An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study.
Journal: 2020/May - The Lancet
ISSN: 1474-547X
Abstract:
The Bergamo province, which is extensively affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, is a natural observatory of virus manifestations in the general population. In the past month we recorded an outbreak of Kawasaki disease; we aimed to evaluate incidence and features of patients with Kawasaki-like disease diagnosed during the SARS-CoV-2 epidemic.All patients diagnosed with a Kawasaki-like disease at our centre in the past 5 years were divided according to symptomatic presentation before (group 1) or after (group 2) the beginning of the SARS-CoV-2 epidemic. Kawasaki- like presentations were managed as Kawasaki disease according to the American Heart Association indications. Kawasaki disease shock syndrome (KDSS) was defined by presence of circulatory dysfunction, and macrophage activation syndrome (MAS) by the Paediatric Rheumatology International Trials Organisation criteria. Current or previous infection was sought by reverse-transcriptase quantitative PCR in nasopharyngeal and oropharyngeal swabs, and by serological qualitative test detecting SARS-CoV-2 IgM and IgG, respectively.

Findings
Group 1 comprised 19 patients (seven boys, 12 girls; aged 3·0 years [SD 2·5]) diagnosed between Jan 1, 2015, and Feb 17, 2020. Group 2 included ten patients (seven boys, three girls; aged 7·5 years [SD 3·5]) diagnosed between Feb 18 and April 20, 2020; eight of ten were positive for IgG or IgM, or both. The two groups differed in disease incidence (group 1 vs group 2, 0·3 vs ten per month), mean age (3·0 vs 7·5 years), cardiac involvement (two of 19 vs six of ten), KDSS (zero of 19 vs five of ten), MAS (zero of 19 vs five of ten), and need for adjunctive steroid treatment (three of 19 vs eight of ten; all p<0·01).

In the past month we found a 30-fold increased incidence of Kawasaki-like disease. Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS. The SARS-CoV-2 epidemic was associated with high incidence of a severe form of Kawasaki disease. A similar outbreak of Kawasaki-like disease is expected in countries involved in the SARS-CoV-2 epidemic.None.
Relations:
Content
Citations
(341)
References
(28)
Diseases
(2)
Chemicals
(4)
Genes
(1)
Organisms
(1)
Processes
(1)
Similar articles
Articles by the same authors
Discussion board
Lancet undefined

An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study

Supplementary Material

Supplementary appendix:

Paediatric Department, Hospital Papa Giovanni XXIII, Bergamo, Italy
Paediatric Cardiology, Hospital Papa Giovanni XXIII, Bergamo, Italy
Paediatric Intensive Care Unit, Hospital Papa Giovanni XXIII, Bergamo, Italy
Lorenzo D'Antiga: ti.32gp-tssa@agitnadl
Correspondence to: Dr Lorenzo D'Antiga, Paediatric Department, Hospital Papa Giovanni XXIII, 24127 Bergamo, Italy ti.32gp-tssa@agitnadl
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Research in context

ESR=erythrocyte sedimentation rate. CRP=C-reactive protein. MAS=Macrophage Activation Syndrome. ALT=alanine aminotransferase. AST=aspartate aminotransferase. KDSS=Kawasaki disease shock syndrome. SBP=systolic blood pressure. CPK=creatine phosphokinase. BNP=B-type natriuretic peptide. nv=normal values. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. IVIG=intravenous immunoglobulin. mPDN=methylprednisolone.

Data are mean (SD) or n/N (%), unless otherwise stated. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. NA=not applicable. CRP=C-reactive protein. ESR=erythrocyte sedimentation rate. AST=aspartate aminotransferase. ALT=alanine aminotransferase. CPK=creatine phosphokinase. BNP=B-type natriuretic peptide. MAS=Macrophage Activation Syndrome. KDSS=Kawasaki disease shock syndrome.

Contributors

LV and LD'A made substantial contributions to the conception or design of the work. LV and AM drafted the work. LV, AM, AG, LM, MR, MC, EB, and LD'A gave final approval for the Article to be published. LV, AM, AG, LM, MR, MC, EB, and LD'A agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. AM, AG, LM, MR, MC, and EB acquired, analysed, or interpreted data for the Article. AG, LM, MR, MC, and EB revised the Article critically for important intellectual content. LD'A prepared the final draft and critically revised the Article for important intellectual content.

Contributors

Declaration of interests

We declare no competing interests and no financial support for this study.

Declaration of interests
Click here to view.(228K, pdf)

