Surveillance of COVID-19–Associated Multisystem Inflammatory Syndrome in Children, South Korea

A concerning development during the coronavirus disease pandemic has been multisystem inflammatory syndrome in children. Reports of this condition in East Asia have been limited. In South Korea, 3 cases were reported to the national surveillance system for multisystem inflammatory syndrome in children. All case-patients were hospitalized and survived with no major disease sequelae.

A concerning development during the coronavirus disease pandemic has been multisystem infl ammatory syndrome in children. Reports of this condition in East Asia have been limited. In South Korea, 3 cases were reported to the national surveillance system for multisystem infl ammatory syndrome in children. All casepatients were hospitalized and survived with no major disease sequelae. treatment consultation, and exchange of knowledge. The study was approved by the Institutional Review Board of Seoul National University Hospital (approval no. 2012-136-118).
During May-November 2020, a total of 2,287 COVID-19 cases in persons 0-19 years of age were reported (Figure). During the surveillance period, 9 suspected cases of MIS-C were reported to the surveillance system. Of the reported cases, 3 (33%) casepatients had evidence of COVID-19 exposure (positive for SARS-CoV-2 by PCR, SARS-CoV-2 antibody detection, or exposure history), and their illness was assessed as COVID-19-associated MIS-C, which likely occurred 3-4 weeks after the diagnosis of CO-VID-19 (Table).
The age of case-patients ranged from 11 to 14 years, 2 were boys, and none had preexisting conditions. All case-patients had fever and abdominal symptoms (abdominal pain, nausea, vomiting, or diarrhea) at admission. Mucocutaneous symptoms and signs (mucosal changes, skin rash, extremity changes) occurred in 2 patients, and all patients had documented hypotension (<50th percentile, adjusted for age, sex, and height). All case-patients had marked leukocytosis or elevated inflammatory markers. Echocardiography showed coronary artery dilatation (z-scores 1.64-3.98 mm for left coronary arteries), mitral regurgitation, or left ventricular dysfunction. Chest radiography or computed tomography showed pulmonary edema or pleural effusion. Abdominal ultrasound or computed tomography showed mesenteric lymphadenopathies, hyperechoic liver, or hypertrophic gall bladder. All 3 case-patients received intravenous immunoglobulin (IVIg); 1 patient (case 3) received methylprednisolone pulse therapy and immunomodulatory agent (Anakinra) because of persistent hypotension after initial IVIg treatment. Two patients received inotropic agents and required transfer to the intensive care unit (ICU), but no patients required mechanical ventilation. The duration of hospitalization was 10-19 days, and duration of ICU admission was 6-7 days. All 3 patients received aspirin and have survived to date with no major disease sequelae.

Conclusions
We describe MIS-C surveillance results from South Korea, an East Asia country with high incidence of Kawasaki disease. As of December 15, 2020, CO-VID-19 had been diagnosed in 4,107 children and adolescents 0-19 years of age in South Korea, which translates roughly to 0.07% of all childhood CO-VID-19 cases reported in South Korea (3). Concern about MIS-C was raised after episodes of increased incidence of Kawasaki-like disease were noted in children after COVID-19 diagnosis in Europe and the United States (4,5). In South Korea, there was no substantial increase in Kawasaki disease-related hospitalizations in 2020 compared with 2016-2019 (6). There might be ethnic differences in susceptibility; only 5% of MIS-C cases in New York (USA) occurred in Asian persons (7). Reports from India (8), Pakistan (9), and Iran (10) underscore the importance of monitoring MIS-C cases; however, surveillance data have not yet been reported for East Asia countries. Alongside genetic susceptibility, the  Although estimates of risk for MIS-C after SARS-CoV-2 infection are not yet available, we report a rough estimate in South Korea, where COVID-19 testing is widely accessible (11). Our findings suggest that the incidence of MIS-C is low among children with COVID-19 in this country. However, COVID-19-as-sociated MIS-C might cause serious clinical outcomes requiring ICU care and might require immunomodulatory agents.
All 3 MIS-C case-patients experienced gastrointestinal symptoms, which is consistent with reports from Italy (5), the United States (12), and the United Kingdom (13) that indicate gastrointestinal symptoms appear to be the most prominent clinical manifestation of MIS-C. Gastrointestinal involvement might also be a predictor of severe CO-VID-19. A systematic review of 83 studies showed that diarrhea (odds ratio 1.50, 95% CI 1.10-2.03; p = 0.01) was observed more often in patients with severe COVID-19 compared with patients with nonsevere COVID-19 (14). Previously, syndromic involvement of the gastrointestinal system has been associated with higher risk for IVIg resistance and coronary aneurysms in patients with Kawasaki disease (15). These features indicate the possibility of a mechanism linking gastrointestinal involvement and syndromic features for MIS-C and Kawasakilike illness, which needs further elucidation.
The first limitation of this study is that, given the intrinsic properties of a passive surveillance system, only a fraction of actual MIS-C cases might have been reported. Pediatricians are more likely to report cases that result in serious conditions; nonetheless, the case definition included hospitalization. Second, a large proportion of SARS-CoV-2 infections in children are asymptomatic; therefore, passive surveillance that relies on the presence of symptoms might underestimate the actual incidence of MIS-C. Despite these limitations, this study suggests that enhanced passive surveillance, including frequent outreach to pediatricians through academic societies, was a manageable scheme to monitor MIS-C in South Korea. Given that the level of SARS-CoV-2 community transmission was low during the surveillance period, passive surveillance was considered a robust plan to capture MIS-C cases at a national level.
Despite the introduction of vaccines, the global COVID-19 pandemic could continue for months. Therefore, surveillance is a critical tool for the detection and evaluation of serious complications in vulnerable population. Our experience offers a possible surveillance model for other countries concerned about COVID-19-associated MIS-C. MIS-C surveillance data in South Korea call for enhanced monitoring through syndromic and laboratory-based combination surveillance approaches.