Skip to main content
Top
Published in: Digestive Diseases and Sciences 11/2021

01-11-2021 | Famotidine | Original Article

Does Famotidine Reduce the Risk of Progression to Severe Disease, Death, and Intubation for COVID-19 Patients? A Systemic Review and Meta-Analysis

Authors: Chenyu Sun, Yue Chen, Lei Hu, Yile Wu, Mingming Liang, Mubashir Ayaz Ahmed, Chandur Bhan, Zhichun Guo, Hongru Yang, Yijing Zuo, Yue Yan, Qin Zhou

Published in: Digestive Diseases and Sciences | Issue 11/2021

Login to get access

Abstract

Background

Famotidine was reported to potentially provide benefits to Coronavirus Disease 2019 (COVID-19) patients. However, it remains controversial whether it is effective in treating COVID-19.

Aims

This study aimed to explore whether famotidine use is associated with reduced risk of the severity, death, and intubation for COVID-19 patients.

Methods

This study was registered on International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42020213536). A comprehensive search was performed to identify relevant studies up to October 2020. I-squared statistic and Q-test were utilized to assess the heterogeneity. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated through the random effects or fixed effects model according to the heterogeneity. Subgroup analyses, sensitivity analysis, and publication bias assessment were also conducted.

Results

Five studies including 36,635 subjects were included. We found that famotidine use was associated with a statistically non-significant reduced risk of progression to severe disease, death, and intubation for Coronavirus Disease 2019 (COVID-19) patients (pooled RR was 0.82, 95% CI = 0.52–1.30, P = 0.40).

