Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
권호 표지
DOI QR코드

DOI QR Code

Clinical features, diagnosis, and outcomes of multisystem inflammatory syndrome in children associated with coronavirus disease 2019

  • 투고 : 2020.11.17
  • 심사 : 2020.12.17
  • 발행 : 2021.02.15
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading worldwide since December 2019. Hundreds of cases of children and adolescents with Kawasaki disease (KD)-like hyperinflammatory illness have been reported in Europe and the United States during the peak of the COVID-19 pandemic with or without shock and cardiac dysfunction. These patients tested positive for the polymerase chain reaction or antibody test for SARS-CoV-2 or had a history of recent exposure to COVID-19. Clinicians managing such patients coined new terms for this new illness, such as COVID-19-associated hyperinflammatory response syndrome, pediatric inflammatory multisystem syndrome temporally associated with COVID-19, or COVID-19-associated multisystem inflammatory syndrome in children (MIS-C). The pathogenesis of MIS-C is unclear; however, it appears similar to that of cytokine storm syndrome. MIS-C shows clinical features similar to KD, but differences between them exist with respect to age, sex, and racial distributions and proportions of patients with shock or cardiac dysfunction. Recommended treatments for MIS-C include intravenous immunoglobulin, corticosteroids, and inotropic or vasopressor support. For refractory patients, monoclonal antibody to interleukin-6 receptor (tocilizumab), interleukin-1 receptor antagonist (anakinra), or monoclonal antibody to tumor necrosis factor (infliximab) may be recommended. Patients with coronary aneurysms require aspirin or anticoagulant therapy. The prognosis of MIS-C seemed favorable without sequelae in most patients despite a reported mortality rate of approximately 1.5%.

