Main Article Content
COVID-19, SARS Cov-2, children, Kawasaki disease.
Background and aim: Kawasaki disease is an acute systemic febrile illness of unknown aetiology, which usually affects children under 5 years of age. It is well known that Kawasaki disease is one of the most common causes of acquired heart diseases in children in the developed countries. Many studies, have suggested that heterogeneous infectious agents, such as common viruses, may trigger Kawasaki disease in young children with genetic background. Nowadays we are facing a pandemic caused by a Novel Coronavirus named SARS-CoV-2. Consequently, it could be possible that once exposed to this new coronavirus, some children, genetically predisposed, may mount an exaggerated inflammatory response which clinically manifests as Kawasaki Disease. Methods: from January to May 2020 a systematic search was performed on Pubmed for the following search terms: “COVID-19”, “children”, “SARS-CoV-2”, “complications”, “Kawasaki disease”, “cytokine storm”. Results: Usually, infants and children present milder symptoms of SARS-CoV-2 disease with a better outcome than adults. At variance, some children may be genetically disposed to a more robust inflammatory response to SARS-CoV-2, similar to Kawasaki disease. In fact, Kawasaki disease is the result of an abnormal immune response, in susceptible children, to an external trigger such as an infection. Thus, according to the pathogenesis of Kawasaki disease, paediatricians may expect an increase in cases of Kawasaki disease during the COVID-19 pandemic.
2. Fujita Y et al. Kawasaki disease in families. Pediatrics. 1989. 84:666–669
3. Onouchi Y, et al. Common variants in CASP3 confer susceptibility to Kawasaki disease. Hum Mol Genet. 2010; 19:2898–2906.
4. Onouchi Y, et al. A genome-wide association study identifies three new risk loci for Kawasaki disease. Nat Genet. 2012; 44:517–521.
5. Rowley AH, et al. Ultrastructural, immunofluorescence, and RNA evidence support the hypothesis of a “new” virus associated with Kawasaki disease. J Infect Dis. 2011; 203:1021–1030.
6. Chang LY, Lu CY, Shao PL, Lee PI, Lin MT, Fan TY, et al. Viral infections associated with Kawasaki disease. J Formos Med Assoc 2014; 113:148–54
7. Tang Y et al. Kawasaki disease associated with Mycoplasma pneumoniae. Ital J Pediatr. 2016 Sep 8;42(1):83.
8. Matsubara K, Fukaya T. The role of superantigens of group A Streptococcus and Staphylococcus aureus in Kawasaki disease. Curr Opin Infect Dis 2007; 20:298–303
9. Esper F et al. Association between a novel human coronavirus and Kawasaki disease. J Infect Dis. 2005 Feb 15;191(4):499-502.
10. Weng KP et al. Enterovirus Infection and Subsequent Risk of Kawasaki Disease: A Population-based Cohort Study. Pediatr Infect Dis J. 2018 Apr;37(4):310-315.
11. Kim GB, Park S, Kwon BS, Han JW, Park YW, Hong YM. Evaluation of the Temporal Association between Kawasaki Disease and Viral Infections in South Korea.Korean Circ J. 2014 Jul;44(4):250-4
12. Turnier JL, Anderson MS, Heizer HR, Jone PN, Glodé MP, Dominguez SR. Concurrent Respiratory Viruses and Kawasaki Disease.Pediatrics. 2015 Sep;136(3):e609-14.
13. 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):e783–9
14. Li Y, et al. Kawasaki disease shock syndrome: clinical characteristics and possible use of IL-6, IL-10 and IFN-γ as biomarkers for early recognition. Pediatric Rheumatology. 2019. 17(1):1
15. WHO. Coronavirus disease (Covid-19) situation report 14.07.2020
16. European Centre for Disease Prevention and Control. Paediatric inflammatory multisystem syndrome and SARS-CoV-2 infection in children – 15 May 2020. ECDC: Stockholm; 2020.
17. Verdoni L 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. https://doi.org/10.1016/S0140-6736(20)31103-X
18. 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. doi:10.1001/jama.2020.10369
19. Zhang W 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 May; 214:108393.
20. Anne H Rowley, Stanford T Shulman. The Epidemiology and Pathogenesis of Kawasaki Disease. Front Pediatr. 2018 Dec 11; 6:374.
21. Anne H Rowley and al. Ultrastructural, Immunofluorescence, and RNA Evidence Support the Hypothesis of a "New" Virus Associated With Kawasaki Disease. J Infect Dis. 2011 Apr 1;203(7):1021-30.
22. Jordan-Villegas A, Chang ML, Ramilo O, Mejías A. Concomitant respiratory viral infections in children with Kawasaki disease. Pediatr Infect Dis J 2010;29:770–2
23. Turnier JL, Anderson MS, Heizer HR, Jone PN, Glodé MP, Dominguez SR. Concurrent respiratory viruses and Kawasaki disease. Pediatrics 2015;136:e609–14.
24. G Nigro, M Midulla. Retrovirus and Kawasaki Disease. Lancet 1986 Nov 1;2(8514):1045.
25. G Enders, M Biber, G Meyer, E Helftenbein. Prevalence of Antibodies to Human Herpesvirus 6 in Different Age Groups, in Children With Exanthema Subitum, Other Acute Exanthematous Childhood Diseases, Kawasaki Syndrome, and Acute Infections With Other Herpesviruses and HIV Infection Jan-Feb 1990;18(1):12-5.
26. S Shatizadeh Malekshahi, T Mokhtari Azad, Sh Shahmahmoodi, J Yavarian, F Rezaei, M Naseri. First Report of Respiratory Syncytial Virus and Human Metapneumovirus Co-Infection in a 2-year-old Kawasaki Patient in Iran. Iran J Public Health 2010;39(4):140-2. Epub 2010 Dec 31.
27. Demet Toprak, Özge Serçe, Özden Türel, Serkan Atici, Ahmet Soysal, Mustafa Bakir. Is Varicella Zoster Virus an Etiologic Factor in Kawasaki Disease? A Case Report and Review of the Literature Glob Pediatr Health. 2015; 2: 2333794X14567194.
28. Osato T et al. Kawasaki disease and Epstein-Barr virus infection. Prog Clin Biol Res. 1987;250:113-6.
29. Hu P, Guan Y, Fan XC, Lu FY, Song LM. Incomplete Kawasaki disease induced by measles in a 6-month-old male infant. Int J Dermatol. 2016 Jan;55(1):e34-6. doi: 10.1111/ijd.13122. Epub 2015 Oct 30.
30. Esper F, Shapiro ED, Weibel C, Ferguson D, Landry ML, Kahn JS. Association between a novel human coronavirus and Kawasaki disease. J Infect Dis 2005; 191:499–502.
31. Guleria S, Jindal AK, Pandiarajan V, Singh MP, Singh S. Dengue-Triggered Kawasaki Disease: A Report of 2 Cases. J Clin Rheumatol. 2018 Oct;24(7):401-404. doi: 10.1097/RHU.0000000000000704.
32. Akihiro Nakamura, Kazuyuki Ikeda, and Kenji Hamaoka. Aetiological Significance of Infectious Stimuli in Kawasaki Disease. Front Pediatr. 2019; 7: 244.
33. Ravelli A, Martini A.Kawasaki disease or Kawasaki syndrome? Ann Rheum Dis 2020. doi:10.1136/annrheumdis-2020-218110