The literature has demonstrated that children experience severe acute respiratory syndrome(SARS) CoV-2 infection less frequently and on average develop milder disease but post inflammatory conditions have been associated with COVID-19 (in particular Long COVID). The exact mechanisms are yet to be defined, but it can be due to a stronger innate immune response to SARS CoV-2, a more robust antibody response, an altered distribution and activity of the ACE2 receptor and trained immunity. On the other hand, an abnormal viral or immunological response or a hyper inflammation or oxidative stress may contribute to the Long COVID. Following these hypotheses, we enrolled(September-March,2021-T0) 130 consecutive children and adolescents (aged 0-18 years) who were diagnosed SARS-CoV2 infected, through PCR on nasopharyngeal swabs (NPS) (cases), and 20 first-degree relatives who were exposed to SARS-CoV2 but resulted negative (controls). All children were proposed to join the study and were asked to return after 10-30(T1), 30-60(T2), 180(T3) and 360 days(T4) from the first positive sample to collect data on symptoms and acquire a whole blood venous samples. We propose a large longitudinal project with the aim of studying serum IgA and IgG responses, neutralizing Abs and PBMC immunophenotyping and circulating receptor binding domain-specific antibody¿secreting cells in symptomatic and asymptomatic SARS CoV-2 infected children and controls and analyzing the relationship between neurotrophins, oxidative stress and inflammatory markers in a subgroup of Long COVID children. To date this study represents the first longitudinal study on SARS CoV 2-related immunity in pediatric age. The unique pediatric cohort of children with a confirmed SARS CoV-2 infection and of exposed healthy controls, and the strict follow-up make this project significantly powerful in the understanding of the immunoregulatory events in disease progression and the pathogenesis of SARS-CoV-2 infection in children.
