Multisystem Inflammatory Syndrome in Children-United States, February 2020-July 2021.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory condition in persons aged <21 years associated with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to describe MIS-C cases reported to Centers for Disease Control and Prevention's (CDC's) national surveillance since the coronavirus disease 2019 (COVID-19) pandemic began. METHODS: We included patients meeting the MIS-C case definition with onset date from 19 February 2020 through 31 July 2021, using CDC's MIS-C case report form, which collects information on demographics, clinical presentation, and laboratory results. Trends over time across 3 MIS-C pandemic waves were assessed using Cochran-Armitage test for categorical and Jonckheere-Terpstra test for continuous variables. RESULTS: Of 4901 reported cases, 4470 met inclusion criteria. Median patient age increased over time (P < .001), with a median of 9 years (interquartile range, 5-13 years) during the most recent (third) wave. Male predominance also increased (62% in third wave, P < .001). A significant (P < .001) increase in severe hematologic and gastrointestinal involvement was observed across the study period. Frequency of several cardiovascular complications (ie, cardiac dysfunction, myocarditis, and shock/vasopressor receipt) and renal failure declined (P < .001). Provision of critical care including mechanical ventilation (P < .001) and extracorporeal membrane oxygenation (ECMO; P = .046) decreased, as did duration of hospitalization and mortality (each P < .001). CONCLUSIONS: Over the first 3 pandemic waves of MIS-C in the United States, cardiovascular complications and clinical outcomes including length of hospitalization, receipt of ECMO, and death decreased over time. These data serve as a baseline for monitoring future trends associated with SARS-CoV-2 B.1.617.2 (Delta) or other variants and increased COVID-19 vaccination among children.

Racial and Ethnic Disparities in Multisystem Inflammatory Syndrome in Children in the United States, March 2020 to February 2021.

BACKGROUND: The incidence of multisystem inflammatory syndrome in children (MIS-C) varies by race and ethnicity. This study assessed whether disparities in MIS-C in the United States by race and ethnicity exceed known disparities in coronavirus disease 2019 (COVID-19) incidence. METHODS: We compared the distribution of race and ethnicity among patients with MIS-C (<21 years of age, termed children) with onset March 2020 to February 2021 to that of children with COVID-19 and in the general population. Analysis was restricted to 369 counties with high completeness of race and ethnicity reporting for MIS-C and COVID-19. For each racial and ethnic group, observed numbers of patients with MIS-C were compared with expected numbers (observed/expected ratio) in children with COVID-19 and in the general population within these counties. RESULTS: Compared with children in the general population, MIS-C was more frequent among Hispanic (139% of expected) and non-Hispanic Black children (183%) and less frequent among non-Hispanic White (64%) and non-Hispanic Asian children (48%). Compared with children with COVID-19, MIS-C was more frequent in non-Hispanic Black children (207% of expected) and less frequent in non-Hispanic White children (68%); however, frequency was not different among Hispanic (102%) and non-Hispanic Asian (74%) children. CONCLUSIONS: Disparities in MIS-C by race and ethnicity exist, even after controlling for COVID-19 disparities and geographic variations. The high proportion of MIS-C among Hispanic children and low proportion among non-Hispanic Asian children align with COVID-19 rates, while the high proportion among non-Hispanic Black children and low proportion among non-Hispanic White children are not explainable by COVID-19 rates.

Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a newly identified and serious health condition associated with SARS-CoV-2 infection. Clinical manifestations vary widely among patients with MIS-C, and the aim of this study was to investigate factors associated with severe outcomes. METHODS: In this retrospective surveillance study, patients who met the US Centers for Disease Control and Prevention (CDC) case definition for MIS-C (younger than 21 years, fever, laboratory evidence of inflammation, admitted to hospital, multisystem [≥2] organ involvement [cardiac, renal, respiratory, haematological, gastrointestinal, dermatological, or neurological], no alternative plausible diagnosis, and either laboratory confirmation of SARS-CoV-2 infection by RT-PCR, serology, or antigen test, or known COVID-19 exposure within 4 weeks before symptom onset) were reported from state and local health departments to the CDC using standard case-report forms. Factors assessed for potential links to severe outcomes included pre-existing patient factors (sex, age, race or ethnicity, obesity, and MIS-C symptom onset date before June 1, 2020) and clinical findings (signs or symptoms and laboratory markers). Logistic regression models, adjusted for all pre-existing factors, were used to estimate odds ratios between potential explanatory factors and the following outcomes: intensive care unit (ICU) admission, shock, decreased cardiac function, myocarditis, and coronary artery abnormalities. FINDINGS: 1080 patients met the CDC case definition for MIS-C and had symptom onset between March 11 and Oct 10, 2020. ICU admission was more likely in patients aged 6-12 years (adjusted odds ratio 1·9 [95% CI 1·4-2·6) and patients aged 13-20 years (2·6 [1·8-3·8]), compared with patients aged 0-5 years, and more likely in non-Hispanic Black patients, compared with non-Hispanic White patients (1·6 [1·0-2·4]). ICU admission was more likely for patients with shortness of breath (1·9 [1·2-2·9]), abdominal pain (1·7 [1·2-2·7]), and patients with increased concentrations of C-reactive protein, troponin, ferritin, D-dimer, brain natriuretic peptide (BNP), N-terminal pro B-type BNP, or interleukin-6, or reduced platelet or lymphocyte counts. We found similar associations for decreased cardiac function, shock, and myocarditis. Coronary artery abnormalities were more common in male patients (1·5 [1·1-2·1]) than in female patients and patients with mucocutaneous lesions (2·2 [1·3-3·5]) or conjunctival injection (2·3 [1·4-3·7]). INTERPRETATION: Identification of important demographic and clinical characteristics could aid in early recognition and prompt management of severe outcomes for patients with MIS-C. FUNDING: None.

Multisystem Inflammatory Syndrome in Children Associated with Severe Acute Respiratory Syndrome Coronavirus 2: A Systematic Review.

OBJECTIVE: To develop a more comprehensive description of multisystem inflammatory syndrome in children (MIS-C), a novel syndrome linked to severe acute respiratory syndrome coronavirus 2, by conducting a systematic analysis of studies from different settings that used various inclusion criteria. STUDY DESIGN: MIS-C studies were identified by searching PubMed and Embase as well as preprint repositories and article references to identify studies of MIS-C cases published from April 25, 2020, through June 29, 2020. MIS-C study metadata were assessed and information on case demographics, clinical symptoms, laboratory measurements, treatments, and outcomes were summarized and contrasted between studies. RESULTS: Eight studies were identified representing a total of 440 MIS-C cases. Inclusion criteria varied by study: 3 studies selected patients diagnosed with Kawasaki disease, 2 required cardiovascular involvement, and 3 had broader multisystem inclusion criteria. Median age of patients by study ranged from 7.3 to 10 years, and 59% of patients were male. Across all studies, the proportion of patients with positive results for severe acute respiratory syndrome coronavirus 2 reverse transcriptase-polymerase chain reaction tests ranged from 13% to 69% and for serology, from 75% to 100%. Patients with MIS-C had high prevalence of gastrointestinal (87%), dermatologic/mucocutaneous (73%), and cardiovascular (71%) symptoms. Prevalence of cardiovascular, neurologic, and respiratory system involvement significantly differed by study inclusion criteria. All studies reported elevated C-reactive protein, interleukin-6, and fibrinogen levels for at least 75% of patients in each study. CONCLUSIONS: This systematic review of MIS-C studies assists with understanding this newly identified syndrome and may be useful in developing a refined, universal case definition of MIS-C.