with treatment. |
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Late treatment study
Late treatment study
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Hydroxychloroquine and Azithromycin Treatment of Hospitalized Patients Infected with SARS-CoV-2 in Senegal from March to October 2020 |
Taieb et al., J. Clin. Med. 2021, doi:10.3390/jcm10132954 |
Retrospective 926 patients in Senegal, 674 treated with HCQ+AZ, showing significantly higher hospital discharge at day 15 with treatment.
risk of no hospital discharge, 38.7% lower, OR 0.61, p = 0.02, treatment 674, control 252, multivariate, RR approximated with OR.
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Taieb et al., 6/30/2021, retrospective, Senegal, peer-reviewed, 29 authors, average treatment delay 6.0 days.
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Submit Corrections or Comments
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Late |
Gerlovin et al., American Journal of Epidemiology, doi:10.1093/aje/kwab183 |
death, ↑22.0%, p=0.18 |
Pharmacoepidemiology, Machine Learning and COVID-19: An intent-to-treat analysis of hydroxychloroquine, with or without azithromycin, and COVID-19 outcomes amongst hospitalized US Veterans |
Details
Retrospective 1,769 hospitalized patients in the USA showing no significant differences for HCQ, and higher intubation for HCQ+AZ. |
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Late treatment study
Late treatment study
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Pharmacoepidemiology, Machine Learning and COVID-19: An intent-to-treat analysis of hydroxychloroquine, with or without azithromycin, and COVID-19 outcomes amongst hospitalized US Veterans |
Gerlovin et al., American Journal of Epidemiology, doi:10.1093/aje/kwab183 |
Retrospective 1,769 hospitalized patients in the USA showing no significant differences for HCQ, and higher intubation for HCQ+AZ.
risk of death, 22.0% higher, HR 1.22, p = 0.18, treatment 90 of 429 (21.0%), control 141 of 770 (18.3%), adjusted, HCQ+AZ.
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risk of death, 21.0% higher, HR 1.21, p = 0.33, treatment 49 of 228 (21.5%), control 141 of 770 (18.3%), adjusted, HCQ.
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risk of mechanical ventilation, 55.0% higher, HR 1.55, p = 0.02, treatment 64 of 429 (14.9%), control 69 of 770 (9.0%), adjusted, HCQ+AZ.
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risk of mechanical ventilation, 33.0% higher, HR 1.33, p = 0.25, treatment 32 of 228 (14.0%), control 69 of 770 (9.0%), adjusted, HCQ.
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Gerlovin et al., 6/24/2021, retrospective, USA, peer-reviewed, 21 authors.
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Submit Corrections or Comments
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In Silico |
Yadav et al., Research Square, doi:10.21203/rs.3.rs-628277/v1 (Preprint) |
In Silico |
Repurposing the Combination Drug of Favipiravir, Hydroxychloroquine and Oseltamivir as a Potential Inhibitor Against SARS-CoV-2: A Computational Study |
Details
In Silico study showing stronger inhibition of SAR-CoV-2 for HCQ+favipiravir+oseltamivir compared to any of these alone or combinations of two of these drugs. |
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In Silico
In Silico
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Repurposing the Combination Drug of Favipiravir, Hydroxychloroquine and Oseltamivir as a Potential Inhibitor Against SARS-CoV-2: A Computational Study |
Yadav et al., Research Square, doi:10.21203/rs.3.rs-628277/v1 (Preprint) |
In Silico study showing stronger inhibition of SAR-CoV-2 for HCQ+favipiravir+oseltamivir compared to any of these alone or combinations of two of these drugs.
Yadav et al., 6/21/2021, preprint, 2 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
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Submit Corrections or Comments
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Late |
Schwartz et al., CMAJ Open, doi:10.9778/cmajo.20210069 |
ICU, ↑133.3%, p=1.00 |
Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized controlled trial |
Details
Small early terminated late treatment RCT not showing significant differences. The HCQ group was a median of 7 days from symptom onset at baseline, which may not include the delay delivering the medication. From the 4 HCQ hospitalizations.. |
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Late treatment study
Late treatment study
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Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized controlled trial |
Schwartz et al., CMAJ Open, doi:10.9778/cmajo.20210069 |
Small early terminated late treatment RCT not showing significant differences. The HCQ group was a median of 7 days from symptom onset at baseline, which may not include the delay delivering the medication. From the 4 HCQ hospitalizations, only one is in the per-protocol analysis, and that patient was hospitalized one day after randomization (authors do not specify if the patient received and took any HCQ before the hospitalization). The trial was terminated early due to the fraudulent Lancet article (wording here is notably different between the submitted and published versions). Per-protocol analysis, the submitted version, and the peer-review comments (two reviewers, only one with substantial feedback) are in the supplementary material.
risk of ICU admission, 133.3% higher, RR 2.33, p = 1.00, treatment 1 of 111 (0.9%), control 0 of 37 (0.0%), continuity correction due to zero event.
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risk of hospitalization, 533.3% higher, RR 6.33, p = 0.57, treatment 4 of 111 (3.6%), control 0 of 37 (0.0%), continuity correction due to zero event.
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risk of ICU admission, 141.9% higher, RR 2.42, p = 1.00, treatment 1 of 74 (1.4%), control 0 of 31 (0.0%), continuity correction due to zero event, per-protocol.
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risk of hospitalization, 141.9% higher, RR 2.42, p = 1.00, treatment 1 of 74 (1.4%), control 0 of 31 (0.0%), continuity correction due to zero event, per-protocol.
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Schwartz et al., 6/18/2021, Double Blind Randomized Controlled Trial, Canada, peer-reviewed, 20 authors, average treatment delay 7.0 days, dosage 800mg day 1, 400mg days 2-5.
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Submit Corrections or Comments
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In Vitro |
Purwati et al., PLOS One, doi:10.1371/journal.pone.0252302 (In Vitro) |
In Vitro |
An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia |
Details
In Vitro study of combinations of drugs showing antiviral efficacy of HCQ alone and in combination with AZ, favipiravir, and doxycycline. No high levels of cytotoxicity were observed, and authors conclude that using a combination of drugs.. |
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In Vitro
In Vitro
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An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia |
Purwati et al., PLOS One, doi:10.1371/journal.pone.0252302 (In Vitro) |
In Vitro study of combinations of drugs showing antiviral efficacy of HCQ alone and in combination with AZ, favipiravir, and doxycycline. No high levels of cytotoxicity were observed, and authors conclude that using a combination of drugs can reduce the degree of cytotoxicity, increase antiviral activity, reduce the effect on pro-inflammatory markers, and increase anti-inflammatory response.
Purwati et al., 6/18/2021, peer-reviewed, 16 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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Late |
Turrini et al., Vaccines, 10.3390/vaccines9060640 |
death, ↓9.8%, p=0.15 |
Clinical Course and Risk Factors for In-Hospital Mortality of 205 Patients with SARS-CoV-2 Pneumonia in Como, Lombardy Region, Italy |
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Retrospective 205 patients in Italy, 160 treated with HCQ, showing lower mortality with treatment in multivariate analysis, but not reaching statistical significance. |
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Late treatment study
Late treatment study
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Clinical Course and Risk Factors for In-Hospital Mortality of 205 Patients with SARS-CoV-2 Pneumonia in Como, Lombardy Region, Italy |
Turrini et al., Vaccines, 10.3390/vaccines9060640 |
Retrospective 205 patients in Italy, 160 treated with HCQ, showing lower mortality with treatment in multivariate analysis, but not reaching statistical significance.
risk of death, 9.8% lower, RR 0.90, p = 0.15, treatment 103 of 160 (64.4%), control 33 of 45 (73.3%), NNT 11, adjusted, OR converted to RR, multivariate.
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Turrini et al., 6/11/2021, retrospective, Italy, peer-reviewed, 16 authors.
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Late |
Saib et al., PLOS ONE, doi:10.1371/journal.pone.0252388 |
death/int., ↑125.0%, p=0.23 |
Lack of efficacy of hydroxychloroquine and azithromycin in patients hospitalized for COVID-19 pneumonia: A retrospective study |
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203 hospitalized patients in France, not showing significant differences with treatment. Confounding by indication is likely. Authors do not discuss confounding. |
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Late treatment study
Late treatment study
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Lack of efficacy of hydroxychloroquine and azithromycin in patients hospitalized for COVID-19 pneumonia: A retrospective study |
Saib et al., PLOS ONE, doi:10.1371/journal.pone.0252388 |
203 hospitalized patients in France, not showing significant differences with treatment. Confounding by indication is likely. Authors do not discuss confounding.
risk of death/intubation, 125.0% higher, RR 2.25, p = 0.23, treatment 9 of 52 (17.3%), control 4 of 52 (7.7%), PSM.
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Excluded in after exclusion results of meta analysis:
substantial unadjusted confounding by indication likely.
Saib et al., 6/9/2021, prospective, propensity score matching, France, peer-reviewed, 9 authors, average treatment delay 7.2 days.
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Late |
Singh et al., medRxiv, doi:0.1101/2021.06.06.21258091 (Preprint) |
death, ↓47.5%, p=0.45 |
Safety and efficacy of antiviral therapy alone or in combination in COVID-19 - a randomized controlled trial (SEV COVID Trial) |
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Very small early terminated RCT in India, showing lower mortality but without statistical significance with the very small sample size. Time since symptom onset is not provided. The recovery percentage for non-severe group B (86.7%) does .. |
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Late treatment study
Late treatment study
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Safety and efficacy of antiviral therapy alone or in combination in COVID-19 - a randomized controlled trial (SEV COVID Trial) |
Singh et al., medRxiv, doi:0.1101/2021.06.06.21258091 (Preprint) |
Very small early terminated RCT in India, showing lower mortality but without statistical significance with the very small sample size. Time since symptom onset is not provided. The recovery percentage for non-severe group B (86.7%) does not match any number of recoveries, we have used the closest number (15/17).
risk of death, 47.5% lower, RR 0.53, p = 0.45, treatment 3 of 20 (15.0%), control 6 of 21 (28.6%), NNT 7.4, severe.
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risk of death, 50.0% lower, RR 0.50, p = 0.48, treatment 3 of 37 (8.1%), control 6 of 37 (16.2%), NNT 12, all patients.
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risk of no recovery, 14.1% lower, RR 0.86, p = 0.76, treatment 9 of 20 (45.0%), control 11 of 21 (52.4%), NNT 14, severe.
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risk of no recovery, 8.3% lower, RR 0.92, p = 1.00, treatment 11 of 37 (29.7%), control 12 of 37 (32.4%), NNT 37, all patients.
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Singh et al., 6/8/2021, Randomized Controlled Trial, India, preprint, 13 authors, this trial uses multiple treatments in the treatment arm (combined with ribavirin) - results of individual treatments may vary.
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PrEP |
Badyal et al., Journal of the Association of Physicians of India, Volume 69, June 2021 |
cases, ↓60.1%, p<0.0001 |
Hydroxychloroquine for SARS CoV2 Prophylaxis in Healthcare Workers – A Multicentric Cohort Study Assessing Effectiveness and Safety |
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Prophylaxis study with 12,089 Indian healthcare workers, showing lower risk of COVID-19 cases with treatment, and increasingly lower risk for longer durations of HCQ prophylaxis. The appendices are not currently available. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Hydroxychloroquine for SARS CoV2 Prophylaxis in Healthcare Workers – A Multicentric Cohort Study Assessing Effectiveness and Safety |
Badyal et al., Journal of the Association of Physicians of India, Volume 69, June 2021 |
Prophylaxis study with 12,089 Indian healthcare workers, showing lower risk of COVID-19 cases with treatment, and increasingly lower risk for longer durations of HCQ prophylaxis. The appendices are not currently available.
risk of case, 60.1% lower, RR 0.40, p < 0.001, treatment 247 of 617 (40.0%), control 611 of 1,473 (41.5%), adjusted, OR converted to RR, >=6 weeks, logistic regression.
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risk of case, 35.1% lower, RR 0.65, p = 0.003, treatment 88 of 185 (47.6%), control 611 of 1,473 (41.5%), adjusted, OR converted to RR, 4-5 weeks, logistic regression.
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risk of case, 23.2% lower, RR 0.77, p = 0.04, treatment 80 of 181 (44.2%), control 611 of 1,473 (41.5%), adjusted, OR converted to RR, 2-3 weeks, logistic regression.
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Badyal et al., 6/7/2021, prospective, India, peer-reviewed, 18 authors.
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Late |
Lagier et al., Therapeutics and Clinical Risk Management, doi:10.2147/TCRM.S364022 |
death, ↓32.0%, p=0.004 |
Outcomes of 2,111 COVID-19 hospitalised patients treated with 2 hydroxychloroquine/azithromycin and other regimens in Marseille, France: a 3 monocentric retrospective analysis |
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Retrospective 2,011 hospitalized patients in France, median age 67, showing lower mortality with HCQ+AZ, and further benefit with the addition of zinc. |
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Late treatment study
Late treatment study
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Outcomes of 2,111 COVID-19 hospitalised patients treated with 2 hydroxychloroquine/azithromycin and other regimens in Marseille, France: a 3 monocentric retrospective analysis |
Lagier et al., Therapeutics and Clinical Risk Management, doi:10.2147/TCRM.S364022 |
Retrospective 2,011 hospitalized patients in France, median age 67, showing lower mortality with HCQ+AZ, and further benefit with the addition of zinc.
risk of death, 32.0% lower, HR 0.68, p = 0.004, treatment 93 of 1,270 (7.3%), control 146 of 841 (17.4%), NNT 10.0, adjusted, multivariable, Cox proportional hazards.
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Lagier et al., 6/4/2021, retrospective, France, peer-reviewed, 32 authors.
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Late |
Byakika-Kibwika et al., Research Square, doi:10.21203/rs.3.rs-506195/v1 (Preprint) |
recov. time, 0.0%, p=0.91 |
Safety and Efficacy of Hydroxychloroquine for Treatment of Non-Severe COVID-19 in Adults in Uganda: A Randomized Open Label Phase II Clinical Trial |
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Small 105 patient RCT in Uganda showing no significant differences. No mortality was reported. The patients were very young (median age 32), recovering in a median time of 3 days with standard of care, so there is little room for a treatm.. |
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Late treatment study
Late treatment study
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Safety and Efficacy of Hydroxychloroquine for Treatment of Non-Severe COVID-19 in Adults in Uganda: A Randomized Open Label Phase II Clinical Trial |
Byakika-Kibwika et al., Research Square, doi:10.21203/rs.3.rs-506195/v1 (Preprint) |
Small 105 patient RCT in Uganda showing no significant differences. No mortality was reported. The patients were very young (median age 32), recovering in a median time of 3 days with standard of care, so there is little room for a treatment to make improvements. Time since symptom onset is not specified, but the distribution of symptoms at baseline suggests that the enrollment is relatively late within a cohort of low risk patients.
recovery time, no change, relative time 1.00, p = 0.91, treatment 36, control 29.
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relative improvement in Ct value, 29.3% better, RR 0.71, p = 0.47, treatment 15, control 15.
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risk of no viral clearance, 2.6% higher, RR 1.03, p = 1.00, treatment 35 of 55 (63.6%), control 31 of 50 (62.0%), day 6.
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risk of no viral clearance, 6.7% higher, RR 1.07, p = 0.85, treatment 27 of 55 (49.1%), control 23 of 50 (46.0%), day 10.
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Byakika-Kibwika et al., 6/4/2021, Randomized Controlled Trial, Uganda, preprint, 17 authors.
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Late |
Sivapalan et al., European Respiratory Journal, doi:10.1183/13993003.00752-2021 |
death, ↓92.0%, p=0.32 |
Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19–a randomised double-blinded placebo-controlled trial |
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Early terminated late stage (8 days from onset, 59% on oxygen) RCT not showing statistically significant differences. NCT04322396 ProPAC-COVID. NNF20SA0062834. |
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Late treatment study
Late treatment study
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Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19–a randomised double-blinded placebo-controlled trial |
Sivapalan et al., European Respiratory Journal, doi:10.1183/13993003.00752-2021 |
Early terminated late stage (8 days from onset, 59% on oxygen) RCT not showing statistically significant differences. NCT04322396 ProPAC-COVID. NNF20SA0062834.
risk of death, 92.0% lower, RR 0.08, p = 0.32, treatment 1 of 61 (1.6%), control 2 of 56 (3.6%), adjusted.
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risk of ICU admission, 22.4% higher, RR 1.22, p = 1.00, treatment 4 of 61 (6.6%), control 3 of 56 (5.4%).
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relative days alive and discharged from hospital within 14 days (inverse), 8.4% worse, RR 1.08, p = 0.36, treatment 61, control 56, adjusted.
