key: cord-0296561-ptn9ntoq authors: Yousaf, A. R.; Cortese, M.; Taylor, A. W.; Broder, K. R.; Oster, M. E.; Wong, J. M.; Guh, A. Y.; McCormick, D. W.; Kamidani, S.; Schlaudecker, E.; Edwards, K.; Creech, C. B.; Staat, M. A.; Belay, E. D.; Marquez, P.; Su, J. R.; Salzman, M. B.; Thompson, D.; Campbell, A. P.; Group, MIS-C Investigation Authorship title: Reported Cases of Multisystem Inflammatory Syndrome in Children Aged 12 to 20 Years in the United States Who Received COVID-19 Vaccine, December 2020 through August 2021 date: 2022-01-05 journal: nan DOI: 10.1101/2022.01.03.22268681 sha: 26395bd5fbdad6765e7cd8cd76e5bed7a8d949eb doc_id: 296561 cord_uid: ptn9ntoq Multisystem inflammatory syndrome (MIS-C) in children is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the United States, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorizations. This case series describes persons aged 12 to 20 years with MIS-C following COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to CDC. We investigated potential cases of MIS-C after COVID-19 vaccination reported to health department-based national CDC MIS-C surveillance, the Vaccine Adverse Event Reporting System (VAERS, co-administered by CDC and the U.S. FDA), and the Clinical Immunization Safety Assessment Project (CISA) from December 14, 2020, to August 31, 2021. We describe cases meeting the CDC MIS-C case definition. Any positive SARS-CoV-2 serology test satisfied the case criteria although anti-nucleocapsid antibody indicates SARS-CoV-2 infection, while anti-spike protein antibody indicates either infection or COVID-19 vaccination. We identified 21 persons with MIS-C after COVID-19 vaccination. Of these 21 persons, median age was 16 years (range, 12 to 20 years); 13 (62%) were male. All were hospitalized; 12 (57%) had intensive care unit admission, and all were discharged home. Fifteen (71%) of the 21 had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. Through August 2021, 21,335,331 persons aged 12 to 20 years had received one or more doses of COVID-19 vaccine, making the overall reporting rate for MIS-C following vaccination 1.0 case per million persons receiving one or more vaccine doses in this age group. The reporting rate for those without evidence of SARS-CoV-2 infection was 0.3 cases per million vaccinated persons. In our case series, we describe a small number of persons with MIS-C who had received one or more COVID-19 vaccine dose before illness onset. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted. surveillance has limitations, but our findings suggest that MIS-C as identified in this report following COVID-19 vaccination is rare. In evaluating persons with a clinical presentation consistent with MIS-C after COVID-19 vaccination it is important to consider alternative diagnoses, and anti-nucleocapsid antibody testing may be helpful. Continued surveillance for MIS-C illness after COVID-19 vaccination is warranted, especially as pediatric COVID-19 vaccination expands. Providers are encouraged to report potential MIS-C cases after COVID-19 vaccination to VAERS. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. ; https://doi.org/10.1101/2022.01.03.22268681 doi: medRxiv preprint Multisystem inflammatory syndrome in children (MIS-C), also known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), is a rare but serious complication of SARS-CoV-2 infection in children and adolescents that generally occurs 2-6 weeks after SARS-CoV-2 infection. 1, 2 MIS-C, first recognized in April, 2020, is characterized by fever, systemic inflammation, shock, and multisystem organ involvement. [1] [2] [3] [4] [5] [6] From May 14, 2020, through November 30, 2021, 5,973 cases were reported to the CDC's MIS-C national surveillance system. 7 The pathogenesis of MIS-C is hypothesized to involve a dysregulated immune response to SARS-CoV-2 infection; host genetics may alter susceptibility to developing MIS-C. [8] [9] [10] [11] CDC and the Food and Drug Administration (FDA) included MIS-C on a list of adverse events of special interest (AESI) for COVID-19 vaccine safety monitoring after emergency use authorization of COVID-19 vaccines in the United States, because of its known association with SARS-CoV-2 infection. 12, 13 All COVID-19 vaccines currently authorized for use in the United States require reporting of this condition after COVID-19 vaccination. 