A link between the COVID-19 pandemic and Kawasaki-like multi-system inflammatory syndrome in children
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Pediatrics Department, National Research Centre, Cairo, Egypt
Corresponding author
Manal Fouad Elshamaa   

33 Elbohous street, Dokki, Cairo, Egypt, postal code,12311, Pediatrics Department,National Research Centre
J Pre Clin Clin Res. 2020;14(4):151-155
COVID-19 (coronavirus disease 2019) – the epidemic outbreak caused by coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – is a global public health problem. Children are less affected and have a mild form of the illness. The association between SARS-CoV-2 disease, COVID-19 and late symptoms of vasculitis is often suspected, in particular in young asymptomatic patients, especially due to the post-viral immune response.

The aim of the review is to describe the characteristics of children and adolescents affected by the development of Kawasaki-like mult-system inflammatory syndrome (KD) (MISC), and assesses its possible temporal association with SARS-CoV-2 infection

Brief description of the state of knowledge:
A group of children who presented with KD-type MISC during the COVID-19 pandemic have been identified in the United Kingdom, the United States, and Italy. Some children were diagnosed with SARS-CoV-2 infection by real-time polymerase chain reaction and IgG antibodies. SARS-CoV-2 infection and hyperinflammation in COVID-19 can serve as an ‘initial trigger’ for KD. IVIG should be administered within seven days of onset of illness until KD symptoms disappear and COVID-19 test is negative. Large numbers of children in African countries with the SARS-CoV-2 epidemic are likely to be affected by KD, and in such cases, a shortage of IVIG supplies is expected.

This article suggests a correlation between COVID-19 and Kawasaki-like MISC, which is important for the care of sick children. However, the definitive relationship between childhood KD and COVID-19 needs to be confirmed by a large cohort study on a large numbers of infant and children patients worldwide.

