Rationale:~Following infection with SARS-CoV-2, some children develop the potentially life-threatening disease Multi-System Inflammatory Syndrome in Children (MIS-C) and some children develop post-COVID condition (formerly 'long COVID'). It is unknown why some children develop severe or prolonged symptoms after SARS-CoV-2 infection, while most children have asymptomatic or mild disease. We hypothesize that rare variants in genes associated with the immune system predispose children to develop MIS-C or post-COVID condition after infection with SARS-CoV-2.~Objective:~Primary objective: To identify rare, high impact genetic variants in immunological genes and pathways in children with a history of MIS-C or pediatric post-COVID condition.~Secondary objectives: To analyze the clinical characteristics and long-term effects of pediatric COVID-19 and MIS-C. To characterize the functional and clinical impact of genetic variants in MIS-C and post-COVID condition and identify targets for therapy.~Study design:~We will do an observational study. We will perform Whole Exome Sequencing (WES) using Next Generation Sequencing (NGS) on DNA from blood or saliva. We will include: (1) MIS-C cases: Children with a history of MIS-C; (2) post-COVID condition cases: Children with post-COVID condition; and (3) Controls: SARS-CoV-2 exposed age-matched control group: children who were infected with SARS-CoV-2 but did not develop moderate to severe COVID-19, MIS-C or post-COVID condition.~Study population:~Children 0-19 years old with a history of MIS-C (n=100), post-COVID condition (n=100), or uncomplicated SARS-CoV-2 infection (n=200).~Main study parameters/endpoints:~To evaluate if some children with MIS-C or post-COVID condition have an inborn error of immunity by determining the presence of pathogenic or likely pathogenic variants in immunological genes~To evaluate if a larger proportion of cases with MIS-C or post-COVID condition have rare and presumably deleterious variants in immunological genes than children with an asymptomatic or mild infection
We will perform Whole Exome Sequencing on DNA from saliva. We will include: Children with a history of MIS-C; children with post-COVID condition; and controls in order to identify rare, high impact genetic variants in immunological genes and pathways in children with a history of MIS-C or pediatric post-COVID condition.