키워드

참고문헌

  1. Korean Society of Infectious Diseases, Korean Society of Pediatric Infectious Diseases, Korean Society of Epidemiology, Korean Society for Antimicrobial Therapy, Korean Society for Healthcare-associated Infection Control and Prevention, Korea Centers for Disease Control and Prevention. Report on the epidemiological features of coronavirus disease 2019 (COVID-19) outbreak in the Republic of Korea from January 19 to March 2, 2020. J Korean Med Sci 2020;35:e112-22. https://doi.org/10.3346/jkms.2020.35.e112
  2. Castagnoli R, Votto M, Licari A, Brambilla I, Bruno R, Perlini S, et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatr 2020;174:882-9. https://doi.org/10.1001/jamapediatrics.2020.1467
  3. Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al. Epidemiology of COVID-19 among children in China. Pediatrics 2020;145:e20200702. https://doi.org/10.1542/peds.2020-0702
  4. Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, et al. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA 2020;324:259-69. https://doi.org/10.1001/jama.2020.10369
  5. Belhadjer Z, Meot M, Bajolle F, Khraiche D, Legendre A, Abakka S, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation 2020 May 17 [Epub]. https://doi.org/10.1161/CIRCULATIONAHA.120.048360.
  6. Toubiana J, Poirault C, Corsia A, Bajolle F, Fourgeaud J, Angoulvant F, et al. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study. BMJ 2020 Jun 3 [Epub]. https://doi.org/10.1136/bmj.m2094.
  7. Godfred-Cato S, Bryant B, Leung J, Oster ME, Conklin L, Abrams J, et al. COVID-19-associated multisystem inflammatory syndrome in children - United States, March-July 2020. Morb Mortal Wkly Rep 2020;69:1074-80. https://doi.org/10.15585/mmwr.mm6932e2
  8. World Health Organization. Multisystem inflammatory syndrome in children and adolescents with COVID-19 [Internet]. Geneva (Switzerland): World Health Organization; [cited 2020 May 18]. Available from: https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19.
  9. Centers for Disease Control and Prevention. Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) [Internet]. Atlanta (GA): Centers for Disease Control and Prevention; [cited 2020 May 18]. Available from: https://emergency.cdc.gov/han/2020/han00432.asp.
  10. Royal College of Paediatrics and Child Health. Guidance: paediatric multisystem inflammatory syndrome temporally associated with COVID-19 [Internet]. London: Royal College of Paediatrics and Child Health; [cited 2020 May 18]. Available from: https://www.rcpch.ac.uk/resources/guidance-paediatric-multisystem-inflammatory-syndrome-temporally-associated-covid-19.
  11. Korea Disease Control Agency. Case definition of coronavirus-disease-2019-associated multisystem inflammatory syndrome in children [Internet]. Cheongju (Korea): Korea Disease Control Agency; [cited 2020 May 18]. Available from: http://ncov.mohw.go.kr/upload/140/202010/1601875824179_20201005143024.pdf.
  12. Morris SB, Schwartz NG, Patel P, Abbo L, Beauchamps L, Balan S, et al. Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection - United Kingdom and United States, March-August 2020. Morb Mortal Wkly Rep 2020;69:1450-6. https://doi.org/10.15585/mmwr.mm6940e1
  13. McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation 2017;135:e927-99. https://doi.org/10.1161/CIR.0000000000000484
  14. Kim GB, Park SH, Eun LY, Han JW, Lee SY, Yoon KL, et al. Epidemiological and clinical features of Kawasaki disease in South Korea, 2012-2014. Pediatr Infect Dis J 2017;36:482-5. https://doi.org/10.1097/INF.0000000000001474
  15. Radia T, Williams N, Agrawal P, Harman K, Weale J, Cook J, et al. Multisystem inflammatory syndrome in children & adolescents (MIS-C): a systematic review of clinical features and presentation. Paediatr Respir Rev 2020;S1526-0542(20)30117-2.
  16. Kim H, Shim JY, Ko JH, Yang A, Shim JW, Kim DS, et al. Multisystem inflammatory syndrome in children related to COVID-19: the first case in Korea. J Korean Med Sci 2020;35:e391-8. https://doi.org/10.3346/jkms.2020.35.e391
  17. Jain S, Sen S, Lakshmivenkateshiah S, Bobhate P, Venkatesh S, Udani S, et al. Multisystem inflammatory syndrome in children with COVID-19 in Mumbai, India. Indian Pediatr 2020;57:e1015-9.
  18. Clark BC, Sanchez-de-Toledo J, Bautista-Rodriguez C, Choueiter N, Lara D, Kang Hechaan, et al. Cardiac abnormalties seen in Pediatric patients during the SARS-CoV-2 pandemic: an international experience. J Am Heart Assoc 2020;9:e018007. https://doi.org/10.1161/JAHA.120.018007
  19. Mamishi S, Movahedi Z, Mohammadi M, Ziaee V, Khodabandeh M, Abdolsalehi MR, et al. Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in 45 children: a first report from Iran. Epidemiol Infect 2020;148:e196. https://doi.org/10.1017/s095026882000196x
  20. Moraleda C, Serna-Pascual M, Soriano-Arandes A, Simo S, Epalza C, Santos M, et al. Multi-inflammatory syndrome in children related to SARS-CoV-2 in Spain. Clin Infect Dis 2020;ciaa1042.
  21. Antunez-Montes OY, Escamilla MI, Figueroa-Uribe AF, Arteaga-Menchaca E, Lavariega-Sarachaga M, Salcedo-Lozada P, et al. COVID-19 and multisystem inflammatory syndrome in Latin American children: a multinational study. Pediatr Infect Dis J 2021;40:e1-6. https://doi.org/10.1097/INF.0000000000002949
  22. Rowley AH. Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. Nat Rev Immunol 2020;20:453-4. https://doi.org/10.1038/s41577-020-0367-5
  23. Raba AA, Abobaker A. COVID-19 and Kawasaki disease: An etiology or coincidental infection? Pediatr Infect Dis J 2020;39:e213. https://doi.org/10.1097/INF.0000000000002779
  24. Jiang L, Tang K, Levin M, Irfan O, Morris SK, Wilson K, et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect Dis 2020;20:e276-88. https://doi.org/10.1016/S1473-3099(20)30651-4
  25. Pouletty M, Borocco C, Ouldali N, Caseris M, Basmaci R, Lachaume N, et al. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort. Ann Rheum Dis 2020;79:999-1006. https://doi.org/10.1136/annrheumdis-2020-217960
