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

BACKGROUNDA key trial (NCT04308668) of post-exposure prophylaxis found hydroxychloroquine-associated (HCQ) reductions of Covid-19 by 17% overall and 31% to 49% in subgroups. To understand these trends, we re-analyzed the dataset. METHODSOur protocol conformed to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT). We compared the incidence of Covid-19 after HCQ or placebo, stratifying by intervention lag, age, and gender. RESULTSNewly requested data missing from the dataset revealed that 52% and 19% of subjects received medication 1-2 days after intended and assumed overnight delivery or four-day intervention lag respectively. After re-analysis, we found reduced HCQ-associated incidence of Covid-19 with Early (up to 3 days post-exposure) (RR 0.58, 95%CI 0.35 - 0.97; p=0.044; NNT 14.5) but not Late (RR 1.22, 95%CI 0.72 - 2.04) prophylaxis. We found a significant HCQ-associated Covid-19 reduction in subjects 18 to 45 years old with Early (RR 0.54, 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. Although, we did not detect effects of gender, folate, zinc, or ascorbate, confounding effects cannot be excluded. CONCLUSIONSUsing novel data and prospective re-analysis, hydroxychloroquine, in an age-dependent manner, was associated with reduced Covid-19 compatible illness when supplied for post-exposure prophylaxis between 1 and 3 days after high- or moderate-risk exposure, at higher loading and maintenance doses than in similar studies. The original study conclusions are controverted, and our finding warrants prospective confirmation. Protocol registered at Open Science Framework: osf.io/fqtnw (last revised September 27, 2020, HighlightsO_LIMissing data integrated with dataset re-analysis reversed findings of original study C_LIO_LIHydroxychloroquine associated reduction (42%) of Covid-19 compatible illness found C_LIO_LIEffect in Post-exposure Prophylaxis when received 1-3 days after exposure C_LIO_LIRisk Ratio 0.58 (95% CI 0.35-0.97, p=0.044, NNT14.5) C_LIO_LIFindings controvert the conclusions of original study C_LI