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HCQ study #90 of 320   Meta Analysis
7/16 Early treatment study
Mitjà et al., Clinical Infectious Diseases, ciaa1009, doi:10.1093/cid/ciaa1009 (Peer Reviewed)
Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial
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This paper has conflicting values, table S2 shows 12 control hospitalizations, while table 2 shows 11. The original report for this paper had more conflicting values, with values reported in Table 2 and the abstract corresponding to 12 control hospitalizations, while others corresponded to 11 control hospitalizations. The counts in table S2 also do not match - n=290 is given for secondary endpoints but the three groups add up to n=238. The sum of the secondary endpoint counts for the control group in table 2 do not match the group size. One missing patient may be the 12th control hospitalization but there are 2 more missing.
There was a 16% reduction in hospitalization and 34% reduction in the risk of no symptom resolution, without statistical significance due to small samples.
Treatment delay is unknown at this time. They report a delay of up to 120 hours after symptoms plus an additional unspecified delay where medication was provided to patients at the first home visit. We have asked for details of the treatment delay and will update when hearing back. They do not break down results by treatment delay.
The paper does not mention zinc. Zinc deficiency in Spain has been reported at 83% [1], this may significantly reduce effectiveness. HCQ is a zinc ionophore which increases cellular uptake, facilitating significant intracellular concentrations of zinc, and zinc is known to inhibit SARS-CoV RNA-dependent RNA polymerase activity, and is widely thought to be important for effectiveness with SARS-CoV-2 [2].
Undetectable viral load was changed to 3 log10 copies/mL potentially masking effectiveness. For viral load authors use nasopharyngeal swabs, we note that viral activity in the lung may be especially important for COVID-19, and that research has shown HCQ concentrations can be much higher in the lung compared to plasma [3]. We also note that viral detection by PCR does not equate to viable virus [4]. Accuracy of the tests is not provided.
Nasopharyngeal viral load analysis issues include test unreliability and temporo-spatial differences in viral shedding [5].
293 low-risk patients with no deaths. No serious adverse events. We asked for more details on the treatment delay and viral load change but received no response.
Also see this open letter: [6]

Mitjà et al., 7/16/2020, Randomized Controlled Trial, Spain, Europe, peer-reviewed, 45 authors, dosage 800mg day 1, 400mg days 2-7.
risk of hospitalization, 16.0% lower, RR 0.84, p = 0.64, treatment 8 of 136 (5.9%), control 11 of 157 (7.0%).
risk of no recovery, 34.0% lower, RR 0.66, p = 0.38, treatment 8 of 136 (5.9%), control 14 of 157 (8.9%).
relative change in viral load from baseline, 2.0% lower, relative load 0.98, treatment 136, control 157, day 7.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. For an individual study the most serious outcome may have a smaller number of events and lower statistical signficance, however this provides the strongest evidence for the most serious outcomes when combining the results of many trials.
All 320 studies   Meta Analysis
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