According to an online survey of more than 53,000 Americans using proton pump inhibitors (PPIs) or heartburn medications, once or twice daily use significantly increases the likelihood of a positive test for coronavirus disease 2019 (COVID-19).

The results of the large population-based, online survey were recently published in The American Journal of Gastroenterology. The authors explained that the goal of the survey was to assess any association between the use of PPIs and the risk of COVID-19.

“We developed this hypothesis at the beginning of the COVID-19 pandemic when we started to see a high incidence of [gastrointestinal] symptoms and learned that the virus sheds into saliva, and thus can be swallowed into the stomach. We have now tested the hypothesis in a rigorous study of more than 50,000 Americans and found it to bear out, albeit in an observational study,” said Christopher Almario, MD, MSHPM, of Cedars-Sinai in Los Angeles and co-author of the study, in a press release.

According to the researchers, PPIs have the potential to increase risk of enteric infections. They explained that this is connected to PPI-induced hypochlorhydria, which is low levels of gastric acid.

The authors noted that although the effects of acid suppression on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still unknown, prior data from severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) showed that pH ≤3 can impair the infectivity of the virus. For this reason, the authors pursued analyzing the use of PPIs in relation to the likelihood of acquiring COVID-19.

Of the 53,130 total participants in the online survey, 6.4% reported a positive COVID-19 test. In the regression analysis conducted by the researchers, patients using PPIs up to once daily (OR 2.15; 95% CI, 1.90–2.44) or twice daily (OR 3.67; 95% CI, 2.93–4.60) had a higher likelihood of reporting a positive COVID-19 test compared with those not taking PPIs. Additionally, the researchers found that the patients taking histamine-2 receptor antagonists (H2RAs) were not at an increased risk.

“There is a reason we have acid in our stomach, namely, to kill pathogens before they enter the digestive tract,” commented co-author Brennan Spiegel, MD, MSHS, FACG of Cedars-Sinai and co-editor-in chief of The American Journal of Gastroenterology, in a press release. “Coronaviruses are easily destroyed at a gastric pH of less than 3, but survive in a more neutral pH, including the range created by drugs like omeprazole and esomeprazole.”

Spiegel noted that they found a strong, independent effect of using PPIs on the increased likelihood of testing positive for COVID-19, including a dose-response relationship with nearly a 4 times increased risk for those taking PPIs twice daily. However, he noted they found no relationship between COVID-19 and H2RAs, such as famotidine or cimetidine.

“Previous research has already demonstrated that PPIs slightly increase the risk of enteric infections, but the strong link found here speaks to COVID-19 pathogenesis through the GI tract, where the expression of the receptors the virus uses to enter the body, known as ACE-2 receptors, is roughly 100-fold higher than in any other part of the body, including the lungs,” Spiegel said in a press release.

Although the data in this study had many important elements demonstrating the findings’ potential efficacy, the authors noted that further investigation would be needed to confirm the correlation between PPIs and COVID-19.

“The results of this large survey study, from an experienced team of clinicians and researchers, are intriguing and add novel, clinically relevant information to the rapidly evolving field of COVID-19 during this devastating pandemic,” said Brian Lacy, MD, PhD, FACG, co-editor-in-chief of The American Journal of Gastroenterology, in a press release. “However, as the authors carefully point out in their thoughtful analysis, this is not a randomized, placebo-controlled study, but rather a study demonstrating an association, and thus studies from other groups should be analyzed to confirm these novel findings.”

REFERENCE
Observational Study of More than 53,000 Americans Suggests an Association Between Proton Pump Inhibitors and Risk of COVID-19 [news release]. Bethesda, MD: The American Journal of Gastroenterology; July 7, 2020. Accessed July 8, 2020.