Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine: Prospective re-analysis of a public dataset incorporating novel data

Abstract

BACKGROUND: A recent trial (NCT04308668) found that post-exposure prophylaxis with hydroxychloroquine (HCQ) was associated with a reduced incidence of Covid-19 by 17% overall; 36% in younger subjects, 31% in household contacts and 49% given within one day. To understand these trends, we prospectively re-analyzed the released dataset. METHODS: Our protocol conformed to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT). We compared the incidence of Covid-19 after HCQ or placebo, stratifying primarily by time to drug receipt, age and gender. RESULTS: Requesting additional data, we found that 52% of subjects received medication 1-2 days after the intended overnight delivery; 19% of them outside the intended four-day window from exposure. After re-analysis, there was a reduced incidence of Covid-19 associated with HCQ compared with placebo (9.6% vs. 16.5%) when received up to 3 days (Early) after exposure (RR 0.58, 95%CI 0.35 - 0.97; p=0.044; NNT 14.5) but not later (Late) (RR 1.22, 95%CI 0.72 - 2.04). We found a significant HCQ-associated reduction in subjects 18 to 45 years old associated with Early (RR 0.53, 95%CI 0.29-0.97; p=0.0448, NNT 11.5) but not Late (RR 1.02, 95%CI 0.55-1.89) prophylaxis, attenuated in older subjects (RR 0.75, 95%CI 0-27-2.05) and by co-morbidities. There were reductions associated with Early prophylaxis in household contacts (RR 0.35, 95%CI 0.13-0.89; p=0.025, NNT 5.7) and Health Care Workers (RR 0.74, 95%CI 0.4-1.38). We did not detect effects of gender, folate, zinc, or ascorbic acid. CONCLUSIONS: Using novel data with a prospective post hoc re-analysis, hydroxychloroquine, in an age-dependent manner, was associated with reduced illness compatible with Covid-19 or confirmed infection when supplied for post-exposure prophylaxis between 1 and 3 days after high-risk or moderate-risk exposure. This finding warrants prospective confirmation. Registered with the Open Science Framework (last revised September 27, 2020, osf.io/fqtnw).

Which features of an outpatient treatment for COVID-19 would be most important for pandemic control? A modelling study

“…However, and since most of the patients arriving in the Amiens University Hospital are symptomatic, only confirmed individuals are treated in our model. As noted by Wiseman et al [28], it would be interesting to be able to perform this very early treatment of exposed individuals.…”

“…As noted by Wiseman et al . [ 28 ], it would be interesting to be able to perform this very early treatment of exposed individuals.…”

Pre-Exposure Prophylaxis for COVID-19 in Pregnant Women.

“…Because the studies were terminated prematurely they were underpowered to show a treatment benefit, however, and additional RCTs of early HCQ treatment for COVID-19 have been recommended. 42,43 Since RCTs require an average of 5.5 years for completion at an average cost of over a million dollars, it may take a long time to obtain conclusive results from these studies. 1…”

Pre-Exposure Prophylaxis for COVID-19 in Pregnant Women

“…Because the studies were terminated prematurely they were underpowered to show a treatment benefit, however, and additional RCTs of early HCQ treatment for COVID-19 have been recommended. 42 , 43 Since RCTs require an average of 5.5 years for completion at an average cost of over a million dollars, it may take a long time to obtain conclusive results from these studies. 1 …”