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Global HCQ/CQ studies
January 18, 2022
HCQ COVID-19 studies. 371 studies, 276 peer reviewed, 305 comparing treatment and control groups. HCQ is not effective when used very late with high dosages over a long period (RECOVERY/SOLIDARITY), effectiveness improves with earlier usage and improved dosing. Early treatment consistently shows positive effects. Negative evaluations typically ignore treatment time, often focusing on a subset of late stage studies. In Vitro evidence made some believe that therapeutic levels would not be attained, however that was incorrect, e.g. see [Ruiz]. Recently added: Juneja Tyson Atipornwanich McKinnon. HCQ or CQ has been officially adopted for early treatment in all or part of 37 countries (53 including non-government medical organizations). Submit updates/corrections.
Restrict:    All    Early    Late    PrEP    PEP
Jan 14
Early, Late, PrEP, PEP Covid Analysis (Preprint) (meta analysis)
meta-analysis v170
HCQ for COVID-19: real-time meta analysis of 305 studies
Details   • 32 of the 34 early treatment studies report a positive effect. 20 show statistically significant improvements in isolation (14 for the most serious outcome). • Late treatment is less successful, with only 67% of the 204 studies reporti..
Jan 13
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..
Jan 7
PrEP Juneja et al., Journal of Basic and Clinical Physiology and Pharmacology, doi:10.1515/jbcpp-2021-0221 (Peer Reviewed)
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.
Dec 23
PrEP McKinnon et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.12.343 (Peer Reviewed)
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 PrEP 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 ..
Dec 4
PrEP Rao et al., Expert Review of Anti-infective Therapy, doi:10.1080/14787210.2022.2015326 (Peer Reviewed)
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..
Nov 26
Late Ferreira et al., Revista da Associação Médica Brasileira, doi:10.1590/1806-9282.20210661 (Peer Reviewed)
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 ..
Nov 23
Late Calderón et al., PAMJ - Clinical Medicine, doi:10.11604/pamj-cm.2021.7.15.30981 (Peer Reviewed)
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..
Nov 23
PrEP Ahmed et al., BioMed Research International, doi:10.1155/2021/1676914 (Peer Reviewed)
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.
Nov 17
PrEP Samajdar et al., Journal of the Association of Physicians India, 69:11 (Peer Reviewed)
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..
Nov 5
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..
Nov 2
Late Sarhan et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2021.10.024 (Peer Reviewed)
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.
Oct 25
Late Guglielmetti et al., Scientific Reports, doi:10.1038/s41598-021-00243-4 (Peer Reviewed)
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).
Oct 5
Late Atipornwanich et al., SSRN Electronic Journal, doi:10.2139/ssrn.3936499 (Peer Reviewed)
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..
Oct 1
Late Babalola et al., Research Square, doi:10.21203/ (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.
Oct 1
PrEP Fung et al., medRxiv, doi:10.1101/2021.09.28.21264186 (Preprint)
death, ↓15.0%, p=0.10
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..
Sep 30
Late Menardi et al., PharmAdvances, doi:10.36118/pharmadvances.2021.15 (Peer Reviewed)
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.
Sep 15
Late Uygen et al., Northern Clinics of Istanbul, doi:10.14744/nci.2021.65471 (Peer Reviewed)
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.
Sep 15
Late Çivriz Bozdağ et al., Turk. J. Haematol., doi:10.4274/tjh.galenos.2021.2021.0287 (Peer Reviewed)
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..
Sep 14
Late Alotaibi et al., International Journal of General Medicine, 2021:14 (Peer Reviewed)
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. Confounding b..
Sep 14
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.
Sep 14
Early Accinelli et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2021.102163 (Peer Reviewed) 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.
Sep 9
Early Sawanpanyalert et al., Southeast Asian Journal of Tropical Medicine and Public Health, 52:4 (Peer Reviewed)
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..
Aug 25
Early Rodrigues et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2021.106428 (Peer Reviewed)
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.
Aug 25
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..
Aug 24
PrEP Patil et al., Research Square, doi:10.21203/ (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..
Aug 16
Late Eldeen et al., Microbes and Infectious Diseases, doi:10.21608/mid.2021.85877.1177 (Peer Reviewed) 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..
Aug 14
N/A Tai et al., Pharmaceutics, doi:10.3390/pharmaceutics13081260 (Peer Reviewed) Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19
Details   Analysis of HCQ solutions suitable for nebulization for COVID-19.
Aug 10
PEP Shabani et al., Pulmonary Pharmacology & Therapeutics, doi:10.1016/j.pupt.2021.102069 (Peer Reviewed)
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.
Aug 5
Meta Stricker et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2021.08.001 (Peer Reviewed) (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.
Aug 4
Late Özuygur Ermiş et al., Turkish Journal of Medical Sciences, doi:10.3906/sag-2009-64 (Peer Reviewed) 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.
Aug 4
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..
Aug 4
Late Alghamdi et al., Saudi Pharmaceutical Journal, doi:10.1016/j.jsps.2021.08.008 (Peer Reviewed)
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.
Jul 31
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.
Jul 29
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. ..
Jul 20
PrEP Küçükakkaş et al., Research Square, doi:10.21203/ (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..
Jul 16
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..
Jul 13
Late Barrat-Due et al., Annals of Internal Medicine, doi:10.7326/M21-0653 (Peer Reviewed)
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.
Jul 10
Late Roger et al., Anaesthesia Critical Care & Pain Medicine, doi:10.1016/j.accpm.2021.100931 (Peer Reviewed)
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..
Jul 6
Late Jacobs et al., The Annals of Thoracic Surgery, doi:10.1016/j.athoracsur.2021.06.026 (Peer Reviewed)
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..
Jun 30
Late Taieb et al., J. Clin. Med. 2021, doi:10.3390/jcm10132954 (Peer Reviewed)
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.
Jun 24
Late Gerlovin et al., American Journal of Epidemiology, doi:10.1093/aje/kwab183 (Peer Reviewed)
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.
Jun 21
In Silico Yadav et al., Research Square, doi:10.21203/ (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.
Jun 18
Late Schwartz et al., CMAJ Open, doi:10.9778/cmajo.20210069 (Peer Reviewed)
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..