14 International vaccine and pharmacovigilance experts have also supported the need for close monitoring of MIS-C after COVID-19 vaccination. 15, 16 Conducting surveillance for MIS-C after COVID-19 vaccination is challenging because MIS-C in general is a difficult diagnosis to make as it has no specific biomarker and may resemble other disease processes, including acute COVID-19 infection, Kawasaki disease, and toxic shock syndrome. [1] [2] [3] [4] [5] Also, with wide circulation of SARS-CoV-2 occurring concurrently with administration of millions of COVID-19 vaccine doses, some cases of MIS-C caused by SARS-CoV-2 infections acquired before vaccine protection are expected to occur by chance alone and will appear to be temporally associated with vaccine; after a full vaccine series, some MIS-C cases from SARS-CoV-2 infection may occur as protection against infection is <100%. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. We investigated reports of potential MIS-C in persons aged 12-20 years who had previously received COVID-19 vaccine during the initial months of the U.S. COVID-19 vaccination program, a period when there was widespread SARS-CoV-2 circulation. We aimed to describe the demographic and clinical features of MIS-C after COVID-19 vaccination, including information on past SARS-CoV-2 infection and COVID-19 vaccination. We identified potential MIS-C cases occurring any time after COVID-19 vaccination in persons aged 12─20 years at time of MIS-C illness onset through CDC's MIS-C national surveillance system, VAERS, and clinician or health department outreach to CDC and the CISA Project. 7, 17-19 We investigated reports to determine if the illnesses met the CDC MIS-C case definition. The CDC MIS-C case definition requires fever, hospitalization with an illness with multisystem organ involvement, laboratory evidence of inflammation, and a positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR), viral antigen, or serology test or recent exposure to a confirmed COVID-19 case ( Figure 1 ). 6 This definition was published before COVID-19 vaccination authorization. While anti-nucleocapsid antibody is indicative of prior or current SARS-CoV-2 infection, anti-spike protein antibody may be induced either by SARS-CoV-2 infection or by COVID-19 vaccination (including the three vaccines authorized in the United States). 14 A positive anti-spike or anti-nucleocapsid antibody can be used to satisfy the SARS-CoV-2 test criterion of the CDC case definition. CDC's national MIS-C surveillance is a passive reporting system in which health departments voluntarily report cases of MIS-C; collection of COVID-19 vaccination status began May 21, 2021. 7 We All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. ; https://doi.org/10.1101/2022.01.03.22268681 doi: medRxiv preprint queried the national MIS-C surveillance system twice weekly for persons with MIS-C illness onset date after vaccination date. We reviewed reports weekly of persons with MIS-C onset after COVID-19 vaccination made to VAERS, a passive national surveillance system for vaccine adverse events jointly managed by CDC and FDA which receives spontaneous reports from healthcare providers, health departments, vaccine manufacturers, and the public. 18, 19 We searched VAERS weekly for reports with coding or free text mention of possible multisystem inflammation or MIS-C (Supplemental Table 1 ). Additionally, clinicians at CDC and FDA reviewing selected VAERS reports as part of COVID-19 surveillance vaccine safety surveillance referred reports of potential MIS-C to our team for further review. We also received notification of potential MIS-C cases if a provider contacted the MIS-C national surveillance team or requested a CISA consultation. 