People exposed to proton pump inhibitors shortly preceding COVID-19 diagnosis are not at an increased risk of subsequent hospitalizations and mortality: a nation-wide matched cohort study

Aim

To assess whether exposure to proton pump inhibitors (PPIs) shortly preceding COVID-19 diagnosis affected the risk of subsequent hospitalizations and mortality.

Methods

This population-based study embraced first COVID-19 episodes in adults diagnosed up to August 15 2021 in Croatia. Patients were classified based on exposure to PPIs and burden of PPI-requiring morbidities as “non-users” (no issued prescriptions, no recorded treatment-requiring conditions between January 1 2019 and COVID-19 diagnosis), “possible users” (no issued prescriptions, but morbidities present; self-medication possible) and “users” (at least one prescription within 3 months prior to the COVID-19 diagnosis; morbidities present). Subsets were mutually exactly matched for pre-COVID-19 characteristics. The contrast between “users” and “possible users” informed about the effect of PPIs that is separate of the effect of PPI-requiring conditions.

Results

Among 433609 patients, “users” and “possible users” were matched 41195 (of 55098) to 17334 (of 18170) in the primary and 33272 to 16434 in the sensitivity analysis. There was no relevant difference between them regarding mortality [primary: RR=0.93 (95%CI 0.85-1.02; RD= - 0.34% (−0.73, 0.03); sensitivity: RR=0.88 (0.78-0.98); RD=-0.45% (−0.80, -0.11)] or hospitalizations [primary: RR=1.04 (0.97-1.13); RD=0.29% (−0.16, 0.73); sensitivity: RR=1.05 (0.97-1.15); RD=0.32% (−0.12, 0.75)]. The risks of both were slightly higher in “possible users” or “users” than in “non-users” (absolutely by ∼0.4%-1.6%) indicating the effect of PPI-requiring morbidities.

Conclusion

Pre-morbid exposure to PPIs does not affect the risk of death or hospitalization in adult COVID-19 patients, but PPI-requiring morbidities seemingly slightly increase the risk of both.

What is already known about this subject?

• It appears biologically plausible that pre-morbid exposure to proton pump inhibitors (PPIs) might contribute to unfavorable course of COVID-19 disease

• Two population-based studies in the early pandemics stage indicated no effect of PPIs, while one suggested a higher risk of death/severe COVID-19 disease in PPI pre-exposed subjects

What this study adds?

• Exposure to PPIs directly preceding SarsCov-2 infection has no effect on the risk of subsequent hospitalizations and mortality

• Conditions requiring PPI treatment seem to mildly increase the risk of both