Sujets)
Anticorps antiviraux/sang , Complexe antigène-anticorps/sang , Antigènes viraux/immunologie , COVID-19/diagnostic , Glycoprotéines/immunologie , SARS-CoV-2/immunologie , Antigènes viraux/sang , Antigènes viraux/génétique , Marqueurs biologiques/sang , COVID-19/sang , COVID-19/immunologie , COVID-19/virologie , Études cas-témoins , Chromatographie d'affinité , Glycoprotéines/sang , Glycoprotéines/génétique , Humains , Sérums immuns/composition chimique , Immunoglobuline A/sang , Immunoglobuline G/sang , Spectrométrie de masse en tandemRésumé
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.
Sujets)
Anticorps antiviraux/immunologie , Complexe antigène-anticorps/immunologie , COVID-19/immunologie , Immunoglobuline G/immunologie , Activation des neutrophiles/immunologie , Adulte , Sujet âgé , Anticorps antiviraux/sang , Complexe antigène-anticorps/sang , Antigènes CD/immunologie , Antigènes CD11b/immunologie , Molécules d'adhérence cellulaire/immunologie , Femelle , Protéines liées au GPI/immunologie , Humains , Immunoglobuline G/sang , Interleukine-8/immunologie , Mâle , Adulte d'âge moyen , Granulocytes neutrophiles/immunologie , Récepteurs du fragment Fc des IgG/immunologie , SARS-CoV-2/immunologie , Jeune adulteRésumé
Multisystem inflammatory syndrome associated with the SARS-CoV-2 pandemic has recently been described in children (MIS-C), partially overlapping with Kawasaki disease (KD). We hypothesized that (a) MIS-C and prepandemic KD cytokine profiles may be unique and justify the clinical differences observed, and (b) SARS-CoV-2-specific immune complexes (ICs) may explain the immunopathology of MIS-C. Seventy-four children were included: 14 with MIS-C, 9 patients positive for SARS-CoV-2 by PCR without MIS-C (COVID), 14 with prepandemic KD, and 37 healthy controls (HCs). Thirty-four circulating cytokines were quantified in pretreatment serum or plasma samples and the presence of circulating SARS-CoV-2 ICs was evaluated in MIS-C patients. Compared with HCs, the MIS-C and KD groups showed most cytokines to be significantly elevated, with IFN-γ-induced response markers (including IFN-γ, IL-18, and IP-10) and inflammatory monocyte activation markers (including MCP-1, IL-1α, and IL-1RA) being the main triggers of inflammation. In linear discriminant analysis, MIS-C and KD profiles overlapped; however, a subgroup of MIS-C patients (MIS-Cplus) differentiated from the remaining MIS-C patients in IFN-γ, IL-18, GM-CSF, RANTES, IP-10, IL-1α, and SDF-1 and incipient signs of macrophage activation syndrome. Circulating SARS-CoV-2 ICs were not detected in MIS-C patients. Our findings suggest a major role for IFN-γ in the pathogenesis of MIS-C, which may be relevant for therapeutic management.