Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Apr 26, 2021; 9(12): 2763-2777
Published online Apr 26, 2021. doi: 10.12998/wjcc.v9.i12.2763
Paradoxical relationship between proton pump inhibitors and COVID-19: A systematic review and meta-analysis
Maddalena Zippi, Sirio Fiorino, Roberta Budriesi, Matteo Micucci, Ivan Corazza, Roberta Pica, Dario de Biase, Claudio Giuseppe Gallo, Wandong Hong
Maddalena Zippi, Roberta Pica, Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Rome 00157, Italy
Sirio Fiorino, Unit of Internal Medicine, Maggiore Hospital, Local Health Unit of Bologna, Bologna 40133, Italy
Roberta Budriesi, Matteo Micucci, Food Chemistry and Nutraceuticals Laboratory, Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum, University of Bologna, Bologna 40133, Italy
Ivan Corazza, Experimental, Diagnostic and Speciality Medicine Department, University of Bologna, Bologna 40138, Italy
Dario de Biase, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40138, Italy
Claudio Giuseppe Gallo, Internal Medicine Unit, Budrio Hospital Azienda USL, Bologna 40138, Italy
Wandong Hong, Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
Author contributions: Zippi M, Budriesi R, Micucci M, Corazza I and Fiorino S made substantial contributions to study conception and design; Pica R, de Biase D, Gallo CG and Hong W were involved in acquisition, analysis and interpretation of data; Zippi M and Hong W were involved in drafting the article, revising it critically for important intellectual content and gave final approval of the version to be published.
Conflict-of-interest statement: The authors declare no conflicts of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Maddalena Zippi, MD, PhD, Medical Assistant, Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Via dei Monti Tiburtini 385, Rome 00157, Italy. maddyzip@yahoo.it
Received: December 8, 2020
Peer-review started: December 8, 2020
First decision: December 30, 2020
Revised: January 1, 2021
Accepted: February 12, 2021
Article in press: February 12, 2021
Published online: April 26, 2021
ARTICLE HIGHLIGHTS
Research background

Coronavirus disease 2019 (COVID-19) is an emerging infection increasingly found in clinical practice, and is now a pandemic. Conventional pharmacotherapies, including proton pump inhibitors, are commonly used in the treatment of such patients. However, their clinical efficacy, as well as the risk of severe adverse events, remain a problem in their clinical application. Based on the fact that the use of this class of drugs seems to show both negative, particularly in terms of severity and mortality, and positive effects on the course of this disease, it is neither realistic nor definitive to consider not using these medicinal products in these patients.

Research motivation

Several basic and clinical studies have reported a relationship between proton pump inhibitors (PPIs) use and COVID-19. As the results obtained so far regarding these drugs are both against their use and in favor of it, these discordant conclusions may create confusion among doctors regarding their treatment choices.

Research objectives

The main objectives of this review were to critically analyze the available data from studies accessible from the literature. Moreover, by following the extracted outcomes, future research is needed.

Research methods

We searched three electronic databases up to 30 November 2020, for studies that examined the safety and efficacy of the administration of PPIs in patients suffering from COVID-19. Two endpoints were considered: the severity and the mortality rates in this cohort. In order to calculate the estimated risks in this meta-analysis, fixed and random effects models were used.

Research results

The pooled incidence of severe events did not differ between patients with and without PPIs [odds ratio 1.65, 95% confidence interval (CI): 0.62-4.35] (P = 0.314), or for mortality (odds ratio 1.77, 95%CI: 0.62-5.03) (P = 0.286).

Research conclusions

This review analyzed the possible effects of PPIs in COVID-19 patients with the aim of trying to understand if their administration may be deleterious or may interfere with the clinical course of the disease. The role of PPIs in the progression of severe acute respiratory syndrome coronavirus 2 infection is still not fully understood.

Research perspectives

The paradoxical relationship between PPIs and COVID-19 should not be a confounding factor for doctors but should prompt them to proceed with further studies in this regard.