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Multisystem inflammatory syndrome in children: another COVID-19 sequel

Published online by Cambridge University Press:  06 July 2023

Christophe El Rassi ,
Rana Zareef Open the ORCID record for Rana Zareef [Opens in a new window] ,
Rawan Honeini ,
Christelle Latouf ,
Fadi Bitar Open the ORCID record for Fadi Bitar [Opens in a new window]  and
Mariam Arabi Open the ORCID record for Mariam Arabi [Opens in a new window]
Christophe El Rassi
Affiliation:
American University of Beirut, Beirut, Lebanon
Rana Zareef
Affiliation:
Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon Department of Pediatrics and Adolescent Medicine, Division of Pediatric Cardiology, Children’s Heart Center, American University of Beirut Medical Center, Beirut, Lebanon
Rawan Honeini
Affiliation:
Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon
Christelle Latouf
Affiliation:
Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon
Fadi Bitar
Affiliation:
Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon Department of Pediatrics and Adolescent Medicine, Division of Pediatric Cardiology, Children’s Heart Center, American University of Beirut Medical Center, Beirut, Lebanon
Mariam Arabi*
Affiliation:
Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon Department of Pediatrics and Adolescent Medicine, Division of Pediatric Cardiology, Children’s Heart Center, American University of Beirut Medical Center, Beirut, Lebanon
*
Corresponding author: M. Arabi; Email: ma81@aub.edu.lb
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Abstract

With the rapid expansion of the COVID-19 pandemic, the disease burden and its consequences on the paediatric population has been progressively recognised. Although COVID-19 infection in children presents as asymptomatic to mild illness, instances of hyperinflammation and multi-organ involvement following the viral infection have been described. This condition, known as the multisystem inflammatory syndrome in children (MIS-C), has gained a wide global attention. Despite the global efforts to uncover the disease characteristics and management, a clear pathogenesis and a unified treatment regimen have not been reached yet. This paper tackles the epidemiology of the MIS-C, discusses its suggested pathogenesis, drives through its varying clinical presentations, and evaluates the different treatment regimens employed in managing MIS-C.

Keywords

COVID-19multisystem inflammatory syndrome in childrencoronavirus
Type
Review
Information
Cardiology in the Young , Volume 33 , Issue 8 , August 2023 , pp. 1418 - 1428
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Copyright
© The Author(s), 2023. Published by Cambridge University Press

