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Proton-pump inhibitor use is not associated with severe COVID-19-related outcomes: a propensity score-weighted analysis of a national veteran cohort
  1. Shailja Shah1,2,
  2. Alese Halvorson3,
  3. Brandon McBay4,
  4. Chad Dorn5,
  5. Otis Wilson6,7,
  6. Sony Tuteja8,9,
  7. Kyong-Mi Chang8,9,
  8. Kelly Cho10,11,
  9. Richard Hauger12,13,
  10. Ayako Suzuki14,15,
  11. Christine Hunt14,15,
  12. Edward Siew7,16,
  13. Michael Matheny5,7,16,
  14. Adriana Hung6,16,
  15. Robert Greevy3,6,
  16. Christianne Roumie6,17,18
  1. 1 Gastroenterology Section, VA San Diego Healthcare System, San Diego, California, USA
  2. 2 Division of Gastroenterology, University of California, San Diego, California, USA
  3. 3 Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
  4. 4 Department of Public Health, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
  5. 5 Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
  6. 6 Clinical Services Research and Development, VA Tennessee Valley, Nashville, TN, USA
  7. 7 Health Services Research and Development, VA Tennessee Valley, Nashville, Tennessee, USA
  8. 8 The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
  9. 9 University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
  10. 10 VA Boston Healthcare System, Boston, Massachusetts, USA
  11. 11 Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
  12. 12 Department of Psychiatry, University of California San Diego, La Jolla, California, USA
  13. 13 Center of Excellence for Stress & Mental Health, VA San Diego Healthcare System, San Diego, California, USA
  14. 14 Division of Gastroenterology, Duke University Medical Center, Durham, North Carolina, USA
  15. 15 Gastroenterology Section, Durham VA Health Care System, Durham, North Carolina, USA
  16. 16 Division of Nephrology & Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee, USA
  17. 17 Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
  18. 18 VA Geriatrics Research Education and Clinical Center (GRECC), VA Tennessee Valley Health System, Nashville, Tennessee, USA
  1. Correspondence to Dr Shailja Shah, Gastroenterology, VA San Diego Healthcare System, La Jolla, CA 92161, USA; s6shah{at}

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We read with interest the study by Lee et al.1 The authors conducted a propensity score (PS)-matched analysis of a national South Korean cohort evaluating the association between proton pump inhibitor (PPI) use and SARS-CoV-2 susceptibility (primary outcome) and COVID-19 clinical severity (secondary outcome). Between January and May 2020, 4785 patients tested positive for SARS-CoV-2 (3.6% positivity); 267 current PPI users and 148 former PPI users were 1:1 PS-matched to non-users for the secondary outcomes. The authors reported current PPI use versus non-use was associated with a statistically significant increased risk of the composite endpoints: (1) oxygen therapy, intensive care unit (ICU) admission, mechanical ventilation use or death (composite OR 1.63; 95% CI, 1.03–2.53); and (2) ICU admission, mechanical ventilation or death (composite OR 1.79; 95% CI, 1.30 to 3.10).

We assembled a national retrospective cohort of US veterans who tested positive for SARS-CoV-2 (index date). Current outpatient PPI use up to and including the index date (primary exposure) was compared with non-use, defined as no PPI prescription fill in the 365 days prior to the index date (online supplemental figure 1). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome also included hospital or ICU admission. In contrast to PS matching, PS weighting allowed inclusion of all patients. Weighted logistic regression models evaluated severe COVID-19 …

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  • Contributors SS helped in study concept, study design, dataset verification, interpretation of data and statistical analysis, drafting of initial manuscript and critical revision of the manuscript. AH and RG were responsible for study design, primary statistical analysis, dataset verification, interpretation of data and statistical analysis, critical revision of the manuscript and methodological oversight. CD and OW helped in dataset creation and stewardship. BM, ST, KC, AS, CH, ES, MM and AH performed manuscript revision. CR helped in study design, interpretation of data and statistical analysis, methodological and study oversight and critical revision of manuscript. All authors approved the final version of the manuscript.

  • Funding American Gastroenterological Association 2019 Research Scholar Award (SS); US Dept of Veterans Affairs ICX002027A01 (SS), Million Veteran Programme Core MVP000 (KC); National Institute of Health K23HL143161A01 (ST).

  • Competing interests The authors report no conflicts of interest that are relevant to this article. Dr. Shah is an ad hoc consultant for Phathom Pharmaceuticals.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.