Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection

Nat Med. 2020 Nov;26(11):1701-1707. doi: 10.1038/s41591-020-1054-6. Epub 2020 Aug 18.


Recent reports highlight a new clinical syndrome in children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1-multisystem inflammatory syndrome in children (MIS-C)-which comprises multiorgan dysfunction and systemic inflammation2-13. We performed peripheral leukocyte phenotyping in 25 children with MIS-C, in the acute (n = 23; worst illness within 72 h of admission), resolution (n = 14; clinical improvement) and convalescent (n = 10; first outpatient visit) phases of the illness and used samples from seven age-matched healthy controls for comparisons. Among the MIS-C cohort, 17 (68%) children were SARS-CoV-2 seropositive, suggesting previous SARS-CoV-2 infections14,15, and these children had more severe disease. In the acute phase of MIS-C, we observed high levels of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, IL-17, interferon-γ and differential T and B cell subset lymphopenia. High CD64 expression on neutrophils and monocytes, and high HLA-DR expression on γδ and CD4+CCR7+ T cells in the acute phase, suggested that these immune cell populations were activated. Antigen-presenting cells had low HLA-DR and CD86 expression, potentially indicative of impaired antigen presentation. These features normalized over the resolution and convalescence phases. Overall, MIS-C presents as an immunopathogenic illness1 and appears distinct from Kawasaki disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Blood Coagulation / physiology
  • COVID-19 / blood*
  • COVID-19 / complications
  • COVID-19 / epidemiology
  • COVID-19 / immunology*
  • Cardiomyopathies / blood
  • Cardiomyopathies / etiology
  • Cardiomyopathies / immunology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Humans
  • Immunophenotyping
  • Inflammation / blood
  • Inflammation / etiology
  • Inflammation / immunology
  • Leukocytes / classification*
  • Leukocytes / immunology
  • Leukocytes / pathology*
  • Male
  • SARS-CoV-2 / immunology*
  • Systemic Inflammatory Response Syndrome / blood*
  • Systemic Inflammatory Response Syndrome / complications
  • Systemic Inflammatory Response Syndrome / epidemiology
  • Systemic Inflammatory Response Syndrome / immunology*

Supplementary concepts

  • pediatric multisystem inflammatory disease, COVID-19 related