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References

Atzrodt, CL, Maknojia, I, McCarthy, RD, et al. A guide to COVID-19: a global pandemic caused by the novel coronavirus SARS-CoV-2. FEBS J 2020; 287: 3633–3650.CrossRefGoogle ScholarPubMed
Wu, C, Chen, X, Cai, Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan. Chin JAMA Intern Med 2020; 180: 934–943.CrossRefGoogle ScholarPubMed
Radia, T, Williams, N, Agrawal, P, et al. Multi-system inflammatory syndrome in children & adolescents (MIS-C): a systematic review of clinical features and presentation. Paediatr Respir Rev 2021; 38: 51–57.Google ScholarPubMed
Merli, M, Perricone, G, Lauterio, A, et al. Coronaviruses and immunosuppressed patients: the facts during the third epidemic. Liver Transpl 2020; 26: 1543–1544.CrossRefGoogle ScholarPubMed
Bhopal, SS, Bagaria, J, Olabi, B, Bhopal, R. Children and young people remain at low risk of COVID-19 mortality. Lancet Child Adolesc 2021; 5: e12–e13.CrossRefGoogle Scholar
Feldstein, LR, Rose, EB, Horwitz, SM, et al. Multisystem inflammatory syndrome in US children and adolescents. N Engl J Med 2020; 383: 334–346.CrossRefGoogle Scholar
Zare-Zardini, H, Soltaninejad, H, Ferdosian, F, Hamidieh, AA, Memarpoor-Yazdi, M. Coronavirus disease 2019 (COVID-19) in children: prevalence, diagnosis, clinical symptoms, and treatment. Int J Gen Med 2020; 13: 477–482.CrossRefGoogle ScholarPubMed
She, J, Liu, L, Liu, W. COVID-19 epidemic: disease characteristics in children. J Med Virol 2020; 92: 747–754.CrossRefGoogle ScholarPubMed
Whittaker, E, Bamford, A, Kenny, J, et al. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA 2020; 324: 259–269.CrossRefGoogle ScholarPubMed
Holstein, B. Multisystem inflammatory syndrome in children. J Nurse Pract 2021; 17: 941–945.CrossRefGoogle ScholarPubMed
Siebach, MK, Piedimonte, G, Ley, SH. COVID-19 in childhood: transmission, clinical presentation, complications and risk factors. Pediatr Pulmonol 2021; 56: 1342–1356.CrossRefGoogle ScholarPubMed
Verdoni, L, Mazza, A, Gervasoni, A, 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: 1771–1778.CrossRefGoogle ScholarPubMed
Riphagen, S, Gomez, X, Gonzalez-Martinez, C, Wilkinson, N, Theocharis, P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020; 395: 1607–1608.CrossRefGoogle ScholarPubMed
Pavlyshyn, H, Slyva, V, Dyvonyak, O, Horishna, I. Multisystem inflammatory syndrome in children (MIS-C) temporally associated with SARS-CoV-2: the first clinical case in Ternopil. Ukraine Germs 2021; 11: 120–127.CrossRefGoogle ScholarPubMed
Matucci-Cerinic, C, Caorsi, R, Consolaro, A, Rosina, S, Civino, A, Ravelli, A. Multisystem inflammatory syndrome in children: unique disease or part of the Kawasaki disease spectrum? Front Pediatr 2021; 9: 531.CrossRefGoogle ScholarPubMed
Levin, M. Childhood multisystem inflammatory syndrome—a new challenge in the pandemic. N Engl J Med 2020; 383: 393–395.CrossRefGoogle ScholarPubMed
Swann, OV, Holden, KA, Turtle, L, et al. Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study. BMJ 2020; 370: m3249.CrossRefGoogle Scholar
Riollano-Cruz, M, Akkoyun, E, Briceno-Brito, E, et al. Multisystem inflammatory syndrome in children related to COVID-19: a New York city experience. J Med Virol 2021; 93: 424–433.CrossRefGoogle ScholarPubMed
Toubiana, J, Poirault, C, Corsia, A, et al. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study. BMJ 2020; 369: m2094.CrossRefGoogle ScholarPubMed
Consiglio, CR, Cotugno, N, Sardh, F, et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell 2020; 183: 968–981 e967.CrossRefGoogle ScholarPubMed
Kawasaki, T, Kosaki, F, Okawa, S, Shigematsu, I, Yanagawa, H. A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics 1974; 54: 271–276.CrossRefGoogle ScholarPubMed
Takashi Ebihara, RE, Ma, Xiaoming, Ishiguro, Nobuhisa, Kikuta, Hideaki. Lack of association between new Haven coronavirus and Kawasaki disease. J Infect Dis 2005; 192: 351–352.CrossRefGoogle Scholar
Turnier, JL, Anderson, MS, Heizer, HR, Jone, PN, Glode, MP, Dominguez, SR. Concurrent respiratory viruses and kawasaki disease. Pediatrics 2015; 136: e609–614.CrossRefGoogle ScholarPubMed
Sidiq, KR, Sabir, DK, Ali, SM, Kodzius, R. Does early childhood vaccination protect against COVID-19? Front Mol Biosci 2020; 7: 120.CrossRefGoogle ScholarPubMed
Bunyavanich, S, Do, A, Vicencio, A. Nasal gene expression of angiotensin-converting Enzyme 2 in children and adults. JAMA 2020; 323: 2427–2429.CrossRefGoogle ScholarPubMed
Lingappan, K, Karmouty-Quintana, H, Davies, J, Akkanti, B, Harting, MT. Understanding the age divide in COVID-19: why are children overwhelmingly spared? Am J Physiol Lung Cell Mol Physiol 2020; 319: L39–L44.CrossRefGoogle ScholarPubMed
