Renin-angiotensin system inhibitors and the severity of coronavirus disease 2019 in Kanagawa, Japan: a retrospective cohort study

Hypertens Res. 2020 Nov;43(11):1257-1266. doi: 10.1038/s41440-020-00535-8. Epub 2020 Aug 21.


Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak initiated on the Diamond Princess Cruise Ship at Yokohama harbor in February 2020, we have been doing our best to treat COVID-19 patients. In animal experiments, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) are reported to suppress the downregulation of angiotensin converting enzyme 2 (ACE2), and they may inhibit the worsening of pathological conditions. We aimed to examine whether preceding use of ACEIs and ARBs affected the clinical manifestations and prognosis of COVID-19 patients. One hundred fifty-one consecutive patients (mean age 60 ± 19 years) with polymerase-chain-reaction proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were admitted to six hospitals in Kanagawa Prefecture, Japan, were analyzed in this multicenter retrospective observational study. Among all COVID-19 patients, in the multiple regression analysis, older age (age ≥ 65 years) was significantly associated with the primary composite outcome (odds ratio (OR) 6.63, 95% confidence interval (CI) 2.28-22.78, P < 0.001), which consisted of (i) in-hospital death, (ii) extracorporeal membrane oxygenation, (iii) mechanical ventilation, including invasive and noninvasive methods, and (iv) admission to the intensive care unit. In COVID-19 patients with hypertension, preceding ACEI/ARB use was significantly associated with a lower occurrence of new-onset or worsening mental confusion (OR 0.06, 95% CI 0.002-0.69, P = 0.02), which was defined by the confusion criterion, which included mild disorientation or hallucination with an estimation of medical history of mental status, after adjustment for age, sex, and diabetes. In conclusion, older age was a significant contributor to a worse prognosis in COVID-19 patients, and ACEIs/ARBs could be beneficial for the prevention of confusion in COVID-19 patients with hypertension.

Keywords: Angiotensin II type-1 receptor blockers; Angiotensin converting enzyme inhibitors; COVID-19.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Betacoronavirus*
  • COVID-19
  • Confusion / prevention & control
  • Coronavirus Infections / mortality*
  • Coronavirus Infections / psychology
  • Coronavirus Infections / therapy
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / mortality*
  • Pneumonia, Viral / psychology
  • Pneumonia, Viral / therapy
  • Retrospective Studies
  • SARS-CoV-2
  • Severity of Illness Index


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors