Multisystem inflammatory syndrome in children in Canada

This article provides a summary of the epidemiology of multisystem inflammatory syndrome in children (MIS-C) cases reported nationally in Canada by provincial and territorial health authorities. Multisystem inflammatory syndrome in children is a post-viral inflammatory syndrome that temporally follows coronavirus disease 2019 (COVID-19). Symptoms may include fever, abdominal pain, vomiting, diarrhea, skin rash and other signs of inflammation. In Canada, MIS-C is rare, with 269 cases reported to the Public Health Agency of Canada between March 11, 2020 and October 2, 2021. One hundred forty-two (53%) of these cases were lab-confirmed COVID-19 cases or epidemiologically-linked with COVID-19 cases. Cases have been reported in infants as young as one week to youth as old as 18 years, with a median age of six years. Cases were more likely to occur in males than females (58% vs 42%, respectively; p =0.006). Almost all MIS-C cases (99%) required hospitalization and 36% required intensive care unit admission. No deaths have been reported to date. The time trend of MIS-C aligns with the incidence rate time trend of COVID-19 reported in children, with a two to six-week lag.


Introduction
Since the emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19), data on children and youth aged 19 years and younger infected with SARS-CoV-2 indicate that they usually experience mild disease with less severe outcomes compared with adults. However, on April 26, 2020, clinicians in the United Kingdom reported an increase in accounts of previously healthy children presenting with a severe inflammatory syndrome with features similar to toxic shock syndrome and incomplete Kawasaki disease (1). These cases occurred in children who tested positive for recent or current infection with SARS-CoV-2 or who had an epidemiological link to a COVID-19 case (1). Since then, additional cases of children presenting with a severe inflammatory syndrome with evidence of COVID-19 infection have been reported worldwide. This illness has been labelled multisystem inflammatory syndrome in children (MIS-C) by the Centers for Disease Control and Prevention and the World Health Organization (WHO), and is defined by the WHO as follows (2): Children and adolescents 0-19 years of age with fever for three or more days AND Two of the following: • Rash or bilateral non-purulent conjunctivitis or mucocutaneous inflammation signs (oral, hands or feet) • Hypotension or shock • Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated troponin/N-terminal pro-brain natriuretic peptide (NT-proBNP) • Evidence of coagulopathy (by prothrombin time, partial thromboplastin time, elevated D-dimer) • Acute gastrointestinal problems (diarrhea, vomiting or abdominal pain)

AND
Elevated markers of inflammation such as C-reactive protein, erythrocyte sedimentation rate or procalcitonin

AND
No other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes

Strengths and limitations
The data in this report are subject to several limitations. First, data are incomplete as not all provinces and territories participated in the national surveillance of MIS-C and one province only reported cases that were lab-confirmed. Second, case reporting may also be delayed due to limited capacity at provincial and territorial health authorities. Case counts for the most recent couple of months in particular should be interpreted with caution. Third, it is difficult to discern whether cases were infected with COVID-19 or not due to several factors: RT-PCR testing may be negative if completed too late in the course of infection; serology testing may not be available; there are inherent challenges in interpreting serology results; and patients may not know that they have been in contact with a case of COVID-19. For this reason, cases with no known evidence of SARS-CoV-2 infection or exposure to a COVID-19 case were included in the analysis; however, these cases may not be COVID-19-related and, therefore, not true cases of MIS-C. Due to similarities between the symptoms of MIS-C and Kawasaki disease and the difficulties in diagnosing these diseases, there may be misclassification of cases, especially the cases without a known COVID-19 link. More detailed laboratory testing data is needed to further differentiate between cases related and unrelated to COVID-19.

Conclusion
Cases of MIS-C in Canada are rare; however, when illness does occur it is severe, with nearly all cases requiring hospitalization and one third requiring admission to the intensive care unit. All children in Canada with MIS-C have recovered or are recovering, with no deaths reported. The time trend of MIS-C aligns with the time trend of the incidence of COVID-19 in children, with a two-to six-week lag. This pattern has been reported in other publications, supporting 1) the temporal association of MIS-C with COVID-19 and 2) the current understanding that MIS-C results from a delayed immunologic response to SARS-CoV-2 infection (7). In Canada, MIS-C is more likely to occur in males then females.
Although MIS-C is rare, it is serious, and it is not yet known why some children develop this syndrome and others do not. Furthermore, the long-term effects of MIS-C remain largely unknown. The most effective way to prevent cases of serious illness in children is to follow public health measures that prevent the spread of COVID-19, including physical distancing, wearing masks, hand hygiene, staying home when sick and getting vaccinated against COVID-19 when eligible. The Public Health Agency of Canada will continue to work with provincial and territorial partners to monitor cases of serious inflammatory illness in children and keep the public informed of the risk to children and youth.