The “perfect” storm: Current evidence on pediatric inflammatory multisystem disease during SARS-CoV-2 pandemic
COVID19 and pediatric inflammatory multisystem disease
Keywords:
COVID-19,, Kawasaki disease, SARS-CoV-2, children, multisystem inflammatory syndromeAbstract
Current data suggest that during the global pandemic of COVID 19 children are less affected than adults and most of them are asymptomatic or with mild symptoms. However, recently, cases of pediatric patients who have developed severe inflammatory syndrome temporally related to SARS-CoV-2 have been reported both in USA and Europe. These reports, although sharing features with other pediatric syndromes such as Kawasaki disease (KD), Kawasaki disease shock syndrome (KDSS), macrophage activated syndrome (MAS) and shock toxic syndrome (TSS), seem to outline a novel entity syndrome, characterized by cytokine storm with elevated inflammatory markers and typical clinical finding. Clinical characteristics are greater median age than KD, higher frequency of cardiac involvement and gastrointestinal symptoms, lower frequency of coronary anomalies. We report a summary of the current evidence about clinical features, pathogenesis, therapy strategies and outcome of this novel syndrome.
References
Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID 19 among children in China. Pediatrics. 2020; 145(6):e20200702. doi: 10.1542/peds.2020-0702.
Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965): 450-454.
Castagnoli R, Votto M, Licari A, et al. Severe acute respiratory syndrome coronavi- rus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatr 2020 April 22. doi: 10.1001/jamapediatrics.2020.1467. Online ahead of print.
Koné-Paut I, Cimaz R. Is it Kawasaki shock syndrome, Kawasaki-like disease or pediatric inflammatory multisystem disease? The importance of semantic in the era of COVID-19 pandemic. RMD Open 2020;6:e001333.
Parri, N., Magistà, A.M., Marchetti, F. et al. Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks. Eur J Pediatr 179, 1315–1323 (2020). https://doi.org/10.1007/s00431-020-03683-8
Verdoni L, Mazza A, Gervasoni A, et al . An outbreak of severe Kawasaki-like disease at the Italian epicenter of the SARS-CoV-2 epidemic: an observational cohort study. Lancet 2020;395(10239):1771-1778.
Jones VG, Mills M, Suarez D, et al. COVID-19 and Kawasaki Disease: Novel Virus and Novel Case. Hosp Pediatr 2020; 10:537-540
Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020; 23;395(10237):1607-1608.
Belhadjer Z, Méot M, Bajolle F, et al.; Acute heart failure in multisystem inflammatory syndrome children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation 2020 doi.org/10.1161/CIRCULATIONAHA.120.048360 Online ahead of print.
Licciardi F, Pruccoli G, Denina M, et al. SARS-CoV-2–induced Kawasaki-like hyperinflammatory syndrome: a novel COVID phenotype in children. Pediatrics. 2020; May 21;e20201711. doi: 10.1542/peds.2020-1711
Toubiana J., Poirault C., Corsia A., Bajolle F., Fourgeaud J., Angoulvant F. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study. BMJ. 2020; Jun 3;369:m2094. doi: 10.1136/bmj.m2094.
Marchesi A, Tarissi de Jacobis I, Rigante D. Kawasaki disease: guidelines of the Italian Society of Pediatrics, part I - definition, epidemiology, etiopathogenesis, clinical expression and management of the acute phase. Ital J Pediatr. 2018;44:102
Makino N, Nakamura Y, Yashiro M et al.Descriptive epidemiology of Kawasaki disease in Japan, 2011–2012: from the results of the 22nd nationwide survey. J Epidemiol. 2015; 25: 239-245
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.
Ebihara T, Endo R, Ma X, Ishiguro N, Kikuta H. Lack of association between New Haven coronavirus and Kawasaki disease. J Infect Dis. 2005; 192: 351-352
Shirato K, Imada Y, Kawase M, Nakagaki K, Matsuyama S, Taguchi F Possible involvement of infection with human coronavirus 229E, but not NL63, in Kawasaki disease. J Med Virol. 2014; 86: 2146-2153
Ravelli A, Minoia F, Davì S, et al. 2016 Classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Ann Rheum Dis. 2016; 75: 481-489
Kanegaye JT, Wilder MS, Molkara D. Recognition of a Kawasaki disease shock syndrome. Pediatrics. 2009;123:e783–e789
Chuang, Y-Y, Huang, Y-C,Lin T-Y Toxic Shock Syndrome in Children. Pediatric Drugs. 2005; 7(1): 11–25.
Royal College of Paediatrics and Child Health (RCPCH). Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19.May 2020 https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf last access July 30, 2020
Centers for Disease Control and Prevention: Information for Healthcare Providers about Multisystem Inflammatory Syndrome in Children (MIS-C). 14 May 2020. https://www.cdc.gov/mis-c/hcp/ last access July 30, 2020
Istituito Superiore di Sanità. Indicazioni ad interim su malattia di Kawasaki e sindrome infiammatoria acuta multisistemica in età pediatrica e adolescienziale nell’attuale scenario emergenziale da infezione Sars-CoV-2. 2020, Rapporto ISS COVID-19 n. 29/2020
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 Jun 12:1-11. doi: 10.1007/s00246-020-02391-2. Online ahead of print.
Belot A, Antona D, Renolleau S et al.SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020. Euro Surveill. 2020 Jun;25(22):2001010. doi: 10.2807/1560-7917.ES.2020.25.22.2001010. (22) (2020)
Pouletty M, Borocco C, Ouldali N et al. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicenter cohort. Ann Rheum Dis 2020 Aug;79(8):999-1006.
Chiotos K, Bassiri H, Behrens E M, et al. Multisystem Inflammatory Syndrome in Children During The Coronavirus 2019 Pandemic: A Case Series. J Pediatric Infect Dis Soc. 2020 Jul 13;9(3):393-398.
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? PloSone. 2018;13(9): e0202658. doi: 10.1371/journal.pone.0202658
Henderson LA, Canna SW, Schulert GS. On the alert for cytokine storm: immunopathology in COVID-19. Arthritis Rheumatol. 2020 Jul;72(7):1059-1063
Molloy EJ, Bearer CF. COVID-19 in children and altered inflammatory responses. Pediatr Res. 2020 doi: 10.1038/s41390-020-0881-y. published online April 3
Roncati L., Ligabue G., Fabbiani L., Malagoli C. Type 3 hypersensitivity in COVID-19 vasculitis. Clin Immunol. 2020;217
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. doi:10.1016/S0140-6736(20)30183 5.
Nakra, NA, Blumberg DA, Herrera-Guerra A, Lakshminrusimha S. Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed management. Children 2020, 7, 69
The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19 — preliminary report. N Engl J Med. DOI: 10.1056/NEJMoa2021436.
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020, 30, 269–271
Wang Y, Zhang, D.; Du, G.; Du, R.; Zhao, J.; Jin, Y.; Fu, S.; Gao, L.; Cheng, Z.; Lu, Q.; et al. Remdesivir in adults with severe COVID-19: A randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020, 395, 1569–1578
Feldstein LR, Rose EB, Horwitz SM et al Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med. 2020 Jul 23;383(4):334-346.
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