Abstract: medRxiv preprint doi: https://doi.org/10.1101/2020.11.29.20235218; this version posted July 5, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Effective post-exposure prophylaxis of Covid-19 associated with hydroxychloroquine: Prospective dataset reanalysis incorporating novel, missing data Running Title: Postexposure hydroxychloroquine Covid-19 prophylaxis: Reanalysis, missing data David M. Wiseman, PhD, MRPharmS;a Pierre Kory, MD, MPA;b Samir A Saidi, PhD, MB ChB;c Dan Mazzucco, PhD.d a Synechion, b Aurora Inc., Dallas, TX, USA St. Luke’s Medical Center, Milwaukee, WI, USA. and Front Line Critical Care Alliance. pierrekory@icloud.com c Central d Clinic School, University of Sydney, Australia, sam.saidi@sydney.edu.au Third Eye Associates, Cherry Hill, NJ, USA. dmazzucco@zsxmedical.com Address for correspondence: Dr. David Wiseman, Synechion, Inc., 18208 Preston Road, Suite D9-405, Dallas, 75252 synechion@aol.com Telephone: 972 931 5596 Fax: 972 931 5476 Word count: 3989 words Funding source: None ORCID DMW 0000-0002-8367-6158 PK 0000-0002-0816-9682 SAS 0000-0001-5165-2461 DM 0000-0003-3578-4610 NOTE: preprint reports new research thatCOVID-19 has not beenpost-exposure certified by peer prophylaxis review and should not be used to guide clinical practice. Wiseman et al.This Exploratory reanalysis – HCQ: REV070221 Page 1 of 28 medRxiv preprint doi: https://doi.org/10.1101/2020.11.29.20235218; this version posted July 5, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Abstract BACKGROUND: A 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 reanalyzed the 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 by intervention lag, age, and gender. RESULTS: Newly 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. CONCLUSIONS: Using 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..