When compared with people not taking a PPI, individuals taking a PPI once daily were twice as likely to report testing positive for COVID-19, while for those on a twice daily dose of the medication that risk was nearly fourfold. “Proton pump inhibitors and infection risk is something that’s been linked for a long time, certainly in hospital safety work,” says Iahn Gonsenhauser, MD, chief quality and patient safety officer at The Ohio State University Wexner Medical Center in Columbus. Dr. Gonsenhauser was not involved with this research. “It’s compelling that not only did they find an association between PPIs and risk, but they found the relationship increased with the twice-daily users as opposed to the once-daily users,” says Gonsenhauser. “That suggests a higher likelihood that there’s a true connection and not just an association between these variables,” he says. For the study, researchers decided to look at the relationship between PPIs and COVID-19 due to the virus’s impact on the gut, says lead author Christopher V. Almario, MD, an assistant professor in residence and gastroenterologist at Cedars Sinai in Los Angeles, and lead author on the study. “The most serious issue that brings people to the hospital is the respiratory symptoms related to COVID-19, but we know it causes GI symptoms in about half the people,” says Dr. Almario. “Our stomach acid exists for a reason: It helps eliminate bacteria and viruses. Our thought was that because PPIs decrease acid in the stomach it could increase the likelihood of a person acquiring COVID-19,” he says. The study used data gathered from an online survey collected from May 3 to June 24, 2020. A total of 53,130 individuals were included from a nationwide, representative sample based on U.S. Census data on age, sex, and region of the country. The participants were 48 percent male, 51 percent female, and 1 percent people who preferred not to say. Subjects were 64.8 percent white, 8 percent Black, 15.3 percent Latino, 4.5 percent Asian, and 7.5 percent who didn’t identify in any of those groups or who preferred not to say. A total of 3,386 people (6.4 percent) reported a positive COVID-19 test. People who reported using a PPI once daily were 2.15 times more likely to report a positive test, and people taking the medication twice daily were 3.67 times more likely to have a positive test compared with people not taking a PPI. The study also examined people who reported taking H2 blockers, such as Tagamet and Pepcid, which are common medicines taken for GERD. “We didn’t see that same elevated risks with those medicines, which makes sense because those medications don’t reduce acid to the degree that PPIs do,” says Almario. It’s possible that people who take PPIs might have some of the other risk factors that increase the risk of developing COVID-19, says Almario. “In our study we tried to account for that by controlling for body mass index (BMI), age, race and ethnicity, other medical conditions, as well as socio-demographics, such as income and education level. The results still showed an independent increased risk in people taking PPIs for reporting COVID-19,” he says. Almario cautions against reading too much into the results. “This is an observational study; we found an association; we’re not definitively proving that PPIs increase the risk for COVID-19,” he says. Even so, there are factors that suggest that the PPIs are causing the increased risk, he says. “Because of the impact on stomach acid, it is biologically plausible, and we’re seeing a dose response. As you increase the dose of the PPI, and therefore increase the amount of acid suppression, we’re seeing an increased risk for reporting COVID-19,” he says. RELATED: Are Heartburn Drugs Safe?
PPIs and Increased Risk of Infection
Proton pump inhibitors are often prescribed for gastroesophageal reflux disease (GERD). They work by lowering stomach acid levels, thereby relieving many GERD symptoms, such as heartburn, chest pain, or regurgitation of food or sour liquid. The reason lowering stomach acid can affect infection risk is actually pretty simple, says Gonsenhauser. “Many people don’t realize that our digestive tract is one of the passive immune defenses that our body has. The normal stomach is highly acidic, which makes it difficult for things to live there,” he says. “When you reduce the acidity of the stomach by using a PPI, it’s a gentler environment,” he says. That makes it easier for things to live there — including things like viruses and bacteria, says Gonsenhauser. There’s been a lot of research about the association between infection risk and PPIs, says Gonsenhauser. A meta-analysis of observational studies published in Infection Control Hospital Epidemiology found that the risk of C. difficile infection (C. diff) was found to be higher in people on a PPI compared with those who weren’t taking the drug. The risk for community-acquired pneumonia (CAP), which is pneumonia found in people who have not been in the hospital or another healthcare facility, such as a nursing home or rehab facility, is also higher for people taking PPIs. A meta-analysis published in June 2015 in the journal PLos One found that PPI use was associated with a greater risk of CAP and a greater risk of hospitalization due to CAP.
Should People Who Are Taking a PPI Talk to Their Doctor?
This is still an early study, and further investigation is required before treatment practices change significantly, agrees Gonsenhauser. “The practice of twice-daily PPIs is certainly one to question though, especially if you’re in a group that’s at greater risk for having a severe case of COVID-19, but really for anybody,” he says. We’re not telling anyone to stop taking their PPI right now because of these findings, says Almario. “I’m a gastroenterologist, and I’m still prescribing PPIs, but only when it’s appropriate, and there’s a real clinical indication to do so,” he says. But the findings could be a good opportunity for people on PPIs to have a discussion with their doctor about the necessity of taking the drug.
