The results showed a significant decrease in LDH (P = 0.01) and length of stay (P = 0.04) in hospitalized patients with COVID-19 in the group treated with Famotidine compared to the control group. There was also a significant increase in oxygen saturation in the group treated with Famotidine compared to the control group. Cough improvement was also higher in the oral Famotidine group compared to the control group (P = 0.02).
The results of a computer simulation by Wu et al. showed the potential effect of Famotidine on 3CLpro in SARS-COV-2 virus (8–10). The results of a study by Gupta et al. and other studies also showed that Famotidine could also act as a papain-like protease (PLpro) inhibitor in the SARS-COV-2 virus, thereby inhibiting virus replication (11). The results of a computer study by Ortega et al. suggested administering other antiviral medications in combination with Famotidine (2, 3). They also investigated the pharmacokinetic effects of Famotidine on SARS-COV-2 virus and reported only intravenous administration of Famotidine as effective on viral proteases. (12). Loffredo et al. showed the ineffectiveness of Famotidine on the amount of 3CLpro and PLpro proteases in cultured cell lines (1). They also showed that, unlike computer studies, Famotidine had no antiviral effects on the replication of the SARS-COV-2 virus (10). In this regard, Malone et al. also showed the effects of Famotidine only on the H2R receptor (8–10)
The effects of Famotidine on H2R can reduce the mediators of the immune system, and can lead to a decrease in proinflammatory factors as well as a decrease in airway inflammation through TH1 lymphocytes (11). Furthermore, another effect of Famotidine on the immune system is a reduction in the histamine release from mast cells, which are major producers of histamine in respiratory viral infections (8–10). Besides, Hogan et al. applied dual histamine blockade with cetirizine and Famotidine, and reported the promising effect of Famotidine on cytokine storm and a reduction in the signs and complaints of patients with COVID-19 (11)
To date, no clinical trial has evaluated the effect of Famotidine on the improvement of inpatients with COVID-19. A retrospective study by Freedberg et al. and a case series study by Janowitz et al. were the only studies that have reported the effect of Famotidine on the improvement of patients with COVID-19 (2, 3). The present study, as the first clinical trial to examine the effect of Famotidine on inpatients with COVID-19, evaluated the effect of high-dose oral Famotidine on the improvement of these patients. (2, 3)
Our results showed a significant increase in oxygen saturation in the oral Famotidine group compared to the control group (P = 0.01). Oxygen saturation in the case series reported by Malone et al. over a period of 2 hours showed changes from 93–98% on day 15 after starting the Famotidine treatment regimen (13). Similar to the present study, Janowitz et al. also reported an increase in oxygen saturation after Famotidine administration (13). However, we cannot compare the effectiveness of Famotidine or the recovery of patients based on an antiviral medication regimen because their study did not have a control group.
The present study also showed a significant reduction in the length of stay in patients with COVID-19 in the oral Famotidine group (P = 0.04). Cough improvement was also significantly higher in the oral Famotidine group compared to the control group in this study (P = 0.02). In the case reported in the study by Malone et al., a similar improvement in coughs was observed after administering Famotidine (2, 3). The improvement of cough in patients with COVID-19 has also been evaluated in the study by Janowitz et al. which was a case series study and reported a successful reduction in cough in patients after treatment with Famotidine (12)
LDH in patients with COVID-19 has been introduced as a marker for disease severity in various studies (14–18), and our results also showed a significant decrease in LDH levels in the Famotidine-treated group compared to the control group (P = 0.01). Our results also showed a significant decrease in WBC in the treatment group taking Famotidine compared to the control group taking placebo (P = 0.04).
The results of a retrospective study by Freedberg et al. on 1620 patients with COVID-19 showed a significant reduction in mortality and intubation risk in patients taking Famotidine (orally or intravenously, 40 or 20 mg daily); while patients taking proton pump inhibitors (PPIs) did not show a significant reduction in the above variables (10). However, our results showed a successful reduction in patients’ respiratory complaints with Famotidine.
Our results regarding the gender of patients did not show a significant difference between the study groups. We also examined lung involvement on CT scan of patients and their age in both groups, which did not show a significant difference.
One of the limitations of our study was its small population, which presented itself in a decrease in statistical power in some tests which did not reach a significant level. Also, it was impossible to follow up patients after discharge.
Despite the small statistical population, our results showed improvement in patients taking oral Famotidine, which can be generalized to a larger population and suggests adding Famotidine to the treatment of patients with COVID-19. Furthermore, although our study does not determine the mechanism of action of Famotidine in these patients, according to the review of literature further studies are recommended on the effects of Famotidine on cytokine storm in patients with COVID-19.