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Sivapalan et al., 6/3/2021, Double Blind Randomized Controlled Trial, Denmark, peer-reviewed, 32 authors, average treatment delay 8.0 days, trial NCT04322396 (history).
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PrEP |
Korkmaz et al., Authorea, doi:10.22541/au.162257516.68665404/v1 (Preprint) |
death, ↓82.1%, p=0.19 |
The effect of Hydroxychloroquine use due to rheumatic disease on the risk of Covid-19 infection and its course |
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Retrospective 683 patients in a rheumatology department, 384 chronic HCQ users and 299 control patients, showing no mortality for HCQ users vs. 2 deaths in the control group, and significantly fewer cases for HCQ users. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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The effect of Hydroxychloroquine use due to rheumatic disease on the risk of Covid-19 infection and its course |
Korkmaz et al., Authorea, doi:10.22541/au.162257516.68665404/v1 (Preprint) |
Retrospective 683 patients in a rheumatology department, 384 chronic HCQ users and 299 control patients, showing no mortality for HCQ users vs. 2 deaths in the control group, and significantly fewer cases for HCQ users.
risk of death, 82.1% lower, RR 0.18, p = 0.19, treatment 0 of 385 (0.0%), control 2 of 299 (0.7%), NNT 150, relative risk is not 0 because of continuity correction due to zero events.
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risk of case, 93.7% lower, RR 0.06, p < 0.001, treatment 2 of 395 (0.5%), control 24 of 299 (8.0%), NNT 13.
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Korkmaz et al., 6/1/2021, retrospective, Turkey, preprint, 4 authors.
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PrEP |
Kamstrup et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.05.076 |
hosp., ↑44.0%, p=0.25 |
Hydroxychloroquine as a primary prophylactic agent against sars-cov-2 infection: a cohort study |
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Retrospective HCQ users in Denmark, not showing a significant difference, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Authors appear unaware of research in the area, for exa.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Hydroxychloroquine as a primary prophylactic agent against sars-cov-2 infection: a cohort study |
Kamstrup et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.05.076 |
Retrospective HCQ users in Denmark, not showing a significant difference, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients.Authors appear unaware of research in the area, for example saying that "currently, no obvious connection exists between a known rheumatological disorder and the risk of contracting SARS-CoV-2". Many papers show that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, e.g., Ferri et al. show OR 4.42, p<0.001 [Ferri].Supplementary data is not currently available.
risk of hospitalization, 44.0% higher, OR 1.44, p = 0.25, treatment 5,488, control 54,846, RR approximated with OR.
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risk of case, 10.0% lower, HR 0.90, p = 0.23, treatment 188 of 5,488 (3.4%), control 2,040 of 54,846 (3.7%), NNT 340, adjusted Cox proportional hazards regression.
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Excluded in after exclusion results of meta analysis:
not fully adjusting for the different baseline risk of systemic autoimmune patients.
Kamstrup et al., 6/1/2021, retrospective, population-based cohort, Denmark, peer-reviewed, 21 authors.
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Late |
Ramírez-García et al., Archivos de Medicina Universitaria |
death, ↓67.0%, p<0.0001 |
Hydroxychloroquine and Tocilizumab in the Treatment of COVID-19: A Longitudinal Observational Study |
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Retrospective 403 hospitalized patients in Spain, showing lower mortality with treatment, however authors do not adjust for the differences between the groups. Confounding by indication is likely. |
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Late treatment study
Late treatment study
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Hydroxychloroquine and Tocilizumab in the Treatment of COVID-19: A Longitudinal Observational Study |
Ramírez-García et al., Archivos de Medicina Universitaria |
Retrospective 403 hospitalized patients in Spain, showing lower mortality with treatment, however authors do not adjust for the differences between the groups. Confounding by indication is likely.
risk of death, 67.0% lower, RR 0.33, p < 0.001, treatment 48 of 350 (13.7%), control 22 of 53 (41.5%), NNT 3.6.
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risk of ICU admission, 6.0% higher, RR 1.06, p = 1.00, treatment 35 of 350 (10.0%), control 5 of 53 (9.4%).
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Excluded in after exclusion results of meta analysis:
excessive unadjusted differences between groups, substantial unadjusted confounding by indication likely.
Ramírez-García et al., 5/31/2021, retrospective, Spain, peer-reviewed, 5 authors.
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Late |
Smith et al., medRxiv, doi:10.1101/2021.05.28.21258012 (Preprint) |
death, ↓27.2%, p=0.002 |
Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic |
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Retrospective 255 mechanical ventilation patients in USA, showing that weight-adjusted HCQ+AZ improved survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ serum level. Although authors mention immorta.. |
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Late treatment study
Late treatment study
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Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic |
Smith et al., medRxiv, doi:10.1101/2021.05.28.21258012 (Preprint) |
Retrospective 255 mechanical ventilation patients in USA, showing that weight-adjusted HCQ+AZ improved survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ serum level.Although authors mention immortal time bias, full details on the timing of HCQ administration is not provided and this is not fully addressed. Survival curves indicate immortal time bias will significantly change results, although the observed benefit appears to exceed the potential bias.
risk of death, 27.2% lower, RR 0.73, p = 0.002, treatment 19 of 37 (51.4%), control 182 of 218 (83.5%), NNT 3.1, OR converted to RR, >3g HCQ and >1g AZ, multivariable cox proportional hazard regression.
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risk of death, 92.9% lower, OR 0.07, p < 0.001, ≥80mg/kg HCQ and >1g AZ, RR approximated with OR.
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Excluded in after exclusion results of meta analysis:
immortal time bias may significantly affect results.
Smith et al., 5/31/2021, retrospective, USA, preprint, 4 authors.
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Dosing |
Ali et al., Journal of Pharmaceutical Research International, doi:10.9734/jpri/2020/v32i830468 (Dosing) |
dosing study |
Optimizing the Use of Hydroxychloroquine in the Management of COVID-19 Given Its Pharmacological Profile |
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Review of the mechanisms of action, pharmacokinetics and toxicity of HCQ, recommending use as early as possible with a loading dose in 3-4 divided doses to minimize toxicity, and daily maintenance divided into two doses, continued until r.. |
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Dosing
Dosing
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Optimizing the Use of Hydroxychloroquine in the Management of COVID-19 Given Its Pharmacological Profile |
Ali et al., Journal of Pharmaceutical Research International, doi:10.9734/jpri/2020/v32i830468 (Dosing) |
Review of the mechanisms of action, pharmacokinetics and toxicity of HCQ, recommending use as early as possible with a loading dose in 3-4 divided doses to minimize toxicity, and daily maintenance divided into two doses, continued until remission.
Ali et al., 5/29/2021, peer-reviewed, 8 authors.
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Early |
Million et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm2203116 (preprint 5/27/2021) |
death, ↓83.0%, p=0.0007 |
Early Treatment with Hydroxychloroquine and Azithromycin in 10,429 COVID-19 Outpatients: A Monocentric Retrospective Cohort Study |
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Retrospective 10,429 outpatients in France, 8,315 treated with HCQ+AZ a median of 4 days from symptom onset, showing significantly lower mortality with treatment. |
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Early treatment study
Early treatment study
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Early Treatment with Hydroxychloroquine and Azithromycin in 10,429 COVID-19 Outpatients: A Monocentric Retrospective Cohort Study |
Million et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm2203116 (preprint 5/27/2021) |
Retrospective 10,429 outpatients in France, 8,315 treated with HCQ+AZ a median of 4 days from symptom onset, showing significantly lower mortality with treatment.
risk of death, 83.0% lower, HR 0.17, p < 0.001, treatment 5 of 8,315 (0.1%), control 11 of 2,114 (0.5%), NNT 217, adjusted.
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risk of ICU admission, 44.0% lower, HR 0.56, p = 0.18, treatment 17 of 8,315 (0.2%), control 7 of 2,114 (0.3%), NNT 789, adjusted.
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risk of hospitalization, 4.0% lower, HR 0.96, p = 0.77, treatment 214 of 8,315 (2.6%), control 64 of 2,114 (3.0%), adjusted.
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Million et al., 5/27/2021, retrospective, France, peer-reviewed, 28 authors, average treatment delay 4.0 days, dosage 200mg tid days 1-10, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary.
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PrEP |
Syed et al., Cureus, doi:10.7759/cureus.20572 (preprint 5/17/2021) |
symp. case, ↑59.7%, p=0.41 |
Pre-exposure Prophylaxis With Various Doses of Hydroxychloroquine Among Healthcare Personnel With High-Risk Exposure to COVID-19: A Randomized Controlled Trial |
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Small PrEP RCT of low risk healthcare workers, showing no significant differences. Authors report that there was no hospitalization, ICU care, or death from COVID-19, however table 3 of the preprint shows severe events labeled as "re.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Pre-exposure Prophylaxis With Various Doses of Hydroxychloroquine Among Healthcare Personnel With High-Risk Exposure to COVID-19: A Randomized Controlled Trial |
Syed et al., Cureus, doi:10.7759/cureus.20572 (preprint 5/17/2021) |
Small PrEP RCT of low risk healthcare workers, showing no significant differences. Authors report that there was no hospitalization, ICU care, or death from COVID-19, however table 3 of the preprint shows severe events labeled as "requiring hospitalization". Symptomatology and disease severity results in tables 3 and 4 appear inconsistent. NCT04359537.
risk of symptomatic case, 59.7% higher, RR 1.60, p = 0.41, treatment 10 of 48 (20.8%), control 6 of 46 (13.0%), group 1.
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risk of symptomatic case, 110.5% higher, RR 2.10, p = 0.13, treatment 14 of 51 (27.5%), control 6 of 46 (13.0%), group 2.
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risk of symptomatic case, 16.4% lower, RR 0.84, p = 0.77, treatment 6 of 55 (10.9%), control 6 of 46 (13.0%), NNT 47, group 3.
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risk of case, 91.7% higher, RR 1.92, p = 0.12, treatment 15 of 38 (39.5%), control 7 of 34 (20.6%), group 1.
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risk of case, 136.6% higher, RR 2.37, p = 0.02, treatment 19 of 39 (48.7%), control 7 of 34 (20.6%), group 2.
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risk of case, 21.4% higher, RR 1.21, p = 0.77, treatment 8 of 32 (25.0%), control 7 of 34 (20.6%), group 3.
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Syed et al., 5/17/2021, Randomized Controlled Trial, Pakistan, peer-reviewed, 8 authors, trial NCT04359537 (history).
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PrEP |
Rojas-Serrano et al., medRxiv, doi:10.1101/2021.05.14.21257059 (Preprint) |
symp. case, ↓82.0%, p=0.12 |
Hydroxychloroquine For Prophylaxis Of COVID-19 In Health Workers: A Randomized Clinical Trial |
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Early terminated HCQ PrEP RCT with 62 HCQ and 65 placebo patients, showing 82% lower cases with treatment, p = 0.12. NCT04318015. If the trial is continued and the same event rate is observed, statistical significance will be reached afte.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Hydroxychloroquine For Prophylaxis Of COVID-19 In Health Workers: A Randomized Clinical Trial |
Rojas-Serrano et al., medRxiv, doi:10.1101/2021.05.14.21257059 (Preprint) |
Early terminated HCQ PrEP RCT with 62 HCQ and 65 placebo patients, showing 82% lower cases with treatment, p = 0.12. NCT04318015.If the trial is continued and the same event rate is observed, statistical significance will be reached after adding about 16 patients per arm.
risk of symptomatic case, 82.0% lower, RR 0.18, p = 0.12, treatment 1 of 62 (1.6%), control 6 of 65 (9.2%), NNT 13, adjusted.
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Rojas-Serrano et al., 5/16/2021, Double Blind Randomized Controlled Trial, Mexico, preprint, 8 authors, trial NCT04318015 (history).
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Early |
Drancourt et al., Viruses, doi:10.3390/v13050890 |
SARS-CoV-2 Persistent Viral Shedding in the Context of Hydroxychloroquine-Azithromycin Treatment |
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Retrospective 3,737 patients in France, showing lower risk of persistent viral shedding with HCQ+AZ treatment. |
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Early treatment study
Early treatment study
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SARS-CoV-2 Persistent Viral Shedding in the Context of Hydroxychloroquine-Azithromycin Treatment |
Drancourt et al., Viruses, doi:10.3390/v13050890 |
Retrospective 3,737 patients in France, showing lower risk of persistent viral shedding with HCQ+AZ treatment.
Drancourt et al., 5/12/2021, peer-reviewed, 11 authors, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary.
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Late |
Sammartino et al., PLOS One, doi:10.1371/journal.pone.0251262 |
death, ↑240.0%, p=0.002 |
Predictors for inpatient mortality during the first wave of the SARS-CoV-2 pandemic: A retrospective analysis |
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Retrospective 1,108 hospitalized patients in New York showing significantly higher mortality with HCQ treatment. Time based confounding is very likely because HCQ became increasingly controversial and less used over the time covered (Mar .. |
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Late treatment study
Late treatment study
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Predictors for inpatient mortality during the first wave of the SARS-CoV-2 pandemic: A retrospective analysis |
Sammartino et al., PLOS One, doi:10.1371/journal.pone.0251262 |
Retrospective 1,108 hospitalized patients in New York showing significantly higher mortality with HCQ treatment.Time based confounding is very likely because HCQ became increasingly controversial and less used over the time covered (Mar - Jun 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved. Authors note that for every week or month later that a person was admitted, their risk of death dropped by 16% and 49%, respectively, yet they do not consider time based confounding.
risk of death, 240.0% higher, OR 3.40, p = 0.002, treatment 137, control 191, PSM, model 1a, RR approximated with OR.
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Excluded in after exclusion results of meta analysis:
substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
Sammartino et al., 5/10/2021, retrospective, propensity score matching, USA, peer-reviewed, 7 authors.
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Review |
Vigbedor et al., Journal of Applied Pharmaceutical Science, doi:10.7324/JAPS.2021.110825 (Review) |
review |
Review of four major biomolecular target sites for COVID-19 and possible inhibitors as treatment interventions |
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Review of major target sites in SARS-CoV-2 and the host organism along with potential inhibitors. |
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Review
Review
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Review of four major biomolecular target sites for COVID-19 and possible inhibitors as treatment interventions |
Vigbedor et al., Journal of Applied Pharmaceutical Science, doi:10.7324/JAPS.2021.110825 (Review) |
Review of major target sites in SARS-CoV-2 and the host organism along with potential inhibitors.
Vigbedor et al., 5/8/2021, peer-reviewed, 8 authors.
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Late |
De Rosa et al., J. Clin. Med., doi:10.3390/jcm10091951 |
death, ↓35.0%, p=0.02 |
Risk Factors for Mortality in COVID-19 Hospitalized Patients in Piedmont, Italy: Results from the Multicenter, Regional, CORACLE Registry |
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Retrospective 1,538 hospitalized patients in Italy, showing only HCQ associated with reduced mortality. Authors analyze mortality amongst those that were alive at day 7 to avoid survival time bias due to drug recording requiring a minimum.. |
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Late treatment study
Late treatment study
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Risk Factors for Mortality in COVID-19 Hospitalized Patients in Piedmont, Italy: Results from the Multicenter, Regional, CORACLE Registry |
De Rosa et al., J. Clin. Med., doi:10.3390/jcm10091951 |
Retrospective 1,538 hospitalized patients in Italy, showing only HCQ associated with reduced mortality. Authors analyze mortality amongst those that were alive at day 7 to avoid survival time bias due to drug recording requiring a minimum of 5 days treatment.
risk of death, 35.0% lower, RR 0.65, p = 0.02, treatment 118 of 731 (16.1%), control 80 of 280 (28.6%), NNT 8.0, adjusted, OR converted to RR, multivariate logistic regression, patients alive at day 7.
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risk of death, 36.0% lower, RR 0.64, p < 0.001, treatment 207 of 1,019 (20.3%), control 215 of 519 (41.4%), NNT 4.7, adjusted, OR converted to RR, multivariate logistic regression, all patients.
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De Rosa et al., 5/1/2021, retrospective, Italy, peer-reviewed, 20 authors, average treatment delay 6.0 days.