Jun 18
In Vitro Purwati et al., PLOS One, doi:10.1371/journal.pone.0252302 (Peer Reviewed) (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..
Jun 11
Late Turrini et al., Vaccines, 10.3390/vaccines9060640 (Peer Reviewed)
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
Details   Retrospective 205 patients in Italy, 160 treated with HCQ, showing lower mortality with treatment in multivariate analysis, but not reaching statistical significance.
Jun 9
Late Saib et al., PLOS ONE, doi:10.1371/journal.pone.0252388 (Peer Reviewed)
int./death, ↑125.0%, p=0.23
Lack of efficacy of hydroxychloroquine and azithromycin in patients hospitalized for COVID-19 pneumonia: A retrospective study
Details   203 hospitalized patients in France, not showing significant differences with treatment. Confounding by indication is likely. Authors do not discuss confounding.
Jun 8
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)
Details   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 ..
Jun 7
PrEP Badyal et al., Journal of the Association of Physicians of India, Volume 69, June 2021 (Peer Reviewed)
cases, ↓60.1%, p<0.0001
Hydroxychloroquine for SARS CoV2 Prophylaxis in Healthcare Workers – A Multicentric Cohort Study Assessing Effectiveness and Safety
Details   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.
Jun 4
Late Lagier et al., Preprint (Preprint)
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
Details   Retrospective 2,011 hospitalized patients in France, median age 67, showing lower mortality with HCQ+AZ, and further benefit with the addition of zinc.
Jun 4
Late Byakika-Kibwika et al., Research Square, doi:10.21203/ (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
Details   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..
Jun 3
Late Sivapalan et al., European Respiratory Journal, doi:10.1183/13993003.00752-2021 (Peer Reviewed)
death, ↓92.0%, p=0.32
Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19–a randomised double-blinded placebo-controlled trial
Details   Early terminated late stage (8 days from onset, 59% on oxygen) RCT not showing statistically significant differences. NCT04322396 ProPAC-COVID. NNF20SA0062834.
Jun 1
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
Details   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.
Jun 1
PrEP Kamstrup et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.05.076 (Peer Reviewed)
hosp., ↑44.0%, p=0.25
Hydroxychloroquine as a primary prophylactic agent against sars-cov-2 infection: a cohort study
Details   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 ex..
May 31
Late Ramírez-García et al., Archivos de Medicina Universitaria (Peer Reviewed)
death, ↓67.0%, p<0.0001
Hydroxychloroquine and Tocilizumab in the Treatment of COVID-19: A Longitudinal Observational Study
Details   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.
May 31
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
Details   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 immort..
May 29
Dosing Ali et al., Journal of Pharmaceutical Research International, doi:10.9734/jpri/2020/v32i830468 (Peer Reviewed) (Dosing)
dosing study
Optimizing the Use of Hydroxychloroquine in the Management of COVID-19 Given Its Pharmacological Profile
Details   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..
May 27
Early Million et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm2203116 (preprint 5/27/2021) (Peer Reviewed)
death, ↓83.0%, p=0.0007
Early Treatment with Hydroxychloroquine and Azithromycin in 10,429 COVID-19 Outpatients: A Monocentric Retrospective Cohort Study
Details   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.
May 17
PrEP Syed et al., Cureus, doi:10.7759/cureus.20572 (preprint 5/17/2021) (Peer Reviewed)
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
Details   Small PrEP RCT of low risk patients, 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 ho..
May 16
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
Details   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 aft..
May 12
Early Drancourt et al., Viruses, doi:10.3390/v13050890 (Peer Reviewed) SARS-CoV-2 Persistent Viral Shedding in the Context of Hydroxychloroquine-Azithromycin Treatment
Details   Retrospective 3,737 patients in France, showing lower risk of persistent viral shedding with HCQ+AZ treatment.
May 10
Late Sammartino et al., PLOS One, doi:10.1371/journal.pone.0251262 (Peer Reviewed)
death, ↑240.0%, p=0.002
Predictors for inpatient mortality during the first wave of the SARS-CoV-2 pandemic: A retrospective analysis
Details   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..
May 8
Review Vigbedor et al., Journal of Applied Pharmaceutical Science, doi:10.7324/JAPS.2021.110825 (Review) (Peer Reviewed)
Review of four major biomolecular target sites for COVID-19 and possible inhibitors as treatment interventions
Details   Review of major target sites in SARS-CoV-2 and the host organism along with potential inhibitors.
May 1
Late De Rosa et al., J. Clin. Med., doi:10.3390/jcm10091951 (Peer Reviewed)
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
Details   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..
Apr 30
Late Çiyiltepe et al., South. Clin. Ist. Euras., doi:10.14744/scie.2021.89847 (Peer Reviewed)
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..
Apr 30
Late Bosaeed et al., Infect. Dis. Ther., doi:10.1007/s40121-021-00496-6 (Peer Reviewed)
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..
Apr 29
Late Aghajani et al., Journal of Medical Virology, doi:10.1002/jmv.27053 (Peer Reviewed)
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.
Apr 28
Late Kokturk et al., Respiratory Medicine, doi:10.1016/j.rmed.2021.106433 (Peer Reviewed)
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.
Apr 27
Late Réa-Neto et al., Scientific Reports, doi:10.1038/s41598-021-88509-9 (Peer Reviewed)
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.
Apr 26
Late Mohandas et al., (Peer Reviewed)
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..
Apr 23
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.
Apr 22
Late Reis et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.6468 (Peer Reviewed)
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..
Apr 15
PrEP Alzahrani et al., Rheumatology International , doi:10.1007/s00296-021-04857-9 (Peer Reviewed)
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.
Apr 15
PrEP Alegiani et al., Rheumatology, doi:10.1093/rheumatology/keab348 (Peer Reviewed)
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..
Apr 14
PEP Seet et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.035 (Peer Reviewed)
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 ..
Apr 8
Late Gadhiya et al., BMJ Open, doi:10.1136/bmjopen-2020-042549 (Peer Reviewed)
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..
