Review Article

COVID-19 Associated Multisystem Inflammatory Syndrome: A Systematic Review and Meta-analysis


The prevalence of multisystem inflammatory syndrome in children (MIS-C) has increased since the coronavirus disease 2019 (COVID-19) pandemic started. This study was aimed to describe clinical manifestation and outcomes of MIS-C associated with COVID-19. This systematic review and meta-analysis were conducted on all available literature until July 3rd, 2020. The screening was done by using the following keywords: (“novel coronavirus” Or COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus) and ("MIS-C" or "multisystem inflammatory" or Kawasaki). Data on gender, ethnicity, clinical presentations, need for mechanical ventilation or admission to intensive care unit (ICU), imaging, cardiac complications, and COVID-19 laboratory results were extracted to measure the pooled estimates. Out of 314 found articles, 16 articles with a total of 600 patients were included in the study, the most common presentation was fever (97%), followed by gastrointestinal symptoms (80%), and skin rashes (60%) as well as shock (55%), conjunctivitis (54%), and respiratory symptoms (39%). Less common presentations were neurologic problems (33%), and skin desquamation (30%), MIS-C was slightly more prevalent in males (53.7%) compared to females (46.3%). The findings of this meta-analysis on current evidence found that the common clinical presentations of COVID-19 associated MIS-C include a combination of fever and mucocutaneous involvements, similar to atypical Kawasaki disease, and multiple organ dysfunction. Due to the relatively higher morbidity and mortality rate, it is very important to diagnose this condition promptly.

