, during the peak of the coronavirus disease 2019 (COVID-19) pandemic in Europe, a cluster of children with hyperinflammatory shock with features similar to Kawasaki disease and toxic shock syndrome was reported in England* (1). The patients' signs and symptoms were temporally associated with COVID-19 but presumed to have developed 2-4 weeks after acute COVID-19; all children had serologic evidence of infection with SARS-CoV-2, the virus that causes COVID-19 (1). The clinical signs and symptoms present in this first cluster included fever, rash, conjunctivitis, peripheral edema, gastrointestinal symptoms, shock, and elevated markers of inflammation and cardiac damage (1). On May 14, 2020, CDC published an online Health Advisory that summarized the manifestations of reported multisystem inflammatory syndrome in children (MIS-C), outlined a case definition, † and asked clinicians to report suspected U.S. cases to local and state health departments. As of July 29, a total of 570 U.S. MIS-C patients who met the case definition had been reported to CDC. A total of 203 (35.6%) of the patients had a clinical course consistent with previously published MIS-C reports, characterized predominantly by shock, cardiac dysfunction, abdominal pain, and markedly elevated inflammatory markers, and almost all had positive SARS-CoV-2 test results. The remaining 367 (64.4%) of MIS-C patients had manifestations that appeared to overlap with acute COVID-19 (2-4), had a less severe clinical course, or had features of Kawasaki disease. § Median duration of hospitalization was 6 days; 364 patients (63.9%) required care in an intensive care * https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatricmultisystem-%20inflammatory%20syndrome-20200501.pdf. † The MIS-C case definition included a patient aged <21 years with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem organ involvement (cardiovascular, dermatologic, gastrointestinal, hematologic, neurologic, renal, or respiratory) who tested positive for SARS-CoV-2 or had exposure to COVID-19. https:// www.cdc.gov/mis-c/hcp/. § Kawasaki disease is an acute febrile illness of unknown cause, primarily affecting children, and associated with fever, rash, conjunctivitis, redness in the mouth, cracked lips, and swollen lymph nodes, feet, and hands.

On October 2, 2020, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr). During the course of the coronavirus disease 2019 (COVID-19) pandemic, reports of a new multisystem inflammatory syndrome in children (MIS-C) have been increasing in Europe and the United States (1-3). Clinical features in children have varied but predominantly include shock, cardiac dysfunction, abdominal pain, and elevated inflammatory markers, including C-reactive protein (CRP), ferritin, D-dimer, and interleukin-6 (1). Since June 2020, several case reports have described a similar syndrome in adults; this review describes in detail nine patients reported to CDC, seven from published case reports, and summarizes the findings in 11 patients described in three case series in peer-reviewed journals (4-6). These 27 patients had cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness and concurrently received positive test results for SARS-CoV-2, the virus that causes COVID-19, by polymerase chain reaction (PCR) or antibody assays indicating recent infection. Reports of these patients highlight the recognition of an illness referred to here as multisystem inflammatory syndrome in adults (MIS-A), the heterogeneity of clinical signs and symptoms, and the role for antibody testing in identifying similar cases among adults. Clinicians and health departments should consider MIS-A in adults with compatible signs and symptoms. These patients might not have positive SARS-CoV-2 PCR or antigen test results, and antibody testing might be needed to confirm previous SARS-CoV-2 infection. Because of the temporal association between MIS-A and SARS-CoV-2 infections interventions that prevent COVID-19 might prevent MIS-A. Further research is needed to understand the pathogenesis and long-term effects of this newly described condition. Potential MIS-A patients were identified from several sources: reports from clinicians and health departments, published case reports, and published case series. Clinicians and health departments in the United States voluntarily reported adult patients with suspected MIS-A to CDC using the case report form* developed for MIS-C after a Health Advisory was published on May 14, 2020, calling for reporting of MIS-C

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.

Objective To develop a more comprehensive description of multisystem inflammatory syndrome in children (MIS-C), a novel syndrome linked to SARS-CoV-2, by conducting a systematic analysis of studies from different settings which 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: three studies selected patients diagnosed with Kawasaki disease (KD), two required cardiovascular involvement, and three 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 SARS-CoV-2 RT-PCR tests ranged from 13 to 69% and for serology, from 75 to 100%. MIS-C patients 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.

On March 19, 2021, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr).School closures affected more than 55 million students across the United States when implemented as a strategy to prevent the transmission of SARS-CoV-2, the virus that causes COVID-19 (1). Reopening schools requires balancing the risks for SARS-CoV-2 infection to students and staff members against the benefits of in-person learning (2). During December 3, 2020-January 31, 2021, CDC investigated SARS-CoV-2 transmission in 20 elementary schools (kindergarten through grade 6) that had reopened in Salt Lake County, Utah. The 7-day cumulative number of new COVID-19 cases in Salt Lake County during this time ranged from 290 to 670 cases per 100,000 persons. † Susceptible § school contacts ¶ (students and staff members exposed to SARS-CoV-2 in school) of 51 index patients** (40 students and 11 staff members) were offered SARS-CoV-2 reverse transcriptionpolymerase chain reaction (RT-PCR) testing. Among 1,041 susceptible school contacts, 735 (70.6%) were tested, and five of 12 cases identified were classified as school-associated; the secondary attack rate among tested susceptible school contacts was 0.7%. Mask use among students was high (86%), and the median distance between students' seats in classrooms was 3 ft. Despite high community incidence and an inability to maintain ≥6 ft of distance between students at all times, SARS-CoV-2 transmission was low in these elementary schools.

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Background The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs. COVID-19 are poorly understood. Methods We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the CDC case definition for MIS-C (n=118), acute COVID-19 (n=88), or contemporaneous healthy controls (n=24). We measured SARS-CoV-2 spike receptor binding domain (RBD) IgG titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients. Results Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median 2783 vs. 146, P&lt;0.001), and titers correlated with nucleocapsid IgG. For patients with MIS-C, RBD IgG titers declined in convalescence (median 2783 vs. 1135, P=0.010) in contrast to patients with COVID-19 (146 vs. 4795, P&lt;0.001). MIS-C was characterized by transient acute pro-inflammatory hypercytokinemia, including elevated levels of IL-6, IL-10, IL-17A, and IFN-γ. Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization ≥8 days (PR 3.29 95% CI 1.17-9.23). Conclusions MIS-C was associated with high titers of SARS-COV-2 RBD IgG antibodies and acute hypercytokinemia with IL-6, IL-10, IL-17A, and IFN-γ.

Purpose The purpose of this study was to analyze trends in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and test positivity among persons aged <18 years in a three-site outpatient pediatric practice in Atlanta, Georgia, serving approximately 35,000 pediatric patients. Methods Using electronic medical records, weekly trends in SARS-CoV-2 tests performed and the 14-day moving average of test positivity were examined, overall and by age group, during May 24–December 5, 2020. Results Among 4,995 patients who received at least 1 SARS-CoV-2 test, 6,813 total tests were completed. Overall test positivity was 5.4% and was higher among older pediatric patients (<5 years: 3.3%; 5–11 years: 4.1%; 12–17 years: 8.6%). The number of tests and test positivity increased after holidays and school breaks. Conclusions Families might benefit from communication focused on reducing SARS-CoV-2 transmission during holidays. In addition, given higher test positivity in children aged 12–17 years, tailoring public health messaging to older adolescents could help limit SARS-CoV-2 transmission risk in this population.