Proton Pump Inhibitor Use May Lower Risk of ICU Admission, Mortality in COVID-19

Chronic, prehospital proton pump inhibitor (PPI) use was associated with a lower risk of intensive care unit (ICU) admission, mechanical ventilation, and mortality among patients with COVID-19, according to results from a retrospective case-control study of a real-world United States cohort published by investigators in World Journal of Virology. As one of the most used medications globally, these insights could offer potential for an established and safe prophylaxis method for COVID-19.¹

What Are Proton Pump Inhibitors?

PPIs are a drug class that limits the stomach’s production of acid. Although stomach acid serves numerous purposes, including breaking down food for digestion and destroying harmful germs present in the gut, too much acid can lead to complications like acid reflux or stomach ulcers. By blocking the hydrogen-potassium ATPase pump—an enzyme that produces stomach acid—PPIs prevent harmful acid buildup while still allowing for enough to effectively digest food.²

There are several PPIs that are available over the counter and are commonly prescribed, including omeprazole (Prilosec; AstraZeneca), lansoprazole (Prevacid; Takeda Pharmaceuticals), and esomeprazole (Nexium; AstraZeneca). PPIs are easy to take and often require just a single pill before breakfast, though some may take a higher or lower dose depending on their health care professional’s recommendation. This drug class is one of the most proliferated worldwide, with estimates of up to 25% of adults being prescribed a PPI or reporting off-label use at some point in their lives.^2,3

Could PPIs Impact COVID-19 Outcomes?

Concerns regarding chronic PPI use have been raised in the past, especially regarding altered gut immunity, which could play a significant role in SARS-CoV-2 infections. However, preclinical research has suggested that PPI use could induce anti-inflammatory and antifibrotic properties that play a role in viral pathophysiology. This research is centered on animals, with limited and inconclusive clinical data in human populations.^1,4

Critically, few studies regarding PPI use in COVID-19 have focused on prehospital use, which constitutes a major avenue of PPI utilization. Moreover, their impact on diverse US populations is undetermined. The current authors conducted a retrospective case-control study in a community-based teaching hospital in Worcester, Massachusetts, serving high-risk patients across racial and socioeconomic spectrums. Primarily, they sought to examine if prehospital PPI use was associated with clinical outcomes in hospitalized adults with COVID-19.¹

Prehospital PPI Use Improved Mortality, ICU Admission Risk

A total of 248 patients met the study inclusion criteria, of which 83 (33.5%) had documented prehospital PPI use. Patients’ baseline characteristics were comparable between users and nonusers of PPIs, but PPI users had marginally heightened rates of hypertension and chronic kidney disease. The population was diverse: about 52% were White, 22.6% Hispanic, 13.3% Black, and 9.3% Southeast Asian patients.¹

According to the investigators, PPI users had significantly better outcomes in COVID-19. Patients using PPIs and hospitalized with COVID-19 had lower rates of ICU admission (13.3% vs 24.8%; P = .034), invasive mechanical ventilation (13.3% vs 25.5%; P = .027), and in-hospital mortality (6.0% vs 17.6%; P = .013). Kaplan-Meier survival analysis indicated superior overall survival in PPI users hospitalized with COVID-19.¹

Multivariable regression was employed to adjust for relevant demographics, including age, sex, body mass index, race/ethnicity, vaccination status, and relevant comorbidities. Following these adjustments, prehospital PPI use remained independently associated with improved outcomes (ICU admission: adjusted odds ratio [AOR], 0.462 [95% CI, 0.223–0.955; P = .036]; mechanical ventilation: AOR, 0.447 [95% CI, 0.216–0.923; P = .028]; mortality: AOR, 0.144 [95% CI, 0.031–0.677, P = .014]).¹

Subgroup analyses found that protective effects of PPI use were especially significant in patients aged over 65 years, who experienced 65% lower odds of ICU admission (AOR, 0.35 [95% CI, 0.15–0.85]), and in patients with chronic kidney disease, who experienced significantly reduced mortality (4.1% vs 22.2%; P = .04). Importantly, there were no significant interactions with race or vaccination status.¹

What Should Pharmacists Know?

These insights could indicate the potential for PPI use to act as COVID-19 protection, especially in hospitalized adults. Although further research is required given the vast amount of conflicting data, the current results align with the notion that PPI use can modulate host responses to temper COVID-19 progression. Ultimately, PPI use may not act as a direct prevention or treatment for severe COVID-19, but pharmacists and providers can be assured that continuing treatment during an infection course is safe and recommended.¹

“Future prospective and mechanistic studies are essential to validate this signal and explore its implications in broader infectious disease management,” the study authors concluded. “Until then, clinicians can be reassured that continuation of PPI therapy in COVID-19 patients is not only safe—it may be beneficial.”¹

REFERENCES

1. Geetha HS, Prabhu S, Suresh MG, et al. Pre-hospital proton pump inhibitor use and clinical outcomes in hospitalized COVID-19 patients: A retrospective case-control study. World J Virol. 2025;14(3): doi:10.5501/wjv.v14.i3.109170

2. Proton pump inhibitors. Cleveland Clinic. Last Updated September 28, 2023. Accessed October 9, 2025. https://my.clevelandclinic.org/health/articles/proton-pump-inhibitors

3. Shanika LGT, Reynolds A, Pattison S, Braund R. Proton pump inhibitor use: systematic review of global trends and practices. Eur J Clin Pharmacol. 2023;79(9):1159-1172. doi:10.1007/s00228-023-03534-z

4. Ray A, Sharma S, Sadasivam B. The potential therapeutic role of proton pump inhibitors in COVID-19: hypothesis based on existing evidences. Drug Res (Stuttg). 2020;70(10):484-488. doi:10.1055/a-1236-3041