key: cord-0951292-5gp7v1uh
authors: Rosenberg, Eli S.; Holtgrave, David R.; Udo, Tomoko
title: Clarifying the record on hydroxychloroquine for the treatment of patients hospitalized with COVID-19
date: 2020-07-29
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.07.055
sha: fc420740c1641337c46203b4d250fb17a9fcab17
doc_id: 951292
cord_uid: 5gp7v1uh

nan

To the editors,

The study from Arshad et al on the use of hydroxychloroquine, with and without azithromycin, for the treatment of inpatients with COVID-19 in one healthcare system (Henry Ford Health System) is a new entrant into the rapidly expanding literature on the treatment of this disease [1, 2] . The study's findings of a significant beneficial effect of hydroxychloroquine in the reduction of in-hospital mortality are not consistent with several recent studies and as authors of one of those studies we wish to share a few observations [2] [3] [4] .

In the Discussion section, Arshad et al distinguish their study from our cohort study of 1,438 patients in 25 New York metropolitan region hospitals, which found a generally null association between these medications and mortality [1, 4] . In doing so, the authors make multiple statements that are not factually aligned with our published research. Arshad et al state that the Rosenberg et al "…study included patients who were initiated on hydroxychloroquine therapy at any time during their hospitalization. In contrast, in our patient population, 82% received hydroxychloroquine within the first 24 hours of admission, and 91% within 48 hours of admission." [1] . Although we included those who received hydroxychloroquine or azithromycin at any time during hospitalization, we reported detailed information on length of time from admission to initiation of either therapy (as well as on dosage patterns). In fact, patients in our study had been generally initiated rapidly: "Hydroxychloroquine was initiated at a median of 1 day (Q1-Q3, 1-2) following admission and azithromycin was given at a median of 0 days (Q1-Q3, 0-1)." [4] . This distribution is quite similar to that of the Henry Ford study.

The authors next state the following about our work: "Because treatment regimens likely varied substantially (including delayed initiation) across the 25 hospitals that contributed patients to the study, it is not surprising that the case-fatality rate among the New York patients was significantly higher than J o u r n a l P r e -p r o o f in our study." This statement neglects the extensive statistical adjustment for between-facility variation in our publication, the generalizability benefit of including 25 hospitals into the cohort with differing therapeutic protocols and approaches, and it misrepresents the fatality rate in our study. We reported 20.3% (95% CI: [18. .4%]) fatality from 292 deaths in 1,438 patients, whereas Arshad et al report 18.1% from 460 deaths in 2,541 patients in a later era of the COVID-19 epidemic. We fail to find a difference between these studies' fatality rates both practically and statistically ( 2 df=1 test p=0.09).

These erroneous representations of previous work should be clarified as they have appeared to have led to confusion in subsequent characterizations of the Arshad et al paper relative to our study [5, 6] .

Arshad et al study [7] . We underscore the concerns raised that bias may have been introduced into the inpatient treatment of COVID-19 were stopped early due to lack of efficacy [9, 10] . On July 4, the WHO similarly halted the hydroxycholorquine arm of their Solidarity Trial [11] . Evidence from RECOVERY was a key factor weighed in the US Food and Drug Administration's (FDA) June 15 decision to revoke hydroxychloroquine's Emergency Use Authorization (EUA) for COVID-19 treatment [12] .

We appreciate the opportunity to clarify the record regarding our study as described by 

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