Apr 7
Late Mulhem et al., BMJ Open, doi:10.1136/bmjopen-2020-042042 (Peer Reviewed)
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..
Apr 6
Early Mokhtari et al., International Immunopharmacology, doi:10.1016/j.intimp.2021.107636 (Peer Reviewed)
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.
Apr 5
Safety Edington et al., European Journal of Internal Medicine, doi:10.1016/j.ejim.2021.03.028 (Peer Reviewed)
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..
Mar 31
Late Alghamdi et al., Antibiotics, doi:10.3390/antibiotics10040365 (Peer Reviewed)
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.
Mar 26
Safety Faruqui et al., Indian J. Med. Res., doi:10.4103/ijmr.IJMR_2294_20 (Peer Reviewed)
safety analysis
Safety of hydroxychloroquine in healthcare workers for COVID-19 prophylaxis
Details   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.
Mar 24
PrEP Dev et al., Transactions of The Royal Society of Tropical Medicine and Hygiene, doi:10.1093/trstmh/trab047 (Peer Reviewed)
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..
Mar 23
Late Barry et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.03.058 (Peer Reviewed)
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
Details   605 hospitalized patients in Saudi Arabia showing no mortality with HCQ (only 6 patients received HCQ).
Mar 17
Late Stewart et al., PLoS ONE, doi:10.1371/journal.pone.0248128 (Peer Reviewed)
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 confo..
Mar 17
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..
Mar 12
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 ..
Mar 9
PrEP Vivanco-Hidalgo et al., Eurosurveillance, doi:/10.2807/1560-7917.ES.2021.26.9.2001202 (Peer Reviewed)
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
Details   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..
Mar 8
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.
Mar 4
Late Salvador et al., Cureus, doi:10.7759/cureus.13687 (Peer Reviewed)
death, ↓32.9%, p=0.10
Clinical Features and Prognostic Factors of 245 Portuguese Patients Hospitalized With COVID-19
Details   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.
Mar 2
PrEP Pham et al., Rheumatology Advances in Practice, 10.1093/rap/rkab014 (Peer Reviewed)
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..
Feb 28
Early Thakar et al., Indian J. Med. Res., doi:10.4103/ijmr.IJMR_3665_20 (Peer Reviewed) 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.
Feb 28
PrEP Bhandari et al., International Journal of Medicine and Public Health, doi:10.5530/ijmedph.2021.1.4 (Peer Reviewed) 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.
Feb 26
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). There was no..
Feb 26
Late Tanriverdi et al., Turkish Journal of Medical Sciences, doi:doi:10.3906/sag-2005-82 (Peer Reviewed) 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.
Feb 26
Early Giraud-Gatineau et al., Research Square, (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..
Feb 23
Late Gonzalez et al., medRxiv, doi:10.1101/2021.02.18.21252037 (Preprint)
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.
Feb 20
PrEP Bae et al., Viruses 2021, doi:10.3390/v13020329 (Peer Reviewed)
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
Details   Retrospective database analysis of prior HCQ usage in South Korea, showing non-statistically significantly lower mortality and cases with treatment.
Feb 19
Late Lamback et al., The Brazilian Journal of Infectious Diseases, doi:10.1016/j.bjid.2021.101549 (Peer Reviewed)
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 ..
Feb 18
Late Awad et al., American Journal of Health-System Pharmacy, doi:10.1093/ajhp/zxab056 (Peer Reviewed)
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..
Feb 11
Late Lora-Tamayo et al., J. Infection, doi:10.1016/j.jinf.2021.02.011 (Peer Reviewed)
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.
Feb 10
Early, Late Desai et al., J. Clinical Medicine, doi:10.3390/jcm10040686 (Peer Reviewed) 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.
Feb 9
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.
Feb 9
Meta Lounnas e al., Archives of Microbiology & Immunology, doi: (Peer Reviewed) (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].
Feb 9
Late Purwati et al., Biochemistry Research International, doi:10.1155/2021/6685921 (Peer Reviewed)
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..
Feb 5
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 ..
Feb 5
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 differe..
Feb 5
Late Ouedraogo et al., Revue des Maladies Respiratoires, doi:10.1016/j.rmr.2021.02.001 (Peer Reviewed)
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.
Feb 1
Review Alexander et al., medRxiv, doi:10.1101/2021.01.28.21250706 (Review) (Preprint)
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 ..
Feb 1
Late Ubaldo et al., Critical Care Research and Practice, 10.1155/2021/7510306 (Peer Reviewed)
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.
Jan 31
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.
Jan 31
Late Roig et al., Revista Espanola de Quimioterapia, doi:10.37201/req/130.2020 (Peer Reviewed)
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.
Jan 29
Late Di Castelnuovo et al., Journal of Healthcare Engineering, doi:10.1155/2021/5556207 (preprint 1/29/2021) (Peer Reviewed)
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.
Jan 27
PrEP Trefond et al., Revue du Rhumatisme, doi:10.1016/j.rhum.2021.09.004 (preprint 1/27/2021) (Peer Reviewed)
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..
Jan 26
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..
Jan 25
Early Dabbous et al., Archives of Virology, doi:10.1007/s00705-021-04956-9 (Peer Reviewed) Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study
Details   This study was retracted.
Jan 25
In Silico Hussein et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979 (Peer Reviewed)
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.
Jan 24
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 ..
Jan 23
PrEP Cifuentes et al., Medicina Clínica (English Edition), doi:10.1016/j.medcle.2020.10.012 (Peer Reviewed) 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 ..
Jan 18
Late Li et al., Science China Life Sciences, doi:10.1007/s11427-020-1871-4 (Peer Reviewed)
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..
Jan 12
Late Li et al., Research Square, doi:10.21203/ (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..
Jan 10
PrEP Rangel et al., Journal of the American Academy of Dermatology, doi:10.1016/j.jaad.2020.10.098 (Peer Reviewed)
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..
Jan 8
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.
Jan 7
In Silico Baildya et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129891 (Peer Reviewed)
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..
Jan 6
In Silico Noureddine et al., Journal of King Saud University - Science, doi:10.1016/j.jksus.2020.101334 (Peer Reviewed)
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.
Jan 4
Safety Gautret et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106236 (Peer Reviewed)
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.
