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A Comprehensive Review of SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children

Document Type : Original article

Authors

1 Department of Pediatrics, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran.

2 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

3 MD, Faculty of Medicine, Islamic Azad University – Mashhad Branch, Mashhad, Iran

4 MD, Faculty of Medicine, Islamic Azad University – Mashhad Branch, Mashhad, Iran.

5 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

6 Faculty of Pharmacy, Islamic Azad University – Damghan Branch, Damghan, Iran

7 Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

10.22038/rcm.2025.25979

Abstract

The coronavirus disease 2019 (COVID-19) has affected individuals across all age groups, with a notably high rate of morbidity and mortality. Although most children with COVID-19 exhibit mild symptoms, an increasing proportion are developing a novel multisystem inflammatory syndrome (MIS-C), which shares clinical features with Kawasaki disease. MIS-C is a newly recognized hyperinflammatory condition affecting virtually any organ system. The most common symptoms include fever and gastrointestinal disturbances, although neurologic and dermatologic manifestations are well-documented. The clinical presentation of MIS-C overlaps with that of Kawasaki disease, toxic shock syndrome, and other shock syndromes, making accurate diagnosis challenging. Elevated inflammatory markers are frequently observed in MIS-C patients, and abnormalities on echocardiograms or electrocardiograms may be present. Treatment for MIS-C should consider intravenous immunoglobulin, anticoagulation, and corticosteroids. Despite significant cardiovascular involvement in some cases, most patients recover without complications. However, long-term echocardiographic follow-up is essential, as coronary aneurysms have been documented. This narrative review examines the epidemiology, pathophysiology, clinical manifestations, laboratory findings, diagnostic criteria, and treatment strategies for MIS-C to enhance pediatricians' understanding of this emerging syndrome.

