COVID-19 & Proton Pump Inhibitors (PPI): Are they Friends or Foes?

Here are some of the issues with COVID-19 patients when they are hospitalized. First, they receive high doses of corticosteroids which have an association to GI bleeds. Second, they are (in some institutions) receiving full-dose anticoagulation with heparin, enoxaparin, or a DOAC. This has led many to just go ahead and pull the trigger on starting GI prophylaxis to avoid causing peptic ulcer disease and upper GI bleeds in these already sick patients. As a solution to mitigate this problem, and appropriately so, many clinicians have started patients on proton pump inhibitors (PPI) such as omeprazole, pantoprazole and their other cousins to avoid the incidence of GI bleeds. But what if a PPI is actually doing more harm than good in COVID-19 patients? Let’s review the literature and see if we can tease out the answer to this question.

To move forward with this relative-new disease process, we need to look back at our history. Almario et al. published a paper in December of 2020 stating that a pH of less than or equal to 3 in the stomach did not inactivate acute respiratory syndrome coronavirus 1. A normal pH, however, does inactivate acute respiratory syndrome coronavirus 1. The reason why we care is that although the main place where we contract the SARS-CoV-2 is through the respiratory mucosa, we also can get it through the GI tract.

It getting into the body through the GI tract explains why people have GI symptoms like “gastritis, enteritis, and colitis”. This occurs through the angiotensin-converting enzyme-2 receptor. This also explains why SARS-CoV-2 has been found in stool. In the Almario study which took place in the outpatient setting, they found that patients who were taking PPI had increased odds reporting being positive for COVID-19. They did find that patients on H2 blockers did not have this risk. If the patient was taking PPIs once a day, their odds of catching COVID are higher than the general population and even higher if taking PPIs twice a day ((aOR 2.15; 95% CI, 1.90–2.44) and (aOR 3.67; 95% CI, 2.93–4.60) respectively). They states their limitations to their findings that “this study does not offer evidence of causation in the absence of a prospective trial and should be further investigated in different populations and settings”.

Hariyanto et al. wrote in December 2020 that “the use of proton pump inhibitors (PPI) seems to be associated with an enhanced risk of severity and mortality from COVID-19 infection”. The reasons for this include:

  • “profound hypochlorhydria can diminish the protective effect of gastric acid” and “increase in gastric microbiota and small intestinal bacterial overgrowth”
  • “the fecal-oral route has been raised as one of the potential modes of transmission for COVID-19”
  • “suppression of gastric acid may increase the survival of SARS-CoV-2 in the stomach and increase the ability of the virus to invade the GI epithelial cells”
  • “can increase the viral load which in turn results in a higher chance of developing cytokine storm and severe outcome of the disease”

Due to this rationale, coupled with meta-analysis using retrospective and case-control data aimed at looking at severity and mortality, the authors were able conclude that when it comes to both severe disease and mortality, the use of PPI increases the risk of these two.

Adding to the body of evidence, Lee et al. published a Korean nationwide cohort study with propensity matching in January of 2021 looking at the relationship between PPIs and COVID-19. Unlike the the Almario study where they found that patients on PPIs were at greater risk of catching COVID-19, this population did not have that problem. The problem they did have, however, was in patients who had been on PPIs for less than 30 days and they contracted COVID. Here, being on PPIs for less than 30 days increased the odds of their composite endpoint of “admission to the intensive care unit, invasive ventilation or death” by 90% (OR 1.90 (1.46 to 2.77)).

To wrap it all up and put their nail in the coffin, Li et al. conducted a meta-analysis that should be published next month where they looked at how a PPI can affect outcomes in COVID-19 patients. When it comes to patients who have chronic or regular use of PPIs there is a 67% increased odds of severe outcomes. There was also a trend (not statistically significant) for these patients to stay in the hospital longer.

My personal take on this is that if a patient needs “GI prophylaxis” which is debatable in the first place, then we should not be using a PPI in COVID-19 patients but rather using H2 blockers instead. If a patient has been on a PPI and they are admitted with COVID-19, then it’s likely safe to continue it. Then again, that’s not medical advice and you should read the cited papers below. For more content on COVID-19 click HERE. Let me know what you think.

Citations looking at PPI and COVID-19

Almario CV, Chey WD, Spiegel BMR. Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors. Am J Gastroenterol. 2020 Oct;115(10):1707-1715. doi: 10.14309/ajg.0000000000000798. PMID: 32852340; PMCID: PMC7473791.
Link to Article

Hariyanto TI, Prasetya IB, Kurniawan A. Proton pump inhibitor use is associated with increased risk of severity and mortality from coronavirus disease 2019 (COVID-19) infection. Dig Liver Dis. 2020 Dec;52(12):1410-1412. doi: 10.1016/j.dld.2020.10.001. Epub 2020 Oct 6. PMID: 33092998; PMCID: PMC7538064.
Link to Article

Lee SW, Ha EK, Yeniova AÖ, Moon SY, Kim SY, Koh HY, Yang JM, Jeong SJ, Moon SJ, Cho JY, Yoo IK, Yon DK. Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching. Gut. 2021 Jan;70(1):76-84. doi: 10.1136/gutjnl-2020-322248. Epub 2020 Jul 30. PMID: 32732368.
Link to Article

Li GF, An XX, Yu Y, Jiao LR, Canarutto D, Yu G, Wang G, Wu DN, Xiao Y. Do proton pump inhibitors influence SARS-CoV-2 related outcomes? A meta-analysis. Gut. 2021 Sep;70(9):1806-1808. doi: 10.1136/gutjnl-2020-323366. Epub 2020 Nov 10. PMID: 33172925.
Link to Article

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