Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel pathogen that emerged in December of 2019 and has since infected people of all ages around the world. Children with acute SARS-CoV-2 infection are largely spared of the severe disease seen in adults. However, a life-threatening, post-viral inflammatory condition known as Multisystem Inflammatory Syndrome – Children (MIS-C) develops in a small fraction of children four to six weeks after either past SARS-CoV-2 infection or exposure and is characterized by high fevers, significant gastrointestinal symptoms and severe cardiac complications. Little is known about the lasting immune profiles of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in children, let alone the long-term effects of the disease in this population. This study presents clinical features and serologic immune profiles of forty-nine pediatric patients (ages 12.4 ± 6.7 years) enrolled in the Massachusetts General Hospital Pediatric COVID-19 Biorepository with previous diagnoses of SARS-CoV-2 infection or the COVID-19-related MIS-C. Thirty-two children ages 0-22 years completed a questionnaire which captured lingering clinical symptoms of COVID-19 and MIS-C at the follow-up timepoint. This questionnaire study revealed significant on-going symptoms in both cohorts, including respiratory, gastrointestinal, neurologic and cardiovascular symptoms. To characterize lasting immune responses following the acute presentation, serum antibodies to S, RBD and N proteins of SARS-CoV-2 were quantified at the follow-up timepoint in forty-nine pediatric patients with past COVID-19 or MIS-C at a mean follow-up timepoint of 6.56 ± 1.75 months. Serologic signatures against SARS-CoV-2 in COVID-19 and severe MIS-C patients were compared at acute illness and at follow-up timepoints. Anti-SARS-CoV-2 antibodies remained elevated over time showing adequate seroconversion. Interestingly, anti-SARS-CoV-2 IgA remained elevated in the vast majority of individuals at follow-up, suggesting continued antigen exposure and mucosal inflammation. This research elucidates whether children maintain antibody levels to SARS-CoV-2 over time and speaks to the differences in antibody recovery to baseline in COVID-19 and MIS-C patients. It also highlights the lingering symptoms in both the COVID-19 and MIS-C cohorts, and suggests the need for significant long-term follow-up in children months, or even years after resolution of acute illness or disease. In total, this study addresses the substantial gap in understanding of the recovery of the adaptive immune system after SARS-CoV-2 infection in children. / 2023-11-09T00:00:00Z