In 2020, a South Korean group investigated a possible association between proton pump inhibitor (PPI) exposure and severity of covid-19 in a cohort of adults who tested positive for Sars-CoV-2.

The study included 132 316 patients (average age: 48 years) who had had a PCR test for Sars-CoV-2. 14 163 of these patients were taking a PPI at the time of testing, and 6242 had discontinued PPI therapy more than 30 days before testing (past users). The Sars-CoV-2 PCR test result was positive in 4785 (3.6%) of cases (1).

No association was found between current or past PPI use and the likelihood of a positive PCR test result. However, the risk of severe covid-19, defined using a composite endpoint comprising oxygen therapy, admission to an intensive care unit, invasive ventilation or death, appeared about 1.5 times higher in current PPI users (odds ratio 1.63; 95% confidence interval 1.03-2.53), while no such association was observed in past PPI users. These results took into account various risk factors known to be associated with severe covid-19, including age, diabetes, cardiovascular conditions, chronic obstructive pulmonary disease, hypertension, and chronic kidney disease, but not body mass index. Patients who had taken H2-receptor antagonists during the previous year or non-steroidal anti-inflammatory drugs (NSAIDs, which increase the risk of developing infections) during the previous month were excluded from the study (1).

PPI use is already known to increase the risk of developing various infections, such as pneumonia, pseudomembranous colitis, listeriosis and bacterial peritonitis (infection of ascitic fluid). Suggested mechanisms are direct effects on certain immune cells, and greater susceptibility to acquiring infection via the gastrointestinal tract due to the reduction in gastric acidity (2-5).

In practice. Although not robust, these results constitute a safety signal and one more reason not to trivialise PPI use, especially during the covid-19 epidemic. They also serve as a reminder that the risk of infection must be taken into account when weighing the expected benefits of PPIs against their harms, before recommending or prescribing these drugs.

©Prescrire 15 September 2020

Sources:

• "Inhibiteurs de la pompe à protons : risque plus grand de covid-19 grave" Application Prescrire 15 September 2020

1. Lee SW et al. "Severe clinical outcomes of Covid-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching" Gut 2020; http://dx.doi.org/10.1136/gutjnl-2020-322248. 
2. Prescrire Rédaction "Inhibiteurs de la pompe à protons : pneumopathies bactériennes" Rev Prescrire 2012; 32 (342): 269-271. 
3. Prescrire Rédaction "Inhibiteurs de la pompe à protons : infections à Clostridium difficile" Rev Prescrire 2013; 33 (356): 432-434. 
4. Prescrire Rédaction "Inhibiteurs de la pompe à protons : listérioses" Rev Prescrire 2017; 37 (410): 910. 
5. Prescrire Rédac-tion "Inhibiteurs de la pompe à protons: infections d’ascite" Rev Prescrire 2013; 33 (356): 429.

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