1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-33.
2. Ludvigsson JF. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatrica, International Journal of Paediatrics. 2020;109(6):1088-95.
3. Ren LL, Wang YM, Wu ZQ, Xiang ZC, Guo L, Xu T, et al. Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. Chin Med J. 2020;133(9):1015-24.
4. Yang X, Yu Y, Xu J, Shu H, Xia Ja, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine. 2020;8(5):475-81.
5. Wang W, Tang J, Wei F. Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China. J Med Virol. 2020;92(4):441-7.
6. Baradaran A, Ebrahimzadeh MH, Baradaran A, Kachooei AR. Prevalence of comorbidities in COVID-19 patients: A systematic review and meta-analysis. Archives of Bone and Joint Surgery. 2020;8(SpecialIssue):247-55.
7. 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.
8. Roberts I. Nelson’s textbook of pediatrics (20th edn.), by R. Kliegman, B. Stanton, J. St. Geme, N. Schor (eds). Pediatr Radiol. 2017;47(10):1364-5.
9. 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.
10. Borenstein M, Hedges L, Higgins J, Rothstein H. Comprehensive Meta-Analysis Version 3. 2013.
11. Miller J, Cantor A, Zachariah P, Ahn D, Martinez M, Margolis KG. Gastrointestinal Symptoms as a Major Presentation Component of a Novel Multisystem Inflammatory Syndrome in Children That Is Related to Coronavirus Disease 2019: A Single Center Experience of 44 Cases. Gastroenterology. 2020.
12. 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(4):334-46.
13. 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.
14. 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. Journal of the Pediatric Infectious Diseases Society. 2020;9(3):393-8.
15. Cheung EW, Zachariah P, Gorelik M, Boneparth A, Kernie SG, Orange JS, et al. Multisystem Inflammatory Syndrome Related to COVID-19 in Previously Healthy Children and Adolescents in New York City. JAMA - Journal of the American Medical Association. 2020;324(3):294-6.
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.
17. 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 (Clinical research ed). 2020;369:m2094-m.
18. 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.
19. 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. Annals of Intensive Care. 2020;10(1):69-.
20. Blondiaux E, Parisot P, Redheuil A, Tzaroukian L, Levy Y, Sileo C, et al. Cardiac MRI of Children with Multisystem Inflammatory Syndrome (MIS-C) Associated with COVID-19: Case Series. Radiology. 2020:202288-.
21. 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.
22. 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 - Journal of the American Medical Association. 2020;324(3):259-69.
23. Ramcharan T, Nolan O, Lai CY, Prabhu N, Krishnamurthy R, 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. 2020:1-11.
24. Ng KF, Kothari T, Bandi S, Bird PW, Goyal K, Zoha M, et al. COVID-19 multisystem inflammatory syndrome in three teenagers with confirmed SARS-CoV-2 infection. J Med Virol. 2020;92(11):2880-6.
25. Covid CDC, Covid CDC, Covid CDC, Bialek S, Gierke R, Hughes M, et al. Coronavirus Disease 2019 in Children—United States, February 12–April 2, 2020. Morbidity and Mortality Weekly Report. 2020;69(14):422-.
26. She J, Liu L, Liu W. COVID-19 epidemic: Disease characteristics in children. J Med Virol. 2020;92(7):747-54.
27. Pareek M, Bangash MN, Pareek N, Pan D, Sze S, Minhas JS, et al. Ethnicity and COVID-19: an urgent public health research priority. The Lancet. 2020;395(10234):1421-2.
28. Hooper MW, Nápoles AM, Pérez-Stable EJ. COVID-19 and racial/ethnic disparities. JAMA. 2020.
29. Moazzen N, Imani B, Aelami MH, Haghi NSM, Kianifar HR, Khoushkhui M, et al. How to boost your immune system against coronavirus infection? Archives of Bone and Joint Surgery. 2020;8(SpecialIssue):220-5.
30. Rundle AG, Park Y, Herbstman JB, Kinsey EW, Wang YC. COVID-19–Related School Closings and Risk of Weight Gain Among Children. Obesity. 2020;28(6):1008-9.
31. Holman RC, Belay ED, Christensen KY, Folkema AM, Steiner CA, Schonberger LB. Hospitalizations for Kawasaki syndrome among children in the United States, 1997-2007. Pediatr Infect Dis J. 2010;29(6):483-8.
32. Son MB, Sundel RP. Kawasaki disease. Textbook of pediatric rheumatology. 2016:467.
33. Chang RKR. The incidence of Kawasaki disease in the United States did not increase between 1988 and 1997 [3]. Pediatrics. 2003;111(5 I):1124-5.
34. Sundel R, Klein-Gitelman M, Kaplan SLT. Kawasaki disease: Clinical features and diagnosis. Waltham, MA. 2016.
35. Cruz AT, Zeichner SL. COVID-19 in children: Initial characterization of the pediatric disease. Pediatrics. 2020;145(6).
36. Stafstrom CE, Jantzie LL. COVID-19: Neurological Considerations in Neonates and Children. Children. 2020;7(9):133-.
37. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic Manifestations of Hospitalized Patients with Coronavirus Disease 2019 in Wuhan, China. JAMA Neurology. 2020;77(6):683-90.
38. Wang HY, Li XL, Yan ZR, Sun XP, Han J, Zhang BW. Potential neurological symptoms of COVID-19. Ther Adv Neurol Disord. 2020;13:1756286420917830-.
39. Fabi M, Corinaldesi E, Pierantoni L, Mazzoni E, Landini C, Bigucci B, et al. Gastrointestinal presentation of kawasaki disease: A red flag for severe disease? PLoS One. 2018;13(9):e0202658-e.
40. Kanegaye JT, Wilder MS, Molkara D, Frazer JR, Pancheri J, Tremoulet AH, et al. Recognition of a Kawasaki disease shock syndrome. Pediatrics. 2009;123(5):e783-e9.
41. Tavazzi G, Pellegrini C, Maurelli M, Belliato M, Sciutti F, Bottazzi A, et al. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail. 2020;22(5):911-5.
42. Chuang GT, Tsai IJ, Lin MT, Chang LY. Acute kidney injury in patients with Kawasaki disease. Pediatr Res. 2016;80(2):224-7.
43. Hirsch JS, Ng JH, Ross DW, Sharma P, Shah HH, Barnett RL, et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int. 2020;98(1):209-18.
IssueVol 19 No 6 (2020) QRcode
SectionReview Article(s)
Coronavirus Kawasaki disease Multisystem inflammatory syndrome in children Severe acute respiratory syndrome coronavirus 2

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Baradaran A, Malek A, Moazzen N, Abbasi Shaye Z. COVID-19 Associated Multisystem Inflammatory Syndrome: A Systematic Review and Meta-analysis. Iran J Allergy Asthma Immunol. 2020;19(6):570-588.