Associations of proton pump inhibitors with susceptibility to pneumonia, influenza, and COVID-19: evidence from a large population based cohort study (preprint)

ABSTRACT

Objective Concerns have been raised about the widespread use of proton pump inhibitors (PPIs), and current findings linking the regular use of PPIs to respiratory infections remain inconsistent. Our study aims to evaluate whether PPI use increases the risk of pneumonia, influenza, and COVID-19. Method The presented study included 160,923 eligible participants from the UK Biobank (mean age 56.5 years, 53% women). Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Effect modifications by stratifications, including indications and CYP2C19 phenotypes were tested. Results The regular use of PPIs was associated with increased risks of developing pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26-1.59) and influenza (HR 1.31, 95% CI 1.11-1.55). However, the risk of COVID-19 infection among regular PPI users was not significantly increased (HR 1.05, 95% CI 0.95-1.16). The burden was more notably observed in patients without indications of PPI use (HR 1.52, 95% CI 1.33-1.73 for pneumonia; HR 1.36, 95% CI 1.12-1.64 for influenza). The risk for pneumonia was higher among the CYP2C19 rapid and ultrarapid metabolizers (HR 1.45, 95% CI 1.22-1.73, P for interaction < 0.001). The propensity score-matching analyses yielded similar trends. Conclusions The regular use of PPIs is associated with increased susceptibility to pneumonia and influenza, but not COVID-19 infection. The risks are even higher among recipients without main indications. Our study highlights the appropriate use and de-prescribing of PPIs according to indications and CYP2C19 phenotypes for patients and clinical practitioners.