PPIs for COVID-19: real-time meta analysis of 37 studies

Meta analysis shows 40% [17‑67%] higher mortality, and pooled analysis using the most serious outcome reported shows 46% [27‑68%] higher risk.

Potential mechanisms of harm include increased expression of ACE2, impaired immune responses due to gut microbiome changes, reduced antibacterial activity of neutrophils, easier passage of SARS-CoV-2 through the gastrointestinal tract due to reduced stomach acid, increased risk of secondary bacterial infections, degraded cellular defense mechanisms due to impaired lysosomal function, reduced absorption of nutrients critical for the immune system, potential interactions with COVID-19 medications, lung microbiome alterations, increased oxidative stress, impact on vitamin C and iron levels, potential effects on interferon responses, changes in coagulation factors, hypochlorhydria-induced hypergastrinemia, potential increased vulnerability to gastrointestinal pathogens, and delayed gastric emptying which may impair pharmacokinetics of COVID-19 medications.

All data to reproduce this paper and sources are in the appendix. 8 other meta analyses show significant harm with PPIs for mortality1-3, severity1,2,4-8, and cases2.

8 meta analyses show significant harm with PPIs for mortality1-3, severity1,2,4-8, and cases2.