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Late |
Çiyiltepe et al., South. Clin. Ist. Euras., doi:10.14744/scie.2021.89847 |
death, ↓3.2%, p=0.85 |
The Effect of Pre-admission Hydroxychloroquine Treatment on COVID-19-Related Intensive Care Follow-up in Geriatric Patients |
Details
Retrospective 147 ICU patients in Turkey, showing no significant difference in outcomes based on HCQ treatment before ICU admission. This is not very informative, for example we do not know if HCQ treated patients were much less likely to.. |
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Late treatment study
Late treatment study
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The Effect of Pre-admission Hydroxychloroquine Treatment on COVID-19-Related Intensive Care Follow-up in Geriatric Patients |
Çiyiltepe et al., South. Clin. Ist. Euras., doi:10.14744/scie.2021.89847 |
Retrospective 147 ICU patients in Turkey, showing no significant difference in outcomes based on HCQ treatment before ICU admission. This is not very informative, for example we do not know if HCQ treated patients were much less likely to be admitted to the ICU.
risk of death, 3.2% lower, RR 0.97, p = 0.85, treatment 69 of 95 (72.6%), control 39 of 52 (75.0%), NNT 42.
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Excluded in after exclusion results of meta analysis:
treatment group only includes patients where treatment failed resulting in ICU admission.
Çiyiltepe et al., 4/30/2021, retrospective, Turkey, peer-reviewed, 5 authors.
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Submit Corrections or Comments
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Late |
Bosaeed et al., Infect. Dis. Ther., doi:10.1007/s40121-021-00496-6 |
death, ↓3.7%, p=0.91 |
Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial |
Details
RCT 254 very late stage (93% on oxygen, 17% in ICU at baseline) hospitalized patients in Saudi Arabia not showing significant differences with HCQ+favipiravir treatment. Only SaO2 < 94% patients were eligible, however the actual SaO2 of e.. |
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Late treatment study
Late treatment study
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Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial |
Bosaeed et al., Infect. Dis. Ther., doi:10.1007/s40121-021-00496-6 |
RCT 254 very late stage (93% on oxygen, 17% in ICU at baseline) hospitalized patients in Saudi Arabia not showing significant differences with HCQ+favipiravir treatment. Only SaO2 < 94% patients were eligible, however the actual SaO2 of enrolled patients is not provided.
risk of death, 3.7% lower, RR 0.96, p = 0.91, treatment 14 of 125 (11.2%), control 15 of 129 (11.6%), NNT 234, 90 days.
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risk of death, 28.6% lower, RR 0.71, p = 0.45, treatment 9 of 125 (7.2%), control 13 of 129 (10.1%), NNT 35, 28 days.
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risk of death, 65.1% higher, RR 1.65, p = 0.68, treatment 8 of 125 (6.4%), control 5 of 129 (3.9%), 14 days.
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risk of mechanical ventilation, 8.4% higher, RR 1.08, p = 0.78, treatment 21 of 125 (16.8%), control 20 of 129 (15.5%).
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risk of ICU admission, 31.0% higher, RR 1.31, p = 0.24, treatment 33 of 125 (26.4%), control 26 of 129 (20.2%).
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recovery time, 28.6% higher, relative time 1.29, p = 0.29, treatment 125, control 129.
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hospitalization time, 12.5% higher, relative time 1.12, p = 0.42, treatment 125, control 129.
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risk of no viral clearance, 2.6% lower, RR 0.97, p = 0.75, treatment 100 of 125 (80.0%), control 106 of 129 (82.2%), NNT 46.
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Excluded in after exclusion results of meta analysis:
very late stage, >50% on oxygen/ventilation at baseline.
Bosaeed et al., 4/30/2021, Randomized Controlled Trial, Saudi Arabia, peer-reviewed, 30 authors, average treatment delay 5.85 days.
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Late |
Haji Aghajani et al., Journal of Medical Virology, doi:10.1002/jmv.27053 |
death, ↓19.5%, p=0.09 |
Decreased in-hospital mortality associated with aspirin administration in hospitalized patients due to severe COVID-19 |
Details
Retrospective 991 hospitalized patients in Iran, showing lower mortality with HCQ, not reaching statistical significance. |
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Late treatment study
Late treatment study
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Decreased in-hospital mortality associated with aspirin administration in hospitalized patients due to severe COVID-19 |
Haji Aghajani et al., Journal of Medical Virology, doi:10.1002/jmv.27053 |
Retrospective 991 hospitalized patients in Iran, showing lower mortality with HCQ, not reaching statistical significance.
risk of death, 19.5% lower, HR 0.81, p = 0.09, treatment 553, control 438, adjusted, Cox proportional hazards, RR approximated with OR.
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Haji Aghajani et al., 4/29/2021, retrospective, Iran, peer-reviewed, 7 authors.
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Submit Corrections or Comments
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Late |
Aghajani et al., Journal of Medical Virology, doi:10.1002/jmv.27053 |
death, ↓19.5%, p=0.09 |
Decreased In-Hospital Mortality Associated with Aspirin Administration in Hospitalized Patients Due to Severe COVID-19 |
Details
Retrospective 991 hospitalized patients in Iran focusing on aspirin use but also showing results for HCQ, remdesivir, and favipiravir. |
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Late treatment study
Late treatment study
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Decreased In-Hospital Mortality Associated with Aspirin Administration in Hospitalized Patients Due to Severe COVID-19 |
Aghajani et al., Journal of Medical Virology, doi:10.1002/jmv.27053 |
Retrospective 991 hospitalized patients in Iran focusing on aspirin use but also showing results for HCQ, remdesivir, and favipiravir.
risk of death, 19.5% lower, HR 0.81, p = 0.09, treatment 553, control 438, multivariate Cox proportional regression.
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Aghajani et al., 4/29/2021, retrospective, Iran, peer-reviewed, 7 authors.
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Submit Corrections or Comments
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Late |
Kokturk et al., Respiratory Medicine, doi:10.1016/j.rmed.2021.106433 |
death, ↑3.8%, p=0.97 |
The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients |
Details
Retrospective 1,500 hospitalized late stage (median SaO2 87.7) patients in Turkey, showing no significant difference with HCQ treatment. |
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Late treatment study
Late treatment study
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The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients |
Kokturk et al., Respiratory Medicine, doi:10.1016/j.rmed.2021.106433 |
Retrospective 1,500 hospitalized late stage (median SaO2 87.7) patients in Turkey, showing no significant difference with HCQ treatment.
risk of death, 3.8% higher, RR 1.04, p = 0.97, treatment 62 of 1,382 (4.5%), control 5 of 118 (4.2%), adjusted, OR converted to RR.
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Kokturk et al., 4/28/2021, retrospective, database analysis, Turkey, peer-reviewed, 68 authors.
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Submit Corrections or Comments
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Late |
Réa-Neto et al., Scientific Reports, doi:10.1038/s41598-021-88509-9 |
death, ↑57.0%, p=0.20 |
An open-label randomized controlled trial evaluating the efficacy of chloroquine/hydroxychloroquine in severe COVID-19 patients |
Details
Early terminated very late stage (99% on oxygen, 81% in ICU, 18% on mechanical ventilation at baseline) RCT with 24 CQ patients, 29 HCQ, and 52 control patients, showing worse clinical outcomes with treatment. NCT04420247. |
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Late treatment study
Late treatment study
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An open-label randomized controlled trial evaluating the efficacy of chloroquine/hydroxychloroquine in severe COVID-19 patients |
Réa-Neto et al., Scientific Reports, doi:10.1038/s41598-021-88509-9 |
Early terminated very late stage (99% on oxygen, 81% in ICU, 18% on mechanical ventilation at baseline) RCT with 24 CQ patients, 29 HCQ, and 52 control patients, showing worse clinical outcomes with treatment. NCT04420247.
risk of death, 57.0% higher, RR 1.57, p = 0.20, treatment 16 of 53 (30.2%), control 10 of 52 (19.2%).
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risk of mechanical ventilation, 115.0% higher, RR 2.15, p = 0.03, treatment 53, control 52.
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9-point scale clinical status, 147.0% higher, OR 2.47, p = 0.02, treatment 53, control 52, RR approximated with OR.
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Réa-Neto et al., 4/27/2021, Randomized Controlled Trial, Brazil, peer-reviewed, 6 authors, average treatment delay 8.0 days, trial NCT04420247 (history).
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Submit Corrections or Comments
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Late |
Mohandas et al., |
death, ↑81.0%, p=0.007 |
Clinical review of COVID-19 patients presenting to a quaternary care private hospital in South India: A retrospective study |
Details
Retrospective 3,345 hospitalized patients in India, 11.5% treated with HCQ, showing unadjusted higher mortality with treatment. Confounding by indication and time based confounding (due to declining use over the period when overall treatm.. |
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Late treatment study
Late treatment study
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Clinical review of COVID-19 patients presenting to a quaternary care private hospital in South India: A retrospective study |
Mohandas et al., |
Retrospective 3,345 hospitalized patients in India, 11.5% treated with HCQ, showing unadjusted higher mortality with treatment. Confounding by indication and time based confounding (due to declining use over the period when overall treatment protocols improved dramatically) are likely.
risk of death, 81.0% higher, RR 1.81, p = 0.007, treatment 27 of 384 (7.0%), control 115 of 2,961 (3.9%).
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Excluded in after exclusion results of meta analysis:
substantial unadjusted confounding by indication likely, unadjusted results with no group details, substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
Mohandas et al., 4/26/2021, retrospective, India, peer-reviewed, 6 authors.
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Late |
Corradini et al., Internal and Emergency Medicine, doi:10.1007/s11739-021-02742-8 |
death, ↓70.2%, p<0.0001 |
Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI) |
Details
Retrospective 3,044 hospitalized COVID-19 patients in Italy, showing HCQ significantly associated with survival in light, mild, and moderate cases in multivariable analysis, but not in severe cases. |
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Late treatment study
Late treatment study
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Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI) |
Corradini et al., Internal and Emergency Medicine, doi:10.1007/s11739-021-02742-8 |
Retrospective 3,044 hospitalized COVID-19 patients in Italy, showing HCQ significantly associated with survival in light, mild, and moderate cases in multivariable analysis, but not in severe cases.
risk of death, 70.2% lower, OR 0.30, p < 0.001, treatment 1,439, control 274, adjusted, Table S6, all patients, multivariable, RR approximated with OR.
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risk of death, 67.4% lower, OR 0.33, p = 0.01, treatment 641, control 102, adjusted, Table S6, light condition patients, multivariable, RR approximated with OR, early treatment result.
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risk of death, 76.8% lower, OR 0.23, p < 0.001, treatment 546, control 71, adjusted, Table S6, mild condition patients, multivariable, RR approximated with OR.
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risk of death, 84.2% lower, OR 0.16, p < 0.001, treatment 184, control 64, adjusted, Table S6, moderate condition patients, multivariable, RR approximated with OR.
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risk of death, 29.0% higher, OR 1.29, p = 0.73, treatment 68, control 37, adjusted, Table S6, severe condition patients, multivariable, RR approximated with OR.
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Corradini et al., 4/24/2021, retrospective, Italy, peer-reviewed, 60 authors, dosage not specified.
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Late |
Toya et al., SSRN (Preprint) |
A Cross-Country Analysis of the Determinants of COVID-19 Fatalities |
Details
Country based analysis finding lower mortality with the use of HCQ. |
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Late treatment study
Late treatment study
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A Cross-Country Analysis of the Determinants of COVID-19 Fatalities |
Toya et al., SSRN (Preprint) |
Country based analysis finding lower mortality with the use of HCQ.
Toya et al., 4/23/2021, preprint, 2 authors.
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Submit Corrections or Comments
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Late |
Reis et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.6468 |
death, ↓66.0%, p=1.00 |
Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19 The TOGETHER Randomized Clinical Trial |
Details
Early terminated RCT in Brazil showing lower mortality and hospitalization with HCQ, but not reaching statistical significance. Although the title includes "early treatment", treatment was relatively late, with most patients bei.. |
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Late treatment study
Late treatment study
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Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19 The TOGETHER Randomized Clinical Trial |
Reis et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.6468 |
Early terminated RCT in Brazil showing lower mortality and hospitalization with HCQ, but not reaching statistical significance. Although the title includes "early treatment", treatment was relatively late, with most patients being over 5 days from the onset of symptoms. Adverse events were lower in the HCQ group compared to the control group.The paper indicates the placebo was talc, however the trial protocol shows the "placebo" as vitamin C, for which there are 7 COVID-19 treatment studies as of April 2021 that collectively show significant efficacy.Results differ significantly from those reported prior to publication. Prior to publication, authors reported an RR for hospitalization or death of 1.0 [0.45-2.21] [ajtmh.org].
risk of death, 66.0% lower, RR 0.34, p = 1.00, treatment 0 of 214 (0.0%), control 1 of 227 (0.4%), NNT 227, relative risk is not 0 because of continuity correction due to zero events.
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risk of hospitalization, 24.0% lower, HR 0.76, p = 0.57, treatment 8 of 214 (3.7%), control 11 of 227 (4.8%), NNT 90, ITT, Cox proportional hazards.
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risk of no viral clearance, 4.1% lower, RR 0.96, p = 0.10, treatment 97 of 185 (52.4%), control 102 of 179 (57.0%), NNT 22, adjusted, OR converted to RR, ITT, mixed-effect logistic model.
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Reis et al., 4/22/2021, Double Blind Randomized Controlled Trial, Brazil, peer-reviewed, 18 authors, dosage 800mg day 1, 400mg days 2-10, trial NCT04403100 (history) (TOGETHER).
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Submit Corrections or Comments
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PrEP |
Alzahrani et al., Rheumatology International , doi:10.1007/s00296-021-04857-9 |
death, ↓58.7%, p=1.00 |
Clinical characteristics and outcome of COVID-19 in patients with rheumatic diseases |
Details
Retrospective 47 rheumatic disease patients not finding significant differences with HCQ. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Clinical characteristics and outcome of COVID-19 in patients with rheumatic diseases |
Alzahrani et al., Rheumatology International , doi:10.1007/s00296-021-04857-9 |
Retrospective 47 rheumatic disease patients not finding significant differences with HCQ.
risk of death, 58.7% lower, RR 0.41, p = 1.00, treatment 0 of 14 (0.0%), control 1 of 33 (3.0%), NNT 33, relative risk is not 0 because of continuity correction due to zero events.
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risk of mechanical ventilation, 81.0% lower, RR 0.19, p = 0.54, treatment 0 of 14 (0.0%), control 3 of 33 (9.1%), NNT 11, relative risk is not 0 because of continuity correction due to zero events.
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risk of severe case, 32.7% lower, RR 0.67, p = 0.70, treatment 2 of 14 (14.3%), control 7 of 33 (21.2%), NNT 14.
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Alzahrani et al., 4/15/2021, retrospective, Saudi Arabia, peer-reviewed, 3 authors.
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Submit Corrections or Comments
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PrEP |
Alegiani et al., Rheumatology, doi:10.1093/rheumatology/keab348 |
death, ↑8.0%, p=0.64 |
Risk of COVID-19 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional DMARDs in Italy |
Details
Retrospective database analysis case control study of rheumatic patients. When compared with other cDMARDs, HCQ users had significantly lower hospitalization, however there was no significant difference in mortality. Results differ signif.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Risk of COVID-19 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional DMARDs in Italy |
Alegiani et al., Rheumatology, doi:10.1093/rheumatology/keab348 |
Retrospective database analysis case control study of rheumatic patients. When compared with other cDMARDs, HCQ users had significantly lower hospitalization, however there was no significant difference in mortality. Results differ significantly from previous studies, for example showing mortality OR 0.94 [0.83-1.06] for patients with rheumatic disease and mortality OR 0.88 [0.74-1.05] for patients with RA/SLE. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall.
risk of death, 8.0% higher, OR 1.08, p = 0.64, HCQ vs. other cDMARDs, RR approximated with OR.
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risk of hospitalization, 18.0% lower, OR 0.82, p = 0.03, HCQ vs. other cDMARDs, RR approximated with OR.
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risk of death, 19.0% higher, OR 1.19, p = 0.32, HCQ vs. MTX, RR approximated with OR.
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risk of hospitalization, 12.0% lower, OR 0.88, p = 0.17, HCQ vs. MTX, RR approximated with OR.
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Alegiani et al., 4/15/2021, retrospective, case control, database analysis, Italy, peer-reviewed, 16 authors.
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Submit Corrections or Comments
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PrEP |
Seet et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.035 |
symp. case, ↓35.1%, p=0.047 |
Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial |
Details
Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin .. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial |
Seet et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.035 |
Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C.Only 71.4% reported >70% adherence, limiting efficacy.QTc did not statistically significantly differ between baseline and follow-up readings (mean 379 vs 378ms, paired t-test p=0.387).Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters.There were no hospitalizations and no deaths. NCT04446104.
risk of symptomatic case, 35.1% lower, RR 0.65, p = 0.047, treatment 29 of 432 (6.7%), control 64 of 619 (10.3%), NNT 28.
