Multisystem inflammatory syndrome in children (MIS-C) is rare among 12- to 20-year-olds who have received COVID-19 vaccination, according to a study published in The Lancet Child & Adolescent Health, and reported in a Lancet release.
The researchers investigated reports of individuals aged 12–20 years with MIS-C after COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to the US Centers for Disease Control and Prevention (CDC).
Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the USA, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorizations.
Most cases these researchers investigated had laboratory evidence of SARS-CoV-2 infection, although previous positive NAAT in three individuals occurred outside the typical timeframe for MIS-C (105 days, 191 days, and 238 days before illness onset), and one other had household exposure outside the typical period. In four others, no known exposure was available to inform the timing of infection that resulted in their anti-nucleocapsid antibody positivity.
Overall, the reporting rate for MIS-C was 1·0 case per million vaccinated individuals aged 12–20 years, when including all cases meeting the case definition, regardless of timing of any previous SARS-CoV-2 infection.
Although no direct comparator background rate exists, the reporting rate of illness meeting the MIS-C definition in individuals who had received a COVID-19 vaccine is substantially lower than the previously published incidence of MIS-C among unvaccinated individuals who had SARS-CoV-2 infection.
Using a denominator of SARS-CoV-2 infections among unvaccinated individuals, a previous study estimated an adjusted incidence of MIS-C from April to June, 2020, of 224 per million SARS-CoV-2 infections (95% CI 160–312) in children aged 11–15 years and 164 per million (110–243) in those aged 16–20 years.
The reporting rate for cases of MIS-C that occurred after receipt of COVID-19 vaccine and without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated individuals aged 12–20 years. It has been hypothesized that a dysregulated immune response associated with SARS-CoV-2 infection might also be associated with exposure to a COVID-19 vaccine.
As with the individuals in the investigation who had evidence of previous infection outside of the usual period for development of MIS-C, the contribution of vaccination, if any, to the illnesses in individuals without evidence of infection is unknown and cannot be determined with our surveillance data. It is possible that some of these six individuals had other unrecognized inflammatory conditions.
Though most pediatric COVID-19 infections are mild and self-limiting, MIS-C has confounded clinicians since the beginning of the pandemic. MIS-C usually appears 2 to 6 weeks after COVID-19 infection, and it can cause major organ failure. Initial symptoms often include fever, rash, eye redness, and gastrointestinal complications.
Additionally, given the limitations of laboratory assays and detection sensitivities of each test, some of these six individuals might have been infected with SARS-CoV-2 in the recent past, and vaccination might be coincidental to the subsequent MIS-C illness. Children often have unrecognized SARS-CoV-2 infection associated with mild or absent symptoms.
Individuals with mild or asymptomatic illness might be less likely to generate anti-nucleocapsid antibodies, and anti-nucleocapsid antibodies from a previous infection wane over time, particularly in those with mild infection.
This investigation highlights the challenges of diagnosing MIS-C and importance of a thorough clinical evaluation. Although the CDC's MIS-C case definition can be met with any type of SARS-CoV-2 antibody test (anti-spike, anti-nucleocapsid, or undifferentiated), testing for anti-nucleocapsid antibodies in individuals with suspected MIS-C after COVID-19 vaccination, ideally from a serum sample obtained before administration of intravenous immunoglobulin, might be helpful in identifying those with antibodies induced by SARS-CoV-2 infection.
Though most pediatric COVID-19 infections are mild and self-limiting, MIS-C has confounded clinicians since the beginning of the pandemic. MIS-C usually appears 2 to 6 weeks after COVID-19 infection, and it can cause major organ failure. Initial symptoms often include fever, rash, eye redness, and gastrointestinal complications.
