DEspR neutrophils are associated with critical illness in COVID-19

Document Type


Publication Date



MaineHealth Institute for Research, Center for Molecular Medicine, Critical Care Medicine

Journal Title

Scientific reports

MeSH Headings

Aged; COVID-19 (immunology); Chemokines (metabolism); Cohort Studies; Critical Illness; Cytokines (metabolism); Enzyme-Linked Immunosorbent Assay (methods); Extracellular Traps (metabolism); Female; Humans; Inflammation (metabolism); Male; Middle Aged; Neutrophils (immunology, metabolism); Pseudogenes (genetics, immunology); SARS-CoV-2 (immunology, pathogenicity); Severity of Illness Index


SARS-CoV-2 infection results in a spectrum of outcomes from no symptoms to widely varying degrees of illness to death. A better understanding of the immune response to SARS-CoV-2 infection and subsequent, often excessive, inflammation may inform treatment decisions and reveal opportunities for therapy. We studied immune cell subpopulations and their associations with clinical parameters in a cohort of 26 patients with COVID-19. Following informed consent, we collected blood samples from hospitalized patients with COVID-19 within 72 h of admission. Flow cytometry was used to analyze white blood cell subpopulations. Plasma levels of cytokines and chemokines were measured using ELISA. Neutrophils undergoing neutrophil extracellular traps (NET) formation were evaluated in blood smears. We examined the immunophenotype of patients with COVID-19 in comparison to that of SARS-CoV-2 negative controls. A novel subset of pro-inflammatory neutrophils expressing a high level of dual endothelin-1 and VEGF signal peptide-activated receptor (DEspR) at the cell surface was found to be associated with elevated circulating CCL23, increased NETosis, and critical-severity COVID-19 illness. The potential to target this subpopulation of neutrophils to reduce secondary tissue damage caused by SARS-CoV-2 infection warrants further investigation.

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