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risk of case, 32.0% lower, RR 0.68, p = 0.009, treatment 212 of 432 (49.1%), control 433 of 619 (70.0%), NNT 4.8, adjusted, OR converted to RR, model 6.
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Seet et al., 4/14/2021, Cluster Randomized Controlled Trial, Singapore, peer-reviewed, 15 authors, dosage 400mg day 1, 200mg days 2-42, this trial compares with another treatment - results may be better when compared to placebo, trial NCT04446104 (history).
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Late |
Gadhiya et al., BMJ Open, doi:10.1136/bmjopen-2020-042549 |
death, ↑4.8%, p=0.89 |
Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state |
Details
Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given fo.. |
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Late treatment study
Late treatment study
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Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state |
Gadhiya et al., BMJ Open, doi:10.1136/bmjopen-2020-042549 |
Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered (March 1 to May 31, 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
risk of death, 4.8% higher, RR 1.05, p = 0.89, treatment 22 of 55 (40.0%), control 33 of 216 (15.3%), adjusted, OR converted to RR, multivariate logistic regression.
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Excluded in after exclusion results of meta analysis:
substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
Gadhiya et al., 4/8/2021, retrospective, USA, peer-reviewed, 4 authors.
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Late |
Mulhem et al., BMJ Open, doi:10.1136/bmjopen-2020-042042 |
death, ↑28.3%, p=0.10 |
3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study |
Details
Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06.. |
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Late treatment study
Late treatment study
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3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study |
Mulhem et al., BMJ Open, doi:10.1136/bmjopen-2020-042042 |
Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.
risk of death, 28.3% higher, RR 1.28, p = 0.10, treatment 435 of 2,496 (17.4%), control 81 of 723 (11.2%), adjusted, OR converted to RR, logistic regression.
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Excluded in after exclusion results of meta analysis:
substantial unadjusted confounding by indication likely, substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
Mulhem et al., 4/7/2021, retrospective, database analysis, USA, peer-reviewed, 3 authors.
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Submit Corrections or Comments
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Early |
Mokhtari et al., International Immunopharmacology, doi:10.1016/j.intimp.2021.107636 |
death, ↓69.7%, p<0.0001 |
Clinical outcomes of patients with mild COVID-19 following treatment with hydroxychloroquine in an outpatient setting |
Details
Retrospective 28,759 adult outpatients with mild COVID-19 in Iran, 7,295 treated with HCQ, showing significantly lower hospitalization and mortality with treatment. |
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Early treatment study
Early treatment study
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Clinical outcomes of patients with mild COVID-19 following treatment with hydroxychloroquine in an outpatient setting |
Mokhtari et al., International Immunopharmacology, doi:10.1016/j.intimp.2021.107636 |
Retrospective 28,759 adult outpatients with mild COVID-19 in Iran, 7,295 treated with HCQ, showing significantly lower hospitalization and mortality with treatment.
risk of death, 69.7% lower, RR 0.30, p < 0.001, treatment 27 of 7,295 (0.4%), control 287 of 21,464 (1.3%), NNT 103, adjusted, OR converted to RR.
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risk of hospitalization, 35.3% lower, RR 0.65, p < 0.001, treatment 523 of 7,295 (7.2%), control 2,382 of 21,464 (11.1%), NNT 25, adjusted, OR converted to RR.
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Mokhtari et al., 4/6/2021, retrospective, Iran, peer-reviewed, 11 authors, dosage 400mg bid day 1, 200mg bid days 2-5.
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Submit Corrections or Comments
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Safety |
Edington et al., European Journal of Internal Medicine, doi:10.1016/j.ejim.2021.03.028 |
safety analysis |
Safety of treatment with chloroquine and hydroxychloroquine: A ten-year systematic review and meta-analysis |
Details
Safety analysis of CQ and HCQ covering 46 RCTs with 23,132 patients, showing no mortality attributed to CQ/HCQ. Authors conclude that the data reinforces that CQ and HCQ have a good safety profile though caution is advised when using high.. |
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Safety
Safety
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Safety of treatment with chloroquine and hydroxychloroquine: A ten-year systematic review and meta-analysis |
Edington et al., European Journal of Internal Medicine, doi:10.1016/j.ejim.2021.03.028 |
Safety analysis of CQ and HCQ covering 46 RCTs with 23,132 patients, showing no mortality attributed to CQ/HCQ. Authors conclude that the data reinforces that CQ and HCQ have a good safety profile though caution is advised when using higher than usual doses in hospitalized COVID-19 patients.
Edington et al., 4/5/2021, peer-reviewed, 3 authors.
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Submit Corrections or Comments
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Late |
Alghamdi et al., Antibiotics, doi:10.3390/antibiotics10040365 |
death, ↑6.9%, p=0.88 |
Clinical Efficacy of Hydroxychloroquine in Patients with COVID-19: Findings from an Observational Comparative Study in Saudi Arabia |
Details
Retrospective 775 hospitalized patients in Saudi Arabia showing no significant difference. There was no adjustment for severity or comorbidities. Confounding by indication is likely. |
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Late treatment study
Late treatment study
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Clinical Efficacy of Hydroxychloroquine in Patients with COVID-19: Findings from an Observational Comparative Study in Saudi Arabia |
Alghamdi et al., Antibiotics, doi:10.3390/antibiotics10040365 |
Retrospective 775 hospitalized patients in Saudi Arabia showing no significant difference. There was no adjustment for severity or comorbidities. Confounding by indication is likely.
risk of death, 6.9% higher, RR 1.07, p = 0.88, treatment 44 of 568 (7.7%), control 15 of 207 (7.2%).
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Excluded in after exclusion results of meta analysis:
confounding by indication is likely and adjustments do not consider COVID-19 severity at baseline.
Alghamdi et al., 3/31/2021, retrospective, Saudi Arabia, peer-reviewed, 10 authors.
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Submit Corrections or Comments
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Safety |
Faruqui et al., Indian J. Med. Res., doi:10.4103/ijmr.IJMR_2294_20 |
safety analysis |
Safety of hydroxychloroquine in healthcare workers for COVID-19 prophylaxis |
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Retrospective 1303 health care workers finding that HCQ prophylaxis was well tolerated. 20% reported an adverse event, mostly gastrointestinal. 1.5% received treatment for adverse effects, with none requiring hospitalization. |
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Safety
Safety
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Safety of hydroxychloroquine in healthcare workers for COVID-19 prophylaxis |
Faruqui et al., Indian J. Med. Res., doi:10.4103/ijmr.IJMR_2294_20 |
Retrospective 1303 health care workers finding that HCQ prophylaxis was well tolerated. 20% reported an adverse event, mostly gastrointestinal. 1.5% received treatment for adverse effects, with none requiring hospitalization.
Faruqui et al., 3/26/2021, peer-reviewed, 24 authors.
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PrEP |
Dev et al., Transactions of The Royal Society of Tropical Medicine and Hygiene, doi:10.1093/trstmh/trab047 |
cases, ↓26.0%, p=0.003 |
Risk factors and frequency of COVID-19 among healthcare workers at a tertiary care centre in India: a case–control study |
Details
Retrospective case control study of 3,100 healthcare workers in India showing lower cases with HCQ prophylaxis, and an inverse association between the number of HCQ doses taken and the risk of COVID-19 cases. Low risk population with no m.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Risk factors and frequency of COVID-19 among healthcare workers at a tertiary care centre in India: a case–control study |
Dev et al., Transactions of The Royal Society of Tropical Medicine and Hygiene, doi:10.1093/trstmh/trab047 |
Retrospective case control study of 3,100 healthcare workers in India showing lower cases with HCQ prophylaxis, and an inverse association between the number of HCQ doses taken and the risk of COVID-19 cases. Low risk population with no mortality and no severe cases.
risk of case, 26.0% lower, RR 0.74, p = 0.003, treatment 260, control 499, any number of HCQ doses vs. no HCQ prophylaxis.
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Dev et al., 3/24/2021, retrospective, India, peer-reviewed, 5 authors.
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Late |
Barry et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.03.058 |
death, ↓98.9%, p=0.60 |
Clinical Characteristics and Outcomes of Hospitalized COVID-19 Patients in a MERS-CoV Referral Hospital during the Peak of the Pandemic |
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605 hospitalized patients in Saudi Arabia showing no mortality with HCQ (only 6 patients received HCQ). |
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Late treatment study
Late treatment study
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Clinical Characteristics and Outcomes of Hospitalized COVID-19 Patients in a MERS-CoV Referral Hospital during the Peak of the Pandemic |
Barry et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.03.058 |
605 hospitalized patients in Saudi Arabia showing no mortality with HCQ (only 6 patients received HCQ).
risk of death, 98.9% lower, RR 0.01, p = 0.60, treatment 0 of 6 (0.0%), control 91 of 599 (15.2%), NNT 6.6, relative risk is not 0 because of continuity correction due to zero events.
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Barry et al., 3/23/2021, retrospective, Saudi Arabia, peer-reviewed, 14 authors.
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Late |
Stewart et al., PLoS ONE, doi:10.1371/journal.pone.0248128 |
death, ↑18.0%, p=0.27 |
COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients |
Details
Collection of seven retrospective database analyses in the USA, showing higher mortality with treatment (not statistically significant). Results contradict strong evidence from the RECOVERY/SOLIDARITY trials, suggesting substantial confou.. |
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Late treatment study
Late treatment study
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COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients |
Stewart et al., PLoS ONE, doi:10.1371/journal.pone.0248128 |
Collection of seven retrospective database analyses in the USA, showing higher mortality with treatment (not statistically significant).Results contradict strong evidence from the RECOVERY/SOLIDARITY trials, suggesting substantial confounding by indication.Time based confounding is very likely because HCQ became highly controversial and usage dramatically declined over the time covered, while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.This study includes anyone PCR+ during or prior to their visit, and anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore some patients in the control groups may be asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason.Authors do not mention the possibility of any of these likely confounding factors.
risk of death, 18.0% higher, RR 1.18, p = 0.27, treatment 90 of 429 (21.0%), control 141 of 737 (19.1%), adjusted, VA, HCQ+AZ.
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risk of death, 1.0% lower, RR 0.99, p = 0.95, treatment 66 of 578 (11.4%), control 188 of 1,243 (15.1%), adjusted, TriNetX, HCQ+AZ.
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risk of death, 129.9% higher, RR 2.30, p < 0.001, treatment 32 of 108 (29.6%), control 33 of 256 (12.9%), Synapse, HCQ+AZ.
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risk of death, 9.0% higher, RR 1.09, p = 0.65, treatment 212 of 1,157 (18.3%), control 203 of 1,101 (18.4%), NNT 873, adjusted, Health Catalyst, HCQ+AZ.
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risk of death, 90.0% higher, RR 1.90, p = 0.09, treatment 46 of 208 (22.1%), control 47 of 1,334 (3.5%), adjusted, Dascena, HCQ+AZ.
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risk of death, 16.0% higher, RR 1.16, p = 0.26, treatment 428 of 1,711 (25.0%), control 123 of 688 (17.9%), adjusted, COTA/HMH, HCQ+AZ.
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risk of mechanical ventilation, 29.0% higher, RR 1.29, p = 0.09, treatment 48 of 305 (15.7%), control 95 of 1,302 (7.3%), adjusted, Aetion, HCQ.
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Excluded in after exclusion results of meta analysis:
substantial unadjusted confounding by indication likely, substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons.
Stewart et al., 3/17/2021, retrospective, USA, peer-reviewed, 37 authors.
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In Vitro |
Dang et al., bioRxiv, doi:10.1101/2021.03.16.435741 (Preprint) (In Vitro) |
In Vitro |
Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD/CTD and disruption of LLPS of N protein |
Details
Microscopy/spectroscopy study showing that HCQ binds to both N-terminal domain and C-terminal domain of SARS-CoV-2 nucleocapsid protein to inhibit their interactions with nucleic acids and disrupt NA-induced liquid-liquid phase separation.. |
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In Vitro
In Vitro
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Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD/CTD and disruption of LLPS of N protein |
Dang et al., bioRxiv, doi:10.1101/2021.03.16.435741 (Preprint) (In Vitro) |
Microscopy/spectroscopy study showing that HCQ binds to both N-terminal domain and C-terminal domain of SARS-CoV-2 nucleocapsid protein to inhibit their interactions with nucleic acids and disrupt NA-induced liquid-liquid phase separation essential for the viral life cycle including the package of gRNA and N protein into new virions. These results suggest that HCQ may achieve its anti-SARS-CoV-2 activity by interfering in several key steps of the viral life cycle.
Dang et al., 3/17/2021, preprint, 2 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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Early |
Roy et al., medRxiv, doi:10.1101/2021.03.08.21252883 (Preprint) |
recov. time, ↓2.4%, p=0.96 |
Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study |
Details
Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and .. |
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Early treatment study
Early treatment study
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Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study |
Roy et al., medRxiv, doi:10.1101/2021.03.08.21252883 (Preprint) |
Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and there was no significant difference between the groups.
relative time to clinical response of wellbeing, 2.4% lower, relative time 0.98, p = 0.96, treatment 14, control 15, primary outcome.
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Excluded in after exclusion results of meta analysis:
no serious outcomes reported and fast recovery in treatment and control groups, there is little room for a treatment to improve results.
Roy et al., 3/12/2021, retrospective, database analysis, India, preprint, 5 authors, dosage not specified.
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PrEP |
Vivanco-Hidalgo et al., Eurosurveillance, doi:/10.2807/1560-7917.ES.2021.26.9.2001202 |
hosp., ↑46.0%, p=0.10 |
Incidence of COVID-19 in patients exposed to chloroquine and hydroxychloroquine: results from a population-based prospective cohort in Catalonia, Spain, 2020 |
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Retrospective database analysis of chronic HCQ users and matched control patients, failing to match or adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 fo.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Incidence of COVID-19 in patients exposed to chloroquine and hydroxychloroquine: results from a population-based prospective cohort in Catalonia, Spain, 2020 |
Vivanco-Hidalgo et al., Eurosurveillance, doi:/10.2807/1560-7917.ES.2021.26.9.2001202 |
Retrospective database analysis of chronic HCQ users and matched control patients, failing to match or adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
risk of hospitalization, 46.0% higher, RR 1.46, p = 0.10, treatment 40 of 6,746 (0.6%), control 50 of 13,492 (0.4%), adjusted.
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risk of case, 8.0% higher, RR 1.08, p = 0.50, treatment 97 of 6,746 (1.4%), control 183 of 13,492 (1.4%), adjusted.
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Excluded in after exclusion results of meta analysis:
not fully adjusting for the different baseline risk of systemic autoimmune patients.
Vivanco-Hidalgo et al., 3/9/2021, retrospective, Spain, peer-reviewed, 8 authors.
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Late |
Martin-Vicente et al., medRxiv, doi:10.1101/2021.03.08.21253121 (Preprint) |
death, ↓59.3%, p=0.41 |
Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients |
Details
Retrospective 92 ICU patients with almost all treated with HCQ and only one non-HCQ treated patient that died, showing unadjusted non-statistically significant lower mortality with treatment. |
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Late treatment study
Late treatment study
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Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients |
Martin-Vicente et al., medRxiv, doi:10.1101/2021.03.08.21253121 (Preprint) |
Retrospective 92 ICU patients with almost all treated with HCQ and only one non-HCQ treated patient that died, showing unadjusted non-statistically significant lower mortality with treatment.
risk of death, 59.3% lower, RR 0.41, p = 0.41, treatment 37 of 91 (40.7%), control 1 of 1 (100.0%), NNT 1.7.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details, treatment or control group size extremely small.
Martin-Vicente et al., 3/8/2021, retrospective, Spain, preprint, 38 authors.
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Late |
Salvador et al., Cureus, doi:10.7759/cureus.13687 |
death, ↓32.9%, p=0.10 |
Clinical Features and Prognostic Factors of 245 Portuguese Patients Hospitalized With COVID-19 |
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Prospective study of 245 hospitalized patients, 121 treated with HCQ, showing lower (non-statistically significant) mortality and higher ventilation at 30 days. Confounding by indication is likely. |
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Late treatment study
Late treatment study
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Clinical Features and Prognostic Factors of 245 Portuguese Patients Hospitalized With COVID-19 |
Salvador et al., Cureus, doi:10.7759/cureus.13687 |
Prospective study of 245 hospitalized patients, 121 treated with HCQ, showing lower (non-statistically significant) mortality and higher ventilation at 30 days. Confounding by indication is likely.
risk of death, 32.9% lower, RR 0.67, p = 0.10, treatment 28 of 121 (23.1%), control 58 of 124 (46.8%), NNT 4.2, OR converted to RR, multivariate.
