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Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching
  1. Seung Won Lee1,
  2. Eun Kyo Ha2,
  3. Abdullah Özgür Yeniova3,
  4. Sung Yong Moon1,
  5. So Young Kim4,
  6. Hyun Yong Koh5,
  7. Jee Myung Yang6,
  8. Su Jin Jeong7,
  9. Sun Joon Moon8,
  10. Joo Young Cho9,
  11. In Kyung Yoo9,
  12. Dong Keon Yon7,10
  1. 1 Department of Data Science, Sejong University College of Software Convergence, Seoul, Korea
  2. 2 Department of Pediatrics, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
  3. 3 Division of Gastroenterology, Department of Internal Medicine, Tokat Gaziosmanpaşa University Faculty of Medicine, Tokat, Turkey
  4. 4 Department of Otorhinolaryngology-Head & Neck Surgery, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
  5. 5 F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  6. 6 Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  7. 7 Department of Pediatrics, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
  8. 8 Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
  9. 9 Department of Gastroenterology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
  10. 10 Armed Force Medical Command, Republic of Korea Armed Forces, Seongnam, Korea
  1. Correspondence to Professor Seung Won Lee, Sejong University College of Software Convergence, Seoul 05006, Korea; lsw2920{at}; Professor In Kyung Yoo, CHA University School of Medicine, Seongnam 13497, Korea; lemonherb12{at}; Dr Dong Keon Yon, CHA University School of Medicine, Seongnam 13497, Korea; yonkkang{at}


Objective The adverse effects of proton pump inhibitors (PPIs) have been documented for pneumonia; however, there is no consensus regarding whether the use of PPIs might be harmful regarding the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this regard, we aimed to measure the potential associations of the current use of PPIs with the infection rates of COVID-19 among patients who underwent SARS-CoV-2 testing.

Design Data were derived from a Korean nationwide cohort study with propensity score matching. We included 132 316 patients older than 18 years who tested for SARS-CoV-2 between 1 January and 15 May 2020. Endpoints were SARS-CoV-2 positivity (primary) and severe clinical outcomes of COVID-19 (secondary: admission to intensive care unit, administration of invasive ventilation or death).

Results In the entire cohort, there were 111 911 non-users, 14 163 current PPI users and 6242 past PPI users. After propensity score matching, the SARS-CoV-2 test positivity rate was not associated with the current or past use of PPIs. Among patients with confirmed COVID-19, the current use of PPIs conferred a 79% greater risk of severe clinical outcomes of COVID-19, while the relationship with the past use of PPIs remained insignificant. Current PPI use starting within the previous 30 days was associated with a 90% increased risk of severe clinical outcomes of COVID-19.

Conclusion Patients taking PPIs are at increased risk for severe clinical outcomes of COVID-19 but not susceptible to SARS-CoV-2 infection. This suggests that physicians need to assess benefit–risk assessments in the management of acid-related diseases amid the COVID-19 pandemic.

  • epidemiology
  • proton pump inhibition

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  • SWL, EKH and DKY are joint first authors.

  • Contributors DKY had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors approved the final version before submission. Conception and design: DKY. Analysis and interpretation of the data: SYM, SWL and DKY. Drafting of the article: EKH, SWL, IKY, AÖY and DKY. Critical revision of the article for important intellectual content: SYK, HYK, JMY, SJJ, SJM, JYC and DKY. Final approval of the article: all authors; Statistical expertise: SYM, SWL and DKY. Administrative, technical or logistic support: SWL and DKY. Collection and assembly of data: DKY. DKY is the guarantor.

  • Funding This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF2019R1G1A109977912).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval The study protocol was approved by the institutional review board of Sejong University (SJU-HR-E-2020-003).

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

  • Data availability statement Data are available on reasonable request. Study protocol, statistical code: available from the author DKY (e-mail, Dataset: de-identified datasets generated and analysed during the current study will be made available by request from the Health Insurance Review & Assessment Service of Korea at