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Correspondence to ‘Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort’
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  1. Maria Vincenza Mastrolia1,
  2. Rino Agostiniani2,
  3. Chiara Azzari3,
  4. Roberto Bernardini4,
  5. Ugo Bottone5,
  6. Giovanni Battista Calabri6,
  7. Flavio Civitelli7,
  8. Rita Consolini8,
  9. Roberto Danieli9,
  10. Rosalia Di Silvio10,
  11. Susanna Falorni11,
  12. Luigi Gagliardi12,
  13. Salvatore Grosso13,
  14. Marco Martini14,
  15. Graziano Memmini15,
  16. Diego Peroni16,
  17. Marco Pezzati17,
  18. Giovanni Suriano18,
  19. Luca Tafi19,
  20. Angelina Vaccaro20,
  21. Pier Luigi Vasarri21,
  22. Gabriele Simonini22
  23. On behalf of the Paediatric Tuscany Network
  1. 1Rheumatology Unit, Meyer Children’s University Hospital, Firenze, Italy
  2. 2Pediatric Unit, San Jacopo Hospital, Pistoia, Italy
  3. 3Department of Health Science, Pediatric Immunology Unit, Meyer Children’s University Hospital, Firenze, Italy
  4. 4Pediatric Unit, San Giuseppe Hospital, Empoli, Italy
  5. 5Division of Neonatology and Pediatrics, Lotti Hospital, Pontedera, AUSL Toscana Nord Ovest, Pisa, Italy
  6. 6Cardiology Unit, Meyer Children’s University Hospital, Firenze, Italy
  7. 7Division of Neonatology and Pediatrics, Montepulciano Hospital, Montepulciano, AUSL Toscana Sud Est, Siena, Italy
  8. 8Department of Clinical and Experimental Medicine, Section of Clinical and Laboratory Immunology, University of Pisa, Pisa, Italy
  9. 9Division of Neonatology and Pediatrics, Spedali Riuniti di Livorno, AUSL Toscana Nord Ovest, Livorno, Italy
  10. 10Pediatric Unit, Mugello Hospital, Borgo San Lorenzo, Firenze, Italy
  11. 11Pediatric Unit, Misericordia Hospital, Grosseto, Italy
  12. 12Division of Neonatology and Pediatrics, Versilia Hospital, Viareggio, AUSL Toscana Nord Ovest, Pisa, Italy
  13. 13Department of Molecular Medicine and Development, University of Siena, Clinical Pediatrics, Siena, Italy
  14. 14Pediatric Unit, San Donato Hospital, Arezzo, Italy
  15. 15Division of Neonatology and Pediatrics, Apuane Hospital, AUSL Toscana Nord Ovest, Massa Carrara, Italy
  16. 16Section of Pediatrics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
  17. 17Pediatric Unit, Santa Maria Annunziata Hospital, Bagno a Ripoli, AUSL Toscana Centro, Firenze, Italy
  18. 18Division of Neonatology and Pediatrics, Cecina Hospital, Cecina, AUSL Toscana Nord Ovest, Pisa, Italy
  19. 19Paediatric and Neonatal Unit, Valdarno Hospital, Montevarchi, Arezzo, Italy
  20. 20Division of Neonatology and Pediatrics, San Luca Hospital, AUSL Toscana Nord Ovest, Lucca, Italy
  21. 21Paediatric and Neonatologic Unit, Santo Stefano Hospital, Prato, Italy
  22. 22Rheumatology Unit, Department Neurofarba, Meyer Children’s University Hospital, Firenze, Italy
  1. Correspondence to Dr Gabriele Simonini, Rheumatology Unit, Meyer Children's University Hospital, Department NEUROFARBA, Firenze 50139, Italy; gabriele.simonini{at}unifi.it

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We read with interest the clinical study entitled ‘Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort’ by Pouletty et al.1 In this series, the authors suggest that paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PMIS-TS) may represent a new inflammatory syndrome, different from classical Kawasaki disease (KD) as it occurs at an older age, and with a higher frequency of severe myocarditis.1

Likewise to this study, our Pediatric Tuscany Network (PTN)—16 paediatric units serving a region of 593 606 people aged less than 18 years—worked out the COVASAKI survey to detect the incidence of PMIS-TS cases and the eventual rise of KD in Tuscany during COVID-19 pandemic. Between 1 February 2000 and 30 June 2020, we tracked children with PMIS-TS and KD, aiming to compare the number of KD cases in the same 5 months of the previous 5 years and overall with the total number in the last 5 years.

