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Table of Contents
Year : 2020  |  Volume : 12  |  Issue : 2  |  Page : 31-32

COVID-19 and proton pump inhibitor use: Imperative for caution in prescription

Department of Medicine, University of Nigeria Teaching Hospital, Enugu, Nigeria

Date of Submission16-Nov-2020
Date of Decision18-Nov-2020
Date of Acceptance19-Nov-2020
Date of Web Publication10-Dec-2020

Correspondence Address:
Prof. Sylvester Chuks Nwokediuko
Department of Medicine, University of Nigeria Teaching Hospital, Ituku/Ozalla, PMB 01129, Enugu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2251-0079.302903

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How to cite this article:
Nwokediuko SC. COVID-19 and proton pump inhibitor use: Imperative for caution in prescription. Niger J Gastroenterol Hepatol 2020;12:31-2

How to cite this URL:
Nwokediuko SC. COVID-19 and proton pump inhibitor use: Imperative for caution in prescription. Niger J Gastroenterol Hepatol [serial online] 2020 [cited 2023 Mar 21];12:31-2. Available from: https://www.njghonweb.org/text.asp?2020/12/2/31/302903

As the COVID-19 pandemic continues to ravage the global community, the time to be more cautious in the use of proton pump inhibitors (PPIs) is now.

The human stomach is structurally fortified and functionally versatile. One intriguing function performed by this organ is the production of concentrated hydrochloric acid by the parietal cells of the gastric mucosa. The acid provides protection against microbes that may enter the stomach through food and drinks and, in this way, represents an important aspect of the innate host immunity. The acid also helps in digestion and absorption of nutrients and minerals such as protein, iron, calcium, and Vitamin B12. While performing these functions, the mucosa of the upper gastrointestinal tract is also exposed to the noxious effect of this acid to the extent that various acid-related diseases such as gastroduodenal ulcers, gastroesophageal reflux disease (GERD), Barrett's esophagus, and functional dyspepsia can occur.

PPIs joined the arsenal of management of acid-related diseases in 1988. These drugs target the enzyme H+ K+ ATPase that catalyzes the last step in gastric acid secretion, regardless of whether the stimulus responsible is histamine, acetylcholine, gastrin, or any other mediator. PPIs are among the most commonly prescribed drugs in medical practice globally. A significant proportion of patients seen in any gastroenterology service receive a PPI. The most common uses include treatment of dyspepsia, peptic ulcer disease, eradication of Helicobacter pylori, GERD, eosinophilic esophagitis, and prophylaxis against drug-induced gastropathy. Other uses of PPI include treatment of hypersecretory states such as Zollinger Ellison syndrome and prevention of stress-induced ulcers in critically ill patients. PPIs were adjudged to be highly efficacious, well tolerated, and safe; however, over time, several observational studies raised safety issues concerning long-term use of these drugs.

Among the issues raised are those related to acid suppression, such as gastrointestinal infections, changes in gut microbiome, small intestinal bacterial overgrowth, and spontaneous bacterial peritonitis.[1] One study showed that PPI use at a once-daily dose increased the odds for intestinal infection by 33%.[2] Several meta-analyses have also revealed that PPI use increases the risk of both intestinal infections and small bowel bacterial overgrowth.[3],[4],[5] These results can be explained by the acid-suppressive action of PPI, which in turn interferes with the innate immunity against bacteria and viruses. Disturbance of gut microbiota is another possible consequence of chronic PPI use.[6],[7]

It is now believed that SARS-CoV-2, the virus that causes COVID-19, can enter the body through the gastrointestinal tract,[8],[9] using angiotensin-converting enzyme-2 receptor, which is amply expressed throughout the intestine[10] and consequently invades and replicates within the intestinal cells.[11] By suppressing gastric acid secretion, PPIs may weaken the gastric mucosal barrier to SARS-CoV-2, induce a disturbance of gut microbiota, and cause increased gastrointestinal infections. The concern that emanates from this is that PPIs might also increase the risk of COVID-19. In support of this, thinking is a very recent countrywide study published in the American Journal of Gastroenterology[12] which demonstrated that individuals taking PPI at a twice-daily dose had higher odds for reporting a positive test for COVID-19 compared with individuals who took lower doses or H2-receptor antagonists.

A very important take-home message from the foregoing is the need to be more cautious and judicious in the use of PPIs. They should only be used when indicated and at the lowest effective dose.

  References Top

Kinoshita Y, Ishimura N, Ishihara S. Advantages and disadvantages of long-term proton pump inhibitor use. J Neurogastroenterol Motil 2018;24:182-96.  Back to cited text no. 1
Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O, et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology 2019;157:682-91.e2.  Back to cited text no. 2
Bavishi C, Dupont HL. Systematic review: The use of proton pump inhibitors and increased susceptibility to enteric infection. Aliment Pharmacol Ther 2011;34:1269-81.  Back to cited text no. 3
Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol 2007;102:2047-56.  Back to cited text no. 4
Lo WK, Chan WW. Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: A meta-analysis. Clin Gastroenterol Hepatol 2013;11:483-90.  Back to cited text no. 5
Kanno T, Matsuki T, Oka M, Utsunomiya H, Inada K, Magari H, et al. Gastric acid reduction leads to an alteration in lower intestinal microflora. Biochem Biophys Res Commun 2009;381:666-70.  Back to cited text no. 6
Seto CT, Jeraldo P, Orenstein R, Chia N, DiBaise JK. Prolonged use of a proton pump inhibitor reduces microbial diversity: Implications for Clostridium difficile susceptibility. Microbiome 2014;2:42.  Back to cited text no. 7
Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology 2020;158:1831-3.e3.  Back to cited text no. 8
Trottein F, Sokol H. Potential causes and consequences of gastrointestinal disorders during a SARS-CoV-2 Infection. Cell Rep 2020;32:107915.  Back to cited text no. 9
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004;203:631-7.  Back to cited text no. 10
Lamers MM, Beumer J, van der Vaart J, Knoops K, Puschhof J, Breugem TI, et al. SARS-CoV-2 productively infects human gut enterocytes. Science 2020;369:50-4.  Back to cited text no. 11
Almario CV, Chey WD, Spiegel BM. Increased risk of COVID-19 among users of proton pump inhibitors. Am J Gastroenterol 2020;115:1707-15.  Back to cited text no. 12


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