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1/ UMN hydroxychloroquine PEP trial came out this afternoon.

It is a well-designed study with a fatal flaw.

The conclusion I can draw is HCQ does not prevent *self-reported* COVID19 from developing if taken 1-4 day post exposure.…
2/ It does NOT answer the question whether HCQ helps to expedite COVID19 recovery or reduce disease severity.

The authors have a parallel study that I hope can address this question soon with higher quality data.

a quick look at the problem in the NEJM paper today.
3/ The fatal flaw here is that the vast majority (80%) of COVID19 cases as the end point is self-reported by symptoms, not by rtPCR or antibody or CT scans.

Authors acknowledged this too. This practical limit is not their fault, but it does discount the value of the study.
4/ I was aware of this limit back in March, and thus when @lumosbio invited me to publicize the study and recruit more participants, I did not pull the trigger.
5/ Testing capacity was really inadequate in March/early April, and it was very hard to conduct a study without definitive evidence.
6/ Overall, I am not a big fan of using CQ/HCQ for prophylaxis: too big a risk of QT prolongation and retinopathy for long-term use.

Their use in early (within 24-48hrs of symptom onset) treatment is still perhaps the best approach if their efficacy is proven.
7/ that way, a short-course of HCQ allows one to have only minor symptoms and develop antibodies which confers longer/better protection (than HCQ).

Plus, its impact to HCQ supply is smaller than that of prophylaxis.
8/ minor issues:
1. The low infection rate (11-12%) of unprotected exposure is quite surprising, given the hospital/family clusters we have seen
2. the cohort between Mar17-23 include many people who were not exposed, since +ve PCR test results were not required for exposure
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