Defining Kawasaki Disease and Pediatric Multi-Inflammatory Syndrome During SARS-CoV-2 Epidemic in Italy: Results From A National, Multicenter Survey. (preprint)

Background: There is mounting evidence on the existence of a Pediatric Multi-inflammatory Syndrome related to SARS-CoV-2 (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods: : The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group – KDG) or KD-like (Kawacovid Group - KCG) disease. Demographic, clinical, laboratory data, treatment information, and patients’ outcome were collected in an online anonymized database (RedCAP). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups Results: : One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis and 37,8% with hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated Ferritin and Troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p=0.04 and 71,9% vs 43,4%; p=0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p<0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p<0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.

Sex differences in an Italian pediatric population covid-19 positive (preprint)

Background: Since December 2019 coronavirus disease (COVID-19) emerged in Wuhan and spread rapidly worldwide. Despite the high number of people affected, data on clinical features and prognostic factors in children and adolescents are limited. We propose a retrospective study aimed to evaluate clinical characteristics of children infected with SARS-CoV-2 in Italy.Methods: A pediatric population admitted with COVID-19 to Bambino Gesù Children's Hospital of Rome (Italy) in the period from the end of February to May 2020 has been studied taking into account gender. Medical history, comorbidities, symptoms and laboratory findings were obtained from patients' electronic medical records. Results: In 41 patients (21 males and 20 females) we found that: i) fever and cough were the dominant symptoms, while gastrointestinal symptoms were rare; and ii) all ages of childhood were susceptible to COVID-19. Moreover, we found that females with COVID-19, were significantly (p = 0.04) older than males and required more days of hospitalization (p = 0.01). Moreover, compared to females, a greater number of males had high values of C reactive protein (3 males vs 1 female) and erythrocyte sedimentation rate (2 males vs 1 female).Conclusions: Compared to the adults we found that COVID-19 infection in children is a non-severe inflammatory disease in both males and females. In any case, many detailed studies should be conducted. 

The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19 (preprint)

SARS-CoV-2 infection is typically very mild and often asymptomatic in children. A complication is the rare Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2 and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T-cell subsets, IL-17A and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C. HIGHLIGHTSHyperinflammation in MIS-C differs from that of acute COVID-19 T-cell subsets discriminate Kawasaki disease patients from MIS-C IL-17A drives Kawasaki, but not MIS-C hyperinflammation. Global autoantibodies profiling indicate possibly pathogenic autoantibodies