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
Abstract
BACKGROUND

The proton pump inhibitors (PPIs), used to reduce gastric acid secretion, represent one of the most widely used pharmaceutical classes in the world. Their consumption as a risk factor for the evolution of severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been investigated as well as the mortality of these patients. These risks also appear to be linked to the duration and the dosage. On the other hand, several studies have emerged with regard to the protective or therapeutic effects of these drugs. More and more evidence underlines the immunomodulatory and anti-fibrotic role of PPIs. In addition, their ability to alkalize the contents of endosomes and lysosomes serves as an obstacle to the entry of the virus into the host cells.

AIM

To identify studies on the relationship between the intake of PPIs and coronavirus disease 2019 (COVID-19) in patients affected by SARS-CoV-2 infection, with the main objective of evaluating the outcomes related to severity and mortality.

METHODS

A literature review was performed in November 2020. The MEDLINE/PubMed, Cochrane Library, EMBASE and Google Scholar databases were searched for all relevant articles published in English on this topic. The search terms were identified by means of controlled vocabularies, such as the National Library of Medicine’s MESH (Medical Subject Headings) and keywords. The MESH terms and keywords used were as follows: “COVID-19”, “proton pump inhibitors”, ”PPIs”, “SARS-CoV-2”, “outcomes”, “severity” and “mortality”. The inclusion criteria regarding the studies considered in our analysis were: meta-analysis, case-control, hospital-based case-control, population-based case-control, retrospective studies, online survey, as well as cohort-studies, while articles not published as full reports, such as conference abstracts, case reports and editorials were excluded. We tried to summarize and pool all the data if available.

RESULTS

A total of 9 studies were found that described the use of PPIs, of which only 5 clearly reported the severity and mortality data in SARS-CoV-2 patients. Our pooled incidence analysis of severe events did not differ between patients with and without PPIs (odds ratio 1.65, 95% confidence interval: 0.62-4.35) (P = 0.314), or for mortality (odds ratio 1.77, 95% confidence interval: 0.62-5.03) (P = 0.286).

CONCLUSION

Detailed and larger case studies are needed to accurately understand the role of PPIs in this viral infection.

Keywords: COVID-19, Proton pump inhibitors, SARS-CoV-2, Severity, Mortality

Core Tip: In the scenario of the current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is essential to identify possible risk factors for the occurrence of this disease, including pharmacological therapies commonly taken by the population. Among these drugs, proton pump inhibitors represent one of the classes most widely used. In this review, we have tried to explore the link between the use of proton pump inhibitors and SARS-CoV-2 infection, and to analyze the strengths and weaknesses of this relationship, using the currently available data.