Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the United Kingdom and Ireland: What is new?

The article published in this Journal by Flood et al. [1], is a well-documented survey carried out from March 1st to June 15th 2020 in the United Kingdom and the Republic of Ireland on Pediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 (PIMS-TS). As widely known, the disease, named also as MIS-C (Multi Inflammatory Syndrome in Children) in the USA, occurs in children and adolescents around 2–4 weeks after the onset of COVID-19 symptoms or having been in touch with someone positive for COVID-19, rather than in the acute phase of the coronavirus-induced illness [2]. The data, which were gathered from a great number of Pediatricians across the UK and Ireland, were then compared to that reported in literature by using a complex statistical analysis.

The surveillance confirmed a few things about PIMS-TS which had been already outlined in literature, concerning latency from suspected/confirmed COVID-19 infection or exposure, age distribution, male predisposition, symptoms, low case fatality, reduced number of patients of Asian descent when making a comparison with Kawasaki disease. Conversely, some important differences were noted as well regarding the lower proportion of patients with cardiovascular involvement requiring admission to ICU, and the predominant number of patients who tested positive at PCR, but without any anti-viral antibodies in their blood. Four main groups of patients were identified as well, namely: individuals suffering from isolated PIMS-TS, subjects sharing features of PIMS-TS and Kawasaki disease, those with PIMS-TS and toxic shock syndrome, and others with all the three phenotypes together (PIMS-TS, Kawasaki disease, and toxic shock syndrome). It is in the Authors’ opinion that this way of grouping will help clinicians in managing patients presenting with such a variety of signs and symptoms. For example, at the beginning of the first outbreak, there has been somewhat diagnostic confusion regarding PIMS-TS, which led to coin the definition of “Kawasaki like disease” as well [3].

A few questions remained unanswered, including whether PIMS-TS and Kawasaki disease are a continuum of the same pathological process or not and the reason why the disease in the UK is prevalent among people of Hispanic, Caribbean, and African origin. Regarding the first point, as mentioned by the Authors, the recent Cactus study, with the involvement of Italian and Swedish researchers, showed that the PIMTS-TS and Kawasaki disease share a similar immune and plasma protein features. However, immunology is decidedly different [4]. The authors of the Cactus study found that the differences are related to T-cell subsets and IL-17A (due to an IL-17A mediated hyperinflammation in Kawasaki disease, but not in PIMS-TS). Finally, autoantibody profiling suggests multiple autoantibodies (vs. endoglin and Rpbj proteins) which may be involved in the onset of PIMS-TS by disrupting myocardial and vascular tissue. The autoantibodies are absent in Kawasaki disease and released by T-cells [4]. These results are likely to become a cornerstone in clinical practice, in terms of developing specific tests for an early diagnosis and ad hoc therapies. Concerning the second point, it is still unclear if there is a genetic predisposition to develop PIMS-TS in certain ethnic groups or the wide prevalence of PIMS-TS among the same is linked to the multicultural society living in the UK [5]. Another weakness of the survey is that, for some reasons, very few cases were collected from the Republic of Ireland.

As pointed out by the Authors, the pending uncertainties and inconsistencies in providing clinicians with a unique definition of the disease may hamper making a comparison among different countries and continents regarding its prevalence and features. Mild cases may have been undetected or missed in cases where there was no hospitalized.

Overall, the strengths of this article are in providing the readers with a clear observation about demographics of PIMS-TS in a wide Northern European region, thus highlighting a few local peculiarities. Maintaining low community infection rates with forced isolation, social distancing, hand hygiene, mask wearing is the best way to drop the risk of this uncommon but severe complication in pediatric age [6]. Lastly, since significant number of the patients had clear PIMS-TS features, but did not fulfill the case definition simply because their C-reactive protein levels were below the arbitrary value of 100 mg/L cut-off, the latter should be definitely excluded from the criteria to define the syndrome.

Declaration of Interests

PPB has nothing to declare.