17 We encouraged reporting to VAERS for cases first detected by MIS-C national surveillance or through outreach to CDC. We did not specify a maximum interval from COVID-19 vaccination to illness onset in any system searches. A multidisciplinary team consisting of clinical and surveillance staff from CDC, FDA, and investigators from CDC's CISA Project adjudicated cases together at least twice monthly. CDC physicians reviewed medical records and presented case summaries to the team. Some potential cases were also discussed with the treating clinicians and health department officials when additional information was needed for adjudication. The investigation team sometimes provided suggestions for laboratory testing; however, clinical evaluation of alternative diagnoses was at the discretion of the treating clinicians. Persons in whom the study team considered myocarditis as a plausible alternative diagnosis based on clinical judgment received additional review with CISA cardiologists to differentiate between myocarditis and cardiac manifestations of MIS-C. 20 Persons with potential MIS-C after vaccination were classified into two groups: 1) meeting the CDC MIS-C case definition, or 2) not meeting for the CDC MIS-C case definition. Persons with MIS-C were further stratified by laboratory evidence of past or recent SARS-CoV-2 infection. Laboratory evidence of All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. ; https://doi.org/10.1101/2022.01.03.22268681 doi: medRxiv preprint infection was defined as any positive SARS-CoV-2 nucleic acid amplification test (NAAT), including RT-PCR, or viral antigen test before or during MIS-C illness evaluation, or a positive anti-nucleocapsid antibody test during MIS-C illness evaluation. Persons were classified as having no evidence of SARS-CoV-2 infection if they satisfied all of the following: 1) no known history of a positive SARS-CoV-2 test before MIS-C illness onset, 2) a negative SARS-CoV-2 NAAT and/or viral antigen test during MIS-C illness evaluation, and 3) a negative anti-nucleocapsid antibody test during MIS-C illness evaluation. Persons who met these criteria and tested positive for anti-spike antibody were also considered to have no laboratory evidence of SARS-CoV-2 infection as anti-spike antibody was presumed to be vaccine-derived. All potential cases were also assessed using the case definition of the Brighton Collaboration for MIS-C cases; this definition differs from the CDC MIS-C case definition in that it uses a tiered approach to diagnostic certainty and uniquely includes COVID-19 vaccination status as a criterion. 15 We collected demographic and clinical features of persons with MIS-C from records provided by reporting providers. We defined clinical phenotypes using CDC MIS-C organ system involvement criteria We obtained number of vaccine doses administered to persons in the United States aged 12-20 years and number of persons in this age group who had received ≥1 dose through August 31, 2021 from CDC national vaccine surveillance data. 21 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. ; https://doi.org/10.1101/2022.01.03.22268681 doi: medRxiv preprint This activity was determined by CDC to meet criteria for public health surveillance as defined in 45 CFR §46.102(I) (2) . To protect patient privacy, we present persons by age group, and present some demographic and clinical details in aggregate. Table 3 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. ; https://doi.org/10.1101/2022.01.03.22268681 doi: medRxiv preprint Of the 21 persons with MIS-C, 15 (71%) had evidence of SARS-CoV-2 infection (Tables 1, 2) . Among these 15 persons with laboratory evidence of infection: ten (67%) were NAAT or viral antigen positive, and five (33%) were anti-nucleocapsid antibody positive and NAAT negative during MIS-C illness with no known positive NAAT or viral antigen test before MIS-C (Table 2 ). Of those that were NAAT or antigen positive, four had a positive test during MIS-C illness evaluation, one during and also 133 days before MIS-C illness, and five only before MIS-C illness. Of the five persons who were NAAT or viral antigen positive only before MIS-C illness, four were anti-nucleocapsid antibody positive during MIS-C illness, and one was negative (Table 3) . Seven (47%) were aged 12-15 years, five (33%) aged 16-17 years, and three (20%) aged 18-20 years (Table 1 ). Ten (67%) were male. Four (27%) each were Hispanic and White Non-Hispanic persons and three (20%) were Black Non-Hispanic. The following organ systems were most commonly involved during MIS-C illness: 14 (93%) gastrointestinal, 13 (87%) hematologic, and 13 (87%) cardiac (Supplemental Table 4 ). Upon assessment using the Brighton case definition, 12 (80%) were definitive or probable cases and three (20%) would not be considered cases (Supplemental Table 4 ). All 15 persons with laboratory evidence of SARS-CoV-2 infection had received Pfizer-BioNTech