key: cord-0875660-w1w923im authors: Kuno, Toshiki; So, Matsuo; Takahashi, Mai; Egorova, Natalia N. title: The association between famotidine and in‐hospital mortality of patients with COVID‐19 date: 2021-10-11 journal: J Med Virol DOI: 10.1002/jmv.27375 sha: 7b771890426467da56847a42a345ed05c2db0ba1 doc_id: 875660 cord_uid: w1w923im Famotidine has been considered to be a potential treatment for COVID‐19 but the current data is conflicting. This retrospective study was conducted by utilizing data of 9565 COVID‐19 hospitalized patients. Patients treated with and without famotidine were matched by propensity score using a 1:1 matching scheme. A total of 1593 patients (16.7%) received famotidine. In‐hospital mortality was similar in patients treated with and without famotidine in the propensity‐matched cohorts (28.3% vs. 28.2%, p = 0.97), which remains similar irrespective of severity or concomitant treatment by steroids. Famotidine treatment was not associated with a lower risk of in‐hospital mortality of COVID‐19 patients. tients treated with and without famotidine in the propensity-matched cohorts (28.3% vs. 28.2%, p = 0.97), which remains similar irrespective of severity or concomitant treatment by steroids. Famotidine treatment was not associated with a lower risk of in-hospital mortality of COVID-19 patients. Famotidine has been considered to be a potential treatment for COVID-19 since the pandemic started in 2020. Since the hypothesis derives from the concept that severe acute respiratory syndrome coronavirus 2 infections can cause histamine release via mast cell activation, which leads to systemic inflammation and cytokine release, it has been expected that famotidine can reduce systemic inflammation and cytokine release. 1 Nonetheless, it remains uncertain whether famotidine is effective for the treatment of COVID-19. 1 While some observational studies showed potential benefit of famotidine by decreasing mortality due to COVID-19, 2,3 another study demonstrated no benefit of famotidine. 4 In addition, we hypothesized that steroids treatment which is the standard treatment of COVID-19 as of May 15, 2021, might mitigate the effect of famotidine since steroids also reduce inflammation and cytokine release through mast cells. 5, 6 The aim of this study was to investigate the association between famotidine treatment and mortality for patients with COVID-19. In addition, we aimed to research if this association was changed in cases of steroids treatments. This retrospective study was conducted by analyzing electronic medical records of 9565 patients hospitalized at the Mount Sinai Health System with laboratory-confirmed COVID-19 between March 1, 2020 and March 30, 2021. 7-10 Patients were divided into two groups, those with and those without treatment with famotidine. The primary outcome was in-hospital mortality. Patients treated with famotidine and without famotidine were matched by propensity score using a 1:1 matching scheme without replacement. Good balance (standardized mean difference < 0.10) was achieved for patients' baseline characteristics including age, sex, comorbidities, vital signs at admission, laboratory data, and inhospital treatment including the use of steroids, interleukin-6 (IL-6) inhibitor, convalescent plasma, and remdesivir. As a sensitivity analysis, we performed inverse probability treatment weighted (IPTW) analysis. In addition, multiple imputations for missing data were conducted (R software MICE package). We performed several analyses where we investigated the effect of famotidine on different subgroups of patients. We compared inhospital mortality for patients with steroid treatment (N = 4751, 49.7%), which is the current standard treatment, 5 and those without | 1 All statistical calculations and analyses were performed in R, with p < 0.05 considered statistically significant. Among 9565 patients with COVID-19, 1593 patients (16.7%) received famotidine. Baseline characteristics, treatments, and inhospital outcomes were shown in Table 1 . Patients treated with famotidine were younger, less likely to be male, and had lower oxygen saturation levels at admission. Patients treated with famotidine were likely to receive steroids, remdesivir, IL-6 inhibitor, and convalescent plasma ( Table 1) . After matching by propensity score (N = 1566 in each group) ( We showed that treatment with famotidine was not associated with a decreased risk of in-hospital mortality of COVID-19 irrespective of the severity of COVID infection or concomitant treatment by steroids. Our data supports the most recent observational study. 4 In addition, our data might attract attention because the effect of famotidine was not observed among patients even treated without steroids which could mitigate the effect of famotidine for COVID-19. 6 There is an ongoing clinical trial (Clinical Trials: NCT04370262) which will provide further insights into famotidine treatment for COVID-19. According to an experimental study, famotidine leads to a release of proinflammatory cytokines and chemokines. Famotidine acts as an T A B L E 1 Baseline characteristics of patients admitted with COVID-19 and treated with and without famotidine In conclusion, famotidine treatment was not associated with a lower risk of in-hospital mortality of COVID-19 patients. The authors declare that there are no conflict of interests. 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