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

ABSTRACT

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