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. 2020 Oct;115(10):1707-1715.
doi: 10.14309/ajg.0000000000000798.

Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors

Christopher V Almario  1   2   3   4   5 , William D Chey  6   7 , Brennan M R Spiegel  1   2   3   4   8
Affiliations

Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors

Christopher V Almario et al. Am J Gastroenterol. 2020 Oct.

Abstract

Introduction: Proton pump inhibitors (PPIs) increase the risk for enteric infections that is likely related to PPI-induced hypochlorhydria. Although the impact of acid suppression on severe acute respiratory syndrome coronavirus 2 is unknown thus far, previous data revealed that pH ≤3 impairs the infectivity of the similar severe acute respiratory syndrome coronavirus 1. Thus, we aimed to determine whether use of PPIs increases the odds for acquiring coronavirus disease 2019 (COVID-19) among community-dwelling Americans.

Methods: From May 3 to June 24, 2020, we performed an online survey described to participating adults as a "national health survey." A multivariable logistic regression was performed on reporting a positive COVID-19 test to adjust for a wide range of confounding factors and to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).

Results: Of 53,130 participants, 3,386 (6.4%) reported a positive COVID-19 test. In regression analysis, individuals using PPIs up to once daily (aOR 2.15; 95% CI, 1.90-2.44) or twice daily (aOR 3.67; 95% CI, 2.93-4.60) had significantly increased odds for reporting a positive COVID-19 test when compared with those not taking PPIs. Individuals taking histamine-2 receptor antagonists were not at elevated risk.

Discussion: We found evidence of an independent, dose-response relationship between the use of antisecretory medications and COVID-19 positivity; individuals taking PPIs twice daily have higher odds for reporting a positive test when compared with those using lower-dose PPIs up to once daily, and those taking the less potent histamine-2 receptor antagonists are not at increased risk. These findings emphasize good clinical practice that PPIs should only be used when indicated at the lowest effective dose, such as the approved once-daily label dosage of over-the-counter and prescription PPIs. Further studies examining the association between PPIs and COVID-19 are needed.

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Conflict of interest statement

Guarantor of the article: Brennan M.R. Spiegel, MD, MSHS.

Specific author contributions: C.V.A.; W.D.C.; B.M.R.S.: substantial contributions to the conception and design of the work; acquisition, analysis, and interpretation of data for the work; drafting the work and revising it critically for important intellectual content; final approval of the version to be published.

Financial support: The data used in this analysis were derived from a larger study evaluating gastrointestinal symptoms in America funded by a grant from Ironwood Pharmaceuticals. In response to the COVID-19 pandemic and before launching the parent study, we added additional questions regarding self-reported COVID-19 testing and related symptoms. Separate funding was not received for the analyses presented in this report. The Cedars-Sinai Center for Outcomes Research and Education (CS-CORE) is supported by The Marc and Sheri Rapaport Fund for Digital Health Sciences & Precision Health. C.V.A. and B.M.R.S. are supported by a National Institutes of Health/National Center for Advancing Translational Science UCLA Clinical and Translational Science Institute (CTSI) grant (UL1TR001881).

Potential competing interests: C.V.A. has a stock option grant in My Total Health, has served on advisory boards for Bayer Healthcare and Synergy Pharmaceuticals, has served as a consultant for Alnylam Pharmaceuticals and Arena Pharmaceuticals, and received a one-time speaker's fee from Takeda Pharmaceuticals. After the paper was accepted for publication, C.V.A. served on an advisory board for Phathom Pharmaceuticals. W.D.C. has served as a consultant for Ironwood Pharmaceuticals, Phathom Pharmaceuticals, RedHill Biopharma Ltd., and Takeda Pharmaceuticals. B.M.R.S. has served on advisory boards for Allergan Inc, Alnylam Pharmaceuticals, Arena Pharmaceuticals, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Synergy Pharmaceuticals, and Takeda Pharmaceuticals. B.M.R.S. served as a judge for a digital health competition held by Eli Lilly and Company, and has received research funding to his institution from Alnylam Pharmaceuticals, Ironwood Pharmaceuticals, Pfizer, Shire Pharmaceuticals, and Takeda Pharmaceuticals.

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References

    1. Vaezi MF, Yang YX, Howden CW. Complications of proton pump inhibitor therapy. Gastroenterology 2017;153:35–48. - PubMed
    1. Moayyedi P, Eikelboom JW, Bosch J, 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. - PubMed
    1. 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. - PubMed
    1. 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; quiz 2057. - PubMed
    1. 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. - PubMed

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