PPI and COVID-19
PPIs are medicines that are primarily used to suppress gastric acid production. Examples of PPIs include dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole. PPIs can be very useful in treating acid-related symptoms such as acid reflux, heartburn, and dyspepsia, and to treat and protect from acid-related complications such as reflux oesophagitis and peptic ulcers.
Stomach acid helps to keep the digestive system free of infections by killing swallowed viruses and bacteria that might be in saliva or in food (2). Many viruses are sensitive to low gastric pH, and hence theoretically, hypochlorhydria induced by PPI agents can increase the risk of viral infections (15). It has already been established that PPIs can increase the risk for enteric diseases such as food poisoning, traveller’s diarrhoea and Clostridium diffcile infections (4, 5). Similarly, PPIs may also increase the risk of community-acquired pneumonia (16-18).
Earlier studies have shown that stomach acid can kill coronaviruses (19). Coronaviruses shed into saliva. SARS-CoV-2 uses the angiotensin-converting enzyme–2 receptor to invade enterocytes (10). Therefore, the virus can rapidly invade and replicate within cells lining the intestinal tract (10, 20). As stomach acid can be protective against the acquisition of coronavirus, PPIs induced hypochlorhydria may facilitate an environment in which coronavirus may thrive. As a result of the use of PPIs, the stomach pH will increase above 3. This rise in the gastric pH might allow the virus to enter the GI tract more efficiently, leading to enteritis, colitis, and systemic spread to other organs, including the lungs. Therefore, there is a theoretical concern that the use of PPIs could diminish or abolish the neutralising effects of gastric acid on SARS-CoV-2, which could potentially increase the risk of GI manifestations and severity in COVID-19.
In a recently published extensive, nationwide survey of over 53,000 Americans, PPI use was independently associated with increased odds for COVID-19, compared to those not using PPIs (11). Moreover, there was a dose-response relationship between PPI use and the risk of COVID-19.
After adjusting for confounding factors (age, sex, race/ethnicity, education, marital status, household income, body mass index, smoking, alcohol consumption, US region, insurance status, and the GI diseases, diabetes, and HIV/AIDS), the highest risk was seen among those taking PPIs twice a day. This group had almost 4-times the odds of being positive for COVID-19 when compared to people not using PPIs [odds ratio (OR) 3.67; 95% CI, 2.93 – 4.60]. Those taking PPIs up to once a day were twice as likely to have had a positive COVID-19 test result than those who did not take the drugs (OR 2.15; 95% CI, 1.90 – 2.44). The risk of PPIs remained significant regardless of the duration of use, including those who had been on PPIs for six months or greater, before the start of the pandemic (11).
In contrast, the use of the less powerful H2RAs was not associated with an increased risk for COVID-19. The use of lower-dose H2RAs was associated with 15% decreased odds of reporting a positive test, while no association was seen for the higher dose of H2RAs.
Importantly, this study was not a randomised, controlled trial; it does not definitively prove that PPIs increase the risk for COVID-19. Future research is needed to confirm the findings in this new study.
Contrarily to the findings of the above study by Almario et al., a recent survey of a Korean nationwide cohort with propensity score matching, revealed PPI usage, including current and past use, did not increase susceptibility to SARS-CoV-2 infection (12). However, current PPI usage was associated with worse outcomes of COVID-19. The ongoing short-term use of PPIs (<1 month) conferred a 90% increased risk of worse clinical outcomes of COVID-19. These findings continue to highlight the potential risk of continued PPI use in the setting of COVID-19 infection.