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risk of mechanical ventilation, 447.8% higher, RR 5.48, p = 0.003, treatment 32 of 121 (26.4%), control 12 of 124 (9.7%), OR converted to RR, multivariate.
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risk of death/intubation, 16.7% lower, RR 0.83, p = 0.21, treatment 51 of 121 (42.1%), control 63 of 124 (50.8%), NNT 12, OR converted to RR, univariate.
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Salvador et al., 3/4/2021, prospective, Portugal, peer-reviewed, 10 authors.
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PrEP |
Pham et al., Rheumatology Advances in Practice, 10.1093/rap/rkab014 |
death, ↓19.7%, p=0.77 |
Failure of chronic hydroxychloroquine in preventing severe complications of COVID-19 in patients with rheumatic diseases |
Details
Tiny retrospective database analysis of hospitalized COVID-19 patients with rheumatologic disease containing 14 chronic HCQ and 28 control patients. Patients are very poorly matched. Bias against HCQ is clear in the abstract which mention.. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Failure of chronic hydroxychloroquine in preventing severe complications of COVID-19 in patients with rheumatic diseases |
Pham et al., Rheumatology Advances in Practice, 10.1093/rap/rkab014 |
Tiny retrospective database analysis of hospitalized COVID-19 patients with rheumatologic disease containing 14 chronic HCQ and 28 control patients. Patients are very poorly matched. Bias against HCQ is clear in the abstract which mentions differences favoring HCQ but ignores those favoring control (large differences in ethnicity, rheumatic conditions, hypertension, coronary artery disease, solid organ transplant recipients, immunosuppresive drugs). 61% of control patients also received HCQ. Adherence for chronic HCQ patients was not examined. Despite the very large differences between the groups, no adjustments are made. The study claims that HCQ did not prevent severe cases, but the study is among hospitalized patients, i.e., they already have cases severe enough for hospitalization - this study can not identify a protective effect of HCQ that reduces the probability of disease severe enough for hospitalization.
risk of death, 19.7% lower, RR 0.80, p = 0.77, treatment 2 of 14 (14.3%), control 5 of 28 (17.9%), NNT 28, OR converted to RR, univariate.
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risk of ICU admission, 35.5% higher, RR 1.35, p = 0.61, treatment 4 of 14 (28.6%), control 6 of 28 (21.4%), OR converted to RR, univariate.
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Pham et al., 3/2/2021, retrospective, USA, peer-reviewed, 5 authors.
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Early |
Thakar et al., Indian J. Med. Res., doi:10.4103/ijmr.IJMR_3665_20 |
Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial |
Details
Small RCT for CQ nasal drops suggesting efficacy in preventing infection, while no significant difference was seen for patients that already had mild COVID-19. |
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Early treatment study
Early treatment study
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Chloroquine nasal drops in asymptomatic & mild COVID-19: An exploratory randomized clinical trial |
Thakar et al., Indian J. Med. Res., doi:10.4103/ijmr.IJMR_3665_20 |
Small RCT for CQ nasal drops suggesting efficacy in preventing infection, while no significant difference was seen for patients that already had mild COVID-19.
Thakar et al., 2/28/2021, peer-reviewed, 11 authors.
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PrEP |
Bhandari et al., International Journal of Medicine and Public Health, doi:10.5530/ijmedph.2021.1.4 |
A Preventive Study on Hydroxychloroquine Prophylaxis against COVID-19 in Health Care Workers at a Tertiary Care Center in North India |
Details
Retrospective 4,239 healthcare workers using HCQ prophylaxis showing no mortality, 8 mild symptomatic cases, and 85 asymptomatic cases, with the cases occuring mostly in the first week. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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A Preventive Study on Hydroxychloroquine Prophylaxis against COVID-19 in Health Care Workers at a Tertiary Care Center in North India |
Bhandari et al., International Journal of Medicine and Public Health, doi:10.5530/ijmedph.2021.1.4 |
Retrospective 4,239 healthcare workers using HCQ prophylaxis showing no mortality, 8 mild symptomatic cases, and 85 asymptomatic cases, with the cases occuring mostly in the first week.
Bhandari et al., 2/28/2021, India, peer-reviewed, 10 authors.
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Early |
Amaravadi et al., medRxiv, doi:10.1101/2021.02.22.21252228 (Preprint) |
no recov., ↓60.0%, p=0.13 |
Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomized clinical trial |
Details
Tiny early-terminated 34 patient RCT for outpatient treatment showing faster recovery with treatment (not statistically significant). All patients recovered (3 control patients recovered after crossover to the treatment arm) - as per prot.. |
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Early treatment study
Early treatment study
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Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomized clinical trial |
Amaravadi et al., medRxiv, doi:10.1101/2021.02.22.21252228 (Preprint) |
Tiny early-terminated 34 patient RCT for outpatient treatment showing faster recovery with treatment (not statistically significant). All patients recovered (3 control patients recovered after crossover to the treatment arm) - as per protocol mid-recovery results have priority. There was no mortality and only one hospitalization on day 0 before treatment. There were no severe adverse events.
risk of not reaching lowest symptom score at day 7 mid-recovery, 60.0% lower, RR 0.40, p = 0.13, treatment 3 of 15 (20.0%), control 6 of 12 (50.0%), NNT 3.3.
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risk of not reaching lowest symptom score at day 5 mid-recovery, 50.0% lower, RR 0.50, p = 0.13, treatment 5 of 15 (33.3%), control 8 of 12 (66.7%), NNT 3.0.
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relative time to first occurrence of lowest symptom score, 42.9% lower, relative time 0.57, p = 0.38, treatment 15, control 12.
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relative time to release from quarantine, 27.3% lower, relative time 0.73, p = 0.46, treatment 16, control 13, primary outcome.
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Amaravadi et al., 2/26/2021, Double Blind Randomized Controlled Trial, USA, preprint, 20 authors, dosage 400mg bid days 1-14.
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Late |
Tanriverdi et al., Turkish Journal of Medical Sciences, doi:doi:10.3906/sag-2005-82 |
Hydroxychloroquine plus azithromycin and early hospital admission are beneficial in COVID-19 patients: Turkish experience with real-life data |
Details
Retrospective 83 hospitalized patients in Turkey confirming that earlier treatment is better, and showing that the addition of AZ to HCQ reduced hospitalization time. |
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Late treatment study
Late treatment study
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Hydroxychloroquine plus azithromycin and early hospital admission are beneficial in COVID-19 patients: Turkish experience with real-life data |
Tanriverdi et al., Turkish Journal of Medical Sciences, doi:doi:10.3906/sag-2005-82 |
Retrospective 83 hospitalized patients in Turkey confirming that earlier treatment is better, and showing that the addition of AZ to HCQ reduced hospitalization time.
Tanriverdi et al., 2/26/2021, peer-reviewed, 8 authors.
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Early |
Giraud-Gatineau et al., Research Square, doi:rs.3.rs-251817/v1 (Preprint) |
The Need for Early Management in Patients With COVID-19 |
Details
Review of early treatment of COVID-19 at IHU Méditerranée Infection in France, including HCQ+AZ treatment, comparing outcomes to those for all of France. Age-standardized mortality was lower with early treatment for all periods of the epi.. |
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Early treatment study
Early treatment study
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The Need for Early Management in Patients With COVID-19 |
Giraud-Gatineau et al., Research Square, doi:rs.3.rs-251817/v1 (Preprint) |
Review of early treatment of COVID-19 at IHU Méditerranée Infection in France, including HCQ+AZ treatment, comparing outcomes to those for all of France. Age-standardized mortality was lower with early treatment for all periods of the epidemic. Authors recommend early treatment for all age groups.
Giraud-Gatineau et al., 2/26/2021, preprint, 9 authors.
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Late |
Beltran Gonzalez et al., Infectious Disease Reports, doi:10.3390/idr14020020 (preprint 2/23/2021) |
death, ↓62.6%, p=0.27 |
Efficacy and Safety of Ivermectin and Hydroxychloroquine in Patients with Severe COVID-19: A Randomized Controlled Trial |
Details
RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 33 HCQ and 37 control patients not finding significant differences. NCT04391127. |
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Late treatment study
Late treatment study
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Efficacy and Safety of Ivermectin and Hydroxychloroquine in Patients with Severe COVID-19: A Randomized Controlled Trial |
Beltran Gonzalez et al., Infectious Disease Reports, doi:10.3390/idr14020020 (preprint 2/23/2021) |
RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 33 HCQ and 37 control patients not finding significant differences. NCT04391127.
risk of death, 62.6% lower, RR 0.37, p = 0.27, treatment 2 of 33 (6.1%), control 6 of 37 (16.2%), NNT 9.8.
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risk of respiratory deterioration or death, 25.3% lower, RR 0.75, p = 0.57, treatment 6 of 33 (18.2%), control 9 of 37 (24.3%), NNT 16.
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risk of no hospital discharge, 12.1% higher, RR 1.12, p = 1.00, treatment 3 of 33 (9.1%), control 3 of 37 (8.1%).
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Beltran Gonzalez et al., 2/23/2021, Double Blind Randomized Controlled Trial, Mexico, peer-reviewed, mean age 53.8, 13 authors, average treatment delay 7.0 days, trial NCT04391127 (history).
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PrEP |
Bae et al., Viruses 2021, doi:10.3390/v13020329 |
cases, ↓30.3%, p=0.18 |
Recent Hydroxychloroquine Use Is Not Significantly Associated with Positive PCR Results for SARS-CoV-2: A Nationwide Observational Study in South Korea |
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Retrospective database analysis of prior HCQ usage in South Korea, showing non-statistically significantly lower mortality and cases with treatment. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Recent Hydroxychloroquine Use Is Not Significantly Associated with Positive PCR Results for SARS-CoV-2: A Nationwide Observational Study in South Korea |
Bae et al., Viruses 2021, doi:10.3390/v13020329 |
Retrospective database analysis of prior HCQ usage in South Korea, showing non-statistically significantly lower mortality and cases with treatment.
risk of case, 30.3% lower, RR 0.70, p = 0.18, treatment 16 of 743 (2.2%), control 91 of 2,698 (3.4%), NNT 82, OR converted to RR, PSM.
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risk of case, 19.5% lower, RR 0.81, p = 0.50, treatment 16 of 743 (2.2%), control 91 of 2,698 (3.4%), OR converted to RR, PSM, adjusted for region.
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risk of case, 30.3% lower, RR 0.70, p = 0.30, treatment 16 of 743 (2.2%), control 91 of 2,698 (3.4%), NNT 82, OR converted to RR, PSM, adjusted for immunosuppresant use.
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risk of case, 40.2% lower, RR 0.60, p = 0.09, OR converted to RR, PSM, HCQ >= 6 months.
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Bae et al., 2/20/2021, retrospective, propensity score matching, South Korea, peer-reviewed, 8 authors.
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Submit Corrections or Comments
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Late |
Lamback et al., The Brazilian Journal of Infectious Diseases, doi:10.1016/j.bjid.2021.101549 |
death, ↓8.9%, p=0.83 |
Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19 |
Details
Retrospective 193 hospitalized patients in Brazil not finding a significant difference with HCQ. The control group was composed of patients refusing HCQ or with contraindications. Time based confounding is very likely because HCQ became m.. |
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Late treatment study
Late treatment study
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Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19 |
Lamback et al., The Brazilian Journal of Infectious Diseases, doi:10.1016/j.bjid.2021.101549 |
Retrospective 193 hospitalized patients in Brazil not finding a significant difference with HCQ.The control group was composed of patients refusing HCQ or with contraindications. Time based confounding is very likely because HCQ became more controversial in Brazil over the time covered (Mar - Jun 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients (those refusing HCQ) likely come later in the period when treatment protocols were greatly improved.The paper does not mention the word "confounding" or make any adjustments.
risk of death, 8.9% lower, RR 0.91, p = 0.83, treatment 11 of 101 (10.9%), control 11 of 92 (12.0%), NNT 94.
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risk of ICU admission, 19.9% higher, RR 1.20, p = 0.61, treatment 25 of 101 (24.8%), control 19 of 92 (20.7%).
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hospitalization time, 12.5% lower, relative time 0.88, treatment 101, control 92.
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Excluded in after exclusion results of meta analysis:
substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
Lamback et al., 2/19/2021, retrospective, Brazil, peer-reviewed, 10 authors.
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Submit Corrections or Comments
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Late |
Awad et al., American Journal of Health-System Pharmacy, doi:10.1093/ajhp/zxab056 |
death, ↑19.1%, p=0.60 |
Impact of hydroxychloroquine on disease progression and ICU admissions in patients with SARS-CoV-2 infection |
Details
This paper has inconsistent values - the number of treatment and control patients differs in the text and Table 1, we have used treatment 188 and control 148. Retrospective 336 hospitalized patients in the USA showing higher mortality, IC.. |
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Late treatment study
Late treatment study
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Impact of hydroxychloroquine on disease progression and ICU admissions in patients with SARS-CoV-2 infection |
Awad et al., American Journal of Health-System Pharmacy, doi:10.1093/ajhp/zxab056 |
This paper has inconsistent values - the number of treatment and control patients differs in the text and Table 1, we have used treatment 188 and control 148. Retrospective 336 hospitalized patients in the USA showing higher mortality, ICU admission, and intubation with treatment. Confounding by indication is likely. Time varying confounding is also likely due to declining usage over the early period when overall treatment protocols were also improving dramatically. Authors and reviewers appear to be unfamiliar with either of these.
risk of death, 19.1% higher, RR 1.19, p = 0.60, treatment 56 of 188 (29.8%), control 37 of 148 (25.0%).
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risk of mechanical ventilation, 460.7% higher, RR 5.61, p < 0.001, treatment 64 of 188 (34.0%), control 9 of 148 (6.1%), adjusted, OR converted to RR.
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risk of ICU admission, 463.4% higher, RR 5.63, p < 0.001, treatment 67 of 188 (35.6%), control 9 of 148 (6.1%), adjusted, OR converted to RR.
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Excluded in after exclusion results of meta analysis:
substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
Awad et al., 2/18/2021, retrospective, USA, peer-reviewed, 4 authors.
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PrEP |
Mahto et al., American Journal of Blood Research, 11:1 |
IgG+, ↓26.9%, p=0.38 |
Seroprevalence of IgG against SARS-CoV-2 and its determinants among healthcare workers of a COVID-19 dedicated hospital of India |
Details
Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with HCQ prophylaxis in unadjusted results. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Seroprevalence of IgG against SARS-CoV-2 and its determinants among healthcare workers of a COVID-19 dedicated hospital of India |
Mahto et al., American Journal of Blood Research, 11:1 |
Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with HCQ prophylaxis in unadjusted results.
risk of IgG positive, 26.9% lower, RR 0.73, p = 0.38, treatment 9 of 89 (10.1%), control 84 of 600 (14.0%), NNT 26, unadjusted, OR converted to RR.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Mahto et al., 2/15/2021, retrospective, India, peer-reviewed, 6 authors.
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Submit Corrections or Comments
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Late |
Lora-Tamayo et al., J. Infection, doi:10.1016/j.jinf.2021.02.011 |
death, ↓50.5%, p<0.0001 |
Early Lopinavir/ritonavir does not reduce mortality in COVID-19 patients: results of a large multicenter study |
Details
Lopinavir/ritonavir retrospective study also showing univariate results for HCQ, with significantly lower mortality. |
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Late treatment study
Late treatment study
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Early Lopinavir/ritonavir does not reduce mortality in COVID-19 patients: results of a large multicenter study |
Lora-Tamayo et al., J. Infection, doi:10.1016/j.jinf.2021.02.011 |
Lopinavir/ritonavir retrospective study also showing univariate results for HCQ, with significantly lower mortality.
risk of death, 50.5% lower, RR 0.50, p < 0.001, treatment 7,192, control 1,361, OR converted to RR, univariate, control prevalence approximated with overall prevalence.
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Lora-Tamayo et al., 2/11/2021, retrospective, Spain, peer-reviewed, 10 authors.
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Submit Corrections or Comments
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Early, Late |
Desai et al., J. Clinical Medicine, doi:10.3390/jcm10040686 |
The Use of Antiviral Agents against SARS-CoV-2: Ineffective or Time and Age Dependent Result? A Retrospective, Observational Study among COVID-19 Older Adults |
Details
Retrospective 143 COVID-19 hospitalized patients >65yo, showing adjusted OR for antiviral treatment starting within 6 days of 0.44 [0.2-0.9], p = 0.02, compared to treatment started later. |
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Details
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Early, Late
Early, Late
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The Use of Antiviral Agents against SARS-CoV-2: Ineffective or Time and Age Dependent Result? A Retrospective, Observational Study among COVID-19 Older Adults |
Desai et al., J. Clinical Medicine, doi:10.3390/jcm10040686 |
Retrospective 143 COVID-19 hospitalized patients >65yo, showing adjusted OR for antiviral treatment starting within 6 days of 0.44 [0.2-0.9], p = 0.02, compared to treatment started later.
