Paeds · infectious-diseases
COVID-19 and multisystem inflammatory syndrome in children
Also known as Multisystem inflammatory syndrome in children · MIS-C · Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 · PIMS-TS · Paediatric inflammatory multisystem syndrome · Kawa-COVID-19
Fellowship guide to COVID-19 and multisystem inflammatory syndrome in children (MIS-C/PIMS-TS): the delayed post-SARS-CoV-2 hyperinflammatory phenotype, recognition of the toxic febrile school-age child, differentiation from Kawasaki disease and toxic shock, the pivotal echocardiogram and cardiac biomarkers, immunomodulation with IVIG and corticosteroids, cautious fluid resuscitation, anticoagulation decisions, and cardiac follow-up.
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Red flags
- A school-age child with persistent fever, abdominal pain, and shock appearing two to six weeks after a COVID-19 illness or exposure
- Persistent fever with conjunctivitis, rash, red cracked lips, and tachycardia suggesting Kawasaki-like vasculitis
- Hypotension or poor perfusion with raised inflammatory markers and a falling or rising troponin or BNP
- An infant or child with a SARS-CoV-2 PCR that is negative yet serology positive, fitting the post-infectious interval
- Severe abdominal pain mimicking appendicitis in a febrile, toxic child after recent COVID-19
- Coronary artery dilation or aneurysm, depressed left ventricular function, or pericardial effusion on echocardiography
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- Recognises multisystem inflammatory syndrome in children as a delayed post-COVID-19 hyperinflammatory emergency
- Distinguishes MIS-C from acute paediatric COVID-19, Kawasaki disease, and septic shock
- Initiates resuscitation and early referral when a school-age child presents with persistent fever and organ dysfunction
- Justifies immunomodulation with IVIG and corticosteroids and the role of adjunctive biologics
- Interprets cardiac biomarkers, inflammatory markers, and echocardiographic coronary Z-scores
- Manages shock, cardiac dysfunction, and prothrombotic complications of MIS-C
- Initial management of a school-age child with persistent fever, abdominal pain, and shock following COVID-19
- Role of SARS-CoV-2 serology and echocardiography in confirming MIS-C
- Cautious fluid resuscitation and early vasoactive support in MIS-C shock
- Bedside assessment of the toxic febrile school-age child with multiorgan involvement
- Communication of the MIS-C diagnosis, immunomodulation plan, and cardiac follow-up
- Balancing sepsis exclusion with timely immunomodulation
- Level 1: Recognises the unwell child and the possibility of MIS-C after SARS-CoV-2
- Level 2: Investigation and initial management including IVIG, steroids, and echocardiography
- Level 3: Management of refractory MIS-C, coronary complications, and long-term follow-up
- Case definition, epidemiology, and pathophysiology of MIS-C
- Differential diagnosis and distinguishing MIS-C from Kawasaki disease and toxic shock
- Immunomodulation, anticoagulation, and cardiac surveillance in MIS-C
- History and examination of the child with persistent fever and multiorgan involvement
- Communication of the diagnosis and management plan with the family
- Structured assessment of the child with shock following COVID-19
- Recognition and resuscitation of the child with multisystem inflammatory syndrome
- Echocardiographic assessment and cardiac biomarker interpretation
- Immunomodulation strategy and anticoagulation decisions
- Appropriate use of inflammatory, cardiac, and SARS-CoV-2 testing
- Multidisciplinary management and follow-up planning
- Canadian Paediatric Society approach to MIS-C recognition and management
- Cardiac surveillance including coronary Z-scores and serial echocardiography
- Public health notification and surveillance of post-COVID inflammatory syndromes
Overview & Definition
Picture a previously well nine-year-old who had a mild sore throat and fever three weeks ago, dismissed as a virus. Today she returns with unremitting fever, abdominal pain, a strange rash, red eyes, and a heart rate that will not settle. This is the signature presentation of multisystem inflammatory syndrome in children, a delayed, immune-driven, hyperinflammatory condition that follows SARS-CoV-2 infection by two to six weeks. It is not acute COVID-19 — the virus has largely been cleared — but the immune response that follows it. The UK and Europe historically called it paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2, abbreviated PIMS-TS, while North America uses multisystem inflammatory syndrome in children, or MIS-C. The two terms describe the same entity, and recognising that this is a post-infectious syndrome rather than a new infection is the single most important conceptual step. [2]
The case definition turns on four pillars: persistent fever, laboratory evidence of inflammation, involvement of at least two organ systems, and current or recent SARS-CoV-2 infection or exposure, with no alternative diagnosis to explain it. Most affected children are school-age, previously healthy, and look strikingly toxic. Roughly half to two thirds develop shock needing vasoactive support, and the heart and coronary arteries bear the brunt of the damage. [1]
What makes MIS-C dangerous is that it masquerades as more familiar things — gastroenteritis, appendicitis, Kawasaki disease, or straightforward sepsis — and the consequences of missing the cardiac component are severe. The unifying principle is that a school-age child with persistent fever and organ dysfunction in the weeks after a COVID-19 illness must be presumed to have MIS-C until proven otherwise, and the echocardiogram and cardiac biomarkers are the tests that change management. [3]
References12ShowHide
- [1]Feldstein LR Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med, 2020.PMID 32598831
- [2]Whittaker E Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA, 2020.PMID 32511692
- [3]Riphagen S Hyperinflammatory shock in children during COVID-19 pandemic. Lancet, 2020.PMID 32386565
- [4]Verdoni L An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet, 2020.PMID 32410760
- [5]Davies P Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study. Lancet Child Adolesc Health, 2020.PMID 32653054
- [6]Dufort EM Multisystem Inflammatory Syndrome in Children in New York State. N Engl J Med, 2020.PMID 32598830
- [7]Belhadjer Z Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic. Circulation, 2020.PMID 32418446
- [8]Godfred-Cato S COVID-19-Associated Multisystem Inflammatory Syndrome in Children - United States, March-July 2020. MMWR Morb Mortal Wkly Rep, 2020.PMID 32790663
- [9]Radia T Multi-system inflammatory syndrome in children & adolescents (MIS-C): A systematic review of clinical features and presentation. Paediatr Respir Rev, 2021.PMID 32891582
- [10]Rowley AH Immune pathogenesis of COVID-19-related multisystem inflammatory syndrome in children. J Clin Invest, 2020.PMID 32870815
- [11]Pouletty M Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort. Ann Rheum Dis, 2020.PMID 32527868
- [12]McArdle AJ Treatment of Multisystem Inflammatory Syndrome in Children. N Engl J Med, 2021.PMID 34133854