key: cord-1035097-k6eokmmp
authors: Know, Chia Siang; Sattar Burud, Ismail Abdul; Hasan, Syed Shahzad
title: Use of Famotidine and Risk of Severe Course of Illness in Patients With COVID-19: A Meta-Analysis
date: 2021-03-05
journal: Mayo Clin Proc
DOI: 10.1016/j.mayocp.2021.03.001
sha: 3ebc44db3f0a12448e940126cf9a7fdeab6c657a
doc_id: 1035097
cord_uid: k6eokmmp

nan

To the Editor: The discussion by Ghosh et al. 1 where famotidine potentially regulates innate and adaptive immune responses provides a rationale to repurpose famotidine for the treatment of coronavirus disease 2019 (COVID-19). There have been few studies evaluated the use of famotidine in patients with COVID-19, and thus we performed a meta-analysis to summarize the overall effect of famotidine on the clinical outcomes in this patient population.

We searched PubMed, Google Scholar, and medRxiv (preprint repository) databases, up to 07

November 2020, for studies evaluating the risk of a severe course of illness in COVID-19 among famotidine users compared to non-famotidine users, with the following keywords and their MeSH terms: "COVID-19", "famotidine", and "histamine-2 receptor antagonist" without language restrictions. Studies were included if they were original, observational (prospective or retrospective) studies, included patients with COVID-19 with documented use of famotidine, and reported adjusted estimates for mortality and/or other severe clinical outcomes with the use of famotidine relative to non-use of famotidine. Each included article was independently evaluated by two authors (CSK and SSH) who extracted the study characteristics and measures of effect. The quality of observational studies was evaluated using the Newcastle-Ottawa Scale. 2 The outcome of interest was the development of a severe course of illness in COVID-19 characterized by death and/or other severe clinical outcomes. Adjusted measures of association and the corresponding 95% CIs from each study were pooled using a random-effects model using Meta XL, version 5.3 (EpiGear International, Queensland, Australia). Cochran's Q heterogeneity test (Q test) and a related metric, the I 2 statistics were used to evaluate heterogeneity.

Our literature search yielded 46 unique abstracts. After deduplication and application of the eligibility criteria, six relevant articles were shortlisted for inclusion through full-text examination. Of J o u r n a l P r e -p r o o f these, two studies were excluded since they reported no mortality and/or other severe clinical outcomes in COVID-19. [4] [5] [6] [7] Study characteristics are depicted in Table 1 . All studies were retrospective and are deemed good quality with a Newcastle-Ottawa Scale ranging from 7 to 8 ( Table 1) . The meta-analysis of 3 studies (n=28,419) which provided adjusted hazard ratio revealed a nonsignificant association between the use of famotidine and the hazard for a severe course of illness in patients with COVID-19, relative to non-use of famotidine (Figure 1 1 In the study by Cheung et al. [3] , the severe course of illness was defined as presence of critical complication (respiratory failure, septic shock and/or multiple organ dysfunction), requirement for ventilatory support, intensive care unit admission, and/or death.; in the study by Yeramaneni et al. [4] , the severe course of illness was defined as death within 30 days of hospitalization; in the study by Shoaibi et al. [5] , the severe course of illness was defined as combined death and/or the requirement for mechanical ventilation, tracheostomy, or extracorporeal membrane oxygenation; in the study by Mather et al. [6] , the severe course of illness was defined as a composite of death or requirement for ventilation; in the study by Freedberg et al. [7] , the severe course of illness was defined as a composite of death or endotracheal intubation from day 2 to day 30 of hospitalization. 

Famotidine Against SARS-CoV2: A Hope or Hype?

The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses

Association between famotidine use and COVID-19 severity in Hong Kong: a territory-wide study

Famotidine Use Is Not Associated With 30-day Mortality: A Coarsened Exact Match Study in 7158 Hospitalized COVID-19 Patients from a Large Healthcare System

Comparative Effectiveness of Famotidine in Hospitalized COVID-19 Patients

Impact of Famotidine Use on Clinical Outcomes of Hospitalized Patients With COVID-19

Famotidine Use Is Associated With Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study

J o u r n a l P r e -p r o o f