Taking a common form of heartburn medication may moderately raise the risk of contracting COVID-19, according to a new study.

Based on an online survey of more than 86,600 people, more than 3,300 of whom caught COVID-19, the results suggest that those who take proton pump inhibitors (PPIs) may be about 2.2 to 3.7 times more likely to catch the virus than those who don’t take that type of heartburn medication. The report was published July 7 in The American Journal of Gastroenterology.

But before you toss your prescription, know that the survey cannot establish cause-and-effect; it only highlights a potential link between PPIs and your chance of catching COVID-19. To show that PPIs actually increase your odds of getting COVID-19, doctors would need to examine the medical records of patients with verified positive COVID-19 test results to see if disproportionately high numbers use the drugs, and to rule out that those patients don’t share other characteristics that may also raise infection risk, experts told Live Science.

“By no means do we say that people need to stop their PPIs,” said study author Dr. Christopher Almario, a gastroenterologist and assistant professor of medicine at Cedars-Sinai, nonprofit academic health care organization in Los Angeles. “We found an association here; again, this needs to be confirmed.” Many U.S. residents take PPIs for severe acid reflux, heartburn or peptic ulcers, and these people should not lower their dose or switch medications without first consulting a health care provider, Almario added. 

“The last thing you want to do is create panic for unnecessary reasons,” said Dr. Dhyanesh Arvind Patel, a gastroenterologist and assistant professor of Medicine at Vanderbilt University in Nashville, Tennessee, who was not involved in the study.

“My sense would be that there are a lot of unmeasured confounders” in the survey results, meaning that some unknown factor shared among PPI users, but unrelated to their medication, may have elevated their risk of infection, he said.

Stomach acid as an immune defence  

PPIs reduce the amount of acid released into the stomach by permanently blocking proton pumps, which are proteins that spew out positively charged molecules out of stomach cells. The drugs wear off as the blocked proton pumps get replaced by new ones, since both stomach cells and the pumps on their surfaces get replaced continuously, Almario said.

A single dose of PPIs can inhibit acid production by about 90% for 24 hours, according to the textbook “Medical Pharmacology and Therapeutics” (Elsevier Ltd., 2018). Practically, this means that PPIs can maintain the stomach around a pH level of 6, when it usually dips to a pH 3 after we eat, Almario said. (The pH scale ranges from 0 to 14, with 0 being the most acidic and 14 being the least acidic — or most alkaline. A pH of 6 is 1000 times less acidic than a pH of 3.) 

“These medications have been game-changing” for treating people with gastroesophageal reflux disease (GERD) and peptic ulcers, Patel said. But while reducing stomach acid can be beneficial, it may also leave the intestines vulnerable to some infections. 

For example, taking PPIs once a day may increase the risk of contracting Clostridium difficile infection, according to a 2019 report in the journal Gastroenterology. Acids with a pH level of 3 or lower can kill the bacteria, and thus guard the intestines from harm. Similarly, acids of pH 3 or lower hinder the ability of the SARS coronavirus, which causes severe acute respiratory syndrome, to infect cells in a petri dish, according to a 2004 report published in The Journal of Virological Methods. The SARS coronavirus, or SARS-CoV, was responsible for an outbreak in 2002-2003.

“We’re learning that COVID-19 can infect the GI system,” Almario said. Given previous findings about the related coronavirus SARS-CoV, “Could decreasing the acid in the stomach, could that increase the odds of catching COVID?”

A huge grain of salt 

The question led Almario and his colleagues to conduct their survey, in which participants were asked about their history of gastrointestinal conditions and whether they were taking a PPI or a less powerful heartburn medication, called a histamine 2 (H2) blocker, which block receptors for the compound histamine, one of several substances that trigger stomach acid production.. 

The survey participants were also asked whether they had been tested for COVID-19, and if so, whether they tested positive and what symptoms they experienced. People who began taking a heartburn medication after being diagnosed with COVID-19 were classified as “non-users,” since the treatment would not have affected their chances of catching the virus. 

The authors found that people who took PPIs were more likely to test positive for COVID-19 than both those who took H2 blockers and those who took no heartburn medications. In addition, people who took two doses of PPIs daily were more likely to test positive than those who only took one.

“The takeaway is that PPI use, particularly the common but non-approved twice-daily dose, may increase risk of #COVID19,” author Dr. Brennan Spiegel, Director of Health Services Research for Cedars-Sinai Health System and Professor of Medicine and Public Health at the University of California, Los Angeles, tweeted on July 7. “Always worth considering whether twice-daily is needed, particularly for those especially vulnerable to severe disease,” such as elderly people or those with existing medical conditions.

That said, the survey results might not be representative of all patients who take PPIs, Patel said. “If you look at the demographics of the patient populations … it’s a highly unbalanced cohort,” he noted.

Roughly 86% of people who tested positive for COVID-19 in the study were 39 years old or younger, which does not reflect the distribution of COVID-19 infections in the population as a whole. There’s no clear explanation for why PPI use would make younger people at higher risk of infection than older, which hints that some confounding factor skewed the results, he said. Also odd is that very few of those younger patients reported being diagnosed with GERD, which is the main reason younger adults take PPIs, he said. This could reflect that people did not fill out the survey accurately, but “you can’t verify any of this information,” he noted. 

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In addition, the survey did not suggest that PPI use was associated with an increased risk of severe gastrointestinal symptoms among people who caught COVID-19, which might also be expected if PPIs allowed the virus to infect the intestines more easily, Patel noted. PPIs wouldn’t be expected to ease the GI symptoms associated with COVID-19, which include vomiting, nausea and diarrhea.

To confirm the potential link between PPIs and COVID-19 risk, Patel said that researchers would need to collect data in a hospital or doctor’s office where confounding factors could be better controlled. For example, doctors could track whether COVID-19 patients taking PPIs experience severe gastrointestinal symptoms, get hospitalized, require oxygen supplementation or die from the virus more often than those who do not take the medications. If those trends prove true, the follow-up question would be whether PPIs can be linked to more severe respiratory symptoms, as well, as the virus primarily attacks the respiratory system, he added.

Thoughts from other esophageal/GI docs? Does this study change your clinical practice?@AllonKahn @KristleLynchMD @WalterChanMD @RishiNaikMD @MTPapaD @AfrinKamalMD @JPandolfinoMD @ZubairMalik_MD @DJodorkovskyMD @JHorsleySilvaMD @BaldeepPablaMD#MedEd #GITwitterJuly 8, 2020

Roughly 1 in 10 people in the U.S. use a PPI, Patel said. Both he and Almario noted that, regardless of their link to COVID-19, PPIs should be taken at the lowest possible dose to achieve a therapeutic effect, with the fewest side effects. For people taking two PPIs a day, they both recommended checking with a health care provider about potentially switching to one dose a day, or a weaker H2 blocker, especially if their symptoms are under control.

“That’s just a good practice, not because of the study,” Patel said.

Originally published on Live Science. 

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