Keywords

References
  1. Sinha IP, Harwood R, Semple MG, Hawcutt DB, Thursfield R, Narayan O, et al. COVID-19 infection in children. Lancet Respir Med. 2020;8(5):446-7. doi:10.1016/S2213-2600(20)30152-1 PMid:32224304
  2. Farhat AS, Sayedi SJ, Akhlaghi F, Hamedi A, Ghodsi A. Coronavirus (COVID-19) infection in newborns. Int J Pediatr. 2020;8(6):11513-7.
  3. Gorbalenya AE, Baker SC, Baric R, Groot RJ de, Drosten C, Gulyaeva AA, et al. Severe acute respiratory syndrome-related coronavirus: The species and its viruses-a statement of the Coronavirus Study Group. 2020; doi: 10.1101/2020.02.07.937862
  4. DeBiasi RL, Delaney M. Symptomatic and asymptomatic viral shedding in pediatric patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): under the surface. Jama Pediatr. 2021;175(1):16-8.
    doi :10.1001/jamapediatrics.2020.3996 PMid:32857158
  5. Ghodsi A, Azarfar A, Ghahremani S. A Review of Coronavirus Disease (COVID-19) in Children. J Pediatr Nephrol. 2020;8(3).
  6. 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. The Lancet. 2020;395(10239):1771-8.
    doi:10.1016/S0140-6736(20)31103-X PMid:32410760
  7. Malek A, Ghodsi A, Hamedi A. The Negative Predictive Value of Harada Scoring for Coronary Artery Dilatation or Aneurysm in Children with Kawasaki Disease: A Cross-sectional Study. Iran J Med Sci. 2022;
  8. Centers for Disease Control and Prevention. Multisystem Inflammatory Syndrome in Children Associated with Coronavirus Disease 2019. Available online at: https://emergency.cdc.gov/han/2020/han00432.asp.
  9. Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, et al. Multisystem inflammatory syndrome in US children and adolescents. N Engl J Med. 2020;383(4):334-46. doi:10.1056/NEJMoa2021680 PMid:32598831
  10. Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A, Abakka S, et al. Acute heart failure in multisystem inflammatory syndrome in children in the context of global SARS-CoV-2 pandemic. Circulation. 2020;142(5):429-36.
    doi:10.1161/CIRCULATIONAHA.120.048360 PMid:32418446
  11. 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(3):259-69.
    doi:10.1001/jama.2020.10369 PMid:32511692 PMCid:PMC7281356
  12. Lee MS, Liu YC, Tsai CC, Hsu JH, Wu JR. Similarities and differences between COVID-19-related multisystem inflammatory syndrome in children and Kawasaki disease. Front Pediatr. 2021;9:573.
    doi:10.3389/fped.2021.640118 PMid:34222140
  13. Davies P, Evans C, Kanthimathinathan HK, Lillie J, Brierley J, Waters G, 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(9):669-77. doi:10.1016/S2352-4642(20)30215-7
    PMid:32653054
  14. Burns JC, Glode M, Capparelli E, Brown J, Newburger J, Kato H. Kawasaki disease. Oxf Textb Of. 1995;373.
  15. 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(17):e927-99.
    doi:10.1161/CIR.0000000000000484 PMid:28356445
  16. 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.
    doi:10.1016/j.jpeds.2020.06.044
    PMid:32553873 PMCid:PMC7293762
  17. Jones VG, Mills M, Suarez D, Hogan CA, Yeh D, Segal JB, et al. COVID-19 and Kawasaki disease: novel virus and novel case. Hosp Pediatr. 2020;10(6):537-40.
    doi:10.1542/hpeds.2020-0123
    PMid:32265235
  18. Mahase E. Covid-19: concerns grow over inflammatory syndrome emerging in children. British Medical Journal Publishing Group; 2020. doi:10.1136/bmj.m1710 PMid:32345602
  19. 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(32):1074.
    doi:10.15585/mmwr.mm6932e2 PMid:32790663
  20. Laverty M, Salvadori M, Squires SG, Ahmed M, Eisenbeis L, Lee S, et al. Canadian children with multisystem inflammatory syndrome. CCDR. 2021;47:11. doi:10.14745/ccdr.v47i11a03 PMid:35356073
  21. Antúnez-Montes OY, Escamilla MI, Figueroa-Uribe AF, Arteaga-Menchaca E, Lavariega-Saráchaga M, Salcedo-Lozada P, et al. COVID-19 and multisystem inflammatory syndrome in Latin American children: a multinational study. Pediatr Infect Dis J. 2020;40(1):e1-6.
    doi:10.1097/INF.0000000000002949 PMid:33055501
  22. 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.
    doi:10.1017/S095026882000196X PMid:32854812
  23. Nakamura Y. Kawasaki disease: epidemiology and the lessons from it. Int J Rheum Dis. 2018;21(1):16-9.
    doi:10.1111/1756-185X.13211 PMid:29115029
  24. Tang Y, Li W, Baskota M, Zhou Q, Fu Z, Luo Z, et al. Multisystem inflammatory syndrome in children during the coronavirus disease 2019 (COVID-19) pandemic: a systematic review of published case studies. Transl Pediatr. 2021;10(1):121.
    doi:10.21037/tp-20-188 PMid:33633944
