A Granulocytic Signature Identifies COVID-19 and Its Severity

J Infect Dis. 2020 Nov 13;222(12):1985-1996. doi: 10.1093/infdis/jiaa591.

Abstract

Background: An unbiased approach to SARS-CoV-2-induced immune dysregulation has not been undertaken so far. We aimed to identify previously unreported immune markers able to discriminate COVID-19 patients from healthy controls and to predict mild and severe disease.

Methods: An observational, prospective, multicentric study was conducted in patients with confirmed mild/moderate (n = 7) and severe (n = 19) COVID-19. Immunophenotyping of whole-blood leukocytes was performed in patients upon hospital ward or intensive care unit admission and in healthy controls (n = 25). Clinically relevant associations were identified through unsupervised analysis.

Results: Granulocytic (neutrophil, eosinophil, and basophil) markers were enriched during COVID-19 and discriminated between patients with mild and severe disease. Increased counts of CD15+CD16+ neutrophils, decreased granulocytic expression of integrin CD11b, and Th2-related CRTH2 downregulation in eosinophils and basophils established a COVID-19 signature. Severity was associated with emergence of PD-L1 checkpoint expression in basophils and eosinophils. This granulocytic signature was accompanied by monocyte and lymphocyte immunoparalysis. Correlation with validated clinical scores supported pathophysiological relevance.

Conclusions: Phenotypic markers of circulating granulocytes are strong discriminators between infected and uninfected individuals as well as between severity stages. COVID-19 alters the frequency and functional phenotypes of granulocyte subsets with emergence of CRTH2 as a disease biomarker.

Keywords: CD11b; CD16; COVID-19; CRTH2; PD-L1; SARS-CoV-2; basophil; eosinophil; immune checkpoint; neutrophil.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism
  • CD11b Antigen / immunology
  • COVID-19 / blood
  • COVID-19 / diagnosis
  • COVID-19 / immunology*
  • Female
  • France
  • Granulocytes / immunology*
  • Humans
  • Immunophenotyping
  • Leukocyte Count
  • Lymphocytes / immunology
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Prospective Studies
  • Receptors, Immunologic / metabolism*
  • Receptors, Prostaglandin / metabolism*
  • SARS-CoV-2
  • Severity of Illness Index

Substances

  • Biomarkers
  • CD11b Antigen
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • prostaglandin D2 receptor