Desai et al., 2/10/2021, peer-reviewed, 9 authors.
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Late |
Thompson et al., NCT04332991 (Preprint) |
death, ↑6.2%, p=0.85 |
Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease (ORCHID) |
Details
Late stage (65% on oxygen at baseline) low-dose RCT, not showing significant differences with treatment. |
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Details
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Late treatment study
Late treatment study
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Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease (ORCHID) |
Thompson et al., NCT04332991 (Preprint) |
Late stage (65% on oxygen at baseline) low-dose RCT, not showing significant differences with treatment.
risk of death, 6.2% higher, RR 1.06, p = 0.85, treatment 25 of 241 (10.4%), control 25 of 236 (10.6%), NNT 455, adjusted, OR converted to RR, day 28.
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risk of death, 51.0% higher, RR 1.51, p = 0.28, treatment 18 of 241 (7.5%), control 14 of 236 (5.9%), adjusted, OR converted to RR, day 14.
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risk of 7-point scale, 3.1% higher, OR 1.03, p = 0.87, treatment 241, control 236, day 28, RR approximated with OR.
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risk of 7-point scale, 2.0% lower, OR 0.98, p = 0.91, treatment 241, control 236, day 14, RR approximated with OR.
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Thompson et al., 2/9/2021, Double Blind Randomized Controlled Trial, USA, preprint, 1 author.
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Submit Corrections or Comments
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Meta |
Lounnas e al., Archives of Microbiology & Immunology, doi: (meta analysis) |
meta-analysis |
Revisiting a Meta-analysis Shows that Hydroxychloroquine with Azithromycin may be Efficient in Covid-19 patients |
Details
Analysis of the Fiolet meta analysis and correction of bias evaluation, showing HCQ RR 0.45 [0.31-0.59], and HCQ+AZ RR 0.34 [0.06-0.61]. |
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Details
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Meta
Meta
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Revisiting a Meta-analysis Shows that Hydroxychloroquine with Azithromycin may be Efficient in Covid-19 patients |
Lounnas e al., Archives of Microbiology & Immunology, doi: (meta analysis) |
Analysis of the Fiolet meta analysis and correction of bias evaluation, showing HCQ RR 0.45 [0.31-0.59], and HCQ+AZ RR 0.34 [0.06-0.61].
Lounnas et al., 2/9/2021, peer-reviewed, 4 authors.
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Submit Corrections or Comments
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Late |
Purwati et al., Biochemistry Research International, doi:10.1155/2021/6685921 |
viral+, ↓66.3%, p<0.0001 |
A Randomized, Double-Blind, Multicenter Clinical Study Comparing the Efficacy and Safety of a Drug Combination of Lopinavir/Ritonavir-Azithromycin, Lopinavir/Ritonavir-Doxycycline, and Azithromycin-Hydroxychloroquine for Patients Diagnosed with Mild to Moderate COVID-19 Infections |
Details
RCT 754 patients comparing HCQ+AZ along with other treatment groups using lopinavir/ritonavir and doxycycline to a control group taking AZ, finding significantly faster viral clearance with all treatment groups. (The labels in Figure 2 ap.. |
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Details
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Late treatment study
Late treatment study
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A Randomized, Double-Blind, Multicenter Clinical Study Comparing the Efficacy and Safety of a Drug Combination of Lopinavir/Ritonavir-Azithromycin, Lopinavir/Ritonavir-Doxycycline, and Azithromycin-Hydroxychloroquine for Patients Diagnosed with Mild to Moderate COVID-19 Infections |
Purwati et al., Biochemistry Research International, doi:10.1155/2021/6685921 |
RCT 754 patients comparing HCQ+AZ along with other treatment groups using lopinavir/ritonavir and doxycycline to a control group taking AZ, finding significantly faster viral clearance with all treatment groups. (The labels in Figure 2 appear to be reversed).
risk of no viral clearance, 66.3% lower, RR 0.34, p < 0.001, treatment 38 of 121 (31.4%), control 111 of 119 (93.3%), NNT 1.6, day 7.
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Purwati et al., 2/9/2021, Double Blind Randomized Controlled Trial, Indonesia, peer-reviewed, 12 authors.
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Submit Corrections or Comments
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PrEP |
Fitzgerald et al., medRxiv, doi:10.1101/2021.02.03.21251069 (Preprint) |
cases, ↓8.5%, p=0.54 |
Risk Factors for Infection and Health Impacts of the COVID-19 Pandemic in People with Autoimmune Diseases |
Details
Retrospective 4666 people with autoimmune or inflammatory conditions, showing HCQ adjusted risk of COVID-19 OR 0.91 [0.68-1.23]. Results are not adjusted for the significantly different risk of COVID-19 depending on the type and severity .. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Risk Factors for Infection and Health Impacts of the COVID-19 Pandemic in People with Autoimmune Diseases |
Fitzgerald et al., medRxiv, doi:10.1101/2021.02.03.21251069 (Preprint) |
Retrospective 4666 people with autoimmune or inflammatory conditions, showing HCQ adjusted risk of COVID-19 OR 0.91 [0.68-1.23]. Results are not adjusted for the significantly different risk of COVID-19 depending on the type and severity of autoimmune or inflammatory condition.
risk of case, 8.5% lower, RR 0.91, p = 0.54, treatment 65 of 1,072 (6.1%), control 200 of 3,594 (5.6%), adjusted, OR converted to RR.
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Excluded in after exclusion results of meta analysis:
not fully adjusting for the baseline risk differences within systemic autoimmune patients.
Fitzgerald et al., 2/5/2021, retrospective, USA, preprint, 34 authors.
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Late |
Hernandez-Cardenas et al., medRxiv, doi:10.1101/2021.02.01.21250371 (Preprint) |
death, ↓12.0%, p=0.66 |
Hydroxychloroquine for the treatment of severe respiratory infection by COVID-19: a randomized controlled trial |
Details
Very late stage RCT with 214 patients, mean SpO2 65%, 162 on mechanical ventilation, showing no significant difference in mortality. Patients not intubated at baseline show greater improvement, HR 0.43 [0.09-2.03]. Table 4 shows different.. |
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Details
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Late treatment study
Late treatment study
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Hydroxychloroquine for the treatment of severe respiratory infection by COVID-19: a randomized controlled trial |
Hernandez-Cardenas et al., medRxiv, doi:10.1101/2021.02.01.21250371 (Preprint) |
Very late stage RCT with 214 patients, mean SpO2 65%, 162 on mechanical ventilation, showing no significant difference in mortality.Patients not intubated at baseline show greater improvement, HR 0.43 [0.09-2.03].Table 4 shows different results to the abstract - table 4 adjusted HR 0.80 [0.51-1.23], abstract HR 0.88 [0.51-1.53]. There was no significant difference in severe adverse events.
risk of death, 12.0% lower, RR 0.88, p = 0.66, treatment 106, control 108.
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risk of death, 57.0% lower, RR 0.43, p = 0.29, subgroup not intubated at baseline.
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Hernandez-Cardenas et al., 2/5/2021, Randomized Controlled Trial, Mexico, preprint, 6 authors, average treatment delay 7.4 days.
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Submit Corrections or Comments
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Late |
Ouedraogo et al., Revue des Maladies Respiratoires, doi:10.1016/j.rmr.2021.02.001 |
death, ↓33.0%, p=0.38 |
Factors associated with the occurrence of acute respiratory distress and death in patients with COVID-19 in Burkina Faso |
Details
Retrospective 456 patients in Burkina Faso showing lower risk of ARDS (p=0.001) and mortality (p=0.38) with HCQ. |
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Details
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Late treatment study
Late treatment study
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Factors associated with the occurrence of acute respiratory distress and death in patients with COVID-19 in Burkina Faso |
Ouedraogo et al., Revue des Maladies Respiratoires, doi:10.1016/j.rmr.2021.02.001 |
Retrospective 456 patients in Burkina Faso showing lower risk of ARDS (p=0.001) and mortality (p=0.38) with HCQ.
risk of death, 33.0% lower, HR 0.67, p = 0.38, treatment 397, control 59, multivariate.
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risk of ARDS, 68.0% lower, OR 0.32, p = 0.001, treatment 397, control 59, multivariate, RR approximated with OR.
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Ouedraogo et al., 2/5/2021, retrospective, Burkina Faso, peer-reviewed, 14 authors.
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Submit Corrections or Comments
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Review |
Alexander et al., medRxiv, doi:10.1101/2021.01.28.21250706 (Review) (Preprint) |
review |
Early Multidrug Outpatient Treatment of SARS-CoV-2 Infection (COVID-19) and Reduced Mortality Among Nursing Home Residents |
Details
Review of studies on treatment of COVID-19 for nursing home residents, concluding that there is a large >60% mortality risk reduction associated with multidrug treatment using two or more intracellular anti-infectives (HCQ and either AZM .. |
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Details
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Review
Review
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Early Multidrug Outpatient Treatment of SARS-CoV-2 Infection (COVID-19) and Reduced Mortality Among Nursing Home Residents |
Alexander et al., medRxiv, doi:10.1101/2021.01.28.21250706 (Review) (Preprint) |
Review of studies on treatment of COVID-19 for nursing home residents, concluding that there is a large >60% mortality risk reduction associated with multidrug treatment using two or more intracellular anti-infectives (HCQ and either AZM or DOXY) combined with other agents including corticosteroids, anti-thrombotics, and nutraceuticals. Authors note there is also recent focus on ivermectin and favorable evidence for bromhexine.
Alexander et al., 2/1/2021, preprint, 11 authors.
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Submit Corrections or Comments
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Late |
Ubaldo et al., Critical Care Research and Practice, 10.1155/2021/7510306 |
death, ↓18.4%, p=0.64 |
COVID-19: A Single-Center ICU Experience of the First Wave in the Philippines |
Details
Retrospective ICU patients in the Philippines showing unadjusted HCQ RR 0.82, p = 0.64. |
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Details
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Late treatment study
Late treatment study
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COVID-19: A Single-Center ICU Experience of the First Wave in the Philippines |
Ubaldo et al., Critical Care Research and Practice, 10.1155/2021/7510306 |
Retrospective ICU patients in the Philippines showing unadjusted HCQ RR 0.82, p = 0.64.
risk of death, 18.4% lower, RR 0.82, p = 0.64, treatment 17 of 25 (68.0%), control 5 of 6 (83.3%), NNT 6.5, COVID-19 positive patients.
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Excluded in after exclusion results of meta analysis:
substantial unadjusted confounding by indication likely, very late stage, ICU patients, unadjusted results with no group details.
Ubaldo et al., 2/1/2021, retrospective, Philippines, peer-reviewed, 3 authors.
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Submit Corrections or Comments
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PrEP |
Naderi et al., Immunopathologia Persa, doi:10.34172/ipp.2021.29 (Preprint) |
Prophylactic effects of hydroxychloroquine on the incidence of COVID-19 in patients with rheumatic arthritis: an observational cohort study |
Details
Prospective observational study of 215 RA patients treated with HCQ showing 9 cases, 1 hospitalization (without ICU/intubation), and no mortality. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Prophylactic effects of hydroxychloroquine on the incidence of COVID-19 in patients with rheumatic arthritis: an observational cohort study |
Naderi et al., Immunopathologia Persa, doi:10.34172/ipp.2021.29 (Preprint) |
Prospective observational study of 215 RA patients treated with HCQ showing 9 cases, 1 hospitalization (without ICU/intubation), and no mortality.
Naderi et al., 1/31/2021, preprint, 7 authors.
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Submit Corrections or Comments
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Late |
Roig et al., Revista Espanola de Quimioterapia, doi:10.37201/req/130.2020 |
death, ↓15.6%, p=0.76 |
Clinical and pharmacological data in COVID-19 hospitalized nonagenarian patients |
Details
Retrospective 79 hospitalized nonagenarian patients showing unadjusted HCQ mortality RR 0.84, p = 0.76. |
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Late treatment study
Late treatment study
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Clinical and pharmacological data in COVID-19 hospitalized nonagenarian patients |
Roig et al., Revista Espanola de Quimioterapia, doi:10.37201/req/130.2020 |
Retrospective 79 hospitalized nonagenarian patients showing unadjusted HCQ mortality RR 0.84, p = 0.76.
risk of death, 15.6% lower, RR 0.84, p = 0.76, treatment 33 of 67 (49.3%), control 7 of 12 (58.3%), NNT 11.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Roig et al., 1/31/2021, retrospective, Spain, peer-reviewed, 6 authors.
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Submit Corrections or Comments
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Late |
Di Castelnuovo et al., Journal of Healthcare Engineering, doi:10.1155/2021/5556207 (preprint 1/29/2021) |
death, ↓40.0%, p<0.0001 |
Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering |
Details
Retrospective 4,396 hospitalized patients in Italy showing significantly lower mortality with HCQ treatment, and identifying greater efficacy for a subgroup of patients in clustering analysis. |
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Details
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Late treatment study
Late treatment study
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Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering |
Di Castelnuovo et al., Journal of Healthcare Engineering, doi:10.1155/2021/5556207 (preprint 1/29/2021) |
Retrospective 4,396 hospitalized patients in Italy showing significantly lower mortality with HCQ treatment, and identifying greater efficacy for a subgroup of patients in clustering analysis.
risk of death, 40.0% lower, RR 0.60, p < 0.001, treatment 3,270, control 1,000, OR converted to RR, multivariate Cox proportional hazards model 4, control prevalence approximated with overall prevalence.
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Di Castelnuovo et al., 1/29/2021, retrospective, Italy, peer-reviewed, 112 authors.
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Submit Corrections or Comments
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PrEP |
Trefond et al., Revue du Rhumatisme, doi:10.1016/j.rhum.2021.09.004 (preprint 1/27/2021) |
death, ↑16.6%, p=0.80 |
Effet d’un traitement par hydroxychloroquine prescrit comme traitement de fond de rhumatismes inflammatoires chroniques ou maladies auto-immunes systémiques sur les tests diagnostiques et l’évolution de l’infection à SARS CoV-2: étude de 871 patients |
Details
Retrospective 71 chronic HCQ patients compared with 191 matched controls, analyzing only those with a highly suspected or confirmed diagnosis of COVID-19. No significant difference was found in outcomes, however matching failed with extre.. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Effet d’un traitement par hydroxychloroquine prescrit comme traitement de fond de rhumatismes inflammatoires chroniques ou maladies auto-immunes systémiques sur les tests diagnostiques et l’évolution de l’infection à SARS CoV-2: étude de 871 patients |
Trefond et al., Revue du Rhumatisme, doi:10.1016/j.rhum.2021.09.004 (preprint 1/27/2021) |
Retrospective 71 chronic HCQ patients compared with 191 matched controls, analyzing only those with a highly suspected or confirmed diagnosis of COVID-19. No significant difference was found in outcomes, however matching failed with extreme confounding - 77.5% of HCQ patients with systemic autoimmune diseases vs. 21.5% of control patients.Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
risk of death, 16.6% higher, RR 1.17, p = 0.80, treatment 4 of 68 (5.9%), control 12 of 183 (6.6%), adjusted, OR converted to RR.
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risk of death/ICU, 78.2% higher, RR 1.78, p = 0.21, treatment 8 of 71 (11.3%), control 18 of 191 (9.4%), adjusted, OR converted to RR.
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risk of hospitalization, 44.9% higher, RR 1.45, p = 0.12, treatment 24 of 71 (33.8%), control 53 of 191 (27.7%), adjusted, OR converted to RR.
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Excluded in after exclusion results of meta analysis:
not fully adjusting for the different baseline risk of systemic autoimmune patients, significant unadjusted confounding possible, excessive unadjusted differences between groups.
Trefond et al., 1/27/2021, retrospective, France, peer-reviewed, 21 authors.
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Submit Corrections or Comments
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Safety |
Eftekhar et al., medRxiv, doi:10.1101/2021.01.16.21249941 (Preprint) |
safety analysis |
Hydroxychloroquine and azithromycin: As a double edge sword for COVID-19? |
Details
Retrospective 172 hospitalized patients, 83% treated and HCQ+AZ and 17% with HCQ, not finding a significant difference in QTc prolongation, but recommending careful monitoring for the use of HCQ+AZ; especially in males, patients with high.. |
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Details
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Safety
Safety
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Hydroxychloroquine and azithromycin: As a double edge sword for COVID-19? |
Eftekhar et al., medRxiv, doi:10.1101/2021.01.16.21249941 (Preprint) |
Retrospective 172 hospitalized patients, 83% treated and HCQ+AZ and 17% with HCQ, not finding a significant difference in QTc prolongation, but recommending careful monitoring for the use of HCQ+AZ; especially in males, patients with high-risk Tisdale score, and in patients who have baseline QTc interval ≥ 450 milliseconds.
