A Granulocytic Signature Identifies COVID-19 and Its Severity

Abstract

Background An unbiased approach of 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 COVID-19: mild/moderate (n=7) and severe (n=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 mild and severe patients. 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 the emergence of PDL1 checkpoint expression in basophils and eosinophils. This granulocytic signature was accompanied by monocyte and lymphocyte immunoparalysis. Correlation with validated clinical scores supported pathophysiological relevance. Conclusion 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 the emergence of CRTH2 as a disease biomarker.

Heterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severity

“…Recent reports have indicated the increased number of immature neutrophils in severe forms of COVID-19. 29 - 31 Complementing these studies, we here provide evidence for impaired function of these cells in correlation with the severity of COVID-19.…”

Structural assessment of SARS-CoV2 accessory protein ORF7a predicts LFA-1 and Mac-1 binding potential

“…Recent studies have also reported significant reduction in circulating LFA-1 expressing T lymphocytes [ 33 ], a significant increase in Mac-1 expression in monocytes [ 34 , 35 ], and a significant decrease of Mac-1 expression in granulocytes [ 36 ] in symptomatic COVID patients, but no confirmation on whether these cells were infected with SARS-CoV2. Both these observations could be consistent with our predictions and require further in vitro receptor binding assays coupled with histopathological studies from infected cells and tissues to robustly confirm the infectibility of SARS-CoV2 in LFA-1 and Mac-1 expressing cells, and the role of ORF7a in modulating LFA-1 and Mac-1 expressing cells.…”

Peripheral Blood Immune Profiling of Convalescent Plasma Donors Reveals Alterations in Specific Immune Subpopulations Even at 2 Months Post SARS-CoV-2 Infection

“…It has been shown that patients infected with SARS-CoV-2 have a high neutrophil count during the severe phase, and the neutrophil to lymphocyte ratio can be used to predict the degree of disease severity in patients with early-stage COVID-19 [ 32 , 33 ]. SARS-CoV-2 infection is also characterized by changes in the frequency of granulocyte subsets and alteration of their functional phenotypes that correlate with COVID-19 severity [ 34 ]. Granulocytes and mainly their activated CD11b + subset were significantly increased during the active phase in the group of COVID-19 patients, while the CD11b − subset was diminished.…”