Jan 2
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.
Jan 1
Late Lotfy et al., Turk. Thorac. J., doi:10.5152/TurkThoracJ.2021.20180 (Peer Reviewed)
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..
Jan 1
Late Sands et al., International Journal of Infectious Diseases, doi:/10.1016/j.ijid.2020.12.060 (Peer Reviewed)
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 t..
Dec 31
Review Matada et al., Bioorganic & Medicinal Chemistry, doi:10.1016/j.bmc.2020.115973 (Review) (Peer Reviewed)
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.
Dec 31
Late Psevdos et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.721 (Peer Reviewed)
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 su..
Dec 31
Late Texeira et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa439.560 (Peer Reviewed)
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 s..
Dec 31
Late Vernaz et al., Swiss Medical Weekly, doi:10.4414/smw.2020.20446 (Peer Reviewed)
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..
Dec 30
Review McCullough et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.264 (Review) (Peer Reviewed)
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 ..
Dec 30
Early Procter et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.260 (Peer Reviewed) 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 z..
Dec 29
Late Güner et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2020.12.017 (Peer Reviewed)
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.
Dec 28
PrEP Cordtz et al., Rheumatology, doi:10.1093/rheumatology/keaa897 (Peer Reviewed)
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 ..
Dec 24
Late Chari et al., Blood, doi:10.1182/blood.2020008150 (Peer Reviewed)
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).
Dec 23
Early Su et al., BioScience Trends, doi:10.5582/bst.2020.03340 (Peer Reviewed)
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.
Dec 23
Late Taccone et al., The Lancet Regional Health - Europe, doi:10.1016/j.lanepe.2020.100019 (Peer Reviewed)
death, ↓24.7%, p=0.02
The role of organizational characteristics on the outcome of COVID-19 patients admitted to the ICU in Belgium
Details   Retrospective 1,747 ICU patients in Belgium showing lower mortality with HCQ, multivariate mixed effects analysis HCQ aOR 0.64 [0.45-0.92].
Dec 22
Late Cangiano et al., Aging, doi:10.18632/aging.202307 (Peer Reviewed)
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
Details   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..
Dec 19
PrEP Huh et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.12.041 (Peer Reviewed)
progression, ↑251.0%, p=0.11
Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea
Details   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 ..
Dec 18
Late Matangila et al., PLoS ONE, doi:10.1371/journal.pone.0244272 (Peer Reviewed)
death, ↓54.9%, p=0.21
Clinical characteristics of COVID-19 patients hospitalized at Clinique Ngaliema, a public hospital in Kinshasa, in the Democratic Republic of Congo: A retrospective cohort study
Details   55% lower death with HCQ+AZ. Retrospective 160 hospitalized patients in the Democratic Republic of Congo, 92% receiving HCQ+AZ, showing adjusted OR 0.24 [0.03-2.2].
Dec 16
Late Signes-Costa et al., Archivos de Bronconeumología, doi:10.1016/j.arbres.2020.11.012 (Peer Reviewed)
death, ↓47.0%, p=0.0005
Prevalence and 30-day mortality in hospitalized patients with COVID-19 and prior lung diseases
Details   47% lower mortality with HCQ/CQ. Retrospective 1,271 patients with lung disease in Canada, China, Cuba, Ecuador, Germany, Italy and Spain, 83% treated with HCQ/CQ. Multivariable Cox regression HCQ/CQ mortality hazard ratio HR 0.53, p < 0..
Dec 16
PrEP Gönenli et al., Research Square, doi:0.21203/ (Preprint)
progression, ↓29.7%, p=0.77
Prophylactic use of Hydroxychloroquine among Physicians working in Pandemic Hospitals
Details   Small prophylaxis survey showing lower, but not statistically significant, progression to pneumonia (3 of 148 HCQ, 12 of 416 control), RR 0.70, p = 0.77. There was a higher incidence of cases with HCQ, OR 1.19, p = 0.58, which may be due ..
Dec 14
Late De Luna et al., medRxiv, doi:10.1101/2020.12.11.20247437 (Preprint)
death, ↑104.5%, p=0.69
Clinical and Demographic Characteristics of COVID-19 Patients Admitted in a Tertiary Care Hospital in the Dominican Republic
Details   Retrospective 150 patients in the Dominican Republic, 132 treated with HCQ, showing higher mortality with treatment in unadjusted results. Confounding by indication is likely.
Dec 14
Late Sofian et al., Wiener Medizinische Wochenschrift, doi:10.1007/s10354-020-00793-8 (Peer Reviewed) SARS-CoV‑2, a virus with many faces: a series of cases with prolonged persistence of COVID-19 symptoms
Details   Report on a series of 10 patients experiencing prolonged COVID-19 symptoms that were given HCQ 250mg bid for 5 days, with resolution of symptoms in all cases, and patients reporting they felt much better 2 days after treatment initiation.
Dec 14
Late Orioli et al., Diabetes & Metabolic Syndrome: Clinical Research & Reviews, doi:10.1016/j.dsx.2020.12.020 (Peer Reviewed)
death, ↓12.7%, p=1.00
Clinical characteristics and short-term prognosis of in-patients with diabetes and COVID-19: A retrospective study from an academic center in Belgium
Details   Small retrospective study of 73 diabetic patients in Belgium, 55 HCQ patients, showing HCQ RR 0.87, p = 1.0.
Dec 14
Late Naseem et al., medRxiv, doi:10.1101/2020.12.13.20247254 (Preprint)
death, ↓33.3%, p=0.34
Predicting mortality in SARS-COV-2 (COVID-19) positive patients in the inpatient setting using a Novel Deep Neural Network
Details   Retrospective 1,214 hospitalized patients in Pakistan, 77 HCQ patients, showing 33% lower mortality with HCQ, multivariate Cox HR 0.67, p = 0.34.
Dec 14
Late Tan et al., Virus Research, doi:10.1016/j.virusres.2020.198262 (Peer Reviewed)
hosp. time, ↓35.2%, p=0.04
A retrospective comparison of drugs against COVID-19
Details   Retrospective 333 patients in China, with only 8 HCQ patients, showing shorter duration of hospitalization with HCQ.
