key: cord-0694957-xuiqwoao
authors: Tang, Wei; Gartshteyn, Yevgeniya; Guo, Cathy; Chen, Tommy; Giles, Jon; Askanase, Anca
title: Prophylaxis of COVID‐19 with Hydroxychloroquine and Chloroquine
date: 2021-03-28
journal: Arthritis Rheumatol
DOI: 10.1002/art.41742
sha: 31dba0e10afc8a6521aa227742603031e0e25291
doc_id: 694957
cord_uid: xuiqwoao

We read with great interest the paper by Putman et al.(1). The publication reviews data from 45 studies evaluating hydroxychloroquine (HCQ), chloroquine (CQ), anakinra and anti‐IL‐6 therapies in COVID‐19. Except anakinra, none of the other therapies decreased the risk of death in hospitalized COVID‐19 patients. We would like to discuss the evidence evaluating the role of HCQ in the prophylaxis of SARS‐CoV‐2 infections. The in‐vitro antiviral effect of antimalarials suggested a role in preventing disease progression(2).

This article is protected by copyright. All rights reserved

We read with great interest the paper by Putman et al. (1) . The publication reviews data from 45 studies evaluating hydroxychloroquine (HCQ), chloroquine (CQ), anakinra and anti-IL-6 therapies in COVID-19. Except anakinra, none of the other therapies decreased the risk of death in hospitalized COVID-19 patients. We would like to discuss the evidence evaluating the role of HCQ in the prophylaxis of SARS-CoV-2 infections. The in-vitro antiviral effect of antimalarials suggested a role in preventing disease progression (2) . A meta-analysis of 5,577 participants from 5 randomized controlled clinical trials suggested that outpatient HCQ use (as opposed to use in hospitalized patients) reduces the incidence of the composite outcome of SARS-CoV-2 infection, hospitalization, and death. Serious adverse events were not reported and cardiac arrhythmias were rare.(3) Several studies (4) (5) (6) (7) (8) suggested that HCQ has no benefit in the prophylaxis against SARS-CoV-2 (Table 1) .

Only one open-label controlled trial (9) showed lower incidence of COVID-19 in the HCQ group; however, imperfect methodology raises concerns over its validity. The bulk of evidence suggests that HCQ has limited or no utility in the prophylaxis of SARS-CoV-2 infections.

Sixteen clinical studies investigating the preventive role of CQ/HCQ have been registered around the world(10); 5 studies were completed, others were terminated, suspended, or withdrawn. Of note, our own double-blind, placebo-controlled, randomized trial to determine the efficacy of CQ in preventing symptomatic COVID-19 disease among New York Presbyterian Hospital healthcare workers was terminated early because of lack of enrollment. CQ-naïve healthcare workers with moderate/high risk of exposure were randomized to receive placebo or CQ (500 mg daily for 1 week followed by 500 mg weekly). Study participants were followed for 3 months to record SARS-CoV-2 infections and safety events. The primary end point was the percentage of patients with COVID-19

infections. The study started in April 2020 but progressed at a glacial pace due to safety concerns and loss of interest in prophylactic use of CQ/HCQ as the number of COVID-19 infections decreased in NYC over the summer. We enrolled 9 participants and terminated the study early. An additional double-blind, placebo-controlled, randomized trial of HCQ (800 mg on day one followed by 400 mg for 4 additional days) for post-exposure prophylaxis in asymptomatic household contacts was halted in early May 2020 based on the Institutional Review Board (IRB) requirement that QTc prolongation be ruled out prior to enrollment. This effectively terminated the trial, designed to have no contact

This article is protected by copyright. All rights reserved between COVID-19 exposed participants and study staff, before even 20 of the planned 1600 participants were enrolled.

As vaccination of the health care force is almost complete in the US, the prophylactic role of CQ/HCQ has clearly become less relevant. Most treatment data on HCQ in COVID-19 to date has not shown clinical benefit, and final prevention data from the HERO-HCQ trial (ClinicalTrials.gov NCT04334148), which remains active, will hopefully elucidate the role of HCQ in the prophylaxis of SARS-CoV-2 infections and conclude this chapter. 

Antirheumatic Disease Therapies for the Treatment of COVID-19: A Systematic Review and Meta-Analysis

Arthritis Rheumatol

Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro

Randomized Controlled Trials of

Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death: Meta-Analysis

Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial

Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial. medRxiv : the preprint server for health sciences

Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19

Randomized Trial of Hydroxychloroquine for Prevention of Covid-19

Susceptibility to COVID-19 in Patients Treated With Antimalarials: A Population Based Study

Post-exposure prophylaxis with hydroxychloroquine for the prevention of COVID-19