Deep immunophenotyping reveals biomarkers of multisystemic inflammatory syndrome in children in a Latin American cohort

Abstract

BackgroundMultisystemic inflammatory syndrome in children (MIS-C) is a life-threatening disease that occurs 2-5 weeks after SARS-CoV-2 exposure and is characterized by severe multisystemic inflammation. Early recognition of MIS-C is key to prognosis, therefore establishing clinical and laboratory biomarkers that predict complications is urgently needed.ObjectiveTo characterize the immune response and clinical features of patients with acute MIS-C and determine biomarkers of disease in a cohort of 42 Latin American patients.MethodsImmune characterization was performed using flow cytometry from peripheral mononuclear cells and SARS-CoV-2-specific humoral and cellular response was performed using flow cytometry, ELISPOT, ELISA and neutralizing antibody assays.ResultsMIS-C is characterized by robust T cell activation and cytokine storm. We uncovered that while CXCL9, IL-10, CXCL8, CXCL10, IL-6 and IL-18 are significantly elevated in patients with shock, while CCL5 was increased in milder disease. Monocyte dysregulation was specifically associated to Kawasaki-like MIS-C. Interestingly, MIS-C patients show an NK cell degranulation defect that is persistent after 6 months of disease presentation, suggesting it could underlie disease susceptibility. Most MIS-C had gastrointestinal involvement and higher levels of neopterin were identified in their stools, potentially representing a biomarker of intestinal inflammation in MIS-C. SARS-CoV2-specific cellular response and neutralizing antibodies were identifiable in convalescent MIS-C patients suggesting sustained immunity.ConclusionClinical characterization and comprehensive immunophenotyping of Chilean MIS-C cohort provide valuable insights in understanding immune dysregulation in MIS-C and identify relevant biomarkers of disease that could be used to predict severity and organ involvement.CLINICAL IMPLICATIONS STATEMENTMIS-C is distinguished by cytokine storm and decreased NK cell degranulation that is persistent after 6 months. Distinct biomarkers were identified for severe and mild forms of disease.