Original Article
Alimentary Tract
Proton Pump Inhibitor Use Is Not Strongly Associated With SARS-CoV-2 Related Outcomes: A Nationwide Study and Meta-analysis

https://doi.org/10.1016/j.cgh.2021.05.011Get rights and content
Under a Creative Commons license
open access

Background & Aims

Proton pump inhibitor (PPI) use has been associated with increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe outcomes. However, meta-analyses show unclear results, leading to uncertainty regarding the safety of PPI use during the ongoing coronavirus disease 2019 (COVID-19) pandemic.

Methods

We conducted a nationwide observational study including all SARS-CoV-2 cases (n = 83,224) in Denmark as of December 1, 2020. The association of current PPI use with risk of infection was examined in a case-control design. We investigated the risk of severe outcomes, including mechanical ventilation, intensive care unit admission, or death, in current PPI users (n = 4473) compared with never users. Propensity score matching was applied to control for confounding. Finally, we performed an updated meta-analysis on risk of SARS-CoV-2 infection and COVID-19 mortality attributable to PPI use.

Results

Current PPI use was associated with increased risk of infection; adjusted odds ratio, 1.08 (95% confidence interval [CI], 1.03–1.13). Among SARS-CoV-2 cases, PPI use was associated with increased risk of hospital admission; adjusted relative risk, 1.13 (1.03–1.24), but not with other severe outcomes. The updated meta-analysis showed no association between PPI use and risk of infection or mortality; pooled odds ratio, 1.00 (95% CI, 0.75–1.32) and relative risk, 1.33 (95% CI, 0.71–2.48).

Conclusions

Current PPI use may be associated with an increased risk of SARS-CoV-2 infection and hospital admission, but these results with minimally elevated estimates are most likely subject to residual confounding. No association was found for severe outcomes. The results from the meta-analysis indicated no impact of current PPI use on COVID-19 outcomes.

Keywords

PPI
COVID-19
Risk of Infection
Mortality

Abbreviations used in this paper

CI
confidence interval
COVID-19
coronavirus disease 2019
ICU
intensive care unit
NSAID
nonsteroidal anti-inflammatory drug
OR
odds ratio
PPI
proton pump inhibitor
RR
relative risk
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SMD
standardized mean difference

Cited by (0)

Conflicts of interest This author discloses the following: Thomas Benfield reports grants from Novo Nordisk Foundation, grants from Simonsen Foundation, grants and personal fees from GSK, grants and personal fees from Pfizer, personal fees from Boehringer Ingelheim, grants and personal fees from Gilead, personal fees from MSD, grants from Lundbeck Foundation, grants from Kai Hansen Foundation, and personal fees from Pentabase A/S, with no relation to the work reported in this article. The remaining authors disclose no conflicts.

Funding Supported by a grant from Erik and Susanna Olesen’s Charitable Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.