Author: Kenneth R. DeVault, MD reviewing
NEJM Journal Watch
An online survey suggests a dose-dependent association between PPI use and risk for testing positive for COVID-19.
Proton-pump inhibitors (PPIs) have become a mainstay in the treatment of acid-related conditions. They were initially felt to be very safe, but multiple studies published in the past several years show associations with increased risks for both infectious and noninfectious conditions, particularly when taken at higher-than-indicated dosages. This is the first report of an increased risk for COVID-19 test positivity in PPI users.
In a population-based online survey conducted in the U.S. in May and June 2020, 53,130 adults noted ever having upper GI symptoms. Among them, 3386 (6.4%) reported having received a positive COVID-19 test. A regression model found an odds ratio of 2.15 for having a positive COVID-19 test in those on once-daily PPIs and an odds ratio of 3.67 with twice-daily use. No such relationship was found with histamine-2 receptor antagonist use. All reasonable statistical methods were used to control for confounding factors.
As is always the case, association does not prove causality, but there are reasonable biological data showing that lower pH impairs the infectivity of coronaviruses, which provides biological plausibility. How should we react to these data? I would continue to suggest that greater-than-indicated PPI dose (i.e., more than once daily) should only be used in the rare situation when it is required to control mucosal damage. In patients with uncomplicated reflux, acid suppression should be given at the lowest effective dose to provide satisfactory control of symptoms. Finally, lifestyle modifications should be stressed to help patients lower their dependence on these medications. Future studies may support or counter this association, but the above suggestions seem reasonable regardless of those results.