Boulware et al. Affirms HCQ Efficacy, but Misinterpreted

Another anti-HCQ paper (A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19, Boulware et al.) was published in NEJM today at 5 pm. The conclusions of this study should have been:

We gave post-exposure Hydroxychloroquine prophylaxis incorrectly, without Zinc and Azithromycin. Despite that, in the blind placebo-controlled part of the clinical trial, Hydroxychloroquine decreased the COVID-19 ratio more than 1.4 times. 

Another part of the trial consisted of physician and physician assistants, who quickly recognized placebo, and were able to take Hydroxychloroquine themselves.

Instead, the paper incorrectly concludes that the trial “did not demonstrate a significant benefit of hydroxychloroquine.“ The paper has been shared with WaPo (aka China Daily DC) ahead of the NEJM publication. Based on it, WaPo published an article claiming that Hydroxychloroquine “failed to prevent healthy people from getting covid-19 in trial” before the paper appeared online in NEJM.

Enrolling healthcare workers (physicians and physician assistants) was a mistake. Most of them recognized whether they received HCQ or the placebo (“Of the 353 participants in the control group … 126 (35.7%) correctly identified that they received placebo“). Those of them who received a placebo were able to take real HCQ. Anyway, many doctors likely used other preventative measures.

The blind trial numbers are in the Appendix, Table S6, line Household. Out of 125 exposed persons who received HCQ, 18 were diagnosed with COVID-19 (14.4%). Out of 120 exposed persons who did not receive HCQ, 25 were diagnosed with COVID-19 (20.8%). The following line Healthcare Worker is not relevant.

The HCQ treatment was incomplete without AZM and/or Zinc. The authors note that 22.4% in the treatment group (not distinguishing between physicians and laypersons) took Zinc themselves but acknowledge they did not inquire about dosage (“The exact details of zinc formulation, dose, and duration were not queried,” Appendix, p.14). A typical supplemental dose is 10 mg per day, practically nothing compared with 220 mg of Zinc sulfate recommended by Dr. Zelenko.

The dosage of HCQ was excessive, especially 1,400 mg on the first day. That explains the side effects. The side effects were mild, such as diarrhea. There were zero cases of cardiac arrhythmia among 414 HCQ-treated persons. COVID-19 illness was determined by symptoms in most patients. That makes confusion with other infections likely. Giving 1,400 mg of HCQ on the first day and 600 mg for the following four days might have decreased patients’ immunity. Without antibiotics, that might have led to bacterial infections in the treatment groups, which might have been mistaken for COVID-19.

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