Dec 11
Late Bielza et al., Journal of the American Medical Directors Association, doi:10.1016/j.jamda.2020.12.003 (Peer Reviewed)
death, ↓21.5%, p=0.09
Clinical characteristics, frailty and mortality of residents with COVID-19 in nursing homes of a region of Madrid
Details   Retrospective 630 elderly patients in Spain showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.78, p = 0.09. HCQ was used more often with patients that were hospitalized (24% versus 3% use in the nursing homes). Med..
Dec 11
Early Sogut et al., The American Journal of Emergency Medicine, doi:10.1016/j.ajem.2020.12.014 (Peer Reviewed)
safety analysis
Safety and efficacy of hydroxychloroquine in 152 outpatients with confirmed COVID-19: A pilot observational study
Details   Safety study of 152 outpatients concluding that HCQ is safe for COVID-19, was well tolerated, and was not associated with a risk of ventricular arrhythmia due to drug-induced QTc interval prolongation.
Dec 11
PrEP Jung et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.12.003 (Peer Reviewed)
death, ↓59.3%, p=1.00
Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic disease patients: A population-based cohort study
Details   Retrospective cohort study of RA and SLE patients not showing a significant difference in PCR+ cases. PCR+ does not distinguish asymptomatic cases or severity. There was only one death which was in the control group. No other information ..
Dec 10
Late Alqassieh et al., F1000Research, Preprint (Preprint)
hosp. time, ↓18.2%, p=0.11
Clinical characteristics and predictors of the duration of hospital stay in COVID-19 patients in Jordan
Details   Prospective observational study of 131 COVID-19 patients in Jordan, showing 18% shorter hospital stay with HCQ, p = 0.11.
Dec 10
News Italian Council of State (News)
Consiglio di Stato, sì all'uso dell'idrossiclorachina per la cura del Covid
Details   Consiglio di Stato ruling in Italy re-establishes the right of Italian MDs to prescribe HCQ, which was suspended after the retracted Lancet study.
Dec 9
Late Johnston et al., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100773 (preprint 12/9) (Peer Reviewed)
hosp., ↓29.9%, p=0.73
Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk Outpatient Adults: A Randomized Clinical Trial
Details   Small early terminated late treatment RCT comparing vitamin C + folic acid, HCQ + folic acid, and HCQ+AZ, showing non-statistically significantly lower hospitalization with HCQ/HCQ+AZ, and faster viral clearance with HCQ. Enrollment was a..
Dec 9
Early Agusti et al., Enfermedades Infecciosas y Microbiología Clínica, doi:10.1016/j.eimc.2020.10.023 (Peer Reviewed)
progression, ↓68.4%, p=0.21
Efficacy and safety of hydroxychloroquine in healthcare professionals with mild SARS-CoV-2 infection: prospective, non-randomized trial
Details   Small trial of low dose HCQ for healthcare workers with mild SARS-CoV-2 showing 68% lower progression to pneumonia, p = 0.21, and faster, but not statistically significant viral clearance. There were no ICU admissions or deaths. Prospecti..
Dec 9
Late Guglielmetti et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2020.11.012 (Peer Reviewed)
death, ↓35.0%, p=0.22
Severe COVID-19 pneumonia in Piacenza, Italy – a cohort study of the first pandemic wave
Details   Retrospective 218 hospitalized patients in Italy showing non-statistically significant 35% lower mortality with HCQ, hazard ratio aHR 0.65 [0.33–1.30].
Dec 7
PEP Barnabas et al., Annals of Internal Medicine, doi:10.7326/M20-6519 (Peer Reviewed)
hosp., ↑3.7%, p=1.00
Hydroxychloroquine for Post-exposure Prophylaxis to Prevent Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Trial
Details   Early terminated PEP RCT comparing HCQ and vitamin C with 781 low-risk patients (83% household contacts), reporting no significant differences. Different results were reported at IDWeek from the AIM results. The study enrolled people wi..
Dec 4
Late Ozturk et al., Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfaa271 (Peer Reviewed)
death, ↓43.9%, p=0.14
Mortality analysis of COVID-19 infection in chronic kidney disease, haemodialysis and renal transplant patients compared with patients without kidney disease: a nationwide analysis from Turkey
Details   Retrospective 1210 hospitalized patients in Turkey focused on chronic kidney disease, haemodialysis and renal transplant patients, but also showing lower mortality with HCQ. Subject to confounding by indication.
Dec 4
Late Modrák et al., medRxiv, doi:10.1101/2020.12.03.20239863 (Preprint)
death, ↓59.0%, p=0.04
Detailed disease progression of 213 patients hospitalized with Covid-19 in the Czech Republic: An exploratory analysis
Details   Retrospective 213 hospitalized patients in Czech Republic showing lower mortality with HCQ. Subject to confounding by indication.
Dec 4
Late Peng et al., Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfaa288 (Peer Reviewed)
progression, ↓10.8%, p=0.63
Early versus late acute kidney injury among patients with COVID-19—a multicenter study from Wuhan, China
Details   Retrospective 4020 hospitalized patients in China showing non-statistically significant lower risk of acute kidney injury with HCQ.
Dec 2
PEP Wiseman et al., medRxiv, doi:10.1101/2020.11.29.20235218 (Preprint) (meta analysis)
cases, ↓42.0%, p=0.04
Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data
Details   6th independent analysis showing efficacy from the Boulware PEP trial. This prospective analysis corrects an error in the NEJM paper where shipping delays are omitted (still not corrected). 42% reduction in COVID-19 (9.6% vs. 16.5%), RR ..
Dec 1
Late Capsoni et al., Research Square, doi:10.21203/ (Preprint)
ventilation, ↓40.0%, p=0.30
CPAP Treatment In COVID-19 Patients: A Retrospective Observational Study In The Emergency Department
Details   Small 52 patient retrospective study of patients with acute respiratory failure showing lower rates of intubation with HCQ.
