Efficacy of Hydroxychloroquine as Prophylaxis for Covid-19

Secondary analysis of Boulware et al.'s PEP trial and treatment delay-response data, confirming that HCQ is effective when used early, p<0.01.

The effectiveness found is especially notable considering the limitations of the study. Treatment was relatively late, with enrollment up to
4 days after exposure, and an unspecified shipping delay. While the paper does not provide shipping details, the study protocol gives some detail allowing us to estimate the treatment delay as ~70 to 140 hours after exposure on average for the 1-4 days since enrollment specified in the paper (we will update this when authors respond to our request for details). There was only 75% medication adherence, including 16% who did not take the medication at all. The study relies on Internet surveys.

Some issues have been raised with this analysis. 1-tailed vs. 2-tailed tests - this is debatable, an argument can be made for both cases. However, it doesn't affect the conclusion in terms of the delay-response relationship showing statistically significant efficacy. Secondly, the paper projects the "1-4" day results to a day "0" result (in reality about 46 hours later in all cases), while the trend may well continue, we do not know this. However it doesn't change the outcome that the 1-4 day results show a statistically significant delay-response relationship.

9 meta analyses show significant improvements with hydroxychloroquine for mortality1-4, hospitalization1, recovery5, combined death/hospitalization/cases6, cases7,8, and viral clearance9.

Currently there are 8 HCQ for COVID-19 post-exposure prophylaxis studies, showing 46% lower mortality [-80‑84%], 16% lower hospitalization [-69‑58%], and 25% fewer cases [-0‑43%].