No PMIS-TS cases were reported in our region. Ten KD children were diagnosed in 5 units (incidence two per month). Demographics, clinical and imaging findings, treatment and outcome of patients are reported in table 1. No specific intensive support was required. No coronary involvement was reported. Nasopharyngeal swabs (performed in 7/10) and serological test (available in 6/10) for SARS CoV-2 resulted negative.

Table 1

Demographics, clinical findings, imaging findings, treatment and outcome of patients with Kawasaki disease

From 1 January 2015 to 31 January 2020, 165 KD were diagnosed (incidence 2.7 per month): 59 were incomplete; 3 developed macrophage activation syndrome (MAS) and 1 KD shock syndrome (KDSS). Thirty-eight showed coronary involvement, with persistent ectasia/aneurisms in five. Eleven children received steroid pulses and additional three biological therapy. No significant difference has been shown regarding the incidence/month (RR 1.21, 95% CI 0.60 to 2.20), neither limiting the analysis to the 56 children with KD diagnosed during the same corresponding 5 months of the last 5 years: 2.2 versus 2.0 incidence/month (RR 0.89, 95% CI 0.42 to 1.69).

The KD incidence rate adjusted for the 3801 children hospitalised in Tuscany in the 2020 index 5 months resulted 0.26%.

No significant differences were detected among the principal KD outcomes during the COVID-19 time and in the last 5 years: incomplete KD 59 versus 2, χ2=1.03; KDSS 1 versus 0, χ2=0.06; MAS: 3 versus 1, χ2=2.81; coronary involvement 38 versus 0, χ2=2.92. The same results have been observed limiting the analysis to the corresponding index 5 months of the last 5 years (p=n.s, Fisher’s exact test).

From 1 February to 30 June, 8,637 nasopharyngeal swabs have been performed to the Tuscan children admitted to the hospitals: 157 resulted positive for SARS CoV-2. Serological tests have been performed in 2100 children: 127 were positive for antibodies.

Although the 10,500 COVID-19 Tuscany positive cases represent the fifth Italian highest number, our region reported a lower prevalence of infection compared with other high-prevalence areas in the North of Italy.2 This epidemiological context may explain the lack of patients with PIMS-TS. However, our survey, as previously reported in other cohorts,1 3–6 provides epidemiological evidence that the clinical spectrum of PMIS-TS differs from classical KD: median age of our patients with KD was lower (3.5 years), gastrointestinal symptoms were absent, any myocarditis was reported and all patients presented a benign disease course, responsive to a single dose of intravenous immunoglobulins in most of cases. Additionally, no significant increase of KD cases has been documented.

The PIMS-TS may in some cases mimic KD at onset, even if its typical clinical manifestations are characterised by a greater framework of systemic inflammation and haemodynamic involvement. At this regard, Whittaker et al and Cheung et al reported that only 28% (21/75) of PMIS-TS children met the American Heart Association criteria for KD diagnosis.3 4

These clinical differences also lead to pathogenetic implications. Most of patients with PIMS-TS presented a low viral load at diagnosis and/or showed positivity to serological tests. The high rate of SARS CoV-2 IgG positivity, usually mirror of a past infection, seems to suggest a reactive immunological response to a previous viral infection rather to an acute one, that is, instead, traditionally assumed as potential causative trigger of KD.

These considerations pose the clinical question whether different treatment approaches, that is, the immunomodulating agents, may be preferable to that strategies, such as intravenous immunoglobulins, that evidenced benefits in KD.

In conclusion, the epidemiology COVASAKI survey showed a KD incidence rate during COVID-19 pandemic identical to what previously reported in Tuscany along with clinical characteristics of typical KD picture.7

The well-structured collaboration of our PTN has ensured a prompt recognition of children with suspected KD, thus avoiding diagnostic and treatment delay. Keeping updated our register, a comparison between the COVASAKI survey and the worldwide results will better define the multifaceted nature of the paediatric COVID-19 disease and, if any, the potential relationship between PIMS-TS and KD.

Acknowledgments

We thank Eleonora Fusco, MD and Franco Curci, MD for their help in the data collection.

References

Footnotes

  • RA, CA, RB, UB, GBC, FC, RC, RD, RDS, SF, LG, SG, MM, GM, DP, MP, GS, LT, AV, PLV and GS contributed equally.

  • Contributors GS and CA conceptualised and designed the study. GS and MVM drafted the initial manuscript. GS coordinated and supervised data collection, carried out the initial analyses and critically reviewed the manuscript for important intellectual content. RA, RB, UB, GBC, FC, RC, RD, RDS, SF, LG, SG, MM, GM, DP, MP, GS, LT, AV, and PLV actively contributed to the study development at their sites, data collection and development of the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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