  26. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20. https://doi.org/10.1056/NEJMoa2002032
  27. Li H, Liu L, Zhang D, Xu J, Dai H Tang N, et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet 2020;395:1517-20. https://doi.org/10.1016/s0140-6736(20)30920-x
  28. Strippoli R, Caiello I, De Benedetti F. Reaching the threshold: a multilayer pathogenesis of macrophage activation syndrome. J Rheumatol 2013;40:761. https://doi.org/10.3899/jrheum.121233
  29. Han SB, Lee SY. Macrophage activation syndrome in children with Kawasaki disease: diagnostic and therapeutic approaches. World J Pediatr 2020;16:566-74. https://doi.org/10.1007/s12519-020-00360-6
  30. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033-4. https://doi.org/10.1016/s0140-6736(20)30628-0
  31. Nakra NA, Blumberg DA, Herrera-Guerra A, Lakshminrusimha S. Multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management. Children (Basel) 2020;7:69.
  32. de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol 2016;14:523-34. https://doi.org/10.1038/nrmicro.2016.81
  33. Perlman S, Dandekar AA. Immunopathogenesis of coronavirus infections: implications for SARS. Nat Rev Immunol 2005;5:917-27. https://doi.org/10.1038/nri1732
  34. Lamers MM, Beumer J, Vaart JVD, Knoops K, Puschhof J, Breugem TI, et al. SARS-CoV-2 productively infects human gut enterocytes. Science 2020;369:50-54. https://doi.org/10.1126/science.abc1669
  35. 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. Pediatr Infect Dis J 2020;39:e340-6. https://doi.org/10.1097/INF.0000000000002888
  36. Carter MJ, Shankar-Hari M, Tibby SM. Paediatric inflammatory multisystem syndrome temporally-associated with SARS-CoV-2 infection: An Overview. Intensive care med 2020:1-4.
  37. Ahmed M, Advani S, Moreira A, Zoretic S, Martinez J, Chorath K, et al. Multisystem inflammatory syndrome in children: a systematic review. EClinicalMedicine 2020;26:100527. https://doi.org/10.1016/j.eclinm.2020.100527
  38. Kanegaye JT, Wilder MS, Molkara D, Frazer JR, Pancheri J, Tremoulet AH, et al. Recognition of a Kawasaki disease shock syndrome. Pediatrics 2009;123:e783-9. https://doi.org/10.1542/peds.2008-1871
  39. Kaushik S, Aydin SI, Derespina KR, Bansal PB, Kowalsky S, Trachtman R, et al. Multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2 infection (MIS-C): a multi-institutional study from New York city. J Pediatr 2020;224:24-9. https://doi.org/10.1016/j.jpeds.2020.06.045
  40. Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, et al. Multisystem inflammatory syndrome in children in New York state. N Engl J Med 2020;383:347-58. https://doi.org/10.1056/NEJMoa2021756
  41. Riollano-Cruz M, Akkoyun E, Briceno-Brito E, Kowalsky S, Reed J, Posada R et al. Multisystem inflammatory syndrome in children related to COVID-19: A New York City experience. J Med Virol 2020;10.1002/jmv.26224. https://doi.org/10.1002/jmv.26224.
  42. Chiotos K, Bassiri H, Behrens EM, Blatz AM, Chang J, Diorio C, et al. Multisystem inflammatory syndrome in children during the coronavirus 2019 pandemic: a case series. J Pediatric Infect Dis Soc 2020;9:393-8. https://doi.org/10.1093/jpids/piaa069
  43. Capone CA, Subramony A, Sweberg T, Schneider J, Shah S, Rubin L, et al. Characteristics, cardiac involvement, and outcomes of multisystem inflammatory syndrome of childhood associated with severe acute respiratory syndrome coronavirus 2 Infection. J Pediatr 2020;224:141-5. https://doi.org/10.1016/j.jpeds.2020.06.044
  44. Nguyen Y, Corre F, Honsel V, Curac S, Zarrouk V, Burtz CP, et al. A nomogram to predict the risk of unfavourable outcome in COVID-19: a retrospective cohort of 279 hospitalized patients in Paris area. Ann med 2020;52:367-75. https://doi.org/10.1080/07853890.2020.1803499
  45. Henderson LA, Canna SW, Friedman KG, Gorelik M, Lapidus SK, Bassiriet H, 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 1. Arthritis Rheumatol 2020;10.1002/art.41454.
  46. Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med 2020;383:334-46. https://doi.org/10.1056/NEJMoa2021680
  47. Hennon TR, Penque MD, Abdul-Aziz R, Alibrahim OS, McGreevy MB, Prout AJ, et al. COVID-19 associated multisystem inflammatory syndrome in children (MIS-C) guidelines; a Western New York approach. Prog Pediatr Cardiol 2020;101232.
  48. Sperotto F, Friedman KG, Son MBF, VanderPluym CJ, Newburger JW, Dionne A. Cardiac manifestations in SARS-CoV-2-associated multisystem inflammatory syndrome in children: a comprehensive review and proposed clinical approach. Eur J Pediatr 2021;180:307-22. https://doi.org/10.1007/s00431-020-03766-6
  49. Grimaud M, Starck J, Levy M, Marais C, Chareyre J, Khraiche D, et al. Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children. Ann Intensive Care 2020;10:69. https://doi.org/10.1186/s13613-020-00690-8
  50. Alhazzani W, Moller MH, Arabi YM, Loeb M, Gong MN, Fan E, et al. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med 2020;48:e440-69. https://doi.org/10.1097/CCM.0000000000004363
  51. Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet 2020;395:1771-8. https://doi.org/10.1016/s0140-6736(20)31103-x

피인용 문헌

  1. The Spectrum of Manifestations of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) Infection in Children: What We Can Learn From Multisystem Inflammatory Syndrome in Children (MIS-C) vol.8, 2021, https://doi.org/10.3389/fmed.2021.747190
  2. Is multisystem inflammatory syndrome related with coronavirus disease 2019, Kawasaki disease, and angiotensin-converting enzyme 2 in children? vol.64, pp.5, 2021, https://doi.org/10.3345/cep.2021.00031
  3. Case Series of Multisystem Inflammatory Syndrome (MIS-C) in Children during the SARS-CoV-2 Pandemic in Latvia vol.11, pp.2, 2021, https://doi.org/10.3390/clinpract11020051
  4. Early Echocardiographic and Cardiac MRI Findings in Multisystem Inflammatory Syndrome in Children vol.10, pp.15, 2021, https://doi.org/10.3390/jcm10153360