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

Caution: This preprint is a work in progress that has not been peer-reviewed. It should not be relied upon to guide clinical practice or health behaviors, and it should not be reported in news media as established information. We will update this web page if this preprint becomes a peer-reviewed publication. (Not all research reports move past the preprint stage.)

View Preprint on PubMed

Published

July 2025

Journal

medRxiv

Abstract

Pediatric SARS-CoV-2 infection results in clinical presentations ranging from asymptomatic/mild infection to severe pulmonary COVID-19, to Multisystem Inflammatory Syndrome in Children (MIS-C), characterized by hyperinflammation and multi-organ involvement. While various aspects of antibody responses to pediatric SARS-CoV-2 infection manifestations have been reported, parallel studies of antibody responses to viral and self-antigens are understudied. We tested whether clinical presentations of increasing severity corresponded to different antiviral antibody and autoantibody signatures. Using custom arrays, we found that, relative to uninfected subjects, all SARS-CoV-2 infection manifestations were associated with increased autoantibody production, suggesting pediatric SARS-CoV-2 infection as a risk factor for autoimmune complications. Subtle differences were seen in autoantibody patterns among infection groups, with some autoantibodies more associated with mild manifestations and others with severe ones. When we compared MIS-C and severe COVID-19 subjects, we found differences in IgG (mostly IgG1) abundance but not in Fc-mediated effector functions. Thus, MIS-C may be associated with abnormal antibody function, suggesting that this syndrome, and perhaps other post-acute sequelae of SARS-CoV-2 infection, may be associated with antibody dysfunction. Our study shows that the antibody repertoire varies with clinical presentation of SARS-CoV-2 in children and its analysis may help understand long COVID pathogenesis.

Authors

Natalie Bruiners, Rahul Ukey, Katherine C Konvinse, Marlayna Harris, Muge Kalaycioglu, Jason H Yang, Emily Yang, Usha Ganapathi, William Honnen, Tracy Andrews, Benjamin Richlin, Christian Suarez, Sunanda Gaur, Elizabeth Ricciardi, Uzma N Hasan, William Cuddy, Aalok R Singh, Hulya Bukulmez, David C Kaelber, Yukiko Kimura, Abraham Pinter, Stacey Napoli, Sandra Moroso-Fela, Lawrence C Kleinman, Daniel B Horton, Paul J Utz, Maria Laura Gennaro

Keywords

COVID-