During the early stages of the COVID-19 pandemic, it appeared that a hyperinflammatory state was responsible for significant morbidity and mortality in adults with acute COVID-19. In April 2020, however, the first cases of a post-COVID multisystem inflammatory syndrome in children (MIS-C) was described. This condition can be challenging to diagnose, as MIS-C manifests symptoms that are also associated with toxic shock syndrome and Kawasaki disease, but without any distinct disease-specific features. In a pre-print, not yet peer-reviewed, Dr. Joan Robinson from the University of Alberta, CITF Scientific Advisor Dr. Jesse Papenburg and Vaccine Surveillance Reference Group member Dr. Manish Sadarangani, among others, attempt to identify factors associated with a higher risk of admission to intensive care or cardiac events among children hospitalized for MIS-C.


In this study, data from the diagnoses of patients were collected from 15 pediatric hospitals around the world: 13 in Canada, one in Costa Rica and one in Iran.1 Children were under 18 years old, admitted between March 2020 and March 2021, and fulfilled the criteria for MIS-C. Criteria included: fever, systemic inflammation and illness involving two or more systems with no other cause for inflammation, as well as evidence of SARS-CoV-2 infection (i.e., positive COVID-19 serology or real-time PCR positive tests) or likely contact with COVID-19 given high circulating rates in their community.

A total of 232 MIS-C cases were identified. The average age of the child was 5.8 years old.  Almost all (89%) cases demonstrated gastro-intestinal symptoms such as abdominal pain, vomiting and diarrhea. Nearly a third (31%) of these children were admitted to the ICU, but recovery was usually rapid and there were no documented deaths. Importantly, children between 6 and 12 years old and those with an initial ferritin level (ferritin is a blood protein that contains iron) greater than 500 mcg/L were found to be at highest risk for ICU admission. Also, as compared to earlier cases, those identified after October 31, 2020, were associated with increased risk for ICU admission.

The researchers also highlighted some of the challenges associated with the diagnosis of MIS-C. While the US Centers for Disease Control and Prevention (CDC) states that the diagnosis of MIS-C without laboratory confirmation of recent SARS-CoV-2 infection can be based on exposure to a proven case of SARS-CoV-2 within a maximum of four weeks prior to disease manifestation, the World Health Organization (WHO) criteria does not include such specific timelines for exposure. This, and other differences in case definitions, may lead to the misclassification of potential MIS-C cases.

Recently, a review was published in the journal Vaccine by Vaccine Surveillance Reference Group (VSRG) member Dr. Karina Top addressing the heterogeneous case definitions for MIS-C.2 In Dr. Top’s publication, she and her colleagues proposed the Brighton Collaboration Case Definition for MIS-C and MIS-A (in adults) which should help in the correct classification of MIS-C/A for the purposes of vaccine safety surveillance.

Altogether, COVID-19 related-events will continue to be an important area of study as we transition into the next stage of the pandemic.



  1. Merckx J, Cooke S, Tal TE, Laxer RM, Bitnun A, Morris SK, Yeh EA, Yea C, Gill P, Papenburg J, Lefebvre M-A, Ulloa-Gutierrez R, Brenes-Chacon H, Yock-Corrales A, Ivankovich-Escoto G, Soriano-Fallas A, Hernandez-de Mezerville M, Dewan T, Restivo L, Nateghian A, Haghighi Aski B, Manafi A, Dwilow R, Bullard J, Lopez A, Sadarangani M, Roberts A, Barton M, Petel D, Le Saux N, Bowes J, Purewal R, Lautermilch J, Tehseen S, Bayliss A, Wong JK, Leifso K, Foo C, Robinson J. Multicenter cohort study of multisystem inflammatory syndrome in children (MIS-C). medRxiv. 2021 May 19. doi: 10.1101/2021.05.14.21257058.
  2. Vogel TP, Top KA, Karatzios C, Hilmers DC, Tapia LI, Moceri P, Giovannini-Chami L, Wood N, Chandler RE, Klein NP, Schlaudecker EP, Poli MC, Muscal E, Munoz FM. Multisystem inflammatory syndrome in children and adults (MIS-C/A): Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. 2021 May 21;39(22):3037-3049. doi: 10.1016/j.vaccine.2021.01.054.