Eftekhar et al., 1/26/2021, preprint, 6 authors.
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Submit Corrections or Comments
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Early |
Dabbous et al., Archives of Virology, doi:10.1007/s00705-021-04956-9 |
Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study |
Details
This study was retracted. |
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Details
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Early treatment study
Early treatment study
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Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study |
Dabbous et al., Archives of Virology, doi:10.1007/s00705-021-04956-9 |
This study was retracted.
Dabbous et al., 1/25/2021, peer-reviewed, 10 authors.
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Submit Corrections or Comments
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In Silico |
Hussein et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979 |
In Silico |
Molecular Docking Identification for the efficacy of Some Zinc Complexes with Chloroquine and Hydroxychloroquine against Main Protease of COVID-19 |
Details
Molecular dynamics analysis recommending Zn (CQ) Cl2(H2O) and Zn (HCQ) Cl2(H2O) as potential inhibitors for COVID-19 Mpro. Zn (HCQ) Cl2(H2O) exhibited a strong binding to the main protease receptor, forming eight hydrogen bonds. |
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In Silico
In Silico
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Molecular Docking Identification for the efficacy of Some Zinc Complexes with Chloroquine and Hydroxychloroquine against Main Protease of COVID-19 |
Hussein et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979 |
Molecular dynamics analysis recommending Zn (CQ) Cl2(H2O) and Zn (HCQ) Cl2(H2O) as potential inhibitors for COVID-19 Mpro. Zn (HCQ) Cl2(H2O) exhibited a strong binding to the main protease receptor, forming eight hydrogen bonds.
Hussein et al., 1/25/2021, peer-reviewed, 2 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
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Submit Corrections or Comments
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Early |
Zelenko, Z., Preprint (Preprint) |
Nebulized Hydroxychloroquine for COVID-19 Treatment: 80x Improvement in Breathing |
Details
Report on the use of nebulized HCQ showing much more rapid improvement compared to tablets, with 95% of patients experiencing improved breathing within 1 hour. Author notes that the effectiveness of HCQ is time and dose dependent, with a .. |
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Details
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Early treatment study
Early treatment study
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Nebulized Hydroxychloroquine for COVID-19 Treatment: 80x Improvement in Breathing |
Zelenko, Z., Preprint (Preprint) |
Report on the use of nebulized HCQ showing much more rapid improvement compared to tablets, with 95% of patients experiencing improved breathing within 1 hour. Author notes that the effectiveness of HCQ is time and dose dependent, with a primary issue being the time it takes for a therapeutic dosage to reach the lungs, and that treatment with tablets may take an average of 80 hours to achieve significant clinical improvement.Author notes that it may take 3-7 days to achieve optimal alveolar concentrations with tablets, whereas nebulized HCQ administered as microdroplets directly to the lungs achieves optimal alveolar concentration in approximately one hour and is associated with faster clinical improvement, reduction in pulmonary complications, and a reduction in medical costs.
Zelenko et al., 1/24/2021, preprint, 1 author.
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Submit Corrections or Comments
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PrEP |
Cifuentes et al., Medicina Clínica (English Edition), doi:10.1016/j.medcle.2020.10.012 |
Incidence of COVID-19 in patients under chronic treatment with hydroxychloroquine |
Details
Retrospective 3,817 chronic HCQ patients showing 4.4% COVID-19 positive rate, 1.3% severe. There is no comparison with a control group. Authors note that there was a 3.6% incidence among 2,032,863 patients in one of the regions (Castilla .. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Incidence of COVID-19 in patients under chronic treatment with hydroxychloroquine |
Cifuentes et al., Medicina Clínica (English Edition), doi:10.1016/j.medcle.2020.10.012 |
Retrospective 3,817 chronic HCQ patients showing 4.4% COVID-19 positive rate, 1.3% severe. There is no comparison with a control group. Authors note that there was a 3.6% incidence among 2,032,863 patients in one of the regions (Castilla La Mancha), however they provide no information on this group - it is expected that the mostly systemic autoimmune disease patients in the treatment group are older on average. Additonally, other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Cifuentes et al., 1/23/2021, peer-reviewed, 18 authors.
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Submit Corrections or Comments
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Late |
Li et al., Science China Life Sciences, doi:10.1007/s11427-020-1871-4 |
no disch., ↓50.0%, p=0.09 |
Evaluation of the efficacy and safety of hydroxychloroquine in comparison with chloroquine in moderate and severe patients with COVID-19 |
Details
Small RCT comparing HCQ and CQ in China with 88 very late stage (17.6 days from onset to hospitalization and ~10 days to randomization) patients. The primary clinical outcomes (TTCR and TTCI) were not significantly different. Authors note.. |
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Details
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Late treatment study
Late treatment study
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Evaluation of the efficacy and safety of hydroxychloroquine in comparison with chloroquine in moderate and severe patients with COVID-19 |
Li et al., Science China Life Sciences, doi:10.1007/s11427-020-1871-4 |
Small RCT comparing HCQ and CQ in China with 88 very late stage (17.6 days from onset to hospitalization and ~10 days to randomization) patients. The primary clinical outcomes (TTCR and TTCI) were not significantly different. Authors note that HCQ may have more promising efficacy in immune system modulation, indicated by ferritin reduction in the moderate cases and improvement of CT scores and lymphocyte counts in the severe cases. HCQ and CQ were well tolerated.Authors also compare RCT patients to a matched sample of non-RCT patients in the same hospital, showing shorter time to discharge with CQ/HCQ, but not statistically significant due to the small size.
risk of no hospital discharge, 50.0% lower, HR 0.50, p = 0.09, treatment 14, control 14, RCT patients vs. matched sample of non-treated patients.
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Li et al., 1/18/2021, retrospective, China, peer-reviewed, 21 authors.
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Submit Corrections or Comments
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PrEP |
Khoubnasabjafari et al., Postgraduate Medical Journal, doi:10.1136/postgradmedj-2020-139561 |
cases, ↓16.7%, p=0.59 |
Prevalence of COVID-19 in patients with rheumatoid arthritis (RA) already treated with hydroxychloroquine (HCQ) compared with HCQ-naive patients with RA: a multicentre cross-sectional study |
Details
Survey analysis of 1,858 RA patients in Iran, showing no significant difference in cases with HCQ prophylaxis. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Prevalence of COVID-19 in patients with rheumatoid arthritis (RA) already treated with hydroxychloroquine (HCQ) compared with HCQ-naive patients with RA: a multicentre cross-sectional study |
Khoubnasabjafari et al., Postgraduate Medical Journal, doi:10.1136/postgradmedj-2020-139561 |
Survey analysis of 1,858 RA patients in Iran, showing no significant difference in cases with HCQ prophylaxis.
risk of case, 16.7% lower, RR 0.83, p = 0.59, treatment 34 of 1,436 (2.4%), control 12 of 422 (2.8%), NNT 210.
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Khoubnasabjafari et al., 1/13/2021, retrospective, Iran, peer-reviewed, 10 authors.
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Late |
Li et al., Research Square, doi:10.21203/rs.3.rs-119202/v1 (Preprint) |
viral- time, ↑40.0%, p=0.06 |
Treatment of COVID-19 patients with hydroxychloroquine or chloroquine: A retrospective analysis |
Details
Small retrospective database analysis of 37 late stage patients hospitalized in an intensive care center in China, not finding a significant difference in viral shedding. Pateints were all in serious condition. There was only one death ho.. |
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Details
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Late treatment study
Late treatment study
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Treatment of COVID-19 patients with hydroxychloroquine or chloroquine: A retrospective analysis |
Li et al., Research Square, doi:10.21203/rs.3.rs-119202/v1 (Preprint) |
Small retrospective database analysis of 37 late stage patients hospitalized in an intensive care center in China, not finding a significant difference in viral shedding. Pateints were all in serious condition. There was only one death however the group is not specified. Confounding by indication is likely.
time to viral-, 40.0% higher, relative time 1.40, p = 0.06, treatment 18, control 19.
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Li et al., 1/12/2021, retrospective, database analysis, China, preprint, 5 authors.
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PrEP |
Rangel et al., Journal of the American Academy of Dermatology, doi:10.1016/j.jaad.2020.10.098 |
death, ↓25.1%, p=0.77 |
Chronic Hydroxychloroquine Therapy and COVID-19 Outcomes: A Retrospective Case-Control Analysis |
Details
Retrospective 50 COVID-19 patients that take chronic HCQ, compared to a matched sample of patients not taking chronic HCQ, showing lower mortality and ICU admission, and shorter hospitalization for HCQ patients, but not statistically sign.. |
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Details
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Chronic Hydroxychloroquine Therapy and COVID-19 Outcomes: A Retrospective Case-Control Analysis |
Rangel et al., Journal of the American Academy of Dermatology, doi:10.1016/j.jaad.2020.10.098 |
Retrospective 50 COVID-19 patients that take chronic HCQ, compared to a matched sample of patients not taking chronic HCQ, showing lower mortality and ICU admission, and shorter hospitalization for HCQ patients, but not statistically significant due to the small number of events.The actual benefit for HCQ could be much larger. The study does not address the risk of being sick enough to visit the hospital. HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
risk of death, 25.1% lower, RR 0.75, p = 0.77, treatment 4 of 50 (8.0%), control 11 of 103 (10.7%), NNT 37, from all patients.
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risk of hospitalization, 22.2% lower, RR 0.78, p = 0.29, treatment 17 of 50 (34.0%), control 45 of 103 (43.7%), NNT 10.
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hospitalization time, 41.2% lower, relative time 0.59, p = 0.12, treatment 21, control 54.
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Excluded in after exclusion results of meta analysis:
not fully adjusting for the different baseline risk of systemic autoimmune patients.
Rangel et al., 1/10/2021, retrospective, USA, peer-reviewed, 5 authors.
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Late |
Yegerov et al., medRxiv, doi:10.1101/2021.01.06.20249091 (Preprint) |
death, ↓95.3%, p=1.00 |
Epidemiological and Clinical Characteristics, and Virologic Features of COVID-19 Patients in Kazakhstan: a Nation-Wide, Retrospective, Cohort Study |
Details
Retrospective 1,072 hospitalized patients in Kazakhstan showing no mortality for HCQ treated patients, however only 23 patients received treatment - this result is not statistically significant. |
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Details
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Late treatment study
Late treatment study
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Epidemiological and Clinical Characteristics, and Virologic Features of COVID-19 Patients in Kazakhstan: a Nation-Wide, Retrospective, Cohort Study |
Yegerov et al., medRxiv, doi:10.1101/2021.01.06.20249091 (Preprint) |
Retrospective 1,072 hospitalized patients in Kazakhstan showing no mortality for HCQ treated patients, however only 23 patients received treatment - this result is not statistically significant.
risk of death, 95.3% lower, RR 0.05, p = 1.00, treatment 0 of 23 (0.0%), control 20 of 1,049 (1.9%), NNT 52, relative risk is not 0 because of continuity correction due to zero events.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Yegerov et al., 1/8/2021, retrospective, Kazakhstan, preprint, 8 authors, average treatment delay 1.0 days.
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Submit Corrections or Comments
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In Silico |
Baildya et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129891 |
In Silico |
Inhibitory capacity of Chloroquine against SARS-COV-2 by effective binding with Angiotensin converting enzyme-2 receptor: An insight from molecular docking and MD-simulation studies |
Details
Molecular docking study of 16 drugs showing CQ had the highest binding affinity with ACE2, and molecular dynamics study of the docked CQ-ACE2 structure. Authors conclude that CQ binds reasonably strongly with ACE2 and the stable ACE2-CQ m.. |
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Details
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In Silico
In Silico
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Inhibitory capacity of Chloroquine against SARS-COV-2 by effective binding with Angiotensin converting enzyme-2 receptor: An insight from molecular docking and MD-simulation studies |
Baildya et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129891 |
Molecular docking study of 16 drugs showing CQ had the highest binding affinity with ACE2, and molecular dynamics study of the docked CQ-ACE2 structure. Authors conclude that CQ binds reasonably strongly with ACE2 and the stable ACE2-CQ may prevent further binding of ACE2 with the SARS-CoV-2 spike protein.
Baildya et al., 1/7/2021, peer-reviewed, 3 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
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In Silico |
Noureddine et al., Journal of King Saud University - Science, doi:10.1016/j.jksus.2020.101334 |
In Silico |
Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: molecular docking and DFT calculations |
Details
In silico analysis of hydroxychloroquine and hydroxychloroquine sulfate predicting that hydroxychloroquine sulfate is more stable and effective for COVID-19. |
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Details
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In Silico
In Silico
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Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: molecular docking and DFT calculations |
Noureddine et al., Journal of King Saud University - Science, doi:10.1016/j.jksus.2020.101334 |
In silico analysis of hydroxychloroquine and hydroxychloroquine sulfate predicting that hydroxychloroquine sulfate is more stable and effective for COVID-19.
Noureddine et al., 1/6/2021, peer-reviewed, 5 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
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Submit Corrections or Comments
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Safety |
Gautret et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106236 |
safety analysis |
Safety profile of hydroxychloroquine and azithromycin combined treatment in COVID-19 patients |
Details
Report on the safety of HCQ+AZ with 3,737 COVID-19 patients. 138 had contraindications and treatment was discontinued in 12 cases due to QTc prolongation. There were no cases of torsade de pointe or sudden death. |
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Details
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Safety
Safety
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Safety profile of hydroxychloroquine and azithromycin combined treatment in COVID-19 patients |
Gautret et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106236 |
Report on the safety of HCQ+AZ with 3,737 COVID-19 patients. 138 had contraindications and treatment was discontinued in 12 cases due to QTc prolongation. There were no cases of torsade de pointe or sudden death.
Gautret et al., 1/4/2021, peer-reviewed, 4 authors.
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Late |
Sarfaraz et al., medRxiv, doi:10.1101/2020.12.28.20248920 (Preprint) |
death, ↑45.0%, p=0.07 |
Determinants of in-hospital mortality in COVID-19; a prospective cohort study from Pakistan |
Details
Retrospective 186 hospitalized patients in Pakistan showing unadjusted HCQ mortality RR 1.45, p = 0.07. Confounding by indication is likely. |
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Details
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Late treatment study
Late treatment study
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Determinants of in-hospital mortality in COVID-19; a prospective cohort study from Pakistan |
Sarfaraz et al., medRxiv, doi:10.1101/2020.12.28.20248920 (Preprint) |
Retrospective 186 hospitalized patients in Pakistan showing unadjusted HCQ mortality RR 1.45, p = 0.07. Confounding by indication is likely.
risk of death, 45.0% higher, RR 1.45, p = 0.07, treatment 40 of 94 (42.6%), control 27 of 92 (29.3%).
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Excluded in after exclusion results of meta analysis:
substantial unadjusted confounding by indication likely, significant unadjusted confounding possible, unadjusted results with no group details.
Sarfaraz et al., 1/2/2021, retrospective, Pakistan, preprint, 7 authors, average treatment delay 7.0 days.
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Submit Corrections or Comments
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Late |
Lotfy et al., Turk. Thorac. J., doi:10.5152/TurkThoracJ.2021.20180 |
death, ↑24.8%, p=0.76 |
Use of Hydroxychloroquine in Patients with COVID-19: A Retrospective Observational Study |
Details
Retrospective 202 patients in Saudi Arabia not showing significant differences with treatment. No information is provided on how patients were selected for treatment, there may be significant confounding by indication. Time varying confou.. |
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Details
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Late treatment study
Late treatment study
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Use of Hydroxychloroquine in Patients with COVID-19: A Retrospective Observational Study |
Lotfy et al., Turk. Thorac. J., doi:10.5152/TurkThoracJ.2021.20180 |
Retrospective 202 patients in Saudi Arabia not showing significant differences with treatment. No information is provided on how patients were selected for treatment, there may be significant confounding by indication. Time varying confounding is also likely as HCQ became controversial during the period studied, therefore HCQ use was likely more frequent toward the beginning of the period, a time when overall treatment protocols were significantly worse.
risk of death, 24.8% higher, RR 1.25, p = 0.76, treatment 6 of 99 (6.1%), control 5 of 103 (4.9%).
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risk of mechanical ventilation, 41.2% higher, RR 1.41, p = 0.34, treatment 19 of 99 (19.2%), control 14 of 103 (13.6%).