The author thanks the National Research Centre in Cairo, Egypt.
The author declares that there are no conflicts of interest.
Manal Fouad Elshamaa. A link between the COVID-1 pandemic and Kawasaki-like multi-system inflammatory syndrome in children. J Pre-Clin Clin Res. 2020; 14(4): 151–155. doi: 10.26444/jpccr/130368
Lu X, Zhang L, Du H, et al. SARS-CoV-2 infection in children. N Engl J Med. 2020; 382(17): 1663–1665. https: //doi: 10.1056/NEJMc2005073. Epub 2020 Mar 18.
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020; 323(13): 1239–1242. https: //doi:10.1001/jama.2020.2648.
Castagnoli R, Votto M, Licari A, et al. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review. JAMA Pediatr. Published online April 22, 2020. https: //doi: 10.1001/jamapediatrics.2020.1467.
Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 among Children in China. Pediatric 2020: 145(6):e2020–0702. https: //doi:10.1542/peds.2020-0702.
Russell M Viner, Whittaker E. Kawasaki-like disease: emerging complication during the COVID-19 pandemic. Lancet. 2020; 395(10239): 1741–1743. https: //doi: 10.1016/S0140-6736(20)31129-6 [Epub ahead of print].
Lu R, Zhao X, Li, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395: 565–574. https: // -6736(20)30251-8.
Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579: 270–273. 6-020-2012-7.
Chen J, Subbarao K. The Immunobiology of SARS*. Annu Rev Immunol. 2007; 25: 443–472. ev.immun ol.25.02210 6.14170 6.
Du Toit A. Viral infection: changing sides to get in. Nat Rev Microbiol. 2016; 14: 476–477. ro.2016.98.
Hedrich CM. COVID-19—considerations for the paediatric rheumatologist. Clin Immunol. 2020; 214: 108420. https://doi. org/10.1016/j.clim.2020.10842 0.
Channappanavar R, Fehr AR, Vijay R, et al. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe 2016; 19: 181–193.
Cameron MJ, Ran L, Xu L, et al. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J Virol. 2007; 81: 8692–8706. https://doi. org/10.1128/JVI.00527-07.
Ye Q, Wang B, Mao J. The pathogenesis and treatment of the `Cytokine Storm’ in COVID-19. J Infect. 2020; 80(6): 607–613. https://doi. org/10.1016/j.jinf.2020.03.037.
Liu L, Wei Q, Lin Q, et al. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight. 2019; 4(4): e123158. ht.12315 8.
Fu Y, Cheng Y, Wu Y. Understanding SARS-CoV-2-mediated inflamma-tory responses: from mechanisms to potential therapeutic tools. Virol Sin. 2020; 35(3): 266–2711. 0-020-00207-4.
Zhang W, Zhao Y, Zhang F, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the perspectives of clinical immunologists from China. Clin Immunol. 2020; 214: 108393. https:// 3.
Rockx B, Baas T, Zornetzer GA, et al. Early upregulation of acute respiratory distress syndrome-associated cytokines promotes lethal disease in an aged-mouse model of severe acute respiratory syndrome coronavirus infection. J Virol. 2009; 83: 7062–7074. JVI.00127-09.
Smits SL, de Lang A, van den Brand JM, et al. Exacerbated innate host response to SARSCoV in aged non-human primates. PLoS Pathog.2010; 6(2):e1000756. al.ppat.10007 56.
Misra DP, Agarwal V, Gasparyan AY, et al. Rheumatologists’ perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets. Clin Rheumatol.2020; 39(7): 2055–2062. https://doi. org/10.1007/s1006 7-020-05073-9.
Henderson LA, Canna SW, Schulert GS, et al. On the alert for cytokine storm: immunopathology in COVID-19. Arthritis Rheumatol. 2020; 72(7): 1059–1063.
Vardavas CI, Nikitara K. COVID-19 and smoking: a systematic review of the evidence. Tob Induc Dis. 2020; 18: 20. https://doi. org/10.18332 /tid/11932 4.
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395: 1054–1062. https://doi. org/10.1016/S0140-6736(20)30566-3.
Haslak F, Yildiz M, Adrovic A, et al. Childhood rheumatic diseases and COVID-19 pandemic: an intriguing linkage and a New Horizon. Balkan Med J. 2020; 37(4): 184–188. https:/
Lee PI, Hu YL, Chen PY, et al. Are children less susceptible to COVID-19? J Microbiol Immunol Infect. 2020; 53(3): 371–372.
Brodin P. Why is COVID-19 so mild in children? Acta Paediatr. 2020; 109(6): 1082–1083.
Liu Y, Yan LM, Wan L, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis. 2020; 20(6): 656–657.
Nickbakhsh S, Mair C, Matthews L, et al. Virus-virus interactions impact the population dynamics of influenza and the common cold. Proc Natl Acad Sci USA. 2019; 116(52): 27142–50. 83116.
Carsetti R, Quintarelli C, Quinti I, et al. The immune system of children: the key to understanding SARS-CoV-2 susceptibility? The Lancet Child & Adolescent Health. 2020; 4(6): 414–416.
Chen J JQ, Xia X, Liu K, et al. Individual variation of the SARS-CoV2 receptor ACE2 gene expression and regulation. Aging Cell. 2020; 19(7): 10.1111/acel.13168. 19(7): 10.1111/acel.13168.
Barsh GR, Maskatia S, Mathew R. COVID-19 and Kawasaki disease: novel virus and novel case, Hosp Pediatr. 2020; 10(6): 537–540.
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(10239): 1771–1778.
Schnabel A, Hedrich CM. Childhood Vasculitis. Front Pediatr 2019; 6: 421. https: //doi: 10.3389/fped.2018.00421Journal of Pre-Clinical and Clinical ResearchJPCCR Manal Fouad Elshamaa. A link between the COVID-19 pandemic and Kawasaki-like multi-system inflammatory syndrome in children.
Makino N, Nakamura Y, Yashiro M, et al. Nationwide epidemiologic survey of Kawasaki disease in Japan, 2015–2016. Pediatr Int 2019; 61: 397– 403. ht t ps: //doi:10.1111/ped.13809.
