Does PPI use affect clinical outcomes in COVID-19 patients?

According to a Hong Kong study presented at APDW 2021, the use of proton pump inhibitors (PPIs) is not associated with adverse clinical outcomes in individuals with COVID-19.

Studies have implicated the gastrointestinal (GI) system as a primary gateway for SARS-CoV-2. [Am J Gastroenterol 2020;115:1707-1715; Lancet Gastroenterol Hepatol 2020;5:335-337; Lancet Gastroenterol Hepatol 2020;5:434-435] The gut can host SARS-CoV-2 colonies, hence the growing concern about the ability of the virus to spread beyond the GI tract by triggering infection or inflammation in other systems, including the respiratory tract via the ‘gut-lung axis’. [Cell Rep 2020;32:107915; Virus Res 2020;285:198018; Sci Adv 2017;3:eaao4966]

Researchers thus explored the potential role of PPIs in COVID-19 to ascertain whether these agents can help in mitigating the effects of COVID-19. However, data are conflicting, with most implicating an association between PPI use and COVID-19. [Gut 2021;70:1806-1808; Gut 2021;70:76-84; J Intern Med 2021;289:125]

“[As such,] we examined the impact of PPI use on clinical outcomes in COVID-19 patients in a retrospective cohort study,” said Assistant Professor Terry Cheuk-Fung Yip  from The Chinese University of Hong Kong, Hong Kong SAR, China, during his presentation.

A total of 8,675 patients (mean age 46 years, 51 percent female, 98 percent of all reported cases in Hong Kong) diagnosed virologically with COVID-19 between 23 January 2020 and 1 January 2021 were identified using a territory-wide database in Hong Kong. Of these, about 7 percent had a history of PPI use. PPI users were mostly older and more likely to have comorbidities, concomitant medications, and unfavourable laboratory parameters than those with no history of PPI use. [APDW 2021, abstract 536-123]

Five-hundred participants developed the primary endpoint of a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death.

After propensity score (PS) adjustments for demographics, comorbidities, medication use, and laboratory parameters, PPI use was not associated with the development of the primary endpoint, both according to PS weighting (weighted hazard ratio [HR], 1.11, 95 percent confidence interval [CI], 0.83–1.47; p=0.482) and PS matching analyses (weighted HR, 0.81, 95 percent CI, 0.57–1.14, p=0.228).

The results remained robust even after multivariate adjustments (adjusted HR, 0.84, 95 percent CI 0.66–1.07, p=0.151), as well as in subsets of current and past PPI users, noted Yip

“[Taken together, our findings suggest] that PPI use is not associated with adverse clinical outcomes in [this patient setting],” said Yip.

While the findings do not suggest a potential adverse effect of PPIs in individuals with COVID-19, caution is still warranted when using PPIs in this setting. Further in-depth investigations are also warranted to ascertain whether PPIs do affect outcomes or treatment in patients with COVID-19.