  25. 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(11):e340-6. doi:10.1097/INF.0000000000002888 PMid:32925547
  26. 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(4):347-58. doi:10.1056/NEJMoa2021756 PMid:32598830
  27. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. The Lancet. 2020;395(10237):1607-8. doi:10.1016/S0140-6736(20)31094-1 PMid:32386565
  28. Kim H, Shim JY, Ko JH, Yang A, Shim JW, Kim DS, et al. Unusual presentation of Kawasaki disease with multisystem inflammation and antibodies against severe acute respiratory syndrome coronavirus 2: a case report. 2020; doi:10.21203/rs.3.rs-41276/v1
  29. 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(11):e276-88. doi:10.1016/S1473-3099(20)30651-4 PMid:32818434
  30. Belot A, Antona D, Renolleau S, Javouhey E, Hentgen V, Angoulvant F, et al. SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020. Eurosurveillance. 2020;25(22):2001010.doi:10.2807/1560-7917.ES.2020.25.22.2001010 PMid:32524957
  31. Alunno A, Carubbi F, Rodríguez-Carrio J. Storm, typhoon, cyclone or hurricane in patients with COVID-19? Beware of the same storm that has a different origin. RMD Open. 2020;6(1):e001295. doi:10.1136/rmdopen-2020-001295 PMid:32423970
  32. Rowley AH, Shulman ST, Arditi M. Immune pathogenesis of COVID-19-related multisystem inflammatory syndrome in children. J Clin Invest. 2020;130(11):5619-21. doi:10.1172/JCI143840 PMid:32870815
  33. Cheng MH, Zhang S, Porritt RA, Rivas MN, Paschold L, Willscher E, et al. Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation. Proc Natl Acad Sci. 2020;117(41):25254-62. doi:10.1073/pnas.2010722117 PMid:32989130
  34. 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(2):307-22. doi:10.1007/s00431-020-03766-6PMid:32803422 PMCid:PMC7429125
  35. Dolhnikoff M, Ferranti JF, de Almeida Monteiro RA, Duarte-Neto AN, Gomes-Gouvêa MS, Degaspare NV, et al. SARS-CoV-2 in cardiac tissue of a child with COVID-19-related multisystem inflammatory syndrome. Lancet Child Adolesc Health. 2020;4(10):790-4. doi:10.1016/S2352-4642(20)30257-1 PMid:32828177
  36. Sahranavard M, Rezayat AA, Bidary MZ, Omranzadeh A, Rohani F, Farahani RH, et al. Cardiac complications in COVID-19: a systematic review and meta-analysis. Arch Iran Med. 2021;24(2):152. doi:10.34172/aim.2021.24 PMid:33636985
  37. Shulman ST. Pediatric coronavirus disease-2019-associated multisystem inflammatory syndrome. Vol. 9, Journal of the Pediatric Infectious Diseases Society. Oxford University Press US; 2020. p. 285-6. doi:10.1093/jpids/piaa062 PMid:32441751
  38. 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;
    doi:10.1016/j.ppedcard.2020.101232 PMid:32837142
  39. Gottlieb M, Long B, Koyfman A. The evaluation and management of toxic shock syndrome in the emergency department: a review of the literature. J Emerg Med. 2018;54(6):807-14. doi:10.1016/j.jemermed.2017.12.048 PMid:29366615
  40. Bridwell R, Long B, Gottlieb M. Neurologic complications of COVID-19. Am J Emerg Med. 2020;38(7):1549-e3.
    doi:10.1016/j.ajem.2020.05.024 PMid:32425321
  41. LaRovere KL, Riggs BJ, Poussaint TY, Young CC, Newhams MM, Maamari M, et al. Neurologic involvement in children and adolescents hospitalized in the United States for COVID-19 or multisystem inflammatory syndrome. JAMA Neurol. 2021;78(5):536-47.
    doi:10.1001/jamaneurol.2021.0504 PMid:33666649
  42. Giacalone M, Scheier E, Shavit I. Multisystem inflammatory syndrome in children (MIS-C): a mini-review. Int J Emerg Med. 2021;14(1):1-4. doi:10.1186/s12245-021-00373-6 PMid:34507521 PMCid:PMC8432439
  43. Ghodsi A, Mahmoudabadi E, Ghahremani S, Malek A. Cardiac manifestations of multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection. Arch Pediatr Infect Dis. 2021;16. doi:10.5812/pedinfect.109915
  44. Samprathi M, Jayashree M. Biomarkers in COVID-19: an up-to-date review. Front Pediatr. 2021;972.
    doi:10.3389/fped.2020.607647 PMid:33859967 PMCid:PMC8042162
  45. Carlin RF, Fischer AM, Pitkowsky Z, Abel D, Sewell TB, Landau EG, et al. Discriminating multisystem inflammatory syndrome in children requiring treatment from common febrile conditions in outpatient settings. J Pediatr. 2021;229:26-32.
    doi:10.1016/j.jpeds.2020.10.013 PMid:33065115 PMCid:PMC7553071
  46. Carter MJ, Shankar-Hari M, Tibby SM. Paediatric inflammatory multisystem syndrome temporally-associated with SARS-CoV-2 infection: an overview. Intensive Care Med. 2021;47(1):90-3. doi:10.1007/s00134-020-06273-2 PMid:33057783 PMCid:PMC7556601
