Abstract: Gastroenterology 2020;159:1129–1131 Famotidine Use Is Associated With Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study Daniel E. Freedberg,1 Joseph Conigliaro,2,3 Timothy C. Wang,1 Kevin J. Tracey,4 Michael V. Callahan,5,6 and Julian A. Abrams,1 on behalf of the Famotidine Research Group 1 Division of Digestive and Liver Diseases, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York; 2Division of General Internal Medicine, Department of Medicine, Northwell Health, Manhasset, New York; 3 Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York; 4Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York; 5Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; and 6 Office of the Assistant Secretary for Public Health Preparedness and Response, U.S. Department of Health and Human Services, Washington, DC See Covering the Cover synopsis on page 803. Keywords: Coronavirus 2019; SARS-CoV-2; Famotidine; Histamine-2 Receptor Antagonists. C oronavirus Disease 2019 (COVID-19) caused 2 million cases and more than 150,000 deaths worldwide as of mid-April 2020.1 Clinical trials are under way to assess the efficacy of a variety of antiviral drugs; however, many of these drugs have toxicities and thus far no drug has been proven to improve outcomes in patients with COVID-19. Famotidine is a histamine-2 receptor antagonist that suppresses gastric acid production. In vitro, famotidine inhibits human immunodeficiency virus replication.2 Recently, Wu et al.3 used computational methods to predict structures of proteins encoded by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome and identified famotidine as one of the drugs most likely to inhibit the 3chymotrypsin-like protease (3CLpro), which processes proteins essential for viral replication.4 We hypothesized that famotidine would be associated with improved clinical outcomes among hospitalized patients with COVID-19. To explore this, we performed a retrospective cohort study at a single academic center located at the epicenter of the COVID-19 pandemic in the United States. Methods Complete methods are available in the Supplementary Materials. In brief, adults were eligible for the study if they were admitted to our institution from February 25, 2020, to April 13, 2020, and tested positive for SARS-CoV-2 within no more than 72 hours following admission. Patients were excluded if they died or were intubated within 48 hours following hospital admission. The primary exposure was use of famotidine (any dose, form of administration, or duration), classified as present if famotidine was received within 24 hours of hospital admission and otherwise as absent. The primary outcome was a composite of death or endotracheal intubation from hospital day 2 to day 30 (intubation-free survival). This follow-up period avoided immortal time bias because the exposure was classified based on the 24-hour period after hospitalization and the at-risk period began on hospital day 2. Cox proportional hazards modeling was performed on the full cohort, and a matched subset was examined with propensity scoring matching to balance baseline characteristics based on use of famotidine. Results Population and Use of Famotidine A total of 1620 patients met criteria for analysis, including 84 patients (5.1%) who received famotidine within 24..