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Response to ‘Correspondence on ‘Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID19): a multicentre cohort’’ by Mastrolia et al
  1. Charlotte Borocco1,2,
  2. Marie Pouletty3,
  3. Caroline Galeotti1,
  4. Ulrich Meinzer3,4,
  5. Albert Faye3,5,
  6. Isabelle Koné-Paut1,2,
  7. Naim Ouldali3,5,
  8. Isabelle Melki3,6,7
  1. 1Department of Paediatric Rheumatology, Reference Centre for Autoinflammatory Diseases and Amyloidosis (CEREMAIA), Bicêtre University Hospital, AP-HP, Le Kremlin-Bicetre, France
  2. 2University of Paris Sud Saclay, Paris, France
  3. 3General Pediatrics, Infectious Disease and Internal Medicine Department, Reference center for Rheumatic, AutoImmune and Systemic diseases in children (RAISE), Hôpital Robert Debre, AP-HP, Paris, 75019, France
  4. 4Center for Research on Inflammation, UMR1149, INSERM, Paris, France
  5. 5UMR 1123, ECEVE, INSERM, Paris, France
  6. 6Laboratory of Neurogenetics and Neuroinflammation, Institute Imagine Institute of Genetic Diseases, Paris, France
  7. 7Pediatric Hematology-Immunology and Rheumatology Department, Reference center for Rheumatic, AutoImmune and Systemic diseases in children (RAISE), Hôpital Necker-Enfants Malades, AP-HP, Paris, France
  1. Correspondence to Dr Isabelle Melki, General Pediatrics, Infectious Disease and Internal Medicine Department, Reference center for Rheumatic, AutoImmune and Systemic diseases in children (RAISE), Hôpital Robert-Debré, AP-HP, Paris, 75019, France; isabelle.melki{at}

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We thank Mastrolia et al for sharing the paediatric tuscany network (PTN) experience during the first wave of SARS-CoV-2 and their survey to detect the incidence of paediatric inflammatory multisystem syndrome temporally associated with SARS-COV-2 (PIMS-TS) and the rise of Kawasaki disease (KD).1 Interestingly, PTN did not observe any increase in the number of cases of KD and no cases of PIMS-TS in their region between 1 February to 30 June 2020, unlike the many cases described across Europe, North America and Africa.2–9 We believe that several points should be discussed to understand these findings.

First, as notified by our colleagues from PTN, Tuscany has been relatively preserved by the SARS-CoV-2 epidemic compared with the northern regions of Italy. Thus, on 30 June 2020 at the end of this survey, the Italian Ministry of Health10 reported 93 901 cases of COVID-19 in Lombardy, where cases of PIMS-TS were described,3 compared with 10 250 cases in Tuscany. An epidemiological study of PIMS-TS cases was conducted throughout France and 108 cases of PIMS-TS were reported.8 According to the geographical distribution of PIMS-TS in France, many regions with lower incidences of SARS-CoV-2 epidemic were not affected with PIMS-TS case. The large majority occurred in the Great Paris region, one of the most affected COVID-19 areas. In this study, Belot et al estimated that the risk of PIMS-TS would be very low: less than 2 per 10 000 children. These data suggest that the epidemic might have been too weak in Tuscany to observe PIMS-TS cases, despite a highly efficient surveillance network.

Second, the hypothesis of a mutation of the virus during the epidemic could be discussed to explain the absence of PIMS-TS. However, the viral strain found in France seems to have remained the same as the one reported in Italy. The D614G spike protein mutation seems to have appeared mid-January 2020 in Europe, before the PIMS-TS epidemic, and currently seems to be the main strain worldwide.11

Third, different inborn errors of immunity may also predispose individuals for severe SARS-CoV-2 infection or PIMS-TS, according to the specific susceptibility or the inappropriate inflammatory activation they respectively convey. Indeed, Zhang et al raise the hypothesis of monogenic immunodeficiencies that may explain some severe COVID-19 cases, particularly in young patients with no comorbidities.12 Several models of Mendelian susceptibility to viral infections have been indeed already described, such as mutations affecting the type I interferon pathway inducing herpes simplex virus encephalitis or severe influenza.13 14 Moreover, monogenic autoinflammatory diseases are defined by Mendelian hyperactivation of several innate immune pathways (inflammasomopathies, type I interferonopathies).15 Susceptible individuals with specific genetic background might be predisposed to such hyperinflammatory cytokine storm temporally associated to SARS-CoV-2 exposure.

Several studies have revealed that many patients affected with PIMS-TS were of Afro-Caribbean descent: 38%–62% in European cohorts.2 5 7 Conversely, no cases have been described in China, the epicentre of the epidemic, even though the same phenomenon has been reported in Africa and the USA.4 9 These observations remain to be confirmed by studies accounting for social environment factors, which may also play a role in these findings.13 Nevertheless, if some populations are less predisposed to this specific condition, this may also explain why some regions did not report PIMS-TS cases.

Finally, these findings underline the need to further investigate epidemiological, immunological and genetic factors that may be associated with PIMS-TS. Deciphering its pathophysiology may help to better understand the discrepancy in the geographical distribution of this rare but severe condition.



  • Handling editor Josef S Smolen

  • Collaborators Great Paris Region (GPR) Kawa- COVID-19 consortium: Marion Caseris, Brigitte Bader-Meunier, Johanna Lokmer, Cherine Benzouid, Constance Beyler, Romain Basmaci, Noémie Lachaume, Philippe Bensaid, Samia Pichard, Guislaine Carcelain, Mehdi Oualha, Zahir Amoura, Julien Haroche, Juliette Chommeloux, Fanny Bajolle, Stéphane Bonacorsi, Corinne Pondarre, Arielle Maroni, Hanane Kouider, Guillaume Morelle, Irina Craiu, Anna Deho.

  • Contributors CB, NO, MP and IM designed the study and wrote the paper. All authors collected clinical data. CG, AF, UM and IK-P supervised the study. All authors have read final approval of the version published.

  • 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 Commissioned; internally peer reviewed.

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