Multisystem inflammatory syndrome in children characterized by enhanced antigen-specific T-cell expression of cytokines and its reversal following recovery.

Background: Multisystem inflammatory syndrome (MIS) in children is considered to be a post-infectious complication of COVID-19. T-cell responses in children with this condition have not been well-studied. Methods: We aimed to study the immune responses in children with MIS in comparison to children with acute COVID-19 and children with other infections. Whole blood was stimulated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific antigens and flow cytometry was performed to examine CD4+ and CD8+ T-cell responses. Results: Children with MIS had higher frequencies of CD4+ and CD8+ T cells expressing cytokines at baseline and upon SARS-CoV-2 antigen-specific stimulation in comparison to children with COVID-19 and/or other infections. Children with COVID-19 also exhibited higher frequencies of CD4+ and CD8+ T cells expressing cytokines at baseline and upon SARS-CoV-2 antigen-specific stimulation in comparison to children with other infections. At 6-9 months following treatment and recovery, this enhanced response against SARS-CoV-2 antigens was down modulated in children with MIS. Conclusion: Our study, therefore, provides evidence of enhanced activation of CD4+ and CD8+ T-cell responses in children with MIS and reversal following recovery.

Immune Profiles in Multisystem Inflammatory Syndrome in Children with Cardiovascular Abnormalities.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a sequela of severe acute respiratory syndrome coronavirus-2 infection (SARS-CoV2), has been progressively reported worldwide, with cardiac involvement being a frequent presentation. Although the clinical and immunological characteristics of MIS-C with and without cardiac involvement have been described, the immunological differences between cardiac and non-cardiac MIS-C are not well understood. METHODS: The levels of type 1, type 2, type 17, other proinflammatory cytokines and CC chemokines and CXC chemokines were measured using the Magpix multiplex cytokine assay system in MIS-C children with MIS-C cardiac (MIS-C (C) (n = 88)) and MIS-C non-cardiac (MIS-C (NC) (n = 64)) abnormalities. RESULTS: MIS-C children with cardiac manifestations presented with significantly increased levels of cytokines such as IFN-γ, IL-2, TNFα, IL-5, IL-1α, IL-1ß, IL-6, IL-10 and IL-12p70 and chemokines such as CCL2, CCL3, CCL11 and CXCL10 in comparison to MIS-C children without cardiac manifestations. Clustering analysis revealed that cytokines and chemokines could clearly distinguish MIS-C children with and without cardiac manifestations. In addition, these responses significantly diminished and normalized 9 months after treatment. CONCLUSIONS: This is one of the first studies characterizing and differentiating systemic inflammation in MIS-C with and without cardiac involvement from a low- and middle-income country (LMIC). Our study contributes to the existing body of evidence and advances our knowledge of the immunopathogenesis of MIS-C in children.

Enhanced Severe Acute Respiratory Syndrome Coronavirus 2 Antigen-Specific Systemic Immune Responses in Multisystem Inflammatory Syndrome in Children and Reversal After Recovery.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) presents with inflammation and pathology of multiple organs in the pediatric population in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We characterized the SARS-CoV-2 antigen-specific cytokine and chemokine responses in children with MIS-C, coronavirus disease 2019 (COVID-19), and other infectious diseases. RESULTS: MIS-C is characterized by elevated levels of type 1 (interferon-γ, interleukin [IL] 2), type 2 (IL-4, IL-13), type 17 (IL-17), and other proinflammatory cytokines (IL-1α, IL-6, IL-12p70, IL-18, and granulocyte-macrophage colony-stimulating factor) in comparison to COVID-19 and other infectious diseases following stimulation with SARS-CoV-2-specific antigens. Similarly, upon SARS-CoV-2 antigen stimulation, CCL2, CCL3, and CXCL10 chemokines were significantly elevated in children with MIS-C in comparison to the other 2 groups. Principal component analysis based on these cytokines and chemokines could clearly distinguish MIS-C from both COVID-19 and other infections. In addition, these responses were significantly diminished and normalized 6-9 months after recovery. CONCLUSIONS: Our data suggest that MIS-C is characterized by an enhanced production of cytokines and chemokines that may be associated with disease pathogenesis.