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SARS-CoV-2-related MIS-C: A key to the viral and genetic causes of Kawasaki disease?

Vanessa Sancho-Shimizu1,2, Petter Brodin3, Aurélie Cobat4,5,6

  • 1Department of Paediatric Infectious Diseases and Virology, Imperial College London, London, UK.

The Journal of Experimental Medicine
|April 27, 2021
PubMed

Insights

Multisystem inflammatory syndrome in children (MIS-C) is triggered by SARS-CoV-2 infection. Rare inborn errors of immunity may also cause MIS-C, offering new insights into Kawasaki disease.

Area of Science:

  • Pediatric immunology
  • Infectious diseases
  • Genetics

Background:

  • Multisystem inflammatory syndrome in children (MIS-C) emerged in 2020, linked to COVID-19.
  • MIS-C shares similarities with Kawasaki disease (KD), a heterogeneous pediatric inflammatory condition with suspected viral triggers.
  • The precise cause of MIS-C and KD remains incompletely understood.

Purpose of the Study:

  • To explore the potential role of inborn errors of immunity (IEIs) in the pathogenesis of MIS-C.
  • To investigate if identifying genetic factors in MIS-C could illuminate the underlying mechanisms of KD.

Main Methods:

  • Epidemiological analysis linking SARS-CoV-2 infection to MIS-C onset.
  • Hypothesizing the role of rare IEIs in modulating immune responses to SARS-CoV-2.
  • Suggesting a genetic framework for understanding MIS-C and KD.

Main Results:

  • SARS-CoV-2 is identified as the trigger for MIS-C, typically occurring one month post-infection.
  • A hypothesis is proposed that rare IEIs affecting the immune response to SARS-CoV-2 may contribute to MIS-C development in some children.
  • This research supports the idea of viral triggers for classic KD.

Conclusions:

  • The study suggests that rare inborn errors of immunity could be a key factor in MIS-C pathogenesis.
  • Discovering monogenic IEIs underlying MIS-C could provide crucial insights into its mechanisms.
  • This genetic approach may help reframe Kawasaki disease as a spectrum of IEIs triggered by viral infections.

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