Updated November 2020. 

A recent study  pre-published by the American Journal of Gastroenterology has identified a connection between the use of Proton Pump Inhibitors (PPIs) and the risk of COVID-19 infections. The risk of contracting the infection appears to increase with the PPI dose. Here we describe how a pharmacogenetic test can help your prescriber identify the optimal Tecta dose to reduce your long-term health risks, including the risk of contracting COVID-19.

PPIs are the most prescribed medications in North America. They are prescribed for excess stomach acid-related problems, to prevent and treat ulcers in the stomach and for heartburn or gastroesophageal reflux disease (GERD). Commonly used PPIs include Aciphex, Nexium, Prevacid, Prilosec, Protonix and Tecta. PPIs are generally considered a success story – safe and effective medications that target the source of gastrointestinal distress. However, there have been some concerns about overuse and side effects of these medications.

The gastric acid in the stomach, besides contributing to digestion, facilitates iron and vitamin B12 absorption and also acts as a defence against bacteria and viruses. Studies show that once-daily PPI use increases the chance for intestinal infection by 33%, probably due to low levels of stomach acid, which impairs the body’s initial defense against ingested bacteria and viruses.

A study led by Dr. Brennan Spiegel (Cedars-Sinai Medical Center) looked into the possibility that a reduction in stomach acid from PPI use might allow SARS-CoV-2 to gain entry into the cells of the intestinal lining more easily, leading to a systemic spread to other organs, including the lungs.  Did PPI usage increase the risk of acquiring COVID-19?

Higher PPI dose is linked to increased risk of COVID-19

To test the hypothesis, the authors surveyed over 86,000 people. 53,000 of the survey respondents used PPIs, of which 3,300 had tested positive for COVID-19. PPI use was found to be associated with increased odds of reporting a COVID-19 positive test, even after adjusting for a wide range of sociodemographic, lifestyle, and clinical variables. Analyses indicated that people using PPIs, like Tecta, had two- to four times the risk of contracting COVID-19, compared to people not using these medications. The highest risk was observed in individuals taking PPIs twice daily, a common practice in primary and secondary care, resulting in a four times likelihood of reporting COVID-19 positivity when compared to those who did not use PPIs. This does not mean that PPIs like Tecta or similar medications should be immediately discontinued due to fear of contracting COVID-19.

Pharmacogenetic test to guide PPI dose

Studies have emphasized that PPIs should only be used when clinically indicated at the lowest effective dose. Advances in personalized medicine have shown that an ‘effective dose’ can mean different doses for different people. The concentrations of Tecta and other PPIs in an individual’s system is determined by variations in their DNA. Variations in the CYP2C19  gene, which encodes a liver enzyme responsible for PPI processing, can be used to guide PPI dosage.

People who have inherently reduced CYP2C19 function will have reduced clearance of PPIs like Tecta. These individuals should be prescribed lower doses of PPIs to reduce the risk of long-term PPI complications. People with higher CYP2C19 levels, called Rapid Metabolizers, will rapidly process and clear the medication from their bodies. This results in an insufficient concentration of the drug. They suffer from heartburn and ulcers even while taking medication at the regular dose. Clinical guidelines (CPIC) are available to advise on increasing or decreasing an individual’s PPI dose depending on the function of their liver enzyme.

Pharmacogenetic tests like Pillcheck can help assess how your body will process PPIs like Tecta. Pillcheck can help your doctor identify the right dose of PPIs for you. It can also guide the selection of blood pressure medications and statins, which have also been shown to play a role in the severity of COVID-19 disease.

While wearing masks in public places and washing your hands frequently remain the most important protection against COVID-19, personalizing the dose of chronic medications such as PPIs, blood pressure medications and statins is also important for your health.

If you take medications for several chronic conditions besides Tecta for your heartburn, consider taking the Pillcheck pharmacogenetic test to assess how your body metabolizes not just PPIs but also other commonly prescribed medications. The Pillcheck report can help your doctor adjust your treatment to reduce the risk of long-term side effects.

Summary

• Chronic use of PPIs is linked to a higher risk of contracting COVID-19 in a dose-dependent manner.
• Response to PPIs and the risk of long-term side effects is directly related to your genetics
• Pillcheck examines how your body metabolizes Tecta and other PPIs and helps select the optimal drug dose.
• The personalized treatment plan can reduce your risks of long-term side effects.
• Continue to take personal protection measures to reduce your risk of contracting COVID-19.

November 2020 Update

Two recent analyses confirmed the original findings:

• Regular use of PPIs was associated with a higher risk of becoming infected with the SARS-CoV-2 virus.
• PPI users had a 46%-67% higher risk of experiencing severe COVID-19 disease, including intensive care unit admission or death, compared with people who did not use these medications.
• PPI users also had a three times higher risk of developing secondary lung infections
• As a result of these studies, some doctors recommend patients who take PPIs to taper off these medications when they no longer have a compelling indication to continue them.

References

https://journals.lww.com/ajg/Documents/AJG-20-1811_R1(PUBLISH%20AS%20WEBPART).pdf

Moayyedi P et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology 2019;157:682-691.e2

Tetsuhide Ito and Robert T. Jensen Association of Long-term Proton Pump Inhibitor Therapy with Bone Fractures and effects on Absorption of Calcium, Vitamin B12, Iron, and Magnesium Curr Gastroenterol Rep. 2010 Dec; 12(6): 448–457.

Joo MK, Park JJ, Chun HJ. Proton pump inhibitor: The dual role in gastric cancer. World J Gastroenterol 2019; 25(17): 2058-2070

Li WQ et al., Effects of Helicobacter pylori treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial. BMJ. 2019 Sep 11;366:l5016. doi: 10.1136/bmj.l5016.

Ghebremariam YT et al., An Unexpected Effect of Proton Pump Inhibitors: Elevation of the Cardiovascular Risk Factor ADMA. Circulation. 2013 Aug 20; 128(8): 10.1161/CIRCULATIONAHA.113.003602.

Li G-F et al. Do proton pump inhibitors influence SARS-CoV-2 related outcomes? A meta-analysis. Gut 2020 Nov 10; [e-pub].

Kow CS and Hasan SS. Use of proton pump inhibitors and risk of adverse clinical outcomes from COVID-19: A meta-analysis. J Intern Med 2020 Oct 20; [e-pub].