Effective post-exposure prophylaxis of Covid-19 is associated with use of hydroxychloroquine

 

Prospective re-analysis of a public dataset incorporating novel data

 View ORCID ProfileDavid M Wiseman,  View ORCID ProfilePierre Kory,  View ORCID ProfileSamir A Saidi,  View ORCID ProfileDan Mazzucco

doi: https://doi.org/10.1101/2020.11.29.20235218

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2020.11.29.20235218v1.full.pdf

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).

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

NCT04308668

Clinical Protocols

https://osf.io/hyp8k/

https://www.medrxiv.org/content/10.1101/2020.08.19.20178376v2

Funding Statement

There is no external support for this study.

https://www.medrxiv.org/content/10.1101/2020.11.29.20235218v1