Terry Cheuk-Fung Yip1,2,3, Francis Ka-Leung Chan1,2,3, Grace Chung-Yan Lui1,2,4, Vincent Wai-Sun Wong1,2,3, Henry Lik-Yuen Chan1,2,3, Sunny Hei Wong1,2,3, Joyce Wing-Yan Mak1,2,3, Siew-Chien Ng1,2, David Shu-Cheong Hui1,2,4, Grace Lai-Hung Wong1,2,3

1Department of Medicine and Therapeutics, The Chinese University of Hong Kong; Hong Kong SAR, China, 2Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong; Hong Kong SAR, China, 3Institute of Digestive Disease, The Chinese University of Hong Kong; Hong Kong SAR, China, 4Stanley Ho Centre for Emerging Infectious Diseases, Jockey Club School of Public Health & Primary Care, Faculty of Medicine, The Chinese University of Hong Kong; Hong Kong SAR, China

Background/Aims: Evidence regarding use of proton-pump inhibitors (PPIs) in coronavirus disease 2019 (COVID-19) patients remains elusive. We examined the impact of PPI use on clinical outcomes of COVID-19 patients in a territory-wide cohort.

Methods: We performed a retrospective cohort study using data from a territory-wide database in Hong Kong. COVID-19 patients diagnosed virologically between 23 January 2020 and 1 January 2021 were identified. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death. PPI user was identified by PPI use within 12 months before diagnosis of COVID-19. Study was approved by Joint CUHK-NTEC Clinical Research Ethics Committee.

Results: We identified 8,675 COVID-19 patients (mean age 46 years, 49% male, 97.6% of all reported cases in Hong Kong); 579 (6.7%) patients had used PPI. PPI users were older, more likely to have comorbidities, concomitant medications and unfavorable laboratory parameters than non-users; 500/8,675 (5.8%) COVID-19 patients developed the primary endpoint. After propensity score (PS) balancing for patients’ demographics, comorbidities, laboratory parameters, and use of medications, PPI use was not associated with development of primary endpoint in PS weighting (weighted hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.83–1.47, P=0.482), and PS matching analysis (weighted HR 0.81, 95%CI 0.57–1.14, P=0.228) (Figure). Consistent non-association was observed after multivariable adjustment (adjusted HR 0.84, 95%CI 0.66–1.07, P=0.151), and in subgroups of current and past PPI users.

Conclusion: PPI use is not associated with adverse clinical outcomes in COVID-19 patients. The result remains robust after PS weighting, PS matching, and multivariable adjustment.

Keywords: SARS-CoV-2, COVID-19, Proton-pump inhibitor, ICU admission, mortality