Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 U10.9

When isolated children in Europe and North America became ill with a Kawasaki-like clinical picture this spring ( Kawasaki syndrome is rare here), antibodies against SARS-CoV-2 were detected in most children (Iio K et al. 2020), whereas the detection of pathogen genes in the smear was (only) rarely positive. This raised the suspicion that this is a new entity in connection with a Covid-19 infection.

Worldwide, COVID-19 infection caused by coronavirus 2 (SARS-CoV-2) appeared to have a milder clinical course in children compared with adults. However, European and US pediatricians increasingly observed cases of myocarditis sharing some clinical features with toxin shock syndrome, Kawasaki syndrome, and macrophage activation syndrome in otherwise healthy patients (Berardicurti O et al 2020). The spectrum of severity ranged from standard hospitalization to treatment in pediatric intensive care units (Ebina-Shibuya R et al. 2020). For more information, see below. MIS-C.

In the meantime, > 200 cases have been described. More are to be expected. The children belonged to specific ethnic groups. Classic Kawasaki syndrome is seen mainly in Asia, but the novel PIM-TS is not (Iio K et al. 2020). The disease now associated with SARS-CoV-2 occurred in the United Kingdom primarily in children of African American, Caribbean, and Hispanic descent. Of the 58 children in the UK, only 12 were in the white European-descended population. In New York, a cluster of children from the Ashkenazi Jewish group stands out (6 of 17 cases). There, only 2 of the 17 children had ancestors from Europe (Whittaker E et al. 2020).

The temporal relationship between the COVID-19 pandemic peaks and outbreaks of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS) seems to suggest a postinfectious, immune-mediated mechanism. Thus, although rare and different from adults, SARS-CoV2 may be associated with severe and potentially life-threatening systemic inflammatory manifestations in previously healthy children (Schvartz A et al. 2020).

4 months - 17 years; median age was 8 to 9 years (median age of patients with Kawasaki syndrome was < 5 years (median age 2.7 years).

Persistent fever with a sharp increase in inflammatory parameters are the indicative signs of this disease; furthermore, cardiac involvement, gastrointestinal symptoms, mucocutaneous manifestations, hematologic features, or other organ dysfunction.

In a larger case series, 58 children were identified (median age, 9 years; 34% were female) who met criteria for PIMS-TS. In this collective, 78% showed evidence of current or previous SARS-CoV-2 infection. The following data refer to this case series (Whittaker E et al. 2020), with others by Pouletty M et al. (2020).

• All children presented with fever and non-specific symptoms, including:
• Vomiting (26/58 =45%)
• Abdominal pain (31/58 =53 %)
• Diarrhea (30/58 =52 %)
• maculo-papular exanthema (30/ 58 =52 %)
• Edema of hands and feet
• Erythema of the palms (68% -Pouletty M et al. 2020)
• conjunctivitis (26/ 58 =45 %)
• Myocarditis (44 % Pouletty M et al. 2020)
• Of the 58 children, 29 developed symptoms of shock (with biochemical evidence of myocardial dysfunction) and required inotropic support, fluid resuscitation, and mechanical ventilation.
• Thirteen met the American Heart Association definition of Kawasaki syndrome, and 23 had fever and inflammation without features of shock or Kawasaki syndrome. Coronary artery dilatations or aneurysm were detectable in 8 patients (14%) (Whittaker E et al 2020).

Marked signs of inflammation. Elevated were: ESR, C-reactive protein, ferritin (359->1400 μg/L- in 53 of 58 children).

1. Berardicurti O et al (2020) The wide spectrum of Kawasaki-like disease associated with SARS-CoV-2 infection. Expert Rev Clin Immunol 16:1205-1215.
2. Diorio C et al (2020) Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2. J Clin Invest 130:5967-5975.
3. Ebina-Shibuya R et al (2020) Multisystem inflammatory syndrome in children (MIS-C) with COVID-19: insights from simultaneous familial Kawasaki Disease cases. Int J Infect Dis 97:371-373.
4. Iio K et al (2020) Kawasaki disease or Kawasaki-like disease: influence of SARS-CoV-2 infections in Japan. Acta Paediatr:10.1111/apa.15535.
5. McCrindle BW et al. (2020) SARS-CoV-2-Related Inflammatory Multisystem Syndrome in Children: Different or Shared Etiology and Pathophysiology as Kawasaki Disease? JAMA 324:246-248.

6. Pouletty M et al (2020) Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort. Ann Rheum Dis 79:999-1006.

7. Schvartz A et al (2020) Pediatric Inflammatory Multisystem Syndrome and Rheumatic Diseases During SARS-CoV-2 Pandemic. Front Pediatr 8:605807. doi: 10.3389/fped.2020.605807.
8. Whittaker E et al. (2020) Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA 324: 259-269.