Response to: “Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients” and “Re: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis”

Abstract: 1 Response to: “Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients” and “Re: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that SC Harvey A. Risch1,2 Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT 2 Correspondence to: Harvey A. Risch, M.D., Ph.D., Yale School of Public Health, 60 College AN U 1 St., PO Box 208034, New Haven, CT 06520-8034. Telephone: (203) 785-2848. Fax: (203) ED M 785-4497. e-mail: harvey.risch@yale.edu Abbreviations: AZ, azithromycin; Dox, doxycycline; HCQ, hydroxychloroquine; SOC, standard- N AL U Financial Support: None ED IT of-care O RI G IN Running Head: Outpatient Treatment of High-Risk Covid-19 © The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e‐mail: journals.permissions@oup.com. RI P T Should be Ramped-Up Immediately as Key to the Pandemic Crisis” 2 Conflicts of Interest: Dr. Risch acknowledges past advisory consulting work with two of the more than 50 manufacturers of hydroxychloroquine, azithromycin and doxycycline. This past work was not related to any of these three medications and was completed more than two years T ago. He has no ongoing, planned or projected relationships with any of these companies, nor any SC U Dr. Korman’s thesis is that no available treatments are effective in preventing hospitalization for AN the overwhelming majority of COVID-19 patients, and that potential hazards are associated with use of hydroxychloroquine (HCQ) + azithromycin (AZ) (1). The studies that I reviewed (2) M contradict this. Dr. Korman superficially describes the same studies that I discussed at length, ED except with negative adjectives and numerous terms in “quotation” marks to imply, without evidence, their lack of validity. He calls all these studies “anecdotal,” to distinguish from the ED IT “magic” of randomized controlled trials (3), when government medical and scientific regulatory agencies of western countries around the world routinely use epidemiologic evidence to establish N facts of causation, benefit and harm (4). This disingenuous argument has been discussed at U length elsewhere (5). Dr. Korman’s only novel point is that macrolide antibiotics such as AZ can AL lead to development of antibiotic resistance. Such instances can occur but are uncommon, and this issue has seemingly not been of substantial concern in the hundreds of millions of uses of G IN AZ world-over during the past 30 years. RI Drs. Peiffer-Smadja and Costagliola (6) discuss the data in some of the studies that I reviewed. O They first question the small non-randomized trial by Gautret et al. (7). I also have concerns about subject baseline differences between the treated and untreated subjects in that study and thus limit my conclusions to the 26 treated patients. Gautret et al. (7) provided individualsubject data on all 26 which enabled me to carry out my own Cox-regression analyses. The data are that 14 patients received HCQ only, 6 received HCQ+AZ, and under intention-to-treat RI P other potential conflicts-of-interest to..