Development of lung T cell responses in infant respiratory immunity

PROJECT SUMMARYThe emergence of SARS-CoV-2 has resulted in a worldwide pandemic. Infection with SARS-CoV-2 causes aspectrum of disease symptoms ranging from asymptomatic and mild/self-limited disease, to severe diseaseassociated with significant lung damage and high levels of morbidity and mortality. As all individuals areimmunologically naïve to this virus and there are currently no targeted treatments or vaccines against SARS-CoV-2, protection and recovery depend on our own immune responses and supportive clinical care. Initially,children experienced largely asymptomatic or mild disease with severe disease resulting in significant lunginjury a rare occurrence. However, a new multisystem inflammatory disorder in children (MIS-C) related toSARS-CoV-2 has emerged as a late complication of infection. Children with MIS-C commonly present withcardiac dysfunction and shock, most closely resembling Kawasaki disease and toxic shock syndrome.Importantly, some children presenting with MIS-C have been reported to develop coronary artery aneurysms, afinding common to Kawasaki disease. The significant amount of mild/self-limited disease in children contrastedwith the excessive inflammation associated with SARS-CoV-2 suggests distinct immune responses.Additionally, the long-term implications, particularly to the cardiovascular system, of early life infection withSARS-CoV-2 remain unknown. We hypothesize that these distinct clinical manifestations in children, includinglack of symptomatic respiratory infection to SARS-Cov-2 is due to a robust and enhanced T cell response. Theaims of this proposal are to 1) Establish pediatric patient cohorts for comparing outcomes and immuneresponses across the spectrum of pediatric COVID-19 disease, 2) Define the pediatric immune response toSARS-CoV-2 and how it differs across the clinical spectrum of disease, and 3) Define the incidence of andpatient characteristics associated with sustained adverse cardiac outcomes for children with MIS-C andpediatric COVID-19. This project proposes to provide new insights into the pediatric immune and long-termcomplications of SARS-CoV-2 infection by employing a multi-disciplinary approach utilizing a team ofinvestigators including immunologists, pediatricians, and pediatric subspecialists (cardiology/critical caremedicine). These studies will provide invaluable insight that will help guide future decision making for treatmentand preventative strategies for children.