PPI use may increase death risk in COVID-19 patients

Users of proton pump inhibitor (PPI) who tested negative for COVID-19 show higher salivary angiotensin-converting enzyme 2 (ACE2) expression, reports a study. In addition, PPI use seems to heighten the risk of death in COVID-19 patients, particularly African Americans.

“PPI use was recently reported to be associated with increased SARS-CoV-2 infection and worse clinical outcomes,” the investigators said. “The underlying mechanism(s) for this association are unclear.”

A prospective study of hospitalized COVID-19 patients and COVID-negative controls was carried out to understand how PPI use could affect ACE2 expression and stool SARS-CoV-2 RNA. A retrospective cohort analysis was also conducted on hospitalized COVID-19 patients from 15 March to 15 August 2020 to assess the relationship between PPI use and mortality. Predictors of in-hospital mortality were identified by including covariates with clinical relevance to COVID-19 outcomes.

COVID-negative PPI users had higher salivary ACE2 mRNA levels than nonusers (2.39±1.15 vs 1.22±0.92; p=0.02).  Moreover, salivary ACE2 levels and stool SARS-CoV-2 RNA detection rates were similar between PPI users and nonusers.

In 694 hospitalized COVID-19 patients (mean age 58 years, 46 percent men, 65 percent Black), mortality rate was significantly higher among PPI users than nonusers (30 percent vs 12.1 percent). Mortality was predicted by the following factors: PPI use (adjusted odds ratio [AOR], 2.72; p<0.001), age (AOR, 1.66 per decade; p<0.001), race (AOR, 3.03; p=0.002), cancer (AOR, 2.22; p=0.008), and diabetes (AOR, 1.95; p=0.003). Notably, the risk of PPI-related death was higher in Black patients (AOR, 4.16, 95 percent CI, 2.28–7.59) than others (AOR, 1.62, 95 percent CI, 0.82–3.19; p_interaction=0.04).