Clinical Pharmacology of Proton Pump Inhibitors in COVID-19 Management

Proton pump inhibitors (PPIs) are potent suppressors of gastric acid secretion achieved by irreversible inhibition of the H+/K+-ATPase in parietal cells. Beyond their established role in peptic ulcer disease and gastro-oesophageal reflux, PPIs have been investigated for potential modulatory effects on viral infections, including SARS-CoV-2. Acid suppression may alter gastrointestinal barrier function and microbiota composition, with downstream effects on systemic immunity. Pharmacokinetic profiles of PPIs feature rapid absorption, extensive first-pass metabolism via cytochrome P450 isoforms, and variable half-lives supporting once-daily dosing. In COVID-19 management, preclinical studies have explored whether raised gastric pH interferes with viral stability or impairs endosomal processing, while clinical observations have yielded mixed signals on susceptibility, severity and symptom profiles. Drug–drug interactions are of particular concern in hospitalised patients receiving multiple agents, since PPIs may compete for metabolic pathways or influence absorption of concomitant therapies. Overall, the clinical pharmacology of PPIs in the context of SARS-CoV-2 encompasses mechanistic hypotheses around pH-dependent entry, immunomodulation via altered gut flora and the safety profile of long-term acid suppression in vulnerable populations.

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Clinical Pharmacology of Proton Pump Inhibitors in COVID-19 Management publication trend

The graph below shows the total number of articles in clinical pharmacology of proton pump inhibitors in covid-19 management across all publications each year (not limited to Nature Index journals).

Technical terms

Proton pump inhibitor (PPI): Drug class that irreversibly inhibits the gastric H+/K+-ATPase to reduce acid secretion.

Angiotensin-converting enzyme 2 (ACE2): Cell-surface receptor mediating SARS-CoV-2 entry and expressed in respiratory and gastrointestinal epithelia.

TMPRSS2: Transmembrane protease that primes the SARS-CoV-2 spike protein, facilitating viral entry into host cells.

Polypharmacy: Concurrent use of multiple medications, which may increase the likelihood of drug–drug interactions and confounding in observational studies.

References

1. Proton pump inhibitors and gastrointestinal symptoms among patients with COVID-19 infection. Annals of Medicine (2024).
2. Proton Pump Inhibitor Use Is Not Strongly Associated With SARS-CoV-2 Related Outcomes: A Nationwide Study and Meta-analysis. Clinical Gastroenterology and Hepatology (2021).
3. Effect of Common Medications on the Expression of SARS‐CoV‐2 Entry Receptors in Kidney Tissue. Clinical and Translational Science (2020).