Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Dec;73(6):1642-1649.
doi: 10.1007/s43440-021-00263-x. Epub 2021 Apr 11.

Proton pump inhibitor on susceptibility to COVID-19 and its severity: a systematic review and meta-analysis

Raymond Pranata  1 , Ian Huang  1   2 , Sherly Lawrensia  3 , Joshua Henrina  4 , Michael Anthonius Lim  1 , Antonia Anna Lukito  5 , Raden Ayu Tuty Kuswardhani  6 , I Dewa Nyoman Wibawa  7
Affiliations
Meta-Analysis

Proton pump inhibitor on susceptibility to COVID-19 and its severity: a systematic review and meta-analysis

Raymond Pranata et al. Pharmacol Rep. 2021 Dec.

Abstract

Background: The negative impacts of proton pump inhibitor (PPI), including the risk of pneumonia and mortality, have been reported previously. This meta-analysis aimed to address the current interest of whether the administration of PPI could increase the susceptibility and risk of poor outcome in COVID-19.

Methods: We performed a systematic literature search from PubMed, Embase, EBSCOhost, and EuropePMC databases up until 3 December 2020. The main outcome was composite poor outcome which comprised of mortality and severe COVID-19. Severe COVID-19 in this study was defined as patients with COVID-19 that fulfill the criteria for severe CAP, including the need for intensive unit care or mechanical ventilation. The secondary outcome was susceptibility, based on cohort comparing COVID-19 positive and COVID-19 negative participants.

Results: There were a total of 290,455 patients from 12 studies in this meta-analysis. PPI use was associated with increased composite poor outcome (OR 1.85 [1.13, 3.03], p = 0.014; I2 90.26%). Meta-regression analysis indicate that the association does not vary by age (OR 0.97 [0.92, 1.02], p = 0.244), male (OR 1.05 [0.99, 1.11], p = 0.091), hypertension (OR 9.98 [0.95, 1.02], p = 0.317), diabetes (OR 0.99 [0.93, 1.05], p = 0.699), chronic kidney disease (OR 1.01 [0.93, 1.10], p = 0.756), non-steroidal anti-inflammatory drug use (OR 1.02 [0.96, 1.09], p = 0.499), and pre-admission/in-hospital PPI use (OR 0.77 [0.26, 2.31], p = 0.644). PPI use was not associated with the susceptibility to COVID-19 (OR 1.56 [0.48, 5.05], p = 0.46; I2 99.7%).

Conclusion: This meta-analysis showed a potential association between PPI use and composite poor outcome, but not susceptibility.

Prospero id: CRD42020224286.

Keywords: Coronavirus; Gastrointestinal; Infection rate; Proton pump inhibitor; Severity; Susceptibility.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
PRISMA flowchart
Fig. 2
Fig. 2
Proton pump inhibitor and composite poor outcome. The diamond-shaped structure represents the pooled effect estimate. I2 I-squared
Fig. 3
Fig. 3
Proton pump inhibitor and susceptibility to COVID-19. The diamond-shaped structure represents the pooled effect estimate. I2 I-squared
Fig. 4
Fig. 4
Funnel-plot analysis. X-axis represent the effect size (log odds ratio) and Y-axis represent the standard error. The reference (red) effect-size line indicates the estimated θIV
See this image and copyright information in PMC

References

    1. Pranata R, Lim MA, Yonas E, Vania R, Lukito AA, Siswanto BB, et al. Body mass index and outcome in patients with COVID-19: a dose–response meta-analysis. Diabetes Metab. 2020 doi: 10.1016/j.diabet.2020.07.005. - DOI - PMC - PubMed
    1. Yonas E, Alwi I, Pranata R, Huang I, Lim MA, Gutierrez EJ, et al. Effect of heart failure on the outcome of COVID-19—a meta analysis and systematic review. Am J Emerg Med. 2020 doi: 10.1016/j.ajem.2020.07.009. - DOI - PMC - PubMed
    1. Lee SW, Ha EK, Yeniova AÖ, Moon SY, Kim SY, Koh HY, et al. Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching. Gut. 2021;70:76–84. doi: 10.1136/gutjnl-2020-322248. - DOI - PubMed
    1. Charpiat B, Bleyzac N, Tod M. Proton pump inhibitors are risk factors for viral infections: even for COVID-19? Clin Drug Investig. 2020;40:897–899. doi: 10.1007/s40261-020-00963-x. - DOI - PMC - PubMed
    1. Xie Y, Bowe B, Yan Y, Xian H, Li T, Al-Aly Z. Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: Cohort study. BMJ. 2019;365:l1580. doi: 10.1136/bmj.l1580. - DOI - PMC - PubMed

Substances