Abstract

BackgroundIn contrast to adults, children are less likely to develop serious disease upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but are at increased risk for inflammatory and autoimmune diseases linked to the virus (1). The reported incidence of multisystem inflammatory syndrome in children (MIS-C) varied from 0.2 to 11.4/100,000 persons under 21 years (2,3). It is yet unknown whether MIS-C can recur after SARS-CoV-2 reinfection or COVID-19 vaccination.ObjectivesTo estimate the incidence and describe the spectrum of inflammatory and autoimmune diseases linked to SARS-CoV-2 infection and coronavirus (COVID-19) vaccination in pediatric patients from two neighbouring South Central European countries and regions, Slovenia and Friuli Venezia Giulia (FVG), Italy.MethodsWe performed a multi-centre prospective cohort study of all children and adolescents (under 18 years) newly diagnosed with MIS-C or other inflammatory/autoimmune diseases linked to SARS-CoV-2 infection, who were admitted to the pediatric tertiary care hospitals in Slovenia or FVG, Italy during the period from January 1, 2020, to December 31, 2021. These hospitals serve a combined population of 587,053 children and adolescents. Only patients who had positive anti-SARS-CoV-2 antibodies and/or positive SARS-CoV-2 PCR test within 3 months prior to disease onset were considered for estimating the disease incidence. We obtained the number of patients with serious adverse events (SAE) after COVID-19 vaccination and the number of patients with severe COVID-19 in the same population. This study was conducted as a part of the EU interregional Italy-Slovenia project CATTEDRA (Cross border cooperation for innovative diagnosis of rare diseases in paediatrics).Results192 children and adolescents were diagnosed with inflammatory and autoimmune diseases linked to SARS-CoV-2 (Figure 1). Median age at diagnosis was 11.9 years (IQR 7.6 -14.7). All included patients were White. Incidence of MIS-C was one in 921 children and adolescents after SARS-CoV-2 infection and one in 5870 of all children and adolescents. Cumulative incidence of MIS-C since the start of the pandemic was 17/100,000 children and adolescents. Until December 31, 2021, 92,139 children and adolescents (15.7 %) received at least one dose of COVID-19 vaccine. Three patients presented with inflammatory/autoimmune disease after COVID-19 vaccination, including 2 patients with MIS-C and one patient with myositis. All 3 had evidence of recent SARS-CoV-2 infection in form of positive anti-N SARS-CoV-2 antibodies. In the same period, 15 children and adolescents were hospitalised with severe COVID-19. Seven patients from our cohort were vaccinated against COVID-19 median 8 months after MIS-C and further 6 patients had a SARS-CoV-2 reinfection 3-14 months after MIS-C. None of them experienced SAE or recurrence of MIS-C.Figure 1.Inflammatory and autoimmune diseases linked to SARS-CoV-2 and severe COVID-19 in pediatric population in Slovenia and FVG, ItalyCOVID-19=coronavirus disease, FVG=Friuli Venezia Giulia region in Italy, MIS-C=multisystem inflammatory syndrome in children, SARS-CoV-2=severe acute respiratory syndrome coronavirus 2ConclusionMIS-C was the most common manifestation and its incidence in this predominantly white population was higher than previously reported. Based on our limited experience, MIS-C does not seem to recur after SARS-CoV-2 reinfection or COVID-19 vaccination, however long-term data are lacking. Autoimmune diseases were much more common after SARS-CoV-2 infection than after COVID-19 vaccination. Hospitalisations due to MIS-C were seven times as frequent as hospitalisations due to severe COVID-19 in children.

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