Nov 30
Late Abdulrahman et al., medRxiv, doi:10.1101/2020.11.25.20234914 (Preprint)
death, ↓16.7%, p=1.00
The efficacy and safety of hydroxychloroquine in COVID19 patients : a multicenter national retrospective cohort
Details   Retrospective medical record analysis of acute care patients in Bahrain not showing a significant effect of HCQ. Confounding by indication is likely. Matching appears not to have matched for baseline severity - 17.5% of HCQ patients requ..
Nov 29
Late Abd-Elsalam et al., Biological Trace Element Research, doi:10.1007/s12011-020-02512-1 (Peer Reviewed) Do Zinc Supplements Enhance the Clinical Efficacy of Hydroxychloroquine?: a Randomized, Multicenter Trial
Details   191 patient RCT in Egypt comparing the addition of zinc to HCQ, not showing a significant difference. No information on baseline zinc values was recorded. We note that Egypt has a low rate of zinc deficiency so supplementation is less lik..
Nov 28
Late Lambermont et al., Critical Care Explorations, doi:10.1097/CCE.0000000000000305 (Peer Reviewed)
death, ↓32.3%, p=0.46
Predictors of Mortality and Effect of Drug Therapies in Mechanically Ventilated Patients With Coronavirus Disease 2019: A Multicenter Cohort Study
Details   Retrospective 247 mechanically ventilated patients showing lower mortality with HCQ, but not statistically significant on multiple Cox regression. The paper gives the p value for multiple Cox (0.46) and simple Cox (0.02), but does not sp..
Nov 28
N/A Ruiz et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106247 (Peer Reviewed)
dosing study
Hydroxychloroquine lung pharmacokinetics in critically ill patients infected with COVID-19
Details   HCQ lung pharmacokinetic study confirming that lung concentrations can be much higher than plasma. The median lung epithelial lining fluid concentration was 38 times higher than plasma concentrations. 22 COVID-19 patients, median age 59...
Nov 28
Late Rodriguez-Gonzalez et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106249 (Peer Reviewed)
death, ↓22.8%, p=0.26
COVID-19 in hospitalized patients in Spain: a cohort study in Madrid
Details   Retrospective 1255 patients in Spain showing lower mortality with HCQ. Subject to confounding by indication.
Nov 27
Late van Halem et al., BMC Infect Dis., doi:10.1186/s12879-020-05605-3 (Peer Reviewed)
death, ↓31.6%, p=0.05
Risk factors for mortality in hospitalized patients with COVID-19 at the start of the pandemic in Belgium: a retrospective cohort study
Details   Retrospective 319 hospitalized patients in Belgium showing lower mortality with HCQ, although not reported to be statistically significant.
Nov 26
Late Burdick et al., Journal of Clinical Medicine, doi:10.3390/jcm9123834 (Peer Reviewed)
death, ↑59.0%, p=0.12
Is Machine Learning a Better Way to IdentifyCOVID-19 Patients Who Might Benefit fromHydroxychloroquineTreatment?—The IDENTIFY Trial
Details   290 patient observational trial in the USA, not showing a significant difference with HCQ treatment overall, but showing significantly lower mortality in a subgroup of patients where HCQ is expected to be beneficial based on a machine lea..
Nov 24
Late Abbas et al., Int. J. Clin. Pract., doi:10.1111/ijcp.13856 (Peer Reviewed) Assessment of COVID-19 Treatment containing both Hydroxychloroquine and Azithromycin: A Natural Clinical Trial
Details   Prospective study of 161 hospitalized patients in Iraq showing HCQ+AZ appears to help recovery. Most mortality was in patients that were already in critical condition on admission and died before treatment could be effective.
Nov 23
Late Qin et al., Thrombosis Research, doi:10.1016/j.thromres.2020.11.020 (Peer Reviewed)
death, ↓34.3%, p=0.61
Low molecular weight heparin and 28-day mortality among patients with coronavirus disease 2019: A cohort study in the early epidemic era
Details   Low molecular weight heparin study also showing results for HCQ treatment, unadjusted HCQ mortality relative risk RR 0.66, p = 0.61.
Nov 21
PrEP Revollo et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkaa477 (Peer Reviewed)
cases, ↓23.0%, p=0.52
Hydroxychloroquine pre-exposure prophylaxis for COVID-19 in healthcare workers
Details   Retrospective PrEP analysis with 69 healthcare workers on PrEP HCQ, and 418 control. Authors report PCR and IgG results, with no baseline results for either. Authors note they "identified 69 HCWs receiving HCQ" while providing ..
Nov 20
Early Omrani et al., EClinicalMedicine, doi:10.1016/j.eclinm.2020.100645 (Peer Reviewed)
hosp., ↓12.5%, p=1.00
Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19
Details   Low risk patient RCT for HCQ+AZ and HCQ vs. control, not showing any significant differences. Authors note that the results are not applicable to higher risk patients, that positive PCR may simply reflect detection of inactive (non-infec..
Nov 19
Late Falcone et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa563 (Peer Reviewed)
death, ↓65.0%, p=0.20
Role of low-molecular weight heparin in hospitalized patients with SARS-CoV-2 pneumonia: a prospective observational study
Details   Prospective observational study of 315 hospitalized patients in Italy showing 65% lower mortality with HCQ. The median treatment delay was 6 days for survivors and 6.5 days for non-survivors. Mortality relative risk: RR 0.35, p = 0.2, pr..
Nov 18
Late Budhiraja et al., medRxiv, doi:10.1101/2020.11.16.20232223 (Preprint)
death, ↓65.4%, p<0.0001
Clinical Profile of First 1000 COVID-19 Cases Admitted at Tertiary Care Hospitals and the Correlates of their Mortality: An Indian Experience
Details   Retrospective 976 hospitalized patients with 834 treated with HCQ+AZ showing HCQ mortality relative risk RR 0.35, p < 0.0001. Note that in this case HCQ was recommended for mild/moderate cases, so more severe cases may not have received H..
Nov 17
Late Boari et al, Biosci. Rep., doi:10.1042/BSR20203455 (Peer Reviewed)
death, ↓54.5%, p<0.001
Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study
Details   Retrospective 258 hospitalized patients in Italy showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.455, p<0.001. Data is in the supplementary appendix.
