Recently, a study based on a population-based online survey showed that daily use of proton pump inhibitors (PPIs) was associated with increased odds of testing positive for COVID-19. In addition, the study, to be published in an upcoming release of the American Journal of Gastroenterology, showed that the risk was higher among those who took PPIs twice per day than in those who took PPIs just once daily.
The survey, conducted from May to June of 2020, was emailed to a total of 264,058 adults in the U.S. Of the 86,602 eligible respondents who completed the survey, 53,130 (61.3%) reported having acid reflux and similar symptoms and were further questioned about their use of antisecretory medications, such as PPIs and histamine 2-receptor antagonists (H2RAs). Among these, 3,386 (6.4%) reported having a positive COVID-19 test, and of these, 71.9% reported daily or less use of PPIs, with 5.8% reporting twice-daily use.
In regression analysis, individuals using PPIs up to once daily or twice daily had significantly increased odds for reporting a positive COVID-19 test when compared to those not taking PPIs. This led the authors of the study to conclude that there was evidence of an independent, dose-response relationship between the use of PPIs and COVID-19 positivity.
The authors indicated that the study did have its limitations, since the survey was observational in nature and susceptible to residual confounding. Severely ill COVID-19 patients were not likely to have taken the survey and some respondents may have started a PPI in response to certain COVID-19 symptoms, such as nausea and abdominal pain, or to ease the adverse effects of related treatments, such as nonsteroidal anti-inflammatory drugs, for fever.
Proton pump inhibitors are among the most widely used medications in the U.S. and have been linked to several serious adverse effects, such as bone fracture and chronic kidney disease. There is no evidence to suggest that twice-daily use of PPIs offers clinically meaningful benefits over once-daily dosing for gastroesophageal reflux disease.
Recent trials demonstrated that once-daily PPI use also increased the odds for enteric infection, most likely due to drug-induced hypochlorhydria. Prior research found that the closely related SARS-CoV-1 virus was inactivated in the presence of an acidic gastrointestinal environment and, conversely, survived in the more pH neutral environment created by PPIs.
Because SARS-CoV-1 utilizes the angiotensin converting enzyme 2 (ACE2) receptor to invade and replicate within enterocytes, a more neutral pH environment might allow it to gain entry more easily, leading to systemic spread to other organs, including the lungs.
Interestingly, individuals taking H2RAs such as Pepcid (famotidine) and Tagamet (cimetidine) were not at elevated risk. This is of particular importance to dentistry, as research has implicated that the regular use of PPIs also negatively affects the osseointegration of dental implants, while the use of H2RAs seemingly does not.
Ironically, Pepcid is the focus of a study currently being conducted by Northwell Health in New York City for its potential for reducing the severity of COVID-19 symptoms. The study was prompted by early observations that poorer Chinese patients with COVID-19 tended to have better survival rates than wealthier patients. They were also more likely to be taking the less expensive famotidine for heartburn than the more expensive omeprazole. In a rough analysis of the data, the hospitalized patients on famotidine had about half the mortality rate of patients not on the drug, although the difference was not statistically significant.
I talk about connection between PPIs and dental implants in the podcast below with DrBicuspid.com Editor-in-Chief Kevin Henry.
- Almario CV, Chey WD, Spiegel B. Increased risk of COVID-19 among users of proton pump inhibitors. Am J Gastroenterol. July 7, 2020 (preprint).
- Borrell B. New York clinical trial quietly tests heartburn remedy against coronavirus. Science. April 26, 2020. doi:10.1126/science.abc4739.
Tom Viola, RPh, is a clinical educator, professional speaker, and published author in the areas of oral pharmacology and local anesthesia. For more information on this and other pharmacology topics, as well as a list of dates and locations where you can attend his latest seminars, visit his website at www.tomviola.com.
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