Emerging Evidence on Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 Infection : a Systematic Review with Meta-analysis

© The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature 2021..

With the increased spread of severe acute respiratory syndrome coronavirus 2 infection, more patients with multisystem inflammatory syndrome in children (MIS-C) are being reported worldwide. This systematic review with meta-analysis aims to analyse the clinical features, proposed pathogenesis and current treatment options for effective management of children with this novel entity. Electronic databases (Medline, Google Scholar, WHO, CDC, UK National Health Service, LitCovid, and other databases with unpublished pre-prints) were extensively searched, and all articles on MIS-C published from January 1, 2020, to October 10, 2020, were retrieved. English language studies were included. This systematic review analysed 17 studies with 992 MIS-C patients from low-income and middle-income countries (LMICs) and developed countries (France, the UK, Italy, Spain, Chile and the US CDC data). Fever (95%) was the most common clinical manifestation followed by gastrointestinal (78%), cardiovascular (75.5%), and respiratory system (55.3%) involvement. Laboratory or epidemiologic evidence of inflammation and SARS-CoV-2 infection was present. Though the exact pathogenesis remains elusive, virus-induced post-infective immune dysregulation appears to play a predominant role. Features resembling Kawasaki disease, toxic shock syndrome or macrophage activation syndrome were present; 49% had shock; 32% had myocarditis; 18% had coronary vessel abnormalities and 9% had congestive cardiac failure. Sixty-three percent of the patients were admitted in paediatric intensive care unit (PICU); 63% received intravenous immunoglobulin, 58% received corticosteroids and 19% received alternate agents like tocilizumab; there were 22 (2.2%) deaths. Only 9/144 children in LMICs received tocilizumab that was significantly less than children in developed countries (p < 0.0001). This systematic review delineates and summarises recently published data on MIS-C from LMICs and developed countries. Although most needed PICU admission and received treatment with IVIG and steroids, most of the patients survived. Significantly fewer patients in developing countries received tocilizumab therapy than those in developed countries. It is crucial for clinician to recognise MIS-C, to differentiate it from other defined inflammatory conditions and initiate early treatment. Further studies are needed for long-term prognosis, especially relating to cardiac complications of MIS-C.

Supplementary Information: The online version of this article (10.1007/s42399-020-00690-6) contains supplementary material, which is available to authorized users.

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Electronic Article

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SN comprehensive clinical medicine - (07.01.2021), p. 1-10




Sood, Mangla
Sharma, Seema
Sood, Ishaan
Sharma, Kavya
Kaushik, Ashlesha




Hemophagocytic lympho-histiocytosis
Journal Article
Kawasaki disease
Macrophage activation syndrome
Multisystem inflammatory syndrome in children (MIS-C)
Toxic shock syndrome


Date Revised 13.01.2021

published: Print-Electronic

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Copyright: From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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