McCrindle BW, Rowley AH, Newburger JW, et al, American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Epidemiology and Prevention. 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: 10.1161/CIR.0000000000000484.
Hala M Agha and Hala S. Hamza Incomplete Kawasaki disease in Egypt Glob Cardiol Sci Pract. 2017; (3): e201724.1–5. https: //doi: 10.21542/gcsp.2017.24.
Attia TH, Saeed MA and Fathalla D. Kawasaki Disease Presented with Meningitis in an Egyptian Adolescent Journal of Case Reports and Studies 2015 3(6)1–4. https: //doi: 10.15744/2348-9820.3.602.
Turnier JL, Anderson MS, Heizer HR, et al. Concurrent Respiratory Viruses and Kawasaki Disease. Pediatrics 2015; 136: e609–14. https: //doi: 10.1542/peds.2015-0950.
Catalano-Pons C, Quartier P, Leruez-Ville M, et al. Primary cytomegalovirus infection, atypical Kawasaki disease, and coronary aneurysms in 2 infants. Clin Infect Dis 2005; 41: e53–6. https: //doi: 10.1086/432578.
Bajolle F, Meritet JF, Rozenberg F, et al. Markers of a recent bocavirus infection in children with Kawasaki disease: “a year prospective study”. Pathol Biol (Paris) 2014; 62: 365–8. https: //doi:10.1016/j. patbio.2014.06.002.
Esper F, Shapiro ED, Weibel C, et al. Association between a novel human coronavirus and Kawasaki disease. J Infect Dis. 2005; 191: 499–502. https: //doi:10.1086/428291.
Chang LY, Lu CY, Shao PL, et al. Viral infections associated with Kawasaki disease. J Formos Med Assoc 2014; 113: 148–54. https://doi: 10.1016/j.jfma.2013.12.008.
Lehmann C, Klar R, Lindner J, et al. Kawasaki disease lacks association with human coronavirus NL63 and human bocavirus. Pediatr Infect Dis J 2009; 28: 553–4. https://doi: 10.1097/ INF.0b013e31819f41b6.
Kim JH, Yu JJ, Lee J, et al. Detection rate and clinical impact of respiratory viruses in children with Kawasaki disease. Korean J Pediatr 2012; 55: 470–3. https: //doi: 10.3345/kjp.2012.55.12.470.
Rauch AM, Hurwitz ES. Centers for Disease Control [CDC] case definition for Kawasaki syndrome. Pediatr Infect Dis. 1985; 4: 702–703. https://doi: 10.1097/00006454-198511000-00029.
Varga Z, Flammer A.J, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19, Lancet 2020; 395(10234): 1417–1418. https: //doi: 10.1016/S0140-6736(20)30937-5.
World Health Organization, 2020, May 15, Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19 Retrieved from Health City, Texas: Author (Access 2020.6.20).
Harahsheh AS, Dahdah N, Newburger JW, et al. Missed or delayed diagnosis of Kawasaki disease during the 2019 novel coronavirus disease (COVID-19) pandemic, J Pediatr. 2020; 222: 261–262.
Elshamaa MF. Kawasaki disease: The coronary affection perspective. Cardiothorac Vasc Sci. 2017; 1(1): 1–13. doi: 10.15761/CVS.1000105.
Yutani C, Go S, Kamiya T, et al. Cardiac biopsy of Kawasaki disease. Arch Pathol Lab Med. 1981; 105: 470–3. PMID: 6895017.
Kao CH, Hsieh KS, Wang YL, et al. The detection of ventricular dysfunction and carditis in children with Kawasaki disease using equilibrium multigated blood pooling ventriculography and 99Tcm-HMPAO-labelled WBC heart scans. Nucl Med Commun 1993; 14: 539–43. https: //doi: 10.1097/00006231-199307000-00004.
Harada M, Yokouchi Y, Oharaseki T, et al. Histopathological characteristics of myocarditis in acute-phase Kawasaki disease. Histopathology 2012; 61: 1156–67. https: //doi:10.1111/j.1365- 2559.2012.04332.x.
Li Y, Zheng Q, Zou L, et al. Kawasaki disease shock syndrome: clinical characteristics and possible use of IL-6, IL-10 and IFN-γ as biomarkers for early recognition. Pediatr Rheumatol. 2019; 17(1): 1–9 https://doi: 10.1186/s12969-018-0303-4.
Kanegaye JT, Wilder MS, Molkara D, et al. Recognition of a Kawasaki disease shock syndrome. Pediatrics 2009; 123: e783–9. https://doi: 10.1542/peds.2008-1871.
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: 872–8. https://doi: 10.1007/s00134-012-2473-8.
ECDC. Pediatric inflammatory multisystem syndrome and SARSCoV-2infection in children, 2020. sites/default/files/documents/covid-19-risk-assessment pediatric inflammatory- multisystem-syndrome-15-May-2020.pdf, (Access 2020.6.20).
Lee KY, Rhim JW, Kang JH. Kawasaki disease: laboratory findings and an immunopathogenesis on the premise of a “protein homeostasis system”. Yonsei Med J. 2012; 53: 262–75. https://doi: 10.3349/ ymj.2012.53.2.262.
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497–506. https://doi: 10.1016/S0140-6736(20)30183-5.
Mehta P, McAuley DF, Brown M, et al. HLH across speciality collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395: 1033–4. https://doi: 10.1016/S0140-6736(20)30628-0.
Noorani M, Lakhani N. Kawasaki disease: two case reports from the Aga Khan Hospital, Dar es Salaam-Tanzania. BMC Pediatr 2018; 18: 334. https://doi: 10.1186/s12887-018-1306-5.
Holman RC, Belay ED, Christensen KY, et al. Hospitalizations for Kawasaki syndrome among children in the United States, 1997–2007. Pediatr Infect Dis J 2010; 29: 483–8. https://doi: 10.1097/INF.0b013e3181cf8705.
Gardner-Medwin JM, Dolezalova P, Cummins C, et al. Incidence of Henoch-Schonlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet 2002; 360: 1197–202. https: //doi:10.1016/S0140-6736(02)11279-7.
Yancy CW. COVID-19 and African Americans. JAMA. 2020. https://doi: 10.1001/jama.2020.654863.
Giudicessi JR, Roden DM, Wilde AAM, et al. Genetic Susceptibility for COVID-19-Associated Sudden Cardiac Death in African Americans. Heart Rhythm 2020. S1547–527 1(20): 30419–7. https://doi: 10.1016/j.hrthm.2020.04.045.
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