COVID-19 Vaccine Reactogenicity and Vaccine Attitudes Among Children and Parents/Guardians After Multisystem Inflammatory Syndrome in Children or COVID-19 Hospitalization: September 2021-May 2022.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a multiorgan hyperinflammatory condition following SARS-CoV-2 infection. Data on COVID-19 vaccine adverse events and vaccine attitudes in children with prior MIS-C are limited. We described characteristics associated with COVID-19 vaccination, vaccine adverse events and vaccine attitudes in children with a history of MIS-C or COVID-19 and their parents/guardians. METHODS: We enrolled children previously hospitalized for MIS-C or COVID-19 from 3 academic institutions. We abstracted charts and interviewed children and parents/guardians regarding vaccine adverse events and acceptability. RESULTS: Of 163 vaccine-eligible children enrolled with a history of MIS-C and 70 with history of COVID-19, 51 (31%) and 34 (49%), respectively, received mRNA COVID-19 vaccine a median of 10 (Interquartile Range 6-13) months after hospital discharge. Among 20 children with MIS-C and parents/guardians who provided interviews, local injection site reaction of brief duration (mean 1.8 days) was most commonly reported; no children required medical care within 2 weeks postvaccination. Vaccine survey results of interviewed, vaccinated children and their parents/guardians: of 20 children with MIS-C and 15 children with COVID-19, 17 (85%) and 13 (87%), respectively, listed doctors in the top 3 most trusted sources for vaccine information; 13 (65%) and 9 (60%) discussed vaccination with their doctor. CONCLUSIONS: COVID-19 vaccination was well tolerated in children with prior MIS-C or COVID-19 participating in our investigation. Parents/guardians regarded their children's doctors as a trusted source of information for COVID-19 vaccines, and most vaccinated children's parents/guardians had discussed COVID-19 vaccination for their child with their doctor.

Council of State and Territorial Epidemiologists/CDC Surveillance Case Definition for Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 Infection - United States.

This report summarizes the evidence and rationale supporting the components of the CSTE/CDC MIS-C surveillance case definition and describes the methods used to develop the definition. These methods included convening MIS-C clinical experts (i.e., consultants): regarding identification of MIS-C and its distinction from other pediatric conditions, a review of available literature comparing MIS-C phenotype with that of pediatric COVID-19 and other hyperinflammatory syndromes, and retrospective application of different criteria to data from MIS-C cases previously reported to CDC.

Trends in Treatments for Multisystem Inflammatory Syndrome in Children (MIS-C), United States, February 2020 - July 2021.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a novel severe postinfectious condition associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The purpose of this report is to describe nationwide trends in the evolving clinical management of MIS-C. METHODS: Patients with MIS-C were reported from state and local jurisdictions to the Centers for Disease Control and Prevention's (CDC's) MIS-C national surveillance system. Patients' case reports were reviewed to ensure that they met the CDC MIS-C case definition and had sufficient data for analysis. The prevalence of use of treatments for MIS-C, temporal trends in use of these treatments, and frequency of administration of different treatment combinations were analyzed. RESULTS: There were 4470 patients meeting the MIS-C case definition with onset dates from 19 February 2020 to 31 July 2021. The proportion of patients admitted to an intensive care unit (ICU) has declined over time, from 78.7% in April 2020 to 57.5% in June 2021 (P = .001). The most common treatments were intravenous immunoglobulin (IVIG), given to 85.6% of patients; steroids (77.7%), and antiplatelet medications (73.7%); use of each of these treatments has increased over time, particularly in patients not requiring admission to an ICU (all P < .001). Older patients and non-Hispanic Black patients were more likely to receive additional modes of therapy including vasoactive medication, noninvasive respiratory support, anticoagulation medication, and intubation/mechanical ventilation. CONCLUSIONS: IVIG, steroids, and antiplatelet medication have become increasingly utilized as standard treatment for MIS-C patients, while the use of other treatments may be contingent on the type and severity of clinical findings.

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.