Ateş KARA, Dilek YILMAZ ÇİFTDOĞAN, Selda HANÇERLİ TÖRÜN

Multisystem inflammatory syndrome in children

Abstract: As the COVID-19 pandemic continues, children can be infected with the virus that causes COVID-19. Clinical symptoms of children with COVID from China, where the disease was first reported, generally were less severe than adults. However, at the end of April 2020 in Europe, it was observed that some children with SARS-CoV-2 infection developed fever, abdominal pain, shock, myocardial insufficiency and they needed to be taken care of in intensive care unit. This new disease has been called multisystem inflammatory syndrome in children (MIS-C). Although the pathogenesis of MIS-C is unclear, it progresses with signs of multiorgan involvement as a result of uncontrolled inflammation of the immune system and even causes death. Therefore, the diagnosis and treatment of patients with MIS-C should be managed quickly. In this review, the pathophysiology, clinical and laboratory findings, diagnostic methods, and treatment regimens of MIS-C were discussed.Key words: Multisystem inflammatory syndrome, COVID-19, children

PDF

___

1. Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz MK et al. Coronavirus Disease 2019 Case Surveillance - United States The Morbidity and Mortality Weekly Report. 2020; 69:759 doi: 10.15585/mmwr.mm6924e2
2.Dong Y, Mo X, Hu Y, Qi X, Jiang F et al. Epidemiology of COVID-19 Among Children in China. Pediatrics. 2020;145(6):e20200702. doi: 10.1542/peds.2020-0702
3. Davies P, Evans C, Kanthimathinathan HK, Lillie J, Brierley J et al. 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. The Lancet Child and Adolescent Health. 2020 Sep;4(9):669-677. doi:10.1016/S2352-4642(20)30215-7
4. Center for Disease Control and Prevention, Center for Preparedness and Response: Multisystem Inflammatory Syndrome in Children (MIS-C) AssociatedwithCoronavirusDisease 2019 (COVID-19), ClinicianOutreachandCommunication (COCA) Webinar. Website https://emergency.cdc.gov/coca/calls/2020/ callinfo_051920.asp?deliveryName=USCDC_105[accessed May 2020].
5. Pediatric Intensive Care Society. PICS Statement: Increased number of reported cases of novel presentation of multisystem inflammatory disease. Website :https://picsociety. uk/wpcontent/uploads/2020/04/PICS-statement-re-novelKD-C19- presentation-v2-27042020.pdf. [accessed April 2021].
6. Rae S.M. Yeung, Polly J. Ferguson.Is multisystem inflammatory syndrome in children on the Kawasaki syndrome spectrum? The Journal of Clinical Investigation 2020;130(11):5681- 5684. https://doi.org/10.1172/JCI141718
7. National Center forImmunization and Respiratory Diseases (NCIRD).Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States. Website : https://stacks.cdc.gov/view/cdc/106439 [accessed August 2021].
8. Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A et al New York State and Centers for Disease Control and Prevention Multisystem Inflammatory Syndrome in Children Investigation Team. Multisystem Inflammatory Syndrome in Children in New York State. The New England Journal of Medicine. 2020;23: 347-358. doi: 10.1056/NEJMoa2021756
9. Kim YJ, Park H, Choi YY, Kim YK, Yoon Y et al 2020. Defining Association between COVID-19 and the Multisystem Inflammatory Syndrome in Children through the Pandemic Journal of Korean Medicine. Sci. 35:e204. doi:10.3346/ jkms.2020.35.e204
10. Li Y,Zheng Q, Zou L, Wu J, Guo L et al. Kawasaki disease shock syndrome: clinical characteristics and possibleuse of IL-6, IL10 and IFN-γ as biomarkers for early recognition. Pediatric Rheumatology. 2019;17:1-9. doi:10.1186/s12969-018-0303-4
11. Brodin P. Why is COVID-19 somild in children? Acta Paediatrica. 2020;109(6):1082-1083. doi: 10.1111/apa.15271
12. Ludvigsson JF. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatrica. 2020;109(6):1088-1095. doi: 10.1111/apa.15270
13. Weisberg SP, Connors T, Zhu Y, Baldwin M, Lin W-H et al. Antibody responses to SARS-CoV2 are distinct in children with MIS-C compared to adults with COVID-19. medRxiv. 2020; Jul 14;07.12.20151068. doi: 10.1101/2020.07.12.20151068
14. Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020;581(7809):465-9.doi: 10.1038/ s41586-020-2196-x
15. Duarte-Neto AN, Caldini EG, Gomes-Gouvêa MS, Kanamura CT, de AlmeidaMonteiro et al. An autopsystudy of thespectrum of severe COVID-19 in children: From SARS todifferentphenotypes of MIS-C. E Clinical Medicine.2021;35:100850. doi: 10.1016/j.eclinm.2021.100850
16. Schwartz M. MIS-C: post-infectious syndrome or persistent infection? The Lancet Infectious Diseases. 2021;21(5):e116. doi: 10.1016/S1473-3099(20)30786-6
17. Consiglio CR, Cotugno N, Sardh F, Pou C, Amodio D et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 2020;183(4):968-81. e7.doi: 10.1016/j.cell.2020.09.016
18. Noval Rivas M, Porritt RA, Cheng MH, Bahar I, Arditi M. COVID-19-associated multisystem inflammatory syndrome in children (MIS-C): A novel disease that mimics toxic shock syndrome-the superantigen hypothesis. The Journal of Allergy and Clinical Immunology . 2021;147(1):57-59. doi:10.1016/j.jaci.2020.10.008
