Predictors of severe or lethal COVID-19, including angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, in a sample of infected Italian citizens

F. Bravi, M.E. Flacco, T. Carradori, C.A. Volta, G. Cosenza, A. De Togni, C.A. Martellucci, G. Parruti, L. Mantovani, L. Manzoli

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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. © 2020 Bravi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Original languageEnglish
JournalPLoS ONE
Issue number6 June
Publication statusPublished - 2020


  • angiotensin receptor antagonist
  • dipeptidyl carboxypeptidase inhibitor
  • antihypertensive agent
  • adult
  • age
  • aged
  • Article
  • cardiovascular disease
  • case control study
  • chronic obstructive lung disease
  • controlled study
  • coronavirus disease 2019
  • diabetes mellitus
  • disease severity
  • drug use
  • electronic medical record
  • female
  • follow up
  • human
  • hypertension
  • Italian (citizen)
  • kidney disease
  • lethality
  • major clinical study
  • male
  • malignant neoplasm
  • medical record review
  • middle aged
  • prediction
  • retrospective study
  • sex ratio
  • symptom
  • Betacoronavirus
  • complication
  • Coronavirus infection
  • Italy
  • pandemic
  • physiology
  • practice guideline
  • severity of illness index
  • virus pneumonia
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Case-Control Studies
  • Coronavirus Infections
  • Female
  • Guidelines as Topic
  • Humans
  • Hypertension
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral
  • Retrospective Studies
  • Severity of Illness Index


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