Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19

Nat Biotechnol. 2021 Jun;39(6):705-716. doi: 10.1038/s41587-020-00796-1. Epub 2020 Dec 24.

Abstract

In coronavirus disease 2019 (COVID-19), hypertension and cardiovascular diseases are major risk factors for critical disease progression. However, the underlying causes and the effects of the main anti-hypertensive therapies-angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)-remain unclear. Combining clinical data (n = 144) and single-cell sequencing data of airway samples (n = 48) with in vitro experiments, we observed a distinct inflammatory predisposition of immune cells in patients with hypertension that correlated with critical COVID-19 progression. ACEI treatment was associated with dampened COVID-19-related hyperinflammation and with increased cell intrinsic antiviral responses, whereas ARB treatment related to enhanced epithelial-immune cell interactions. Macrophages and neutrophils of patients with hypertension, in particular under ARB treatment, exhibited higher expression of the pro-inflammatory cytokines CCL3 and CCL4 and the chemokine receptor CCR1. Although the limited size of our cohort does not allow us to establish clinical efficacy, our data suggest that the clinical benefits of ACEI treatment in patients with COVID-19 who have hypertension warrant further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiotensin Receptor Antagonists / administration & dosage
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • COVID-19 / complications
  • COVID-19 / drug therapy*
  • COVID-19 / genetics
  • COVID-19 / virology
  • Chemokine CCL3 / genetics*
  • Chemokine CCL4 / genetics*
  • Disease Progression
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / genetics
  • Hypertension / pathology
  • Inflammation / complications
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Inflammation / virology
  • Male
  • Middle Aged
  • RNA-Seq
  • Receptors, CCR1 / genetics*
  • Respiratory System / drug effects
  • Respiratory System / pathology
  • Respiratory System / virology
  • Risk Factors
  • SARS-CoV-2 / pathogenicity
  • Single-Cell Analysis

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • CCL3 protein, human
  • CCL4 protein, human
  • CCR1 protein, human
  • Chemokine CCL3
  • Chemokine CCL4
  • Receptors, CCR1