Multisystem Inflammatory Syndrome in Children (MIS-C)

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DESCRIPTION

  • In December 2019, an outbreak of a novel coronavirus, designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread rapidly throughout Wuhan, China, and subsequently became a global pandemic.
  • In February 2020, the World Health Organization (WHO) designated the disease associated with SARS-CoV-2 as coronavirus disease of 2019 (COVID-19).
  • In April 2020, an unanticipated inflammatory syndrome related to COVID-19 rapidly emerged in children with a presentation similar to Kawasaki disease (KD) or toxic shock syndrome.
  • This entity has now been termed multisystem inflammatory syndrome in children (MIS-C).
ALERT

The condition referred to as MIS-C has also been referred to as pediatric multisystem inflammatory syndrome (PMIS), pediatric hyperinflammatory syndrome, or pediatric hyperinflammatory shock.

EPIDEMIOLOGY

  • First described in the United Kingdom, similar presentations of MIS-C have been reported worldwide, with notably fewer cases in China and other Asian countries.
  • Most cases occur in previously healthy children with a median age of 8 to 11 years old. However, MIS-C can affect children across the age spectrum and into adulthood, called multisystem inflammatory syndrome in adults (MIS-A).
  • In the first years of the COVID pandemic, males and Black and Hispanic children appear to be disproportionately affected, although it is not clear whether this is related to increased risk for acquiring SARS-CoV-2 infection in this patient population versus other reason increasing predisposition for MIS-C.
  • Knowledge of recent SARS-CoV-2 infection or exposure and these other epidemiologic features may help to distinguish MIS-C from KD, which typically occurs in infants and younger children.

Incidence

  • The exact incidence of MIS-C is uncertain; however, it appears to be very rare, occurring in <1% of children with confirmed SARS-CoV-2 infection.
  • MIS-C was more strongly associated with SARS-CoV-2 alpha and delta variants, and the incidence declined with the Omicron variants.

GENERAL PREVENTION

Evidence is emerging to suggest that vaccination against COVID-19 may be protective against the development of MIS-C.

PATHOPHYSIOLOGY

  • The pathophysiology of MIS-C is still not fully understood.
  • In most cases, there appears to be a 3- to 6-week lag between the time of SARS-CoV-2 infection and MIS-C, with patients often demonstrating evidence of prior SARS-CoV-2 infection and positive immunoglobulin G (IgG) serologies.
  • This coincides with the timing of acquired immunity and suggests that MIS-C may represent a postinfectious complication of the virus.
  • Despite clinical features that appear similar to KD and macrophage activation syndrome, MIS-C appears to have a distinct immunophenotype.
  • MIS-C has a strong predisposition for cardiac involvement; however, the mechanisms by which this occurs are still not well characterized.
ALERT

Despite most children having positive SARS-CoV-2 IgG serologies, suggesting prior infection, some children may still have positive polymerase chain reaction (PCR) testing for the virus. It is important to note that viral PCR testing can remain positive or intermittent positive near limits of detection for several weeks to months after infection.

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