  47. 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(8):999-1006.
    doi:10.1136/annrheumdis-2020-217960 PMid:32527868 PMCid:PMC7299653
  48. Felsenstein S, Willis E, Lythgoe H, McCann L, Cleary A, Mahmood K, et al. Presentation, treatment response and short-term outcomes in paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS). J Clin Med. 2020;9(10):3293.
    doi:10.3390/jcm9103293 PMid:33066459 PMCid:PMC7602286
  49. Toosi MB, Ghodsi A, Sarabi M, Ghahremani S, Fazeli N, Ghahremani S. Investigating the Frequency of Infantile Colic in Children with Migraine. J Child Sci. 2021;11(01):e89-92. doi:10.1055/s-0041-1728729
  50. 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. 2021;93(1):424-33.
    doi:10.1002/jmv.26224 PMid:32584487 PMCid:PMC7361761
  51. 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;369.
    doi:10.1136/bmj.m2094 PMid:32493739 PMCid:PMC7500538
  52. Royal College of Paediatrics and Child Health. Paediatric Multisystem Inflammatory Syndrome Temporally Associated with COVID-19-Guidance for Clinicians. Available online at: https://www.rcpch.ac.uk/resources/paediatric-multisystem-inflammatory-syndrome-temporally-associated-covid-19-pims-guidance.
  53. Ghodsi A, Malek A, Ghahremani S. A review of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. cal. 2020;12:13. doi:10.5812/hmj.107048
  54. Ghodsi A, Bijari M, Alamdaran SA, Saberi A, Mahmoudabadi E, Balali MR, et al. Chest computed tomography findings of COVID-19 in children younger than 1 year: a systematic review. World J Pediatr. 2021;1-8. doi:10.1007/s12519-021-00424-1 PMid:33963512 PMCid:PMC8104919
  55. Valverde I, Singh Y, Sanchez-de-Toledo J, Theocharis P, Chikermane A, Di Filippo S, et al. Acute cardiovascular manifestations in 286 children with multisystem inflammatory syndrome associated with COVID-19 infection in Europe. Circulation. 2021;143(1):21-32.
    doi:10.1161/CIRCULATIONAHA.120.050065 PMid:33166189
  56. Blondiaux E, Parisot P, Redheuil A, Tzaroukian L, Levy Y, Sileo C, et al. Cardiac MRI in children with multisystem inflammatory syndrome associated with COVID-19. Radiology. 2020;297(3):E283-8. doi:10.1148/radiol.2020202288 PMid:32515676 PMCid:PMC7294821
  57. World Health Organization. Multisystem Inflammatory Syndrome in Children and Adolescents Temporally Related to COVID-19. Available online at: https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19.
  58. Plunkett A, Tong J. Sepsis in children. Bmj. 2015;350. doi:10.1136/bmj.h3017 PMid:26060188
  59. Ghodsi A, Azarfar A, Sarabi M, Ravanshad Y, Esmaeeli M, Salahi Z. Investigating the Effect of Gift-Giving on Patient's Behavior in the Pediatric Clinic of Dr. Sheikh Hospital of Mashhad. J Child Sci. 2020;10(01):e215-20.
    doi:10.1055/s-0040-1721449
  60. Ghodsi A, Sarabi M, Malek A, Khakshour A. Current Treatment Guidelines of SARS-CoV-2 Related Multisystem Inflammatory Syndrome in Children: A Literature Review and Expert Opinion. J Child Sci. 2021;11(01):e133-40. doi:10.1055/s-0041-1731077
  61. Vogel TP, Top KA, Karatzios C, Hilmers DC, Tapia LI, Moceri P, et al. Multisystem inflammatory syndrome in children and adults (MIS-C/A): Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2021;39(22):3037-49. doi:10.1016/j.vaccine.2021.01.054 PMid:33640145 PMCid:PMC7904456
  62. Ouldali N, Toubiana J, Antona D, Javouhey E, Madhi F, Lorrot M, et al. Association of intravenous immunoglobulins plus methylprednisolone vs immunoglobulins alone with course of fever in multisystem inflammatory syndrome in children. Jama. 2021;325(9):855-64. doi:10.1001/jama.2021.0694 PMid:33523115 PMCid:PMC7851757
  63. Abrams JY, Oster ME, Godfred-Cato SE, Bryant B, Datta SD, Campbell AP, et al. Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study. Lancet Child Adolesc Health. 2021;5(5):323-31. doi:10.1016/S2352-4642(21)00050-X PMid:33711293
  64. Akbari A, Fathabadi A, Razmi M, Zarifian A, Amiri M, Ghodsi A, et al. Characteristics, risk factors, and outcomes associated with readmission in COVID-19 patients: A systematic review and meta-analysis. Am J Emerg Med. 2021;
    doi:10.1016/j.ajem.2021.12.012 PMid:34923196 PMCid:PMC8665665
  65. Sezer M, Çelikel E, Tekin ZE, Aydın F, Kurt T, Tekgöz N, et al. Multisystem inflammatory syndrome in children: clinical presentation, management, and short-and long-term outcomes. Clin Rheumatol. 2022;1-10. doi:10.1007/s10067-022-06350-5 PMid:36018446 PMCid:PMC9411826

 

Reviews in Clinical Medicine
Volume 12, Issue 2
April 2025
Pages 4-11
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