COVID-19 vaccine (the only U.S. COVID-19 vaccine authorized for use in persons aged <18 years during our surveillance), with 10 (66%) receiving one dose and five (33%) receiving two doses before MIS-C illness onset (Table 2) . Median time from most recent vaccine dose to MIS-C onset was eight (range 1-30) days for those who had received only one dose, and five (range 3-48) days for those who had received two doses (Table 3 , Supplemental Figure 1 ). During their MIS-C hospitalization, 13 (87%) persons were treated with intravenous immunoglobulin (IVIG), 12 (80%) with systemic steroids, and five (33%) with an immune modulator (Table 4 ). Eight (53%) were admitted to the intensive care unit (ICU). Median length of hospital stay was seven (range 2-20) days. All 15 persons clinically improved and were discharged home. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. ; https://doi.org/10.1101/2022.01.03.22268681 doi: medRxiv preprint Of the 21 persons with MIS-C, six (29%) had positive anti-spike antibody testing only (Tables 1, 2 ) and were classified as not having laboratory evidence of SARS-CoV-2 infection (Figure 2 ). None of these persons had a history of a positive SARS-CoV-2 test before MIS-C illness, and all had negative SARS-CoV-2 NAAT and anti-nucleocapsid antibody tests during MIS-C illness ( Table 3) . Of the six, three (50%) were aged 12-15 years and three (50%) aged 18-20 years (Table 1) . Three (50%) were male; four (67%) were White Non-Hispanic (Table 1) . These persons presented with varied organ system involvement: six (100%) cardiac (including two with shock), and five (83%) hematologic (Supplemental Table 5 ). Applying the Brighton case definition, all were definitive or probable cases (Supplemental Table 5 ). All had received Pfizer-BioNTech vaccine; one person (11%) received only one dose five days before MIS-C onset, and five (83%) received two doses before MIS-C illness onset (Table 2) . Median time from vaccination with dose 2 to MIS-C onset was 14 (range 0-84) days for those who received two doses (Table 3 , Supplemental Figure 2 ). Four (67%) persons were treated for MIS-C with IVIG, four (67%) with systemic steroids (Table 4 ). Median length of stay was six days (range 3-7) days. Four (67%) were admitted to the ICU; all six clinically improved and were discharged home. As part of the United States' comprehensive efforts to monitor COVID-19 vaccine safety following authorization, we investigated reported potential U.S. MIS-C cases during a period of widespread SARS-CoV-2 circulation. In this case series, we describe 21 persons with illness meeting the CDC MIS-C case definition. All received the Pfizer-BioNTech vaccine, consistent with the age eligibility of All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. We identified six cases of MIS-C that occurred following COVID-19 vaccination without evidence of SARS-CoV-2 infection, a reporting rate of 6/21,335,331, or 0.3 cases per million persons aged 12-20 years who had received ≥1 dose of COVID-19 vaccine. It has been hypothesized that a dysregulated immune response associated with SARS-CoV-2 infection may potentially also be associated with exposure to COVID-19 vaccine. 10, 15, 23 As with our cases who had evidence of prior infection outside of the usual period for development of MIS-C, the contribution of vaccination, if any, to the illnesses in cases without evidence of infection is unknown and cannot be determined with our surveillance data. It is possible some of these six cases had other unrecognized inflammatory conditions. Because the prepandemic background incidence of illnesses with unidentified etiology that would meet the clinical criteria of the MIS-C case definition is unknown, we cannot estimate how often such illnesses would be expected to occur temporally associated with vaccine by chance alone. In addition, given the limitations All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. anti-nucleocapsid antibody testing was not performed. 29 Several adults have also been reported with All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. ; https://doi.org/10.1101/2022.01.03.22268681 doi: medRxiv preprint MIS-A following COVID-19 vaccination, most of whom had evidence of previous SARS-CoV-2 infection. 