Acid suppressant use in association with incidence and severe outcomes of COVID-19: a systematic review and meta-analysis.

PURPOSE: Several observational studies have presented conflicting results on the association between the use of proton pump inhibitors (PPIs) or histamine H2 receptor antagonist (H2RA) and the risk of coronavirus disease 2019 (COVID-19). This systematic review and meta-analysis aimed to examine this association. METHODS: In July 2021, PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched for articles investigating the relationship between the two main acid suppressants and COVID-19. Studies showing the effect estimates as hazard ratio (HR) for severe outcomes or incidence of COVID-19 were evaluated using a random-effects model. RESULTS: A total of 15 retrospective cohort studies with 18,109 COVID-19 cases were included in the current meta-analysis. PPI use was significantly associated with severe outcomes of COVID-19 (hazard ratio [HR] = 1.53; 95% confidence interval [CI]: 1.20-1.95) but not with the incidence of COVID-19, whereas H2RA use was significantly associated with decreased incidence (HR = 0.86, 95% CI: 0.76-0.97). For subgroup analyses of PPIs, increased severe outcomes of COVID-19 were observed in < 60 years, active use, in-hospital use, and Asians. For subgroup analyses of H2RAs, decreased severe outcomes of COVID-19 were observed in > 60 years, while in-hospital use and use in Asia were associated with higher disease severity. CONCLUSIONS: Close observation can be considered for COVID-19 patients who use PPIs to prevent severe outcomes. However, caution should be taken because of substantial heterogeneity and plausible protopathic bias.

Dual-histamine receptor blockade with cetirizine - famotidine reduces pulmonary symptoms in COVID-19 patients.

BACKGROUND: The COVID-19 pandemic due to SARS-CoV-2 infection can produce Acute Respiratory Distress Syndrome as a result of a pulmonary cytokine storm. Antihistamines are safe and effective treatments for reducing inflammation and cytokine release. Combinations of Histamine-1 and Histamine-2 receptor antagonists have been effective in urticaria, and might reduce the histamine-mediated pulmonary cytokine storm in COVID-19. Can a combination of Histamine-1 and Histamine-2 receptor blockers improve COVID-19 inpatient outcomes? METHODS: A physician-sponsored cohort study of cetirizine and famotidine was performed in hospitalized patients with severe to critical pulmonary symptoms. Pulmonologists led the inpatient care in a single medical center of 110 high-acuity patients that were treated with cetirizine 10 mg b.i.d. and famotidine 20 mg b.i.d. plus standard-of-care. RESULTS: Of all patients, including those with Do Not Resuscitate directives, receiving the dual-histamine receptor blockade for at least 48 h, the combination drug treatment resulted in a 16.4% rate of intubation, a 7.3% rate of intubation after a minimum of 48 h of treatment, a 15.5% rate of inpatient mortality, and 11.0 days duration of hospitalization. The drug combination exhibited beneficial reductions in inpatient mortality and symptom progression when compared to published reports of COVID-19 inpatients. Concomitant medications were assessed and hydroxychloroquine was correlated with worse outcomes. CONCLUSIONS: This physician-sponsored cohort study of cetirizine and famotidine provides proof-of-concept of a safe and effective method to reduce the progression in symptom severity, presumably by minimizing the histamine-mediated cytokine storm. Further clinical studies in COVID-19 are warranted of the repurposed off-label combination of two historically-safe histamine receptor blockers.

Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series.

OBJECTIVE: Treatment options for non-hospitalised patients with coronavirus disease 2019 (COVID-19) to reduce morbidity, mortality and spread of the disease are an urgent global need. The over-the-counter histamine-2 receptor antagonist famotidine is a putative therapy for COVID-19. We quantitively assessed longitudinal changes in patient reported outcome measures in non-hospitalised patients with COVID-19 who self-administered high-dose famotidine orally. DESIGN: Patients were enrolled consecutively after signing written informed consent. Data on demographics, COVID-19 diagnosis, famotidine use, drug-related side effects, temperature measurements, oxygen saturations and symptom scores were obtained using questionnaires and telephone interviews. Based on a National Institute of Health (NIH)-endorsed Protocol to research Patient Experience of COVID-19, we collected longitudinal severity scores of five symptoms (cough, shortness of breath, fatigue, headaches and anosmia) and general unwellness on a four-point ordinal scale modelled on performance status scoring. All data are reported at the patient level. Longitudinal combined normalised symptom scores were statistically compared. RESULTS: Ten consecutive patients with COVID-19 who self-administered high-dose oral famotidine were identified. The most frequently used famotidine regimen was 80 mg three times daily (n=6) for a median of 11 days (range: 5-21 days). Famotidine was well tolerated. All patients reported marked improvements of disease related symptoms after starting famotidine. The combined symptom score improved significantly within 24 hours of starting famotidine and peripheral oxygen saturation (n=2) and device recorded activity (n=1) increased. CONCLUSIONS: The results of this case series suggest that high-dose oral famotidine is well tolerated and associated with improved patient-reported outcomes in non-hospitalised patients with COVID-19.