Reports of Kawasaki-like disease in children after the start of the SARS-CoV-2 epidemic in Italy

Polly Clayden, HIV i-Base

A paediatric hospital in the Bergamo province, Italy reported a 30-fold increased incidence of Kawasaki-like disease after the start of the SARS-CoV-2 epidemic. [1]

These findings were described in a retrospective review, published online in The Lancet 13 May 2020.

In children, the respiratory symptoms that are typical in adults appear to be more benign, with almost no deaths reported in this age group.

Kawasaki disease causes swelling of the blood vessels, which can lead to complications in the coronary arteries and almost exclusively affects children. The study authors noted that despite half a century having passed since Tomisaku Kawasaki first reported 50 cases in Japan,the cause of the disease remains unknown. The generally accepted hypothesis supports an abnormal response of the immune system to one or more unidentified pathogens in genetically predisposed patients.

The Bergamo province, has been hugely affected by the SARS-CoV-2 epidemic – the City of Bergamo has the highest rates of deaths from COVID-19 in Italy.

The authors retrospectively reviewed the notes of children diagnosed with Kawasaki disease admitted to the General Paediatric Unit of Hospital Papa Giovanni XXIII between 1 January 2015 and 20 April 2020.

The aim of the study was to describe the incidence and characteristics of new cases of Kawasaki-like presentations admitted to the unit during the SARS-CoV-2 epidemic.

All children diagnosed with a Kawasaki-like disease over the study period were stratified by symptoms before (group 1) or after (group 2) the beginning of the SARS-CoV-2 epidemic.

Kawasaki disease shock syndrome (KDSS) was defined by presence of circulatory dysfunction. Macrophage activation syndrome (MAS) was defined according to the Paediatric Rheumatology International Trials Organisation criteria.

Current or previous infection was diagnosed using reverse-transcriptase quantitative PCR in nasopharyngeal and oropharyngeal swabs, and by serological qualitative test detecting SARS-CoV-2 IgM and IgG, respectively.

Group 1 included 19 children: 7 boys and 12 girls, mean aged 3 years (SD 2·5), diagnosed between 1 January 2015 and 17 February 17 2020. Group 2 included 10 children: 7 boys and 3 girls, mean age 7·5 years (SD 3·5), diagnosed between 18 February and 20 April 2020; 8 of 10 were positive for IgG or IgM, or both.

The authors reported the following differences among children in group 1 vs group 2, respectively: disease incidence, 0·3 vs 10 per month; mean age, 3 vs 7·5 years; abnormal echocardiogram, 2/19 vs 6/10, p=0·0089; met criteria for KDSS and MAS, 0/19 vs 5/10, p=0·02; Kobayashi score of 5 or more, 2/19 vs 7/10, p=0·0021; and need for adjunctive steroid treatment, 4/19 vs8/10, p=0·0045.

The authors suggest that the association between SARS-CoV-2 and Kawasaki-like disease should be taken into account in the paediatric population. But, they added, the Kawasaki-like disease described here remains a rare condition, probably affecting no more than one in 1000 children exposed to SARS-CoV-2. And this estimate is based on the limited data from the case series in this region.

Comment

In an accompanying commentary, the authors explain that although studies from several countries have confirmed that severe illness and death due to COVID-19 among children are rare, attention has now shifted in the understanding of the role of the disease in children. [2]

First, as the degree to which children transmit COVID-19 is key to how countries resume activities after lockdown. Second, the new concerns about a novel severe Kawasaki-like disease in children related to COVID-19, including that described in the Bergamo region above.

Experts in the UK have formulated a case definition for what is provisionally called Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). This has been published by the Royal College of Paediatrics and Child Health. [3]

Correspondence in The Lancet on 6 May 2020, describing nine children with PIMS-TS needing critical care in south London highlights the severe end of this disease. [4]

As that correspondence went to press, one week after the initial submission, the Evelina London Children’s Hospital paediatric intensive care unit had managed more than 20 children with similar symptoms.

References

Verdoni L et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. The Lancet. Published online. 13 May 2020.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31103-X/fulltext
Viner RM and Whittaker E. Kawasaki-like disease: emerging complication during the COVID-19 pandemic. Published online 13 May 2020. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31129-6/fulltext
Royal College of Paediatrics and Child Health Guidance –Paediatric multisystem inflammatory syndrome temporally associated with COVID-19. 5 May 2020.
https://www.rcpch.ac.uk/resources/guidance-paediatric-multisystem-inflammatory-syndrome-temporally-associated-covid-19
Shelley Riphagen et al. Hyperinflammatory shock in children during COVID-19 pandemic. The Lancet. Published online 6 May 2020.
https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)31094-1.pdf (PDF)