Association between renin-angiotensin-aldosterone system inhibitor treatment, neutrophil-lymphocyte ratio, D-Dimer and clinical severity of COVID-19 in hospitalized patients: a multicenter, observational study

J Hum Hypertens. 2021 Jul;35(7):588-597. doi: 10.1038/s41371-020-00405-3. Epub 2020 Aug 24.


The aim of this study was to investigate the possible relationship between worse clinical outcomes and the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in hospitalized COVID-19 patients. A total of 247 adult patients (154 males, 93 females; mean age: 51.3 ± 14.2 years) hospitalized for COVID-19 as confirmed by polymerase chain reaction (PCR) were retrospectively reviewed. Demographic and clinical characteristics and laboratory parameters were analyzed using various statistical modeling. Primary outcomes were defined as the need for intensive care unit (ICU), mechanical ventilation, or occurrence of death. Of the patients, 48 were treated in the ICU with a high flow oxygen/noninvasive mechanical ventilation (NIMV, n = 12) or mechanical ventilation (n = 36). Median length of ICU stay was 13 (range, 7-18) days. Mortality was seen in four of the ICU patients. Other patients were followed in the COVID-19 services for a median of 7 days. There was no significant correlation between the primary outcomes and use of ACEIs/ARBs (frequentist OR = 0.82, 95% confidence interval (CI) 0.29-2.34, p = 0.715 and Bayesian posterior median OR = 0.80, 95% CI 0.31-2.02) and presence of hypertension (frequentist OR = 1.23, 95% CI 0.52-2.92, p = 0.631 and Bayesian posterior median OR = 1.25, 95% CI 0.58-2.60). Neutrophil-to-lymphocyte ratio (NLR) and D-dimer levels were strongly associated with primary outcomes. In conclusion, the presence of hypertension and use of ACEIs/ARBs were not significantly associated with poor primary clinical outcomes; however, NLR and D-dimer levels were strong predictors of clinical worsening.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aldosterone / adverse effects
  • Aldosterone / therapeutic use
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • COVID-19 / diagnosis*
  • COVID-19 Nucleic Acid Testing
  • Female
  • Fibrin Fibrinogen Degradation Products / analysis
  • Humans
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Lymphocytes
  • Male
  • Middle Aged
  • Neutrophils
  • Polymerase Chain Reaction
  • Renin-Angiotensin System
  • Retrospective Studies
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / isolation & purification*


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D
  • Aldosterone