Rouva, G, Vergadi, E, Galanakis, E. Acute abdomen in multisystem inflammatory syndrome in children: a systematic review. Acta Paediatr 2022; 111: 467–472.CrossRefGoogle ScholarPubMed
Belhadjer, Z, Méot, M, Bajolle, F, et al. Acute heart failure in multisystem inflammatory syndrome in children in the context of global SARS-CoV-2 pandemic. Circulation 2020; 142: 429–436.CrossRefGoogle ScholarPubMed
Sahn, B, Eze, OP, Edelman, MC, et al. Features of intestinal disease associated with COVID-related multisystem inflammatory syndrome in children. J Pediatr Gastroenterol Nutr 2021; 72: 384–387.CrossRefGoogle ScholarPubMed
Blumfield, E, Levin, TL, Kurian, J, Lee, EY, Liszewski, MC. Imaging findings in multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease (COVID-19). Am J Roentgenol 2021; 216: 507–517.CrossRefGoogle ScholarPubMed
Lee, PY, Day-Lewis, M, Henderson, LA, et al. Distinct clinical and immunological features of SARS-CoV-2-induced multisystem inflammatory syndrome in children. J Clin Invest 2020; 130: 5942–5950.CrossRefGoogle ScholarPubMed
Sethuraman, U, Kannikeswaran, N, Ang, J, et al. Multisystem inflammatory syndrome in children associated with novel coronavirus SARS-CoV-2: presentations to a pediatric emergency department in Michigan. Am J Emerg Med 2021; 39: 164–167.CrossRefGoogle ScholarPubMed
Palabiyik, F, Akcay, N, Sevketoglu, E, Hatipoglu, N, Sari, EE, Inci, E. Imaging of multisystem inflammatory disease in children (MIS-c) associated with COVID-19. Acad Radiol 2021; 28: 1200–1208.CrossRefGoogle ScholarPubMed
Khesrani, LS, Sadar, FZ, Dahdouh, A, Ladjadj, Y, Bouguermouh, D. Intestinal ischemia secondary to Covid-19. J Pediatr Surg case Rep 2020; 61: 101604.CrossRefGoogle ScholarPubMed
Anderson, JE, Campbell, JA, Durowoju, L, et al. COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) presenting as appendicitis with shock. J Pediatr Surg Case Rep 2021; 71: 101913.CrossRefGoogle ScholarPubMed
Shobhavat, L, Solomon, R, Rao, S, et al. Multisystem inflammatory syndrome in children: clinical features and management—Intensive care experience from a pediatric public hospital in western India. Indian journal of critical care medicine: peer-reviewed, official publication of Indian society of critical care medicine. Indian J Crit Care Med 2020; 24: 1089–1094.Google Scholar
Sethy, G, Mishra, B, Jain, MK, et al. Clinical profile and immediate outcome of multisystem inflammatory syndrome in children associated with COVID-19: a multicentric study. J Glob Infect Dis 2021; 13: 159.Google ScholarPubMed
Dufort, EM, Koumans, EH, Chow, EJ, et al. Multisystem inflammatory syndrome in children in New York state. N Engl J Med 2020; 383: 347–358.CrossRefGoogle ScholarPubMed
Grimaud, M, Starck, J, Levy, M, et al. Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children. Ann Intens Care 2020; 10: 1–5.Google ScholarPubMed
Davies, P, Evans, C, Kanthimathinathan, HK, 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. Lancet Child Adolesc Health 2020; 4: 669–677.CrossRefGoogle Scholar
Kaushik, S, Aydin, SI, Derespina, KR, 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: 24–29.CrossRefGoogle ScholarPubMed
Ramcharan, T, Nolan, O, Lai, CY, et al. Paediatric inflammatory multisystem syndrome: temporally associated with SARS-CoV-2 (PIMS-TS): cardiac features, management and short-term outcomes at a UK tertiary paediatric hospital. Pediatr Cardiol 2020; 41: 1391–1401.CrossRefGoogle Scholar
Zou, H, Lu, J, Liu, J, et al. Characteristics of pediatric multi-system inflammatory syndrome (PMIS) associated with COVID-19: a meta-analysis and insights into pathogenesis. Int J Infect Dis 2021; 102: 319–326.CrossRefGoogle ScholarPubMed
Bayramoglu, Z, Canıpek, E, Comert, RG, et al. Imaging features of pediatric COVID-19 on chest radiography and chest CT: a retrospective, single-center study. Acad Radiol 2021; 28: 18–27.CrossRefGoogle ScholarPubMed
Feldstein, LR, Tenforde, MW, Friedman, KG, 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: 1074–1087.CrossRefGoogle ScholarPubMed
Harwood, R, Allin, B, Jones, CE, et al. A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process. Lancet Child Adolesc Health 2021; 5: 133–141.CrossRefGoogle ScholarPubMed
Mahmoud, S, El-Kalliny, M, Kotby, A, El-Ganzoury, M, Fouda, E, Ibrahim, H. Treatment of MIS-C in children and adolescents. Curr Pediatr Rep 2022; 10: 1–10.CrossRefGoogle ScholarPubMed
McArdle, AJ, Vito, O, Patel, H, et al. Treatment of multisystem inflammatory syndrome in children. N Engl J Med 2021; 385: 11–22.CrossRefGoogle ScholarPubMed
