Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Pre-hospital proton pump inhibitor use and clinical outcomes in hospitalized COVID-19 patients: A retrospective case-control study
Harinivaas Shanmugavel Geetha, Sushmita Prabhu, Mithil Gowda Suresh, George M Abraham, Akshaya Sekar, Safia Mohamed, Abinesh Sekar, Juniali Hatwal, Aalam Sohal, Akash Batta
Harinivaas Shanmugavel Geetha, Sushmita Prabhu, Mithil Gowda Suresh, George M Abraham, Akshaya Sekar, Abinesh Sekar, Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA 01608, United States
Safia Mohamed, Department of Medicine and Surgery, University of Massachusetts Chan Medical School-Baystate Medical Center, Springfield, MA 01199, United States
Juniali Hatwal, Department of Internal Medicine, Post Graduate Institute of Medical Education & Research, Chandigarh 160012, India
Aalam Sohal, Department of Gastroenterology and Hepatology, Creighton University School of Medicine, Phoenix, AZ 85012, United States
Akash Batta, Department of Cardiology, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
Co-corresponding authors: Mithil Gowda Suresh and Akash Batta.
Author contributions: Geetha HS, Prabhu S, Suresh MG, and Batta A designed the research study. Geetha HS collected and analyzed the data. Hatwal J and Sohal A assisted with literature review and manuscript drafting. Abraham GM provided senior review and supervision. Mohamed S and Sekar A contributed to clinical data interpretation and refinement of the manuscript. All authors reviewed and approved the final manuscript. Both Suresh MG and Batta A served as co-corresponding authors due to their substantial and complementary roles throughout the project. Suresh MG coordinated IRB approval, supervised data abstraction and quality control, managed subgroup analyses, and oversaw manuscript drafting and revisions to ensure methodological accuracy and clarity. Batta A provided critical input in study design, guided statistical modeling and data interpretation, strengthened the discussion of cardiovascular and infectious disease implications, and revised the manuscript for conceptual depth and scholarly rigor. He also directed the submission process and response to reviewers. Together, Suresh MG and Batta A ensured the integrity, accuracy, and intellectual leadership of the study. Their complementary contributions in study design, supervision, data analysis, interpretation, and manuscript preparation justify their designation as co-corresponding authors.
Institutional review board statement: The study was approved by the Saint Vincent-MetroWest Medical Center IRB (Approval No. 2020-035).
Informed consent statement: Informed consent was waived due to the retrospective design and use of de-identified data.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
Data sharing statement: Data will be made available on reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Akash Batta, Associate Professor, Department of Cardiology, Dayanand Medical College and Hospital, Tagore Nagar, Civil Lines, Ludhiana 141001, Punjab, India.
akashbatta02@gmail.com
Received: May 6, 2025
Revised: May 28, 2025
Accepted: September 1, 2025
Published online: September 25, 2025
Processing time: 147 Days and 16.1 Hours
BACKGROUND
Proton pump inhibitors (PPIs) are among the most commonly prescribed medications globally. While concerns exist regarding their association with adverse infection-related outcomes, their impact on coronavirus disease 2019 (COVID-19) severity remains uncertain. Emerging preclinical data suggest immunomodulatory and antiviral properties of PPIs, yet clinical evidence is conflicting.
AIM
To investigate whether chronic pre-hospital PPI use is associated with improved outcomes in patients hospitalized with COVID-19.
METHODS
We conducted a retrospective case-control study of adult inpatients with severe acute respiratory syndrome coronavirus 2 infection admitted to a racially and ethnically diverse community hospital in Massachusetts from July 2021 to March 2022. Patients were stratified by documented pre-hospital PPI use. The primary outcomes were intensive care unit (ICU) admission, need for invasive mechanical ventilation, and in-hospital mortality. Multivariable logistic regression was used to adjust for demographics, comorbidities, and treatment variables. Significance was set at P < 0.05.
RESULTS
Among 248 patients, 83 (33.4%) were on PPIs prior to hospitalization. Compared to non-users, PPI users had significantly lower rates of ICU admission (13.3% vs 24.8%, P = 0.034), mechanical ventilation (13.3% vs 25.5%, P = 0.027), and in-hospital mortality (6.0% vs 17.6%, P = 0.013). Multivariable analysis confirmed these associations: ICU admission [adjusted odds ratios (aOR): 0.462, 95%CI: 0.223–0.955], mechanical ventilation (aOR: 0.447, 95%CI: 0.216–0.923), and mortality (aOR: 0.144, 95%CI: 0.031–0.677). Findings were consistent across demographic and comorbidity strata.
CONCLUSION
In this diverse, real-world United States cohort, chronic pre-hospital PPI use was independently associated with lower odds of intensive care unit admission, mechanical ventilation, and mortality among COVID-19 inpatients. These findings highlight a potentially protective role of PPIs and support continued therapy in eligible patients.
Core Tip: This retrospective case-control study investigated the association between pre-hospital proton pump inhibitor (PPI) use and outcomes among patients hospitalized with coronavirus disease 2019 (COVID-19). After adjusting for multiple confounders, pre-hospital PPI use was associated with a lower risk of intensive care unit admission and in-hospital mortality. While the underlying mechanisms remain unclear, the findings suggest that chronic PPI use may not be associated with adverse COVID-19 outcomes.