Nov 13
Late Sheshah et al., Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2020.108538 (Peer Reviewed)
death, ↓80.0%, p<0.001
Prevalence of Diabetes, Management and Outcomes among Covid-19 Adult Patients Admitted in a Specialized Tertiary Hospital in Riyadh, Saudi Arabia
Details   Retrospective 300 hospitalized patients in Saudi Arabia showing HCQ adjusted odds ratio aOR 0.12, p < 0.001.
Nov 12
Early Simova et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100813 (Peer Reviewed)
hosp., ↓93.8%, p=0.01
Hydroxychloroquine for prophylaxis and treatment of COVID-19 in health care workers
Details   100% reduction in hospitalization and cases with early treatment using HCQ+AZ+zinc. Brief report on healthcare workers in Bulgaria. 0 hospitalizations with treatment vs. 2 for control 0 PCR+ at day 14 with treatment vs. 3 for control 33..
Nov 12
PEP Simova et al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100813 (Peer Reviewed)
cases, ↓92.7%, p=0.01
Hydroxychloroquine for prophylaxis and treatment of COVID-19 in health care workers
Details   100% reduction in cases with HCQ+zinc post-exposure prophylaxis. Brief report for healthcare workers in Bulgaria. 0 cases with treatment vs. 3 for control. 156 treatment patients and 48 control patients. No serious adverse events. This..
Nov 12
N/A Tchounga et al., Journal of Pharmaceutical and Biomedical Analysis, doi:10.1016/j.jpba.2020.113761 (Peer Reviewed) (meta analysis)
Composition analysis of falsified chloroquine phosphate samples seized during the COVID-19 pandemic
Details   Analysis of fake CQ tablets finding: - no CQ in six samples, substituted with metronidazole (at sub-therapeutic levels) or paracetamol. - trace levels of paracetamol and chloramphenicol in four and two samples respectively. - CQ levels t..
Nov 11
Late Águila-Gordo et al., Revista Española de Geriatría y Gerontología, doi:10.1016/j.regg.2020.09.006 (Peer Reviewed)
death, ↓67.0%, p=0.10
Mortality and associated prognostic factors in elderly and very elderly hospitalized patients with respiratory disease COVID-19
Details   67% lower mortality with HCQ. Retrospective 416 elderly patients in Spain showing adjusted HCQ mortality hazard ratio HR 0.33, p = 0.1.
Nov 9
Late Khamis et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.11.008 (Peer Reviewed) Randomized Controlled Open Label Trial on the Use of Favipiravir Combined with Inhaled Interferon beta-1b in Hospitalized Patients with Moderate to Severe COVID-19 Pneumonia
Details   Small 89 patient RCT comparing favipiravir and inhaled interferon with HCQ for moderate to severe COVID-19 pneumonia, not finding significant differences.
Nov 9
Late Rodriguez et al., Medicina Intensiva, doi:10.1016/j.medine.2020.05.005 (Peer Reviewed)
death, ↓59.0%, p=0.23
Severe infection due to the SARS-CoV-2 coronavirus: Experience of a tertiary hospital with COVID-19 patients during the 2020 pandemic
Details   Small prospective study of 43 hospitalized patients with 39 taking HCQ, showing unadjusted mortality relative risk RR 0.41, p=0.23.
Nov 9
Late Self et al., JAMA, doi:10.1001/jama.2020.22240 (Peer Reviewed)
death, ↑6.2%, p=0.85
Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial
Details   Early terminated very late stage (65% on supplemental oxygen) RCT with 242 HCQ and 237 control patients not showing a significant difference, 28 day mortality adjusted odds ratio aOR 0.93 [0.48-1.85]. For the subgroup not on supplemental..
Nov 9
Late Brown et al., Annals of the American Thoracic Society, doi:10.1513/AnnalsATS.202008-940OC (Peer Reviewed) Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized, Active Comparator Trial
Details   Small early terminated very late stage (86% on oxygen, 44% enrolled in the ICU) RCT comparing HCQ vs. AZ, not finding a significant difference between the two treatments. There is no comparison with a control group. HCQ patients not in th..
Nov 9
Late Núñez-Gil et al., Intern. Emerg. Med., doi:10.1007/s11739-020-02543-5 (Peer Reviewed)
death, ↓7.9%, p=0.005
Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry
Details   Retrospective database study of 1,021 patients in Ecuador, Germany, Italy, and Spain, showing HCQ propensity score adjusted mortality odds ratio aOR 0.88, p=0.005.
Nov 6
PrEP Mathai et al., J. Marine Medical Society, doi:10.4103/jmms.jmms_115_20 (Peer Reviewed)
cases, ↓89.5%, p<0.0001
Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 in health-care workers: A single-center experience
Details   90% reduction in cases with HCQ pre-exposure prophylaxis. Retrospective 604 healthcare workers.
Nov 6
PrEP Datta et al., Journal of Vaccines & Vaccination, S6:1000002 (Peer Reviewed)
cases, ↓22.1%, p=0.47
No Role of HCQ in COVID-19 Prophylaxis: A Survey amongst Indian Doctors
Details   Survey of Indian doctors not finding a significant effect of HCQ prophylaxis.
Nov 6
PEP Dhibar et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106224 (Peer Reviewed)
cases, ↓41.0%, p=0.03
Post Exposure Prophylaxis with Hydroxychloroquine (HCQ) for the Prevention of COVID-19, a Myth or a Reality? The PEP-CQ Study
Details   41% reduction in cases with HCQ PEP. Prospective open label trial with 132 HCQ patients and 185 control patients showing RR 0.59, p=0.03. 50% reduction in PCR+ cases, 44% reduction in symptomatic cases. No serious adverse events. Relative..
Nov 5
Late Maldonado et al., Nefrología, doi:10.1016/j.nefro.2020.09.002 (Peer Reviewed)
death, ↓90.9%, p=0.17
COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic
Details   Very small retrospective of 12 dialysis patients showing 1/11 deaths with HCQ and 1/1 without HCQ.
