Predictors of severe or lethal COVID-19, including Angiotensin Converting Enzyme inhibitors and Angiotensin II Receptor Blockers, in a sample of infected Italian citizens

PLoS One. 2020 Jun 24;15(6):e0235248. doi: 10.1371/journal.pone.0235248. eCollection 2020.


Aims: This retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs).

Methods and results: All adults with SARS-CoV-2 infection in two Italian provinces were followed for a median of 24 days. ARBs and/or ACEi treatments, and hypertension, diabetes, cancer, COPD, renal and major cardiovascular diseases (CVD) were extracted from clinical charts and electronic health records, up to two years before infection. The sample consisted of 1603 subjects (mean age 58.0y; 47.3% males): 454 (28.3%) had severe symptoms, 192 (12.0%) very severe or lethal disease (154 deaths; mean age 79.3 years; 70.8% hypertensive, 42.2% with CVD). The youngest deceased person aged 44 years. Among hypertensive subjects (n = 543), the proportion of those treated with ARBs or ACEi were 88.4%, 78.7% and 80.6% among patients with mild, severe and very severe/lethal disease, respectively. At multivariate analysis, no association was observed between therapy and disease severity (Adjusted OR for very severe/lethal COVID-19: 0.87; 95% CI: 0.50-1.49). Significant predictors of severe disease were older age (with AORs largely increasing after 70 years of age), male gender (AOR: 1.76; 1.40-2.23), diabetes (AOR: 1.52; 1.05-2.18), CVD (AOR: 1.88; 1.32-2.70) and COPD (AOR: 1.88; 1.11-3.20). Only gender, age and diabetes also predicted very severe/lethal disease.

Conclusion: No association was found between COVID-19 severity and treatment with ARBs and/or ACEi, supporting the recommendation to continue medication for all patients unless otherwise advised by their physicians.

Publication types

  • Observational Study

MeSH terms

  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Antihypertensive Agents / therapeutic use*
  • Betacoronavirus / physiology
  • Case-Control Studies
  • Coronavirus Infections / complications*
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / epidemiology
  • Female
  • Guidelines as Topic
  • Humans
  • Hypertension / drug therapy
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / complications*
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / epidemiology
  • Retrospective Studies
  • Severity of Illness Index


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2

Grant support

The authors received no specific funding for this work