Abstract
Severe coronavirus disease 2019 (COVID-19) is associated with an overactive inflammatory response mediated by macrophages. Here, we analyzed the phenotype and function of neutrophils in patients with COVID-19. We found that neutrophils from patients with severe COVID-19 express high levels of CD11b and CD66b, spontaneously produce CXCL8 and CCL2, and show a strong association with platelets. Production of CXCL8 correlated with plasma concentrations of lactate dehydrogenase and D-dimer. Whole blood assays revealed that neutrophils from patients with severe COVID-19 show a clear association with immunoglobulin G (IgG) immune complexes. Moreover, we found that sera from patients with severe disease contain high levels of immune complexes and activate neutrophils through a mechanism partially dependent on FcγRII (CD32). Interestingly, when integrated in immune complexes, anti-severe acute respiratory syndrome coronavirus 2 IgG antibodies from patients with severe COVID-19 displayed a higher proinflammatory profile compared with antibodies from patients with mild disease. Our study suggests that IgG immune complexes might promote the acquisition of an inflammatory signature by neutrophils, worsening the course of COVID-19.
Keywords: CD32; COVID-19; CXCL8; SARS-CoV-2; immune complexes; inflammation; neutrophils.
【저자키워드】 COVID-19, Neutrophils, SARS-CoV-2, Inflammation, Immune complexes, CD32, CXCL8, 【초록키워드】 coronavirus disease, Neutrophils, Production, IgG, Coronavirus disease 2019, coronavirus, macrophages, severe COVID-19, antibody, neutrophil, D-dimer, Platelets, lactate dehydrogenase, immune, Immune complexes, proinflammatory, Immunoglobulin G, immune complex, IgG antibody, Immunoglobulin, IgG antibodies, sera, Patient, phenotype, respiratory, mechanism, Blood, Mild disease, CD32, CXCL8, association, CD11b, Lactate, Inflammatory, severe disease, plasma concentration, acute respiratory syndrome, severe coronavirus disease, CCL2, worsening, plasma concentrations, Express, CD66b, acquisition, overactive inflammatory response, Course, analyzed, dependent on, correlated, promote, activate, patients with COVID-19, with mild disease,