Multisystem inflammatory syndrome in children and adults (MIS-C/A): Case definition & guidelines for data collection, analysis, and presentation of immunization safety data

Abstract

This is a Brighton Collaboration Case Definition of the term "Multisystem Inflammatory Syndrome in Children and Adults (MIS-C/A)" to be utilized in the evaluation of adverse events following immunization. The case definition was developed by topic experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2. The format of the Brighton Collaboration was followed, including an exhaustive review of the literature, to develop a consensus definition and defined levels of certainty. The document underwent peer review by the Brighton Collaboration Network and by selected expert external reviewers prior to submission. The comments of the reviewers were taken into consideration and edits incorporated into this final manuscript.

Keywords: Adults; Adverse event; Case definition; Children; Guidelines; Immunization; MIS-A; MIS-C; Multisystem inflammatory syndrome.

Fig. 1

Timeline of initial recognition and description of MIS-C. Abbreviations: UK, United Kingdom; PICU, pediatric intensive care unit; RCPCH, Royal College of Paediatricians and Child Health; PIMS-TS, pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2; NY, New York; Dept., department; KD, Kawasaki Disease; CDC, Centers for Disease Control and Prevention; MIS-C, multisystem inflammatory syndrome in children; WHO, World Health Organization.

Fig. 2

Potential post-vaccination scenarios. A. Persons naïve to SARS-CoV-2 infection may be vaccinated against SARS-CoV-2 and then develop an illness for which they are evaluated for MIS-C/A. B. Persons who have had COVID-19 may subsequently be vaccinated to SARS-CoV-2 and then develop an illness for which they are evaluated for MIS-C/A. C. Persons who have already been vaccinated to SARS-CoV-2 (whether or not they previously had COVID-19) may then become infected/reinfected with SARS-CoV-2, and then develop an illness for which they are evaluated for MIS-C/A.

Fig. 3

Algorithm for utilization of the case definition for MIS-C/A. Note: Minimal to mild respiratory symptoms may be present and does not exclude a case of MIS-C/A, however a case must be excluded if there is concern for COVID-19-related pulmonary disease. One of the critical components of the case definition is that it is only applied when there is no clear alternative diagnosis for the reported event. Footnotes: ^a MIS-C=multisystem inflammatory syndrome in children, MIS-A=multisystem inflammatory syndrome in adults, CRP=C reactive protein (detected by any measure), ESR=erythrocyte sedimentation rate, BNP=brain natriuretic protein, NT-proBNP=N terminal pro-BNP, EKG=electrocardiogram, SARS-CoV-2=severe acute respiratory syndrome coronavirus-2, COVID-19=coronavirus disease 2019. ^b rash, erythema or cracking of the lips/mouth/pharynx, bilateral nonexudative conjunctivitis, erythema or edema of the hands or feet. ^c abdominal pain, vomiting, diarrhea. ^d altered mental status, headache, weakness, paresthesias, lethargy. ^e laboratory values are defined as low or high based on local laboratory norms. ^f echocardiographic signs: dysfunction, wall motion abnormality, coronary abnormality (dilation, aneurysm, echobrightness, lack of distal tapering), valvular regurgitation, pericardial effusion, evidence of abnormal left ventricular strain. ^g physical stigmata of heart failure: gallop (IF diagnosed by expert) or rales, lower extremity edema, jugular venous distension, hepatosplenomegaly. ^h EKG changes consistent with myocarditis or myo-pericarditis: abnormal ST segments and/or arrhythmia and/or pathologic Q waves and/or AV conduction delay and/or PR segment depression and/or low voltage QRS. ^I laboratory evidence of SARS-CoV-2 infection: serologic evidence of SARS-CoV-2 infection OR SARS-CoV-2 antigen positivity OR SARS-CoV-2 nucleic acid amplification positivity. ^j if a known or suspected COVID-19 infection has not occurred within the preceding 12 weeks.