Proton-pump inhibitor use is not associated with severe COVID-19-related outcomes: a propensity score-weighted analysis of a national veteran cohort

Abstract

We read with interest the study by Lee et al. The authors conducted a propensity score (PS)matched analysis of a national South Korean cohort evaluating the association between proton pump inhibitor (PPI) use and SARSCoV2 susceptibility (primary outcome) and COVID19 clinical severity (secondary outcome). Between January and May 2020, 4785 patients tested positive for SARSCoV2 (3.6% positivity); 267 current PPI users and 148 former PPI users were 1:1 PSmatched to nonusers for the secondary outcomes. The authors reported current PPI use versus nonuse was associated with a statistically significant increased risk of the composite endpoints: (1) oxygen therapy, intensive care unit (ICU) admission, mechanical ventilation use or death (composite OR 1.63; 95% CI, 1.03–2.53); and (2) ICU admission, mechanical ventilation or death (composite OR 1.79; 95% CI, 1.30 to 3.10). We assembled a national retrospective cohort of US veterans who tested positive for SARSCoV2 (index date). Current outpatient PPI use up to and including the index date (primary exposure) was compared with nonuse, defined as no PPI prescription fill in the 365 days prior to the index date (online supplemental figure 1). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome also included hospital or ICU admission. In contrast to PS matching, PS weighting allowed inclusion of all patients. Weighted logistic regression models evaluated severe COVID19 outcomes between current PPI users versus nonusers. Our analytic cohort included 97 674 veterans with SARSCoV2 testing, of whom 14 958 (15.3%) tested positive (6262 (41.9%) current PPI users, 8696 (58.1%) nonusers). In the unweighted cohort, current PPI users were older, more often current or former smokers, and had more comorbidities than nonusers. After weighting, all covariates were balanced (table 1, online supplemental figure 2). In the unweighted cohort, we observed higher odds of the primary (9.3% vs 7.5%; OR 1.27; 95% CI, 1.131.43) and secondary (25.8% vs 21.4%; OR 1.27; 95% CI, 1.181.37) composite outcomes among PPI users versus nonusers (figure 1, online supplemental table 1). After PS weighting, Letter