23, 26 This investigation highlights the challenges of diagnosing MIS-C and importance of a thorough clinical evaluation. While the CDC MIS-C case definition can be met with any type of SARS-CoV-2 antibody test (anti-spike, anti-nucleocapsid, or undifferentiated), testing for anti-nucleocapsid antibody in persons with suspected MIS-C after COVID-19 vaccination may differentiate between vaccine-versus infection-derived antibody. As noted above, however, antibody titers can wane over time. Conversely, as cumulatively higher rates of SARS-CoV-2 infection result in higher anti-nucleocapsid seroprevalence among children, without a test available to indicate how recently SARS-CoV-2 infection occurred, detection of anti-nucleocapsid antibody may be coincidental and may not distinguish MIS-C from other clinically similar syndromes (e.g., toxic shock syndrome). Therefore, a thorough clinical evaluation to elucidate alternative etiologies is important, as many conditions can mimic MIS-C (Supplemental Table 3 ). All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. ; https://doi.org/10.1101/2022.01.03.22268681 doi: medRxiv preprint vaccination and also symptoms of MIS-C. Clinical and laboratory workup was not standardized across cases, and although cases were adjudicated by an interdisciplinary team, there is no definitive diagnostic test to confirm MIS-C. In conclusion, during the first nine months of the COVID-19 vaccination program in the United States, a period when SARS-CoV-2 was widely circulating, we identified a small number of persons aged 12─20 years with MIS-C after COVID-19 vaccination; most had laboratory evidence of past or recent SARS-CoV-2 infection. The surveillance has limitations, but our findings suggest that MIS-C without evidence of SARS-CoV-2 infection is rare following COVID-19 vaccination (reporting rate <1 case per million vaccinated persons aged 12-20 years). In evaluating persons with an MIS-C clinical presentation after COVID-19 vaccination, it is important to consider alternative diagnoses, and anti-nucleocapsid antibody testing may be helpful. Continued surveillance for MIS-C illness after COVID-19 vaccination is warranted, especially as pediatric COVID-19 vaccination expands, and providers are encouraged to report potential MIS-C cases after COVID-19 vaccination to VAERS at https://vaers.hhs.gov. Tom Shimabukuro. We would like to thank all local, state, and territorial health departments that contributed MIS-C reports to this investigation. We would like to thank all health care providers who made reports to VAERS and who were involved in the care of the patients described in this investigation. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the Food and Drug Administration. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. We declare no competing interests. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. ; https://doi.org/10.1101/2022.01.03.22268681 doi: medRxiv preprint Cardiac involvement includes elevated troponin, elevated B-type natriuretic peptide (BNP)/ N-terminal pro hormone BNP (NT-proBNP), arrythmia, coronary artery aneurysm, cardiac dysfunction, or shock; 2 Renal involvement includes acute kidney injury or renal failure; 3 Respiratory involvement includes pneumonia, acute respiratory distress syndrome (ARDS), pleural effusion; 4 Hematologic involvement includes elevated D-dimer, thrombophilia, thrombocytopenia; 5 Gastrointestinal involvement includes elevated bilirubin, elevated liver enzymes, diarrhea; 6 Dermatologic involvement includes rash or mucocutaneous lesions; 7 Neurologic involvement includes cerebrovascular accident, aseptic meningitis encephalopathy, or headache; 8 Laboratory evidence of inflammation includes elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), interleukin 6 (IL-6), or neutrophils, or reduced lymphocytes or albumin; ⁹For this investigation, this criterion could be satisfied by any type of nucleic acid amplification test (NAAT); 10 The exposure criterion was not used in this investigation Must meet all the following clinical and laboratory criteria: (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. 1 Reports were ruled out by the VAERS report alone if they were the incorrect age or if MIS-C could be clearly ruled out based on the VAERS report. 