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

Simone Bastrup Israelsen*, Martin Thomsen Ernst, Andreas Lundh, Lene Fogt Lundbo, Håkon Sandholdt, Jesper Hallas, Thomas Benfield

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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.

Original languageEnglish
JournalClinical Gastroenterology and Hepatology
Volume19
Issue number9
Pages (from-to)1845-1854.e6
ISSN1542-3565
DOIs
Publication statusPublished - Sept 2021

Keywords

  • COVID-19
  • Mortality
  • PPI
  • Risk of Infection
  • SARS-CoV-2
  • Pandemics
  • Humans
  • Observational Studies as Topic
  • Proton Pump Inhibitors/adverse effects
  • Respiration, Artificial

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