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

Abstract

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Electronic databases (Medline, Google Scholar, WHO, CDC, UK National Health Service, LitCovid, and other databases with unpublished preprints) were extensively searched, and all articles on MIS-C published from January 1, 2020, to October 10, 2020, were retrieved.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. Keywords COVID-19. Hemophagocytic lympho-histiocytosis. Kawasaki disease. SARS-CoV-2. Macrophage activation syndrome. Multisystem inflammatory syndrome in children (MIS-C). Toxic shock syndrome This article is part of the Topical Collection on Covid-19

COVID-19 Infection in Spinal Muscular Atrophy Associated with Multisystem Inflammatory Syndrome

“…e use of cytokine inhibitors tocilizumab, anakinra, and baricitinib is a potential option for the treatment of severe COVID-19 [33], but none of them have been investigated in prospective clinical trials in the pediatric population. In five reviews among patients with MIS-C, the following therapies were employed: intravenous immunoglobulin (63-100%), corticosteroids (49-70%), anakinra (8-13%), tocilizumab (6.5-27%), remdesivir (3-8%), infliximab (1.2-8%), and plasma (n � 3) [24,26,27,29,[36][37][38]. Intravenous immunoglobulin combined with methylprednisolone compared to intravenous immunoglobulin alone is significantly effective in reducing fever, the need for second-line drug therapy, hemodynamic support, and length of intensive care stay [39].…”

A Novel and Severe Clinical Picture Related to COVID-19: Multi-Inflammatory Syndrome in Children

“…13 Similarly, male/female ratio was 1.37:1, and the median age was 7.5 years in another systematic review including 992 MIS-C patients. 14 It is well known that the current pandemic was originated from East Asia. Besides, KD is in the differential diagnosis of MIS-C mostly seen in Asian children.…”

“…There was a slight male predominance, and cases were mostly school-age children and adolescents, similar to the current literature. 13,14 While the PCR tests were negative in most of them, they were seropositive against SARS-CoV-2. Fever and gastrointestinal symptoms were the most common symptoms.…”

“Authors’ Reply: Emerging Evidence on Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 Infection”

“…We thank the reader for reading our review with interest [ 1 ]. This review was undertaken and reported in accordance with the preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines [ 2 ].…”

“…This review was undertaken and reported in accordance with the preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines [ 2 ]. The details have been shared in the supplementary material [ 1 ].…”