19. Hamming I, Timens W, Bulthuis M, Lely A, Navis G et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. The Journal of Pathology: Reviews in Medical Microbiology 2004;203(2):631-7.doi: 10.1002/path.1570
20. Kuba K, Imai Y, Rao S, Jiang C, Penninger JM. Lessons from SARS: control of acute lung failure by the SARS receptor ACE2 The Journal of Molecular Medicine. 2006;84(10):814-20.doi: 10.1007/s00109-006-0094-9
21. Chang LY, Lu CY, Shao PL, Lee PI, Lin MT et al. Viral infections associated with Kawasaki disease. J Formos Med Assoc. 2014;113(3):148-54.doi: 10.1016/j.jfma.2013.12.008
22. Xu Z, Shi L, Wang Y, Zhang J, Huang L,et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine2020;8(4):420-2. doi: 10.1016/S2213-2600(20)30076-X
23. Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation. 2020; Aug 4;142(5):429-436. doi: 10.1161/cırculatıonaha.120.048360
24. Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM et al. Multisystem inflammatory syndrome in US children and adolescents. The New England Journal of Medicine. 2020;383(4):334-46.doi: 10.1056/NEJMoa2021680
25. Carlin RF, Fischer AM, Pitkowsky Z, Abel D, Sewell TB et al. Discriminating MIS-C Requiring Treatment from Common Febrile Conditions in Outpatient Settings. The Journal of Pediatrics2020;229:26-32. doi: 10.1016/j.jpeds.2020.10.013
26. Henderson LA, Canna SW, Friedman KG, Gorelik M, Lapidus SK et al. American College of Rheumatology Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARSCoV-2 and Hyperinflammation in COVID-19. Version 2. Arthritis & Rheumatology. 2020;73(4):13-29.doi: 10.1002/ art.41616
27. Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE et al. Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. Jama. 2020;324(3):259-269. doi: 10.1001/ jama.2020.10369
28. Blumfield E, Levin TL, Kurian J, Lee EY, Liszewski MC. ImagingFindings in MultisystemInflammatorySyndrome in Children (MIS-C) AssociatedWithCoronavirusDisease (COVID-19). American journal of roentgenology. 2021;216(2):507-517. doi: 10.2214/AJR.20.24032
29. Alsaied T, Tremoulet AH, Burns JC, Saidi A, Dionne A et al.Review of Cardiac Involvement in Multisystem Inflammatory Syndrome in Children. Circulation. 2021; 5;143(1):78-88. doi: 10.1161/CIRCULATIONAHA.120.049836
30. Lin KH, Chang SS, Yu CW, Lin SC, Liu SC et al. Usefulness of natriuretic peptide for the diagnosis of Kawasaki disease: a systematic review and meta-analysis. BMJ open. 2015;5(4):e006703. doi: 10.1136/bmjopen-2014-006703
31. Grom AA, Horne A, De Benedetti F. Macrophage activation syndrome in the era of biologic therapy. Nature Reviews Rheumatology. 2016; 12(5):259-68.doi: 10.1038/nrrheum.2015.179
32. Henderson LA, Canna SW, Friedman KG, Gorelik M, Lapidus SK et al. American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 2. Arthritis & rheumatology (Hoboken, NJ). 2021;73(4):e13-e29. doi: 10.1002/art.41454
33. Kaushik A, Gupta S, Sood M, Sharma S, Verma S. A systematic review of multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection. The Pediatric infectious disease journal. 2020;39(11):e340-e6. doi: 10.1097/ INF.0000000000002888
34. Feldstein LR, Tenforde MW, Friedman KG, Newhams M, Rose EB et al. Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19. JAMA.2021;325(11):1074. doi:10.1001/jama.2021.2091
35. Irfan O, Muttalib F, Tang K, Jiang L, Lassi ZS et al.Clinical characteristics, treatment and outcomes of paediatric COVID-19: a systematic review and meta-analysis. Archives of Disease in Childhood 2021;16;106(5):440–8. doi: 10.1136/ archdischild-2020-321385
36 World Health Organization. Multisystem inflammatory syndrome in children and adolescents with COVID-19: Scientific Brief. 2020. website: https://www.who.int/publications-detail/ multisystem-inflammatory-syndrome-in-children-andadolescents-with-covid-19 [accessed May 2021].
37. Cirks BT, Rowe SJ, Jiang SY, Brooks RM, Mulreany MP et al. 16 Weeks Later: Expanding the Risk Period for MIS-C. The official journal of the Pediatric Infectious Diseases Society. 2021; May 28;10(5):686-690. doi: 10.1093/jpids/piab007
38. Godfred-Cato S, Bryant B, Leung J, Oster ME, Conklin L et al. COVID-19-Associated Multisystem Inflammatory Syndrome in Children - United States, March-July 2020. The Morbidity and Mortality Weekly Report. 2020;69(32):1074 doi: 10.15585/ mmwr.mm6932e2
39. Cheung EW, Zachariah P, Gorelik M, Boneparth A, Kernie SG et al. Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York City. Jama. 2020;21;324(3):294-6 doi: 10.1001/jama.2020.10374
40. Capra R, De Rossi N, Mattioli F, Romanelli G, Scarpazza C et al. Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. European journal of internal medicine. 2020 June;76:31-5 doi: 10.1016/j. ejim.2020.05.009
41. Capone CA, Subramony A, Sweberg T, Schneider J, Shah S et al. Characteristics, cardiac involvement, and outcomes of multisystem inflammatory syndrome of childhood associated with severe acute respiratory syndrome coronavirus 2 infection. The Journal of Pediatrics. 2020 Sep;224:141-5 doi: 10.1016/j. jpeds.2020.06.04