2 Two persons were reported to MIS-C national surveillance but not to VAERS, and medical records have not been obtained. Both had reported MIS-C after 1 dose of COVID-19 vaccine, and both had SARS-CoV-2 nucleic acid amplification test (NAAT) and IgG positive; both clinically improved and were discharged home. 3 Defined as an illness meeting the CDC MIS-C clinical and inflammatory criteria with a positive NAAT, viral antigen, or anti-nucleocapsid antibody test during or before MIS-C illness evaluation 4 Defined as an illness meeting the CDC MIS-C clinical and inflammatory criteria with negative NAAT and anti-nucleocapsid antibody tests and a positive anti-spike antibody positive test during MIS-C illness evaluation 5 Three individuals with an illness after vaccination meeting the CDC MIS-C clinical and inflammatory criteria, a negative anti-nucleocapsid antibody test and negative NAAT test during MIS-C evaluation, and anti-spike antibody test not obtained VAERS: Vaccine Adverse Event Reporting System; CISA: Clinical Immunization Safety Assessment Project; FDA: Food and Drug Administration Other race= one with multiple races, one with unknown race 2 Other conditions listed in medical charts included mental health conditions, gastroesophageal reflux disorder, herniated disc with sciatica. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. ; https://doi.org/10.1101/2022.01.03.22268681 doi: medRxiv preprint Table 2 1 (17) 5 (83) 1 Includes five persons with positive SARS-CoV-2 NAAT tests before MIS-C illness, four persons with positive SARS-CoV-2 NAAT tests during MIS-C illness, and one person with a positive SARS-CoV-2 NAAT test before and during MIS-C illness 2 Includes NAAT results from during MIS-C illness evaluation; these individuals did not have any reported positive NAAT results before MIS-C illness All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 5, 2022. ; https://doi.org/10.1101/2022.01.03.22268681 doi: medRxiv preprint Table 3 . SARS-CoV-2 testing and temporal features of 21 persons with multisystem inflammatory syndrome in children (MIS-C) following COVID-19 vaccination-United States, December 2020 through August 2021 Multisystem Inflammatory Syndrome in U.S. Children and Adolescents Multisystem Inflammatory Syndrome in Children in New York State Multisystem inflammatory syndrome in children related to COVID-19: a systematic review Hyperinflammatory shock in children during COVID-19 pandemic Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19 Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum Immune pathogenesis of COVID-19-related multisystem inflammatory syndrome in children No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity Mechanisms underlying genetic susceptibility to multisystem inflammatory syndrome in children (MIS-C) SARS-CoV-2-related MIS-C: A key to the viral and genetic causes of Kawasaki disease? Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines. Vaccine Rapid Cycle Analysis (RCA) to monitor the safety of COVID-19 vaccines in near real-time within the Vaccine Safety Datalink. 2021 14. FDA. COVID-19 Vaccines Multisystem inflammatory syndrome in children and adults Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) Vaccine Adverse Event Reporting System (VAERS) Standard Operating Procedures for COVID-19 Comparison of MIS-C Related Myocarditis, Classic Viral Myocarditis, and COVID-19 Vaccine related Myocarditis in Children About COVID-19 Vaccine Delivered and Administration Data Incidence of Multisystem Inflammatory Syndrome in Children Among US Persons Infected With SARS-CoV-2 Multisystem Inflammatory Syndrome after SARS-CoV-2 Infection and COVID-19 Vaccination. Emerg Infect Dis Rapid Decay of Anti-SARS-CoV-2 Antibodies in Persons with Mild Covid-19 Lack of Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a Large Cohort of Previously Infected Persons Multisystem Inflammatory Syndrome in Adults after SARS-CoV-2 infection and COVID-19 vaccination Multisystem inflammatory syndrome in a male adolescent after his second Pfizer-BioNTech COVID-19 vaccine Treatment and outcomes for 21 persons with multisystem inflammatory syndrome in children (MIS-C) following -+ -NA 2 42 21 18 No -+ -NA 2 35 14 19 No -+ -NA 2 104 84 20 No -+ -NA 2 26 5 21 No -+ -NA 2 Immune modulators: three persons treated with anakinra; two persons treated with infliximab 2 In addition, one person (not counted here) with a positive SARS-CoV-2 NAAT during MIS-C illness received an unspecified anti-viral medication