Antibody repertoire associated with clinically diverse presentations of pediatric SARS-CoV-2 infection

Pediatric SARS-CoV-2 infection can give rise to a range of clinical presentations, from asymptomatic or mild cases to severe pulmonary COVID-19, and to multisystem inflammatory syndrome in children (MIS-C). The latter is characterized by hyperinflammation and involvement of multiple organs. Although various aspects of antibody responses to pediatric SARS-CoV-2 infection have been reported, there has been limited research on the parallel antibody responses to both viral and self-antigens. We examined whether clinical phenotypes were linked to particular antiviral antibody and autoantibody profiles. By using custom arrays, we discovered that all manifestations of SARS-CoV-2 infection were linked to increased autoantibody production when compared to uninfected subjects, suggesting that pediatric SARS-CoV-2 infection may predispose to immune dysregulation. We observed subtle differences in autoantibody patterns among infection groups, with some autoantibodies being more associated with mild symptoms and others linked to severe disease manifestations. In particular, subsets of subjects with MIS-C and/or severe COVID-19 exhibited elevated autoreactive antibody responses against thyroperoxidase, IL-13, and IFN-epsilon, although differences across clinical groups did not reach statistical significance. When we compared subjects with MIS-C to those with severe COVID-19, we noted differences in the abundance of IgG (primarily IgG1), but no differences in Fc-mediated effector functions. Our study shows that the antibody repertoire in children varies with the clinical presentation of SARS-CoV-2. Moreover, MIS-C may be linked to abnormal antibody function, indicating that this syndrome-and potentially other post-acute sequelae of SARS-CoV-2 infection-could be related to antibody dysfunction.