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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.
Reference
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.
