LAUSR

Since the beginning of the COVID-19 pandemic with the first cases reported in December 2019 in the city of Wuhan, it was clear that the pediatric population had low susceptibility to SARS CoV-2 infection as children developed mild or no symptoms in most cases. However, at the end of April 2020, the British National Health Service and the Italian Society of Pediatrics issued a warning about an apparent rise in the number of hospitalized children suffering from a systemic inflammatory syndrome characterized by high fever and multi-organ involvement frequently requiring intensive care support [1–4]. In the early phases of the pandemic, this inflammatory syndrome was associated with Kawasaki syndrome (KS) due to the sharing clinical findings as prolonged fever, mucocutaneous manifestations and frequent cardiac involvement. Subsequent data from epidemiological and clinical observations during the furthermore period suggested some differences: a remarkable frequency in African and Hispanic ethnic groups, a higher average age of onset and the presence of gastrointestinal symptoms sometimes so severe as to simulate a surgical emergency. However, the cardiac involvement has shown peculiar characteristics, as it is more often associated with myocardial damage, ventricular dysfunction, hypotension, and poor perfusion [1–4]. In most cases, the children affected by this inflammatory syndrome showed a negative nasopharyngeal swab for the SARS-CoV-2 viral genome, whilst elevated serum antibody titers. Additionally, all the reported cases developed the disease about 4–5 weeks later on the peak of COVID-19 pandemic in the related geographic area. These observations suggested that this hyperinflammatory state derived from a post-infectious condition and presented an immune-mediated pathogenesis, with the ability to induce a huge cytokine storm [4]. With the increase in the number of cases, the World Health Organization (WHO), the United States Centers for Disease Control and Prevention (CDC) and the Royal College of Pediatrics and Child Health (RCPCH) worked out a specific case definition of this syndrome [5–7] (Table 1). Adopting the WHO definition, we refer to this condition as Multisystemic Inflammatory syndrome in children (MIS-C). The overall percentage of SARS-CoV-2 infected children developing MIS-C is unknown. However, the number may be underestimated since many cases, especially in the first wave of the pandemic, may have been undiagnosed as infectious disease tests for SARS CoV-2 were not available or not performed. According to CDC data updated to 4 October 2021 in the United States, 5217 confirmed cases and 46 MIS-C related deaths were recorded [8]. Most MIS-C cases involved children and adolescents of age between 5 and 13 years old, with an average age of 9 years: 61% of reported cases occurred in subjects with Hispanic or Afro-Caribbean descent (1,444 cases) and 98% of cases tested positive for SARS CoV-2 on nasopharyngeal swab or for antibodies in serum. More than the half (60%) of patients were male [8].