Proton pump inhibitor (PPI) use did not contribute to severe COVID-19 outcomes, according to results of nationwide observational study published in Clinical Gastroenterology and Hepatology.
All residents of Denmark who tested positive for SARS-CoV-2 up to December of 2020 were included in this analysis. The COVID-19 cohort was assessed for clinical outcomes and 10-year medical history. Patients were matched with 4, COVID-19-negative PPI controls included in the Danish health registries. A meta-analysis was performed to assess the risk for SARS-CoV-2 infection and mortality attributed to PPI use.
A total of 83,224 Danish residents tested positive for SARS-CoV-2 during the study period. Among these individuals, 5% were current and 23% former PPI users. The PPI prescriptions were pantoprazole (57%), lansoprazole (19%), omeprazole (17%), and esomeprazole (7%).
Cases and controls were aged median 36 years and fewer than 15% met any criteria for the Charlson’s Comorbidity Index. The most frequent comorbidities were ischemic heart disease, asthma, diabetes, stroke, and chronic obstructive pulmonary disease.
Among the COVID-19 cohort, current PPI users were at higher risk for testing positive (adjusted odds ratio [aOR], 1.08; 95% CI, 1.03-1.13) as were former users (aOR, 1.08; 95% CI, 1.06-1.10). Patients on a high dose of PPI were at increased risk for COVID-19 (aOR, 1.11; 95% CI, 1.05-1.16), while a low dose did not increase COVID-19 risk (aOR, 1.04; 95% CI, 0.98-1.11).
Among a propensity-matched COVID-19 cohort, current PPI use was associated with increased risk for hospital admission (adjusted relative risk [aRR], 1.13; 95% CI, 1.03-1.24) but no associations with transfer to the intensive care unit (aRR, 0.97; 95% CI, 0.73-1.29), mechanical ventilation (aRR, 1.00; 95% CI, 0.69-1.45), or death (aRR, 0.88; 95% CI, 0.72-1.08) were observed. Increased hospital admittance was observed among high dose PPI users (aRR, 1.19; 95% CI, 1.07-1.32) but not for low dose (aRR, 1.03; 95% CI, 0.90-1.17).
In the meta-analysis, 7 studies were combined with these data. With data from 730,941 individuals, the increased risk for SARS-CoV-2 among PPI users was not replicated (OR, 1.00; 95% CI, 0.75-1.32; I2, 98%) nor was there evidence for increased mortality (RR, 1.33; 95% CI, 0.71-2.48; I2, 84%).
This study may have been limited by the significant differences in comorbidities among the propensity-matched cohorts.
These data did not indicate current or former users of PPIs were at increased risk for severe COVID-19 outcomes. It remains unclear whether PPI use is associated with increased risk for infection.
Isralsen SB, Ernst MT, Lundh A, et al. Proton pump inhibitor use is not strongly associated with SARS-CoV-2 related outcomes: a nationwide study and meta-analysis. Clin Gastroenterol Hepatol. Published online May 11, 2021. doi: 10.1016/j.cgh.2021.05.011.