, 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
IMPORTANCE Multiple inflammatory syndrome in children (MIS-C) occurs in association with the COVID-19 pandemic. OBJECTIVE To describe the clinical characteristics and geographic and temporal distribution of the largest cohort of patients with MIS-C in the United States to date. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analysis was conducted on clinical and laboratory data collected from patients with MIS-C. The analysis included patients with illness onset from March 2020 to January 2021 and met MIS-C case definition.MAIN OUTCOMES AND MEASURES Geographic and temporal distribution of MIS-C was compared with that of COVID-19 nationally, by region, and level of urbanicity by county. Clinical and laboratory findings and changes over time were described by age group and by presence or absence of preceding COVID-19.RESULTS A total of 1733 patients with MIS-C were identified; 994 (57.6%) were male and 1117 (71.3%) were Hispanic or non-Hispanic Black. Gastrointestinal symptoms, rash, and conjunctival hyperemia were reported by 53% (n = 931) to 67% (n = 1153) of patients. A total of 937 patients (54%) had hypotension or shock, and 1009 (58.2%) were admitted for intensive care. Cardiac dysfunction was reported in 484 patients (31.0%), pericardial effusion in 365 (23.4%), myocarditis in 300 (17.3%), and coronary artery dilatation or aneurysms in 258 (16.5%). Patients aged 0 to 4 years had the lowest proportion of severe manifestations, although 171 patients (38.4%) had hypotension or shock and 197 (44.3%) were admitted for intensive care. Patients aged 18 to 20 years had the highest proportions with myocarditis (17 [30.9%]), pneumonia (20 [36.4%]), acute respiratory distress syndrome (10 [18.2%]), and polymerase chain reaction positivity (39 [70.9%]). These older adolescents also had the highest proportion reporting preceding COVID-19-like illness (63%). Nationally, the first 2 MIS-C peaks followed the COVID-19 peaks by 2 to 5 weeks. The cumulative MIS-C incidence per 100 000 persons younger than 21 years was 2.1 and varied from 0.2 to 6.3 by state. Twenty-four patients (1.4%) died. CONCLUSIONS AND RELEVANCEIn this cross-sectional study of a large cohort of patients with MIS-C, 2 peaks that followed COVID-19 peaks by 2 to 5 weeks were identified. The geographic and temporal association of MIS-C with the COVID-19 pandemic suggested that MIS-C resulted from delayed immunologic responses to SARS-CoV-2 infection. The clinical manifestations varied by age and by presence or absence of preceding COVID-19.
COVID-19-associated deaths were reported in the United States (1). Understanding the demographic and clinical characteristics of decedents could inform medical and public health interventions focused on preventing COVID-19-associated mortality. This report describes decedents with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19, using data from 1) the standardized CDC case-report form (case-based surveillance) (https://www.cdc.gov/coronavirus/2019-ncov/php/ reporting-pui.html) and 2) supplementary data (supplemental surveillance), such as underlying medical conditions and location of death, obtained through collaboration between CDC and 16 public health jurisdictions (15 states and New York City). Case-based surveillanceDemographic and clinical data about COVID-19 cases are reported to CDC from 50 states, the District of Columbia, New York City, and U.S. territories using a standardized case-report form (case-based surveillance) or in aggregate. Data on 52,166 deaths from 47 jurisdictions among persons with laboratoryconfirmed COVID-19 were reported individually to CDC via case-based surveillance during February 12-May 18, 2020. Among the 52,166 decedents, 55.4% were male, 79.6% were aged ≥65 years, 13.8% were Hispanic/Latino (Hispanic), 21.0% were black, 40.3% were white, 3.9% were Asian, 0.3% were American Indian/Alaska Native (AI/AN), 0.1% were Native Hawaiian or other Pacific Islander (NHPI), 2.6% were multiracial or other race, and race/ethnicity was unknown for 18.0%. (Table 1). Median decedent age was 78 years (interquartile range (IQR) = 67-87 years). Because information about underlying medical conditions was missing for the majority of these decedents (30,725; 58.9%), data regarding medical conditions were not analyzed further using the case-based surveillance data set. Because most decedents reported to the supplementary data program were also reported to case-based surveillance, no statistical comparisons of the decedent characteristics between the data sets were made. * Underlying medical conditions include cardiovascular disease (congenital heart disease, coronary artery disease, congestive heart failure, hypertension, cerebrovascular accident/stroke, valvular heart disease, conduction disorders or dysrhythmias, other cardiovascular disease); diabetes mellitus; chronic lung disease (chronic obstructive pulmonary disease/emphysema, asthma, tuberculosis, other chronic lung diseases); immunosuppression (cancer, human immunodeficiency virus (HIV) infection, identified as being immunosuppressed); chronic kidney disease (chronic kidney disease, end-stage renal disease, other kidney diseases); neurologic conditions (dementia, seizure disorder, other neurologic conditions); chronic liver disease (cirrhosis, alcoholic hepatitis, chronic liver disease, end-stage liver disease, hepatitis B, hepatitis C, nonalcoholic steatohepatitis, other chronic liver diseases); obesity (body mass index ≥30 kg/m 2 ). Information was collected from decedent medical records or death certificates. ...
, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2-associated deaths have been reported in the United States (1,2). Symptoms associated with SARS-CoV-2 infection are milder in children compared with adults (3). Persons aged <21 years constitute 26% of the U.S. population (4), and this report describes characteristics of U.S. persons in that population who died in association with SARS-CoV-2 infection, as reported by public health jurisdictions. Among 121 SARS-CoV-2-associated deaths reported to CDC among persons aged <21 years in the United States during February 12-July 31, 2020, 63% occurred in males, 10% of decedents were aged <1 year, 20% were aged 1-9 years, 70% were aged 10-20 years, 45% were Hispanic persons, 29% were non-Hispanic Black (Black) persons, and 4% were non-Hispanic American Indian or Alaska Native (AI/AN) persons. Among these 121 decedents, 91 (75%) had an underlying medical condition,* 79 (65%) died after admission to a hospital, and 39 (32%) died at home or in the emergency department (ED). † These data show that nearly three quarters of SARS-CoV-2-associated deaths among infants, children, adolescents, and young adults have occurred in persons aged 10-20 years, with a disproportionate percentage among young adults aged 18-20 years and among Hispanics, Blacks, AI/ANs, and persons with underlying medical conditions. Careful monitoring of SARS-CoV-2 * https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/peoplewith-medical-conditions.html. † Location of death for all cases (121): hospital (79 [65.3%]), home (16 [13.2%]), ED (23 [19.0%]), hospice (one [0.8%]), and unknown (2 [1.7%]).
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