Conclusion

Famotidine has no significant protective effect in reducing the risk of developing serious illness, death, and intubation for COVID-19 patients. More original studies are needed to further clarify whether it is associated with reduced risk of the severity, death, and intubation for COVID-19 patients.
Literature
1.
go back to reference Zhu N, Zhang D, Wang W et al. China novel coronavirus investigating and research team. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727–733CrossRef Zhu N, Zhang D, Wang W et al. China novel coronavirus investigating and research team. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727–733CrossRef
2.
go back to reference Wu Z, McGoogan JM. Characteristics of and Important lessons from the coronavirus disease 2019 (COVID-19) outbreak in china: summary of a report of 72,314 cases from the Chinese Center for disease control and prevention. JAMA 2020;323:1239–1242CrossRef Wu Z, McGoogan JM. Characteristics of and Important lessons from the coronavirus disease 2019 (COVID-19) outbreak in china: summary of a report of 72,314 cases from the Chinese Center for disease control and prevention. JAMA 2020;323:1239–1242CrossRef
3.
go back to reference Wu D, Wu T, Liu Q, Yang Z. The SARS-CoV-2 outbreak: what we know. Int J Infect Dis. 2020;94:44–48CrossRef Wu D, Wu T, Liu Q, Yang Z. The SARS-CoV-2 outbreak: what we know. Int J Infect Dis. 2020;94:44–48CrossRef
4.
go back to reference Huang C, Wang Y, Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan China. The Lancet 2020;395:497–506CrossRef Huang C, Wang Y, Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan China. The Lancet 2020;395:497–506CrossRef
6.
go back to reference Freedberg DE, Conigliaro J, Wang TC et al. Famotidine use is associated with improved clinical outcomes in hospitalized COVID-19 patients: a propensity score matched retrospective cohort study. Gastroenterology 2020;159:1129–1131CrossRef Freedberg DE, Conigliaro J, Wang TC et al. Famotidine use is associated with improved clinical outcomes in hospitalized COVID-19 patients: a propensity score matched retrospective cohort study. Gastroenterology 2020;159:1129–1131CrossRef
8.
go back to reference Wilt TJ, Kaka AS, MacDonald R, et al. Remdesivir for adults with COVID-19: A living systematic review for an American college of physicians practice points. Ann Intern Med. 2020;M20–5752. Wilt TJ, Kaka AS, MacDonald R, et al. Remdesivir for adults with COVID-19: A living systematic review for an American college of physicians practice points. Ann Intern Med. 2020;M20–5752.
9.
go back to reference Wu C, Liu Y, Yang Y et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B 2020;10:766–788CrossRef Wu C, Liu Y, Yang Y et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B 2020;10:766–788CrossRef
10.
go back to reference Anand K, Ziebuhr J, Wadhwani P, Mesters JR, Hilgenfeld R. Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs. Science 2003;300:1763–1767CrossRef Anand K, Ziebuhr J, Wadhwani P, Mesters JR, Hilgenfeld R. Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs. Science 2003;300:1763–1767CrossRef
11.
go back to reference Malone RW, Tisdall P, Fremont-Smith P, et al. COVID-19: famotidine, histamine, mast cells, and mechanisms. Res Sq [Preprint]. 2020; 22:rs.3.rs-30934 Malone RW, Tisdall P, Fremont-Smith P, et al. COVID-19: famotidine, histamine, mast cells, and mechanisms. Res Sq [Preprint]. 2020; 22:rs.3.rs-30934
12.
go back to reference Kritas SK, Ronconi G, Caraffa A, Gallenga CE, Ross R, Conti P. Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. J Biol Regul Homeost Agents 2020;34:9–14PubMed Kritas SK, Ronconi G, Caraffa A, Gallenga CE, Ross R, Conti P. Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. J Biol Regul Homeost Agents 2020;34:9–14PubMed
13.
go back to reference Singh VP, El-Kurdi B, Rood C. What underlies the benefit of famotidine formulations used during COVID-19? Gastroenterology. 2020;S0016-5085L:35020-4. Singh VP, El-Kurdi B, Rood C. What underlies the benefit of famotidine formulations used during COVID-19? Gastroenterology. 2020;S0016-5085L:35020-4.
15.
go back to reference Mather JF, Seip RL, McKay RG. Impact of famotidine use on clinical outcomes of hospitalized patients with COVID-19. Am J Gastroenterol. 2020;115:1617–1623CrossRef Mather JF, Seip RL, McKay RG. Impact of famotidine use on clinical outcomes of hospitalized patients with COVID-19. Am J Gastroenterol. 2020;115:1617–1623CrossRef
16.
go back to reference Cheung KS, Hung IF, Leung WK. Association between famotidine use and COVID-19 severity in Hong Kong: a territory-wide study. Gastroenterology 2020;S0016–5085:34940–34944 Cheung KS, Hung IF, Leung WK. Association between famotidine use and COVID-19 severity in Hong Kong: a territory-wide study. Gastroenterology 2020;S0016–5085:34940–34944
17.
go back to reference Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8:336–341CrossRef Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8:336–341CrossRef
18.
go back to reference Stang A. Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–605CrossRef Stang A. Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–605CrossRef
20.
go back to reference Stare J, Maucort-Boulch D. Odds ratio, hazard ratio and relative risk. Metodoloski zvezki. 2016;13:59–67 Stare J, Maucort-Boulch D. Odds ratio, hazard ratio and relative risk. Metodoloski zvezki. 2016;13:59–67
21.
go back to reference Ronksley PE, Brien SE, Turner BJ et al. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ 2011;342:479CrossRef Ronksley PE, Brien SE, Turner BJ et al. Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ 2011;342:479CrossRef
22.
go back to reference Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–1558CrossRef Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–1558CrossRef
23.
go back to reference DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–188CrossRef DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–188CrossRef
24.
go back to reference Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;20:5–13 Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;20:5–13
25.
go back to reference Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135CrossRef Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135CrossRef
