Blood Neutrophils from Children with COVID-19 Exhibit Both Inflammatory and Anti-Inflammatory Markers

Abstract

Background: Perhaps reflecting that children with COVID-19 rarely exhibit severe respiratory symptoms and often remain asymptomatic, little attention has been paid to explore the immune response in pediatric COVID-19. Here, we analyzed the phenotype and function of circulating neutrophils from children with COVID-19.Methods: One seventy-four children with COVID-19, 21 children with multisystem inflammatory syndrome (MIS-C), and 40 healthy children were studied. Neutrophil phenotype was analyzed by flow cytometry in blood samples. Cytokine production and plasma levels of IgG antibodies directed to the spike protein of SARS-CoV-2 were measured by ELISA. Cell-free DNA was quantified by fluorometry.Findings: Compared with healthy controls, neutrophils from children with COVID-19 showed a lower expression of CD11b, CD66b, and L-selectin but a higher expression of the activation markers HLA-DR, CD64 and PECAM-1 and the inhibitory receptors LAIR-1 and PD-L1. No differences in the pattern of cytokine production and NETs were observed when neutrophils from healthy children were compared with neutrophils from children with COVID-19. Interestingly, the expression of CD64 not only distinguished asymptomatic from mild and moderate COVID-19, but also positively correlated with the serum concentration of IgG antibodies directed to the spike protein of SARS-CoV-2.Interpretation: Acute lung injury is a prominent feature of severe COVID-19 in adults. A low expression of adhesion molecules together with a high expression of inhibitory receptors in neutrophils from children with COVID-19 might prevent tissue infiltration by neutrophils preserving lung function.Funding: FONCyT- ANPCyT, UBA, Argentina.Declaration of Interests: The authors have declared that no conflict of interest exists.Ethics Approval Statement: The Institutional Review Board at institutions participants reviewed and approved the sample collection and overall study.