Zhang, QY, Xu, BW, Du, JB. Similarities and differences between multiple inflammatory syndrome in children associated with COVID-19 and Kawasaki disease: clinical presentations, diagnosis, and treatment. World J Pediatr 2021; 17: 335–340.CrossRefGoogle ScholarPubMed
Ahmed, M, Advani, S, Moreira, A, et al. Multisystem inflammatory syndrome in children: a systematic review. EClinicalMedicine 2020; 26: 100527.CrossRefGoogle ScholarPubMed
Toczyłowski, K, Łasecka-Zadrożna, J, Pałyga-Bysiecka, I, et al. Use of broad-spectrum antibiotics in children diagnosed with multisystem inflammatory syndrome temporarily associated with SARS-CoV-2 infection in Poland: the MOIS-CoR study. Int J Infect Dis 2022; 122: 703–709.CrossRefGoogle ScholarPubMed
Hennon, TR, Penque, MD, Abdul-Aziz, R, et al. COVID-19 associated multisystem inflammatory syndrome in children (MIS-C) guidelines; a western New York approach. Prog Pediatr Cardiol 2020; 57: 101232.CrossRefGoogle Scholar
Berard R.A., TH, Scuccimarri, R, Haddad, E, et al. Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (spring 2021 update), Canadian Pediatric Society, Published 2021. Updated May 2, 2021. https://cps.ca/en/documents/position/pims#Figure%201, Accessed October 23, 2022.Google Scholar
AAo, Pediatrics. Multisystem inflammatory syndrome in children (MIS-c) interim guidance. American academy of pediatrics. Published 2022. Updated October 6, 2022. https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/multisystem-inflammatory-syndrome-in-children-mis-c-interim-guidance/, Accessed October 22, 2022.Google Scholar
Soma, VL, Shust, GF, Ratner, AJ. Multisystem inflammatory syndrome in children. Curr Opin Pediatr 2021; 33: 152–158.CrossRefGoogle ScholarPubMed
Goldenberg, NA, Sochet, A, Albisetti, M, et al. Consensus-based clinical recommendations and research priorities for anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illness. J Thromb Haemost 2020; 18: 3099–3105.CrossRefGoogle ScholarPubMed
Patel, JM. Multisystem inflammatory syndrome in children (MIS-c). Curr Allergy Asthma Rep 2022; 22: 53–60.CrossRefGoogle ScholarPubMed
Jonat, B, Gorelik, M, Boneparth, A, et al. Multisystem inflammatory syndrome in children associated with coronavirus disease 2019 in a children’s hospital in new york city: patient characteristics and an institutional protocol for evaluation, management, and follow-up. Pediatr Crit Care Med 2021; 22: e178–e191.CrossRefGoogle Scholar
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: 307–322.CrossRefGoogle ScholarPubMed
Sharma, C, Ganigara, M, Galeotti, C, et al. Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison. Nat Rev Rheumatol 2021; 17: 731–748.CrossRefGoogle ScholarPubMed
Ouldali, N, Toubiana, J, Antona, D, et al. Association of intravenous immunoglobulins plus methylprednisolone vs immunoglobulins alone with course of fever in multisystem inflammatory syndrome in children. JAMA 2021; 325: 855–864.CrossRefGoogle ScholarPubMed
Rauniyar, R, Mishra, A, Kharel, S, et al. IVIG plus glucocorticoids versus IVIG alone in multisystem inflammatory syndrome in children (MIS-c) associated with COVID-19: a systematic review and meta-analysis. Can J Infect Dis Med Microbiol 2022; 2022: 9458653–7.CrossRefGoogle ScholarPubMed
Dolinger, MT, Person, H, Smith, R, et al. Pediatric crohn disease and multisystem inflammatory syndrome in children (MIS-C) and COVID-19 treated with infliximab. J Pediatr Gastroenterol Nutr. 2020; 71: 153–155.CrossRefGoogle ScholarPubMed
Henderson, LA, Canna, SW, Friedman, KG, 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; 72: 1791–1805.CrossRefGoogle ScholarPubMed
Giacalone, M, Scheier, E, Shavit, I. Multisystem inflammatory syndrome in children (MIS-C): a mini-review. Int J Emerg Med 2021; 14: 50.CrossRefGoogle ScholarPubMed
Capone, CA, Misra, N, Ganigara, M, et al. Six month follow-up of patients with multi-system inflammatory syndrome in children. Pediatrics 2021; 148.CrossRefGoogle ScholarPubMed
Nakamura, Y, Yashiro, M, Uehara, R, et al. Epidemiologic features of Kawasaki disease in Japan: results of the 2007-2008 nationwide survey. J Epidemiol 2010; 20: 302–307.CrossRefGoogle ScholarPubMed
Gatterre, P, Oualha, M, Dupic, L, et al. Kawasaki disease: an unexpected etiology of shock and multiple organ dysfunction syndrome. Intensive Care Med 2012; 38: 872–878.CrossRefGoogle ScholarPubMed
Lin, M-T, Fu, C-M, Huang, S-K, Huang, S-C, Wu, M-H. Population-based study of Kawasaki disease shock syndrome in Taiwan. Pediatr Infect Dis J 2013; 32: 1384–1386.CrossRefGoogle ScholarPubMed
Burns, JC, Glodé, MP. Kawasaki syndrome. Lancet 2004; 364: 533–544.CrossRefGoogle ScholarPubMed