26.
go back to reference Bland M. Estimating mean and standard deviation from the sample size, three quartiles, minimum, and maximum. Int J Stats Med. 2015;4:57–64CrossRef Bland M. Estimating mean and standard deviation from the sample size, three quartiles, minimum, and maximum. Int J Stats Med. 2015;4:57–64CrossRef
27.
go back to reference Weir CJ, Butcher I, Assi V et al. Dealing with missing standard deviation and mean values in meta-analysis of continuous outcomes: a systematic review. BMC Med Res Methodol. 2018;18:25CrossRef Weir CJ, Butcher I, Assi V et al. Dealing with missing standard deviation and mean values in meta-analysis of continuous outcomes: a systematic review. BMC Med Res Methodol. 2018;18:25CrossRef
30.
go back to reference Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088–1101CrossRef Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088–1101CrossRef
31.
go back to reference Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–634CrossRef Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–634CrossRef
34.
go back to reference Janowitz T, Gablenz E, Pattinson D et al. Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series. Gut 2020;69:1592–1597CrossRef Janowitz T, Gablenz E, Pattinson D et al. Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series. Gut 2020;69:1592–1597CrossRef
35.
go back to reference Li X, Ge P, Zhu J et al. Deep learning prediction of likelihood of ICU admission and mortality in COVID-19 patients using clinical variables. PeerJ 2020;8:e10337CrossRef Li X, Ge P, Zhu J et al. Deep learning prediction of likelihood of ICU admission and mortality in COVID-19 patients using clinical variables. PeerJ 2020;8:e10337CrossRef
36.
go back to reference Yan L, Zhang HT, Goncalves J et al. An interpretable mortality prediction model for COVID-19 patients. Nat Mach Intell. 2020;2:283–288CrossRef Yan L, Zhang HT, Goncalves J et al. An interpretable mortality prediction model for COVID-19 patients. Nat Mach Intell. 2020;2:283–288CrossRef
37.
go back to reference Mehta P, McAuley DF, Brown M et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033–1034CrossRef Mehta P, McAuley DF, Brown M et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033–1034CrossRef
38.
go back to reference Birch CA, Molinar-Inglis O, Trejo J. Subcellular hot spots of GPCR signaling promote vascular inflammation. Curr Opin Endocr Metab Res 2021;16:37–42CrossRef Birch CA, Molinar-Inglis O, Trejo J. Subcellular hot spots of GPCR signaling promote vascular inflammation. Curr Opin Endocr Metab Res 2021;16:37–42CrossRef
39.
go back to reference Krystel-Whittemore M, Dileepan KN, Wood JG. Mast cell: a multi-functional master cell. Front Immunol. 2016;6:620CrossRef Krystel-Whittemore M, Dileepan KN, Wood JG. Mast cell: a multi-functional master cell. Front Immunol. 2016;6:620CrossRef
40.
go back to reference Hogan Ii RB, Hogan Iii RB, Cannon T et al. Dual-histamine receptor blockade with cetirizine—famotidine reduces pulmonary symptoms in COVID-19 patients. Pulm Pharmacol Ther. 2020;63:101942CrossRef Hogan Ii RB, Hogan Iii RB, Cannon T et al. Dual-histamine receptor blockade with cetirizine—famotidine reduces pulmonary symptoms in COVID-19 patients. Pulm Pharmacol Ther. 2020;63:101942CrossRef
41.
go back to reference Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary pathology of early-phase 2019m novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. J Thorac Oncol 2020;15:700–704CrossRef Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary pathology of early-phase 2019m novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. J Thorac Oncol 2020;15:700–704CrossRef
42.
go back to reference Burde R, Seifert R, Buschauer A, Schultz G. Histamine inhibits activation of human neutrophils and HL-60 leukemic cells viamH2-receptors. Naunyn Schmiedebergs Arch Pharmacol. 1989;340:671–678CrossRef Burde R, Seifert R, Buschauer A, Schultz G. Histamine inhibits activation of human neutrophils and HL-60 leukemic cells viamH2-receptors. Naunyn Schmiedebergs Arch Pharmacol. 1989;340:671–678CrossRef
43.
go back to reference Rabier M, Damon M, Chanez P et al. Inhibition by histamine of platelet-activating-factor-induced neutrophil chemotaxis in bronchial asthma. IntArch Allergy Appl Immunol. 1989;89:314–317CrossRef Rabier M, Damon M, Chanez P et al. Inhibition by histamine of platelet-activating-factor-induced neutrophil chemotaxis in bronchial asthma. IntArch Allergy Appl Immunol. 1989;89:314–317CrossRef
44.
go back to reference Flamand N, Plante H, Picard S, Laviolette M, Borgeat P. Histamine-induced inhibition of leukotriene biosynthesis in human neutrophils: Involvement of the H2 receptor and cAMP. Br J Pharmacol. 2004;141:552–561CrossRef Flamand N, Plante H, Picard S, Laviolette M, Borgeat P. Histamine-induced inhibition of leukotriene biosynthesis in human neutrophils: Involvement of the H2 receptor and cAMP. Br J Pharmacol. 2004;141:552–561CrossRef
45.
go back to reference Ezeamuzie CI, Philips E, Histamine H. (2) receptors mediate the inhibitory effect of histamine on human eosinophil degranulation. Br J Pharmacol. 2000;131:482–488CrossRef Ezeamuzie CI, Philips E, Histamine H. (2) receptors mediate the inhibitory effect of histamine on human eosinophil degranulation. Br J Pharmacol. 2000;131:482–488CrossRef
46.
go back to reference Wadee AA, Anderson R, Sher R. In vitro effects of histamine on eosinophil migration. Int Arch Allergy Appl Immunol. 1980;63:322–329CrossRef Wadee AA, Anderson R, Sher R. In vitro effects of histamine on eosinophil migration. Int Arch Allergy Appl Immunol. 1980;63:322–329CrossRef
Metadata
Title
Does Famotidine Reduce the Risk of Progression to Severe Disease, Death, and Intubation for COVID-19 Patients? A Systemic Review and Meta-Analysis
Authors
Chenyu Sun
Yue Chen
Lei Hu
Yile Wu
Mingming Liang
Mubashir Ayaz Ahmed
Chandur Bhan
Zhichun Guo
Hongru Yang
Yijing Zuo
Yue Yan
Qin Zhou
Publication date
01-11-2021
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 11/2021
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-021-06872-z

Other articles of this Issue 11/2021

Digestive Diseases and Sciences 11/2021 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.