Nov 5
Late Rodriguez-Nava et al., Mayo Clinic Proceedings: Innovations, Quality & Outcomes (Peer Reviewed)
death, ↑6.3%, p=0.77
Clinical characteristics and risk factors for mortality of hospitalized patients with COVID-19 in a community hospital: A retrospective cohort study
Details   Retrospective 313 patients, mostly critical stage and mostly requiring respiratory support, showing unadjusted RR 1.06, p = 0.77. Confounding by indication likely.
Nov 4
Late Salazar et al., The American Journal of Pathology, doi:10.1016/j.ajpath.2020.10.008 (Peer Reviewed)
death, ↑37.0%, p=0.28
Significantly Decreased Mortality in a Large Cohort of Coronavirus Disease 2019 (COVID-19) Patients Transfused Early with Convalescent Plasma Containing High-Titer Anti–Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein IgG
Details   Convalescent plasma study also showing mortality based on HCQ treatment, unadjusted hazard ratio uHR 1.37, p = 0.28. Confounding by indication is likely.
Nov 4
Early Cadegiani et al., New Microbes and New Infections, doi:10.1016/j.nmni.2021.100915 (preprint 11/4/2020) (Peer Reviewed)
death, ↓81.2%, p=0.21
Early COVID-19 Therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in Outpatient Settings Significantly Improved COVID-19 outcomes compared to Known outcomes in untreated patients
Details   Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, ev..
Nov 3
PrEP Behera et al., PLoS ONE, doi:10.1371/journal.pone.0247163 (preprint 11/3) (Peer Reviewed)
cases, ↓27.9%, p=0.29
Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study
Details   Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, ..
Nov 2
Late López et al., Annals of Pediatrics, doi:10.1016/j.anpedi.2020.10.017 (Peer Reviewed)
progression, ↓64.3%, p=0.02
Telemedicine follow-ups for COVID-19: experience in a tertiary hospital
Details   Retrospective 72 pediatric patients showing HCQ associated with a shorter duration of fever (p=0.023), less progression (p=0.016), and fewer return visits to the ER (p=0.017).
Oct 31
Early Szente Fonseca et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101906 (Peer Reviewed)
hosp., ↓64.0%, p=0.0008
Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis
Details   64% lower hospitalization with HCQ. Retrospective 717 patients in Brazil with early treatment, adjusted OR 0.32, p=0.00081, for HCQ versus no medication, and OR 0.45, p=0.0065, for HCQ vs. anything else.
Oct 30
Late Tehrani et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.071 (Peer Reviewed)
death, ↓13.4%, p=0.63
Risk factors for mortality in adult COVID-19 patients: frailty predicts fatal outcome in older patients
Details   Retrospective 255 hospitalized patients, 65 treated with HCQ, showing unadjusted RR 0.87, p=0.63. Confounding by indication is likely.
Oct 27
PrEP Arleo et al., medRxiv, doi:10.1101/2020.10.26.20219154 (Preprint)
death, ↓50.0%, p=0.67
Clinical Course and Outcomes of coronavirus disease 2019 (COVID-19) in Rheumatic Disease Patients on Immunosuppression: A case Cohort Study at a Single Center with a Significantly Diverse Population
Details   Retrospective hospitalized rheumatic disease patients showing 50% lower mortality for patients on HCQ.
Oct 27
Late Choi et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.10.062 (Peer Reviewed)
viral- time, ↑22.0%, p<0.0001
Comparison of antiviral effect for mild-to-moderate COVID-19 cases between lopinavir/ritonavir versus hydroxychloroquine: A nationwide propensity score-matched cohort study
Details   Health insurance database analysis failing to adjust for disease severity and not finding a significant difference in time to PCR- for LPV/r and HCQ. There are large differences in severity across groups. Authors did PSM but chose not to..
Oct 26
Late Frontera et al., Research Square, doi:10.21203/ (Preprint)
death, ↓37.0%, p=0.01
Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study
Details   Retrospective 3,473 hospitalized patients showing lower mortality with HCQ+zinc.
Oct 24
PrEP Goenka et al., SSRN, doi:10.2139/ssrn.3689618 (Preprint)
IgG+, ↓87.2%, p=0.03
Seroprevalence of COVID-19 Amongst Health Care Workers in a Tertiary Care Hospital of a Metropolitan City from India
Details   Study of SARS-CoV-2-IgG antibodies in 1122 health care workers in India finding 87% lower positives for adequate HCQ prophylaxis, 1.3% HCQ versus 12.3% for no HCQ prophylaxis. Adequate prophylaxis is defined as 400mg 1/wk for >6 weeks.
Oct 23
Late Coll et al., American Journal of Transplantation, doi:10.1111/ajt.16369 (Peer Reviewed)
death, ↓45.6%, p<0.0001
Covid‐19 in transplant recipients: the spanish experience
Details   Retrospective 652 transplant recipient patients in Spain showing 46% lower mortality for patients treated with HCQ, unadjusted relative risk RR 0.54, p<0.0001.
Oct 21
Late Lano et al., Clinical Kidney Journal, 13:5, October 2020, 878–888, doi:10.1093/ckj/sfaa199 (Peer Reviewed)
death, ↓33.1%, p=0.28
Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort
Details   33% lower mortality with HCQ+AZ, p=0.28. Retrospective 122 French dialysis patients. 69% lower combined mortality/ICU, p=0.11, for the subgroup not requiring O2 on diagnosis (slightly earlier treatment).
Oct 21
Late Dubee et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2021.03.005 (preprint 10/21) (Peer Reviewed)
death, ↓46.0%, p=0.21
Hydroxychloroquine in mild-to-moderate COVID-19: a placebo-controlled double blind trial
Details   Small early terminated late stage (60% on oxygen) RCT in France showing 46% lower mortality. mortality at 28 days relative risk RR 0.54 [0.21-1.42] combined mortality/intubation at 28 days relative risk RR 0.74 [0.33-1.70] If not stoppe..
Oct 21
Late Ñamendys-Silva et al., Heart & Lung, doi:10.1016/j.hrtlng.2020.10.013 (Peer Reviewed)
death, ↓32.3%, p=0.18
Outcomes of patients with COVID-19 in the Intensive Care Unit in Mexico: A multicenter observational study
Details   Retrospective 164 ICU patients in Mexico showing 32% lower mortality with HCQ+AZ and 37% lowe