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Experts update definition of MIS-C

December 9, 2022

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As of Jan. 1, health officials will be using a new definition of multisystem inflammatory syndrome in children (MIS-C), a severe condition that can occur after a SARS-CoV-2 infection.

The new definition created by the Centers for Disease Control and Prevention (CDC) and the Council of State and Territorial Epidemiologists (CSTE) aims to better distinguish between MIS-C and other inflammatory conditions and improve surveillance and reporting. It does not replace clinical judgment for diagnosis and management.

“Ongoing surveillance is critical, particularly if new SARS-CoV-2 variants arise,” Anna Yousaf, M.D., a medical officer on the CDC’s Severe Respiratory Illness and Multisystem Inflammatory Syndrome Team, said during a CDC webinar.

The definition of MIS-C includes an illness in a person under 21 years requiring hospitalization or resulting in death and is characterized by evidence of systemic inflammation. Some of the changes to the criteria are listed below.

  • Kawasaki disease can serve as an alternative diagnosis.
  • Fever is present for any length of time.
  • Clinical severity includes death.
  • Laboratory evidence of inflammation is C-reactive protein levels at or above 3 milligrams per deciliter.
  • Organ system criteria have been narrowed.
  • Shock is in its own category.
  • Neurologic, renal and respiratory criteria were removed.
  • Required timeframe for SARS-CoV-2 test positivity has changed.

“It is important to remember this new surveillance case definition is intended for public health surveillance and reporting purposes,” Dr. Yousaf said. “It serves as a framework for diagnosis, but … clinicians should use all available clinical features, laboratory results and imaging studies to diagnose and manage MIS-C.”

A CDC analysis found about 87% of cases reported as of Aug. 31, 2022, would meet the new case definition.

As of Nov. 28, there have been 9,139 cases of MIS-C and 74 deaths, according to CDC data from voluntary reporting. The median age of patients was 9 years, and 60% were males. About 53% of cases were children who are Black or Hispanic.

However, experts have seen some shifts in the trends. Case counts have been low since spring, and MIS-C appears to be affecting a younger group than earlier in the pandemic. From April to the present when predominant variants have been omicronBA.2, BA.4 and BA.5, the median age has dropped to 5 years, and the 0-4 age group has had higher case counts than older children and teens.

CDC experts said the changes in MIS-C could be due to high immunity through infection and vaccination plus differences in viral mutations.

“The shifting to a young age in cases really does suggest that MIS-C may result principally from dysregulated immune response to primary SARS-CoV-2 infection among children who are still immunologically naïve,” said Angela Campbell, M.D., M.P.H., FAAP leader of the CDC’s Severe Respiratory Illness and Multisystem Inflammatory Syndrome Team.

The CDC is encouraging children to get vaccinated, which studies have shown to be 80% to 90% effective in protecting them against MIS-C. Children who have had MIS-C can be vaccinated once they have recovered clinically, and it has been at least 90 days since their MIS-C diagnosis.

“COVID-19 vaccination is the best protection against MIS-C,” Dr. Yousaf said.


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