J Korean Med Sci.  2023 Apr;38(13):e99. 10.3346/jkms.2023.38.e99.

Histamine-2 Receptor Antagonists and Proton Pump Inhibitors Are Associated With Reduced Risk of SARS-CoV-2 Infection Without Comorbidities Including Diabetes, Hypertension, and Dyslipidemia: A Propensity ScoreMatched Nationwide Cohort Study

• Kim B
• Jung JH
• Han K
• Kang SK
• Lee E
• Chung H
• Kim SG
• Cho SJ

• KMID: 2541049
• DOI: http://doi.org/10.3346/jkms.2023.38.e99

Abstract

Background
This study aimed to identify the effect of histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) use on the positivity rate and clinical outcomes of coronavirus disease 2019 (COVID-19).
Methods
We performed a nationwide cohort study with propensity score matching using medical claims data and general health examination results from the Korean National Health Insurance Service. Individuals aged ≥ 20 years who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 January and 4 June 2020 were included. Patients who were prescribed H2RA or PPI within 1 year of the test date were defined as H2RA and PPI users, respectively. The primary outcome was SARS-CoV-2 test positivity, and the secondary outcome was the instance of severe clinical outcomes of COVID-19, including death, intensive care unit admission, and mechanical ventilation administration.
Results
Among 59,094 patients tested for SARS-CoV-2, 21,711 were H2RA users, 12,426 were PPI users, and 24,957 were non-users. After propensity score matching, risk of SARS-CoV-2 infection was significantly lower in H2RA users (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.74–0.98) and PPI users (OR, 0.62; 95% CI, 0.52–0.74) compared to non-users. In patients with comorbidities including diabetes, dyslipidemia, and hypertension, the effect of H2RA and PPI against SARS-CoV-2 infection was not significant, whereas the protective effect was maintained in patients without such comorbidities. Risk of severe clinical outcomes in COVID-19 patients showed no difference between users and non-users after propensity score matching either in H2RA users (OR, 0.89; 95% CI, 0.52–1.54) or PPI users (OR, 1.22; 95% CI, 0.60–2.51).
Conclusion
H2RA and PPI use is associated with a decreased risk for SARS-CoV-2 infection but does not affect clinical outcome. Comorbidities including diabetes, hypertension, and dyslipidemia seem to offset the protective effect of H2RA and PPI.

Keyword

COVID-19; SARS-CoV-2; Proton Pump Inhibitors; Histamine H2 Antagonists

Figure

• 

  Fig. 1 Flowchart of population selection.SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2, COVID-19 = coronavirus disease 2019, NSAID = non-steroidal anti-inflammatory drug, H2RA = histamine 2 receptor antagonist, PPI = proton pump inhibitor.

• 

  Fig. 2 Propensity score-matched association of H2RA use with SARS-COV-2 test positivity.H2RA = histamine 2 receptor antagonist, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2, BMI = body mass index, aOR = adjusted odds ratio, CI = confidence interval.

• 

  Fig. 3 Propensity score-matched association of PPI use with SARS-COV-2 test positivity.PPI = proton pump inhibitor, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2, BMI = body mass index, aOR = adjusted odds ratio, CI = confidence interval.

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