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

J Infect Dis. 2022 Sep 28;226(7):1215-1223. doi: 10.1093/infdis/jiac304.

Abstract

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.

Keywords: COVID-19; MIS-C; SARS-CoV-2; chemokines; cytokines; in vitro cell culture; pediatric population.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Antigens, Viral
  • COVID-19* / complications
  • Chemokines
  • Child
  • Communicable Diseases*
  • Cytokines
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Humans
  • Immunity
  • Interferon-gamma
  • Interleukin-13
  • Interleukin-17
  • Interleukin-18
  • Interleukin-4
  • Interleukin-6
  • SARS-CoV-2
  • Systemic Inflammatory Response Syndrome

Substances

  • Antigens, Viral
  • Chemokines
  • Cytokines
  • Interleukin-13
  • Interleukin-17
  • Interleukin-18
  • Interleukin-6
  • Interleukin-4
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor

Supplementary concepts

  • pediatric multisystem inflammatory disease, COVID-19 related