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risk of ICU admission, 16.5% higher, RR 1.17, p = 0.53, treatment 28 of 99 (28.3%), control 25 of 103 (24.3%).
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Excluded in after exclusion results of meta analysis:
substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
Lotfy et al., 1/1/2021, retrospective, Saudi Arabia, peer-reviewed, mean age 55.0, 3 authors.
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Late |
Sands et al., International Journal of Infectious Diseases, doi:/10.1016/j.ijid.2020.12.060 |
death, ↑69.9%, p=0.01 |
No clinical benefit in mortality associated with hydroxychloroquine treatment in patients with COVID-19 |
Details
Retrospective database analysis of 1,669 patients in the US showing OR 1.81, p = 0.01. Confounding by indication is likely. COVID-19 was determined via PCR+ results, therefore authors include patients asymptomatic for COVID-19, but in th.. |
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Late treatment study
Late treatment study
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No clinical benefit in mortality associated with hydroxychloroquine treatment in patients with COVID-19 |
Sands et al., International Journal of Infectious Diseases, doi:/10.1016/j.ijid.2020.12.060 |
Retrospective database analysis of 1,669 patients in the US showing OR 1.81, p = 0.01. Confounding by indication is likely.COVID-19 was determined via PCR+ results, therefore authors include patients asymptomatic for COVID-19, but in the hospital for other reasons. While authors adjust for severity, the method used is very poor. 93.5% of patients are classified as "mild", which is patients with no documented care in a critical care unit within 8 hours of admission. Therefore almost all patients are in the same category, and those in a different category may be due to symptoms unrelated to COVID-19. Lower bias toward male patients in the control group also agrees with the hypothesis that the control group is made up of more people that were in hospital for another reason.Since the analysis covers the initial period of the pandemic in the USA, it is likely that HCQ was used more often earlier in the analysis period when treatment protocols were considerably worse. It's unclear why the analysis only considers patients up to April 27, when the manuscript was submitted in October.For other issues see [ijidonline.com].
risk of death, 69.9% higher, RR 1.70, p = 0.01, treatment 101 of 973 (10.4%), control 56 of 696 (8.0%), OR converted to RR.
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Excluded in after exclusion results of meta analysis:
includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons, substantial unadjusted confounding by indication likely.
Sands et al., 1/1/2021, retrospective, database analysis, USA, peer-reviewed, 10 authors.
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Submit Corrections or Comments
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Late |
Mahale et al., Indian Journal of Critical Care Medicine, doi:10.5005/jp-journals-10071-23599 |
death, ↓28.7%, p=0.36 |
A Retrospective Observational Study of Hypoxic COVID-19 Patients Treated with Immunomodulatory Drugs in a Tertiary Care Hospital |
Details
Retrospective 134 hospitalized COVID-19 patients in India, showing no significant difference with HCQ treatment in unadjusted results. |
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Late treatment study
Late treatment study
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A Retrospective Observational Study of Hypoxic COVID-19 Patients Treated with Immunomodulatory Drugs in a Tertiary Care Hospital |
Mahale et al., Indian Journal of Critical Care Medicine, doi:10.5005/jp-journals-10071-23599 |
Retrospective 134 hospitalized COVID-19 patients in India, showing no significant difference with HCQ treatment in unadjusted results.
risk of death, 28.7% lower, RR 0.71, p = 0.36, treatment 25 of 102 (24.5%), control 11 of 32 (34.4%), NNT 10.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Mahale et al., 12/31/2020, retrospective, India, peer-reviewed, 22 authors, study period 22 March, 2020 - 21 May, 2020.
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Submit Corrections or Comments
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Review |
Matada et al., Bioorganic & Medicinal Chemistry, doi:10.1016/j.bmc.2020.115973 (Review) |
review |
A comprehensive review on the biological interest of quinoline and its derivatives |
Details
Review of quinolone and derivatives, natural and drug sources, and biological activity. |
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Details
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Review
Review
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A comprehensive review on the biological interest of quinoline and its derivatives |
Matada et al., Bioorganic & Medicinal Chemistry, doi:10.1016/j.bmc.2020.115973 (Review) |
Review of quinolone and derivatives, natural and drug sources, and biological activity.
Matada et al., 12/31/2020, peer-reviewed, 3 authors.
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Submit Corrections or Comments
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Late |
Psevdos et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.721 |
death, ↑63.5%, p=0.52 |
Corona Virus Disease-19 (COVID-19) in a Veterans Affairs Hospital at Suffolk County, Long Island, New York |
Details
Retrospective 67 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was sus.. |
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Details
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Late treatment study
Late treatment study
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Corona Virus Disease-19 (COVID-19) in a Veterans Affairs Hospital at Suffolk County, Long Island, New York |
Psevdos et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.721 |
Retrospective 67 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely.Time varying confounding is likely. HCQ became controversial and was suspended during the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse.
risk of death, 63.5% higher, RR 1.63, p = 0.52, treatment 17 of 52 (32.7%), control 3 of 15 (20.0%).
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details, no treatment details, substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
Psevdos et al., 12/31/2020, retrospective, USA, peer-reviewed, 3 authors.
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Submit Corrections or Comments
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Late |
Texeira et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.560 |
death, ↑79.3%, p=0.10 |
Characteristics and outcomes of COVID-19 patients admitted to a regional health system in the southeast |
Details
Retrospective 161 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was su.. |
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Details
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Late treatment study
Late treatment study
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Characteristics and outcomes of COVID-19 patients admitted to a regional health system in the southeast |
Texeira et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.560 |
Retrospective 161 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely.Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse.
risk of death, 79.3% higher, RR 1.79, p = 0.10, treatment 17 of 65 (26.2%), control 14 of 96 (14.6%).
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details, no treatment details, substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
Texeira et al., 12/31/2020, retrospective, USA, peer-reviewed, 6 authors.
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Submit Corrections or Comments
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Late |
Vernaz et al., Swiss Medical Weekly, doi:10.4414/smw.2020.20446 |
death, ↓15.3%, p=0.71 |
Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs |
Details
Retrospective 840 hospitalized patients in Switzerland showing non-statistically significant lower mortality with HCQ but significantly longer hospitalization times. Confounding by indication is likely. PSM fails to adjust for severity wi.. |
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Details
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Late treatment study
Late treatment study
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Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs |
Vernaz et al., Swiss Medical Weekly, doi:10.4414/smw.2020.20446 |
Retrospective 840 hospitalized patients in Switzerland showing non-statistically significant lower mortality with HCQ but significantly longer hospitalization times. Confounding by indication is likely. PSM fails to adjust for severity with a 16% higher mNEWS score for HCQ vs. SOC in the matched cohort.Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse.Authors note: "overall, there was an indication bias, with the reason of prescription being associated with the outcome of interest. Indeed, patients with more severe COVID-19 were more likely to receive experimental therapies."
risk of death, 15.3% lower, RR 0.85, p = 0.71, treatment 12 of 93 (12.9%), control 16 of 105 (15.2%), NNT 43, HCQ vs. SOC, PSM.
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hospitalization time, 49.0% higher, relative time 1.49, p = 0.002, treatment 93, control 105, HCQ vs. SOC, PSM.
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Excluded in after exclusion results of meta analysis:
substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
Vernaz et al., 12/31/2020, retrospective, propensity score matching, Switzerland, peer-reviewed, 15 authors.
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Submit Corrections or Comments
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Review |
McCullough et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.264 (Review) |
review |
Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19) |
Details
Review urging early treatment of COVID-19 with sequential multidrug treatment that has been shown to be safe and effective. Proposed treatment includes zinc, vitamin D & C, quercetin, and depending on age, comorbidities, and symptoms may .. |
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Details
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Review
Review
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Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19) |
McCullough et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.264 (Review) |
Review urging early treatment of COVID-19 with sequential multidrug treatment that has been shown to be safe and effective. Proposed treatment includes zinc, vitamin D & C, quercetin, and depending on age, comorbidities, and symptoms may include >=2 of HCQ, ivermectin, favipiravir; AZM/DOXY; corticosteroids; colchicine; bamlanivimab; aspirin; LMWH; and supplemental oxygen.
McCullough et al., 12/30/2020, peer-reviewed, 58 authors.
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Submit Corrections or Comments
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Early |
Procter et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.260 |
Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection |
Details
Retrospective 922 outpatients, with 320 treated early due to age>50 or comorbidities, showing 2.2% hospitalization and 0.3% death, which authors note is considerably lower than reported in other studies in their region. At least two of zi.. |
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Details
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Early treatment study
Early treatment study
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Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection |
Procter et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.260 |
Retrospective 922 outpatients, with 320 treated early due to age>50 or comorbidities, showing 2.2% hospitalization and 0.3% death, which authors note is considerably lower than reported in other studies in their region.At least two of zinc, HCQ, and ivermectin were used, along with one antibiotic, and budesonide and/or dexamethasone.
Procter et al., 12/30/2020, peer-reviewed, 6 authors.
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Submit Corrections or Comments
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Late |
Güner et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2020.12.017 |
ICU, ↓77.3%, p=0.16 |
Comparing ICU Admission Rates of Mild/Moderate COVID-19 Patients Treated with Hydroxychloroquine, Favipiravir, and Hydroxychloroquine plus Favipiravir |
Details
Retrospective 824 hospitalized patients in Turkey showing lower ICU admission for HCQ vs. favipiravir. |
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Details
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Late treatment study
Late treatment study
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Comparing ICU Admission Rates of Mild/Moderate COVID-19 Patients Treated with Hydroxychloroquine, Favipiravir, and Hydroxychloroquine plus Favipiravir |
Güner et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2020.12.017 |
Retrospective 824 hospitalized patients in Turkey showing lower ICU admission for HCQ vs. favipiravir.
risk of ICU admission, 77.3% lower, RR 0.23, p = 0.16, treatment 604, control 100, IPTW multivariate analysis, HCQ vs. favipiravir.
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Güner et al., 12/29/2020, retrospective, Turkey, peer-reviewed, 23 authors.
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Submit Corrections or Comments
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PrEP |
Cordtz et al., Rheumatology, doi:10.1093/rheumatology/keaa897 |
hosp., ↓24.0%, p=0.67 |
Incidence and severeness of COVID-19 hospitalisation in patients with inflammatory rheumatic disease: a nationwide cohort study from Denmark |
Details
Retrospective 58,052 rheumatic disease patients in Denmark showing that RA patients have a higher risk of COVID-19 hospitalization in general. HCQ treated patients show lower risk, although this is not statistically significant with only .. |
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Details
Source
PDF
Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Incidence and severeness of COVID-19 hospitalisation in patients with inflammatory rheumatic disease: a nationwide cohort study from Denmark |
Cordtz et al., Rheumatology, doi:10.1093/rheumatology/keaa897 |
Retrospective 58,052 rheumatic disease patients in Denmark showing that RA patients have a higher risk of COVID-19 hospitalization in general. HCQ treated patients show lower risk, although this is not statistically significant with only 3 hospitalizations for HCQ treated patients.HR 0.76 [0.23-2.52] time-dependent exposure model HR 0.45 [0.11-1.92] time-fixed exposure model
risk of hospitalization, 24.0% lower, HR 0.76, p = 0.67, treatment 3 of 2,722 (0.1%), control 38 of 26,718 (0.1%), NNT 3124, adjusted, time-dependent exposure model.
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risk of hospitalization, 55.0% lower, HR 0.45, p = 0.28, treatment 3 of 2,722 (0.1%), control 38 of 26,718 (0.1%), adjusted, time-fixed exposure model.
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Cordtz et al., 12/28/2020, retrospective, population-based cohort, Denmark, peer-reviewed, 10 authors.
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Submit Corrections or Comments
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Late |
Chari et al., Blood, doi:10.1182/blood.2020008150 |
death, ↓33.1%, p=0.17 |
Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set |
Details
Retrospective multiple myeloma patients showing lower mortality with HCQ treatment, unadjusted RR 0.67, p = 0.17 (data is in the supplementary material). |
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Details
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Late treatment study
Late treatment study
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Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set |
Chari et al., Blood, doi:10.1182/blood.2020008150 |
Retrospective multiple myeloma patients showing lower mortality with HCQ treatment, unadjusted RR 0.67, p = 0.17 (data is in the supplementary material).
risk of death, 33.1% lower, RR 0.67, p = 0.17, treatment 8 of 29 (27.6%), control 195 of 473 (41.2%), NNT 7.3.
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Excluded in after exclusion results of meta analysis:
unadjusted results with no group details.
Chari et al., 12/24/2020, retrospective, multiple countries, peer-reviewed, median age 69.0, 25 authors.
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Submit Corrections or Comments
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Early |
Su et al., BioScience Trends, doi:10.5582/bst.2020.03340 |
progression, ↓84.9%, p=0.006 |
Efficacy of early hydroxychloroquine treatment in preventing COVID-19 pneumonia aggravation, the experience from Shanghai, China |
Details
85% lower disease progression with early use of HCQ. Retrospective 616 patients in China showing adjusted progression HR 0.15, p = 0.006. |
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Details
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Early treatment study
Early treatment study
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Efficacy of early hydroxychloroquine treatment in preventing COVID-19 pneumonia aggravation, the experience from Shanghai, China |
Su et al., BioScience Trends, doi:10.5582/bst.2020.03340 |
85% lower disease progression with early use of HCQ. Retrospective 616 patients in China showing adjusted progression HR 0.15, p = 0.006.
risk of progression, 84.9% lower, HR 0.15, p = 0.006, adjusted, binary logistic regression.
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improvement time, 24.0% better, relative time 0.76, p = 0.02, adjusted, Cox proportional hazards.
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risk of no viral clearance, 35.8% lower, HR 0.64, p = 0.001, Cox proportional hazards.
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Su et al., 12/23/2020, retrospective, China, peer-reviewed, 9 authors, study period 20 January, 2020 - 30 April, 2020, dosage 400mg days 1-10, 400mg daily for 10-14 days.
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Submit Corrections or Comments
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Late |
Taccone et al., The Lancet Regional Health - Europe, doi:10.1016/j.lanepe.2020.100019 |
death, ↓24.7%, p=0.02 |
The role of organizational characteristics on the outcome of COVID-19 patients admitted to the ICU in Belgium |
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Retrospective 1,747 ICU patients in Belgium showing lower mortality with HCQ, multivariate mixed effects analysis HCQ aOR 0.64 [0.45-0.92]. |
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Late treatment study
Late treatment study
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The role of organizational characteristics on the outcome of COVID-19 patients admitted to the ICU in Belgium |
Taccone et al., The Lancet Regional Health - Europe, doi:10.1016/j.lanepe.2020.100019 |
Retrospective 1,747 ICU patients in Belgium showing lower mortality with HCQ, multivariate mixed effects analysis HCQ aOR 0.64 [0.45-0.92].
risk of death, 24.7% lower, RR 0.75, p = 0.02, treatment 449 of 1,308 (34.3%), control 183 of 439 (41.7%), NNT 14, OR converted to RR.
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Taccone et al., 12/23/2020, retrospective, Belgium, peer-reviewed, 10 authors, average treatment delay 5.0 days.
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Late |
Cangiano et al., Aging, doi:10.18632/aging.202307 |
death, ↓73.4%, p=0.03 |
Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests |
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73% lower mortality with HCQ. Analysis of 98 PCR+ nursing home residents in Italy, mean age 90, showing HCQ mortality RR 0.27, p = 0.03. Subject to confounding by contraindication. The paper provides the p value for regression but not the.. |
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Late treatment study
Late treatment study
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Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests |
Cangiano et al., Aging, doi:10.18632/aging.202307 |
73% lower mortality with HCQ. Analysis of 98 PCR+ nursing home residents in Italy, mean age 90, showing HCQ mortality RR 0.27, p = 0.03. Subject to confounding by contraindication. The paper provides the p value for regression but not the effect size.
risk of death, 73.4% lower, RR 0.27, p = 0.03, treatment 5 of 33 (15.2%), control 37 of 65 (56.9%), NNT 2.4.
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Cangiano et al., 12/22/2020, retrospective, Italy, peer-reviewed, 14 authors.
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PrEP |
Huh et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.12.041 |
progression, ↑251.0%, p=0.11 |
Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea |
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Retrospective database analysis with 17 cases for existing HCQ users and 5 severe cases, showing no significant difference for cases and higher risk for severe cases. However, HCQ users are likely systemic autoimmune disease patients and .. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea |
Huh et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.12.041 |
Retrospective database analysis with 17 cases for existing HCQ users and 5 severe cases, showing no significant difference for cases and higher risk for severe cases. However, HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [ |