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.
To date our 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 what is an efficient response to SARS-CoV-2 infection. Such empirical evidence would serve as an initial bridge over the wide knowledge gap the paediatric scientific community is currently facing, with clinical, research and public health implications. There is a further need for devoted research, not only to limit the spread of viruses but also to understand the pathogenesis of the viruses and human susceptibilities. Notably much remains to be learned about the complexity of SARS CoV-2 specific immunity. In this scenario the multidisciplinary approach of this project (pediatricians, virologists and neurobiologists), using each team specific expertise, will allow to improve our understanding on pathogenesis of SARS-CoV-2 infection. The findings of this research will further our understanding of the immunoregulatory events in disease progression and the pathogenesis of SARS-CoV-2 infection in children.
In the undesirable event that a subset of enrolled subjects will get infected with SARS-CoV-2 during the next winter season, assessment of pre and post infection immune responses will be performed with serial serum samples. Reinfections or infections in vaccinated individuals will be prospectively monitored for 12 months, to appreciate whether a level of any Ab type (IgG, IgA and neutralizing Ab) could correlate with protection.
Thus far, the literature has demonstrated that children experience SARS-CoV-2 infection less frequently and with a milder disease, but post inflammatory conditions have been associated with COVID-19 such as multisystem inflammatory syndrome in children, Kawasaki disease and Long COVID. Interestingly, oxidative stress and inflammation could be considered two sides of the same coin. Oxidative stress can also alter the expression levels of a variety of cytokines, leading to an inflammatory state.
What we would like to establish is the prevalence of the SARS-CoV-2 reinfection. A potential application of the whole project is to evaluate whether the co-infection with other viruses or predisposing factors are involved in the clinical presentation of COVID-19 in children.
With our project, we will try to address many open questions. How long serology persists after SARS CoV-2 infection in children? Are antibody responses or cellular immunity protective against SARS CoV-2 reinfection? Do SARS CoV-2 specific immunity and neuroinflammation play a role in COVID-19 clinical manifestation and in Long-COVID in children?