To the Editor—Children and infants initially appeared to be largely spared from the coronavirus disease 2019 (COVID-19) pandemic. However, the United Kingdom and United States have recently reported an apparent rise in the number of children presenting with multisystem inflammatory disease, some of whom also tested positive for COVID-19.1

A multisystem inflammatory syndrome in children potentially associated with COVID-19 has been reported, with the following suggested definition: persistent fever, inflammation, evidence of single or multi-organ dysfunction; may fulfil full or partial criteria for Kawasaki disease; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction testing maybe positive or negative and other microbial causes excluded.2

About 50% of these patients have no microbiological evidence of COVID-19 infection, which fits into one of the hypothetical scenarios in our epidemiological analysis based on early data from the United Kingdom, suggesting a statistically significant correlation between COVID-19 and Kawasaki disease (P=0.0048) [Table].3 4 The pathophysiology of COVID-19 is likely to be a hyperinflammatory process of a massive cytokine storm; however, this clinical presentation can also be vasculitic in nature as there is evidence of SARS-CoV leading to vasculitis.4 5 This apparent link could also be due to the similarities in clinical presentation between COVID-19 and other sepsis syndromes including systemic inflammatory response syndrome, severe acute respiratory syndrome, toxic shock syndrome, Kawasaki disease shock syndrome, and multi-organ dysfunction syndrome.

Although this phenomenon is reported in Western countries, the majority of cases are non-Caucasians.6 As the incidence of Kawasaki disease is up to 10 times higher in Asian than in Western populations, it is inconceivable that this phenomenon could only be observed in Western countries, unless there is an underlying genetic, environment predisposition, presentation of a new variant of the SARS-CoV-2 virus, or misinterpretation of data.3

We postulate that SARS-CoV-2 may just happen to be one of the many respiratory viruses that can cause a multisystem inflammatory syndrome in children. The ‘novel phenomenon’ is in fact septic or toxic shock syndrome associated with viral triggered inflammation, potentially attributed to a new variant of SARS-CoV-2. However, we shall remain sceptical before any definitive conclusions can be drawn. Meanwhile, we caution the loose coining of too many confusing abbreviations or syndromes associated with SARS-CoV diseases, such as SARS, MERS (Middle East respiratory syndrome), COVID-19, MIS-C (multisystem inflammatory syndrome in children), PIMS/PIMS-TS (paediatric inflammatory multisystem syndrome), COVID toe syndrome, and COVID skin syndrome.7

All authors contributed to the drafting of the letter and critical revision for important intellectual content. All authors approved the final version for publication and take responsibility for its accuracy and integrity.

As the editor of the journal, KL Hon was not involved in the peer review process. Other authors have disclosed no conflicts of interest.

This letter received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

1. Paediatric Intensive Care Society. PICS Statement: Increased number of reported cases of novel presentation of multi system inflammatory disease. 2020. Available from: https://picsociety.uk/wp-content/uploads/2020/04/PICS-statement-re-novel-KD-C19-presentation-v2-27042020. pdf. Accessed 30 Apr 2020.

2. Royal College of Paediatrics and Child Health. Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19. Available from: https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem- inflammatory syndrome-20200501.pdf. Accessed 14 May 2020.

3. Campbell D, Sample I. At least 12 UK children have needed intensive care due to illness linked to Covid-19. The Guardian [newspaper on the internet]. 27 Apr 2020: Health. Available from: https://www.theguardian.com/world/2020/apr/27/nhs-warns-of-rise-in-children-with-new- illness-that-may-be-linked-to-coronavirus. Accessed 30 Apr 2020.

4. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020;395:1607-8. Crossref

5. Ding Y, Wang H, Shen H, et al. The clinical pathology of severe acute respiratory syndrome (SARS): A report from China. J Pathol 2003;200:282-9. Crossref

6. Public Health England. The weekly surveillance report in England (Week 16 April 2020 to 22 April 2020). Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/880848/COVID19_Weekly_Report_22_April.pdf. Accessed 28 Apr 2020.

7. Hon KL, Leung AK, Wong JC. Proliferation of syndromes and acronyms in paediatric critical care: are we more or less confused? Hong Kong Med J 2020;26:260-2.Crossref