EC Pulmonology and Respiratory Medicine

Multisystem inflammatory syndrome in children (MIS-C), or pediatric inflammatory multisystem syndrome (PIMS/PIMS-TS), or systemic inflammatory syndrome in COVID-19 (SISCoV), is a rare systemic illness involving persistent fever and extreme inflammation following exposure to SARS-CoV-2. This is a dysregulated autoimmune-mediated illness following COVID-19 with an interval of 2 - 6 weeks. Despite 5 years of intensive study, there is still no widespread definition of this condition. In the majority of studies researchers are using the definition of the Centers for Disease Control and Prevention (CDC) - Multisystem inflammatory syndrome in children (MIS-C). Median age of patients with MIS-C is 6 - 11 years. Most common manifestations are involvement of respiratory and neurological system, gastrointestinal tract, cardiovascular, hematological and mucocutaneous system. Although clinical manifestations vary in different countries. The mortality rate is 1 - 3%, but there is also significant difference between countries. Management of MIS-C are almost similar to that of Kawasaki disease and mostly consisted to intravenous immunoglobulin, corticosteroids and antibiotics, but again in different countries there are different tactique in management of MIS-C. The main aim of this review article is to show difference in clinical presentations and treatment recommendations in different countries from five continents.

 Keywords: SARS-CoV-2; Multisystem Inflammatory Syndrome in Children (MIS-C); Epidemiology; Children; Clinical Manifestation; Treatment

1. Toepfner N., et al. “Long COVID in pediatrics-epidemiology, diagnosis, and management”. European Journal of Pediatrics 4 (2024): 1543-1553.
2. Feldstein LR., et al. “Multisystem inflammatory syndrome in U.S. children and adolescents”. New England Journal of Medicine 4 (2020): 334-346.
3. Patel JM. “Multisystem inflammatory syndrome in children (MIS-C)”. Current Allergy and Asthma Reports 5 (2022): 53-60.
4. Shyong O., et al. “Multisystem inflammatory syndrome in children: a comprehensive review over the past five years”. Journal of Intensive Care Medicine 17 (2025): 8850666251320558.
5. Lupu A., et al. “Multisystem inflammatory syndrome in children and Kawasaki disease”. Frontiers in Immunology 16 (2025): 1554787.
6. Verdoni L., et al. “An outbreak of severe Kawasaki-like disease at the Italian epicenter of the SARS-CoV-2 epidemic: an observational cohort study”. Lancet10239 (2020): 1771-1778.
7. Belay ED., et al. “Trends in geographic and temporal distribution of U.S. children with multisystem inflammatory syndrome during the COVID-19 pandemic”. JAMA Pediatrics 8 (2021): 837-845.
8. Feldstein LR., et al. “Characteristics and outcomes of US children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compared with severe acute COVID-19”. Journal of the American Medical Association 11 (2021): 1074-1087.
9. Multi-system Inflammatory Syndrome in Children (MIS-C) Temporally Associated with COVID-19 Hasbro Children’s Hospital Clinical Guideline.
10. Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19.
11. Ahmed M., et al. “Multisystem inflammatory syndrome in children: a systematic review”. EClinical Medicine 26 (2020): 100527.
12. Garcı´a-Salido A., et al. “Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain”. Critical Care1 (2020): 666.
13. Mamishi S., et al. “Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in 45 children: a first report from Iran”. Epidemiology and Infection 148 (2020): e196.
14. Shalabi M., et al. “Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, clinical characteristics: A multi-center observational study from Jordan”. Global Epidemiology 9 (2025): 100185.
15. García-Silva J., et al. “Multisystem inflammatory syndrome in children across 16 Latin American countries: A multicenter study from the REKAMLATINA Network”. IJID Regions 12 (2024): 100419.
16. Atamari-Anahui N., et al. “Characteristics of COVID-19-associated multisystemic inflammatory syndrome in children treated in a Peruvian hospital, 2020- 2022”. La Revista Peruana de Medicina Experimental y Salud Pública 3 (2024): 301-308.
17. Nitescu VG., et al. “Clinical characteristics and outcomes in multisystemic inflammatory syndrome in children (MIS-C) associated with COVID-19: A 12-month prospective study”. Microorganisms 6 (2025): 1405.
18. Vijatov-Duri´c G., et al. “Characteristics of multisystem inflammatory syndrome in children across COVID-19 variants in Vojvodina”. Journal of Clinical Medicine 22 (2024): 6672.
19. Amenzoui N., et al. “Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection in Morocco”. Global Pediatric Health 11 (2024): 2333794X241286772.
20. Stacevičienė I., et al. “Multisystem inflammatory syndrome in children (MIS-C) in a Lithuanian Paediatric tertiary care center”. Medicina (Kaunas)11 (2024): 1774.
21. Atamari-Anahui N., et al. “Characteristics of COVID-19-associated multisystemic inflammatory syndrome in children treated in a Peruvian hospital, 2020-2022”. La Revista Peruana de Medicina Experimental y Salud Pública 3 (2024): 301-308.
22. Pediatric Active Enhanced Disease Surveillance-PAEDS.
23. Guideline Paediatric Inflammatory Multisystem Syndrome Temporally Associated with COVID-19.
24. Advice for clinicians: Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-COV-2 (PIMS-TS).