PPIs and Covid-19: A paradoxical association

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The use of proton pump inhibitors (PPIs) has been linked to increased risk of Covid-19 infection and related mortality. The evidence on this however has not been consistent. Adding to the evidence, a new meta-analysis has found that PPIs do not significantly increase risk for COVID-19 infection or death. But it does appear to increase the risk for severe disease and secondary infections. This meta-analysis of 14 articles - randomized controlled trial or an observational study (including cohort and case-control studies) – with over 268,683 participants was conducted to further investigate this association.

The association between PPIs and risk of COVID-19 infection was non-significant (OR 1.64, 95% CI 0.54-5.00, P=0.390), as was the risk for COVID-19 mortality (OR 1.91, 95% CI 0.86-4.24, P=0.11).

The association between PPIs and risk for progression to severe disease was nevertheless significant (OR 1.67, 95% CI 1.37-2.02, P<0.001 for both).

  • Analysis of seven studies on the risk of COVID-19 infection showed no relationship between PPI use and COVID-19 infection risk, either decreased or increased (OR:1.64, 95%CI = 0.54-5.00, P=0.390); the association was non-significant in both Western and Asian countries. No association was found between PPI use and increased or decreased mortality risk for COVID-19 patients (OR=1.91, 95% CI=0.86-4.24).
  • However, results of nine studies from eight original articles showed a 67% increased risk for progression to severe disease with PPIs, which included ICU admission, intubation, or even death (OR 1.67, 95% CI 1.37-2.02, P<0.001).

The meta-analysis also examined the risk of secondary infection and found that use of PPIs had an association with risk for developing secondary infections (OR 4.62, 95% CI 2.55-8.39) such as nosocomial pneumonia. PPIs must be used with caution in immunocompromised patients or those predisposed to secondary infections.

The study authors have cautioned about the use of PPIs in COVID-19 patients hospitalized with gastrointestinal bleeding and in patients taking stress ulcer prophylaxis. But, they also say that in some patients, such as those with GERD, a histamine-2 receptor antagonist like famotidine may not control symptoms. In such cases, one can still consider the use of PPI. Therefore, the decision to use PPIs in Covid-19 patients should be made on a case-to-case basis and benefits vs risks must be weighed before going ahead with the decision to use or not use a PPI in any Covid-19 patient.

This association needs to be investigated in future studies, they added.

The meta-analysis is published in the Japanese Journal of Infectious Diseases.

(Source: Yan C, et al. Will proton pump inhibitors lead to a higher risk of COVID-19 infection and progression to severe disease? A meta-analysis. Jpn J Infect Dis 2021; DOI: 10.7883/yoken.JJID.2021.074)