References

  • 1. Ministero della Salute Nuovo coronavirus: cosa c'è da sapere.
  • 2. Flaxman S, Mishra S, Gandy AEstimating the number of infections and the impact of nonpharmaceutical interventions on COVID-19 in 11 European countries.
  • 3. Zhu N, Zhang D, Wang WA novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727–733.[Google Scholar]
  • 4. Huang C, Wang Y, Li XClinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.[Google Scholar]
  • 5. Yonker LM, Shen K, Kinane TBLessons unfolding from pediatric cases of COVID-19 disease caused by SARS-CoV-2 infection. Pediatr Pulmonol. 2020;55:1085–1086.[Google Scholar]
  • 6. Dong Y, Mo X, Hu YEpidemiology of COVID-19 among children in China. Pediatrics. 2020 doi: 10.1542/peds.2020-0702. published online March 16. [[PubMed][Google Scholar]
  • 7. Nicastro E, Mazza A, Gervasoni A, Di Giorgio A, D'Antiga LA pediatric emergency department protocol to avoid intra-hospital dispersal of SARS-CoV-2 during the outbreak in Bergamo, Italy. J Pediatr. 2020 doi: 10.1016/j.jpeds.2020.04.026. published online April 21. [[PubMed][Google Scholar]
  • 8. Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan HEvidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020;158:1831–1833.[Google Scholar]
  • 9. Henderson LA, Canna SW, Schulert GSOn the alert for cytokine storm: immunopathology in COVID-19. Arthritis Rheumatol. 2020 doi: 10.1002/art.41285. published online April 15. [[PubMed][Google Scholar]
  • 10. D'Antiga L. Coronaviruses and immunosuppressed patients. The facts during the third epidemic. Liver Transpl. 2020 doi: 10.1002/lt.25756. published online March 20. [[PubMed]
  • 11. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJCOVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033–1034.[PubMed][Google Scholar]
  • 12. Kawasaki T, Kosaki F, Okawa S, Shigematsu I, Yanagawa HA new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics. 1974;54:271–276.[PubMed][Google Scholar]
  • 13. Kato H, Sugimura T, Akagi T. Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients. Circulation. 1996;94:1379–1385.[PubMed]
  • 14. Kanegaye JT, Wilder MS, Molkara DRecognition of a Kawasaki disease shock syndrome. Pediatrics. 2009;123:e783–e789.[Google Scholar]
  • 15. Wang W, Gong F, Zhu W, Fu S, Zhang QMacrophage activation syndrome in Kawasaki disease: more common than we thought? Semin Arthritis Rheum. 2015;44:405–410.[PubMed][Google Scholar]
  • 16. Rowley AHIs Kawasaki disease an infectious disorder? Int J Rheum Dis. 2018;21:20–25.[Google Scholar]
  • 17. McCrindle BW, Rowley AH, Newburger JWDiagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135:e927–e999.[PubMed][Google Scholar]
  • 18. Ravelli A, Minoia F, Davì S2016 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.[PubMed][Google Scholar]
  • 19. García-Pavón S, Yamazaki-Nakashimada MA, Báez M, Borjas-Aguilar KL, Murata CKawasaki disease complicated with macrophage activation syndrome: a systematic review. J Pediatr Hematol Oncol. 2017;39:445–451.[PubMed][Google Scholar]
  • 20. Kobayashi T, Saji T, Otani TEfficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial. Lancet. 2012;379:1613–1620.[PubMed][Google Scholar]
  • 21. Shulman ST, Rowley AHKawasaki disease: insights into pathogenesis and approaches to treatment. Nat Rev Rheumatol. 2015;11:475–482.[PubMed][Google Scholar]
  • 22. Nakamura YKawasaki disease: epidemiology and the lessons from it. Int J Rheum Dis. 2018;21:16–19.[PubMed][Google Scholar]
  • 23. Nakamura Y, Yashiro M, Uehara REpidemiologic features of Kawasaki disease in Japan: results of the 2009-2010 nationwide survey. J Epidemiol. 2012;22:216–221.[Google Scholar]
  • 24. Yim D, Curtis N, Cheung M, Burgner DUpdate on Kawasaki disease: epidemiology, aetiology and pathogenesis. J Paediatr Child Health. 2013;49:704–708.[PubMed][Google Scholar]
  • 25. Makino N, Nakamura Y, Yashiro MDescriptive epidemiology of Kawasaki disease in Japan, 2011–2012: from the results of the 22nd nationwide survey. J Epidemiol. 2015;25:239–245.[Google Scholar]
  • 26. Onouchi YThe genetics of Kawasaki disease. Int J Rheum Dis. 2018;21:26–30.[PubMed][Google Scholar]
  • 27. Holman RC, Belay ED, Christensen KY, Folkema AM, Steiner CA, Schonberger LBHospitalizations for Kawasaki syndrome among children in the United States, 1997–2007. Pediatr Infect Dis J. 2010;29:483–488.[PubMed][Google Scholar]
  • 28. Marchesi A, Tarissi de Jacobis I, Rigante DKawasaki 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.[Google Scholar]
  • 29. Esper F, Shapiro ED, Weibel C, Ferguson D, Landry ML, Kahn JSAssociation between a novel human coronavirus and Kawasaki disease. J Infect Dis. 2005;191:499–502.[Google Scholar]
  • 30. McIntosh KCoronaviruses in the limelight. J Infect Dis. 2005;191:489–491.[Google Scholar]
  • 31. Ebihara T, Endo R, Ma X, Ishiguro N, Kikuta HLack of association between New Haven coronavirus and Kawasaki disease. J Infect Dis. 2005;192:351–352.[Google Scholar]
  • 32. Esper F, Shapiro ED, Landry ML, Kahn JSReply to van der Hoek and Berkhout, Ebihara et al., and Belay et al. J Infect Dis. 2005;192:353.[PubMed][Google Scholar]
  • 33. Turnier JL, Anderson MS, Heizer HR, Jone PN, Glodé MP, Dominguez SRConcurrent respiratory viruses and Kawasaki disease. Pediatrics. 2015;136:e609–e614.[PubMed][Google Scholar]
  • 34. Shirato K, Imada Y, Kawase M, Nakagaki K, Matsuyama S, Taguchi FPossible involvement of infection with human coronavirus 229E, but not NL63, in Kawasaki disease. J Med Virol. 2014;86:2146–2153.[Google Scholar]
  • 35. McGonagle D, Sharif K, O'Regan A, Bridgewood CThe role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 2020 doi: 10.1016/j.autrev.2020.102537. published online April 3. [[PubMed][Google Scholar]
  • 36. Molloy EJ, Bearer CFCOVID-19 in children and altered inflammatory responses. Pediatr Res. 2020 doi: 10.1038/s41390-020-0881-y. published online April 3. [[PubMed][Google Scholar]
  • 37. Zhou F, Yu T, Du RClinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062.[PubMed][Google Scholar]
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.