A Granulocytic Signature Identifies COVID-19 and Its Severity. (17th September 2020) - Vitte, Joana
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. Abstract : Unsupervised mapping of leukocyte surface markers identified a granulocytic COVID-19 signature comprising eosinophil and basophil CRTH2 downregulation, increased counts of CD15 + CD16 + neutrophils, and decreased granulocytic CD11b expression, while PD-L1 checkpoint expression in basophils and eosinophils was associated with severity.