Proton pump inhibitor use is not strongly associated with SARS-CoV-2 related outcomes: A nationwide study and meta-analysis

Israelsen, Simone Bastrup; Ernst, Martin Thomsen; Lundh, Andreas; Lundbo, Lene Fogt; Sandholdt, HÃ¥kon; Hallas, Jesper; Benfield, Thomas

Background and aims Proton pump inhibitor (PPI) use has been associated with increased risk of 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 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, ICU admission or death, in current PPI users (n=4,473) compared to 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 (OR) 1.08 (95% CI 1.03-1.13). Among SARS-CoV-2 cases, PPI use was associated with increased risk of hospital admission; adjusted relative risk (RR) 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 OR 1.00 (95% CI 0.75-1.32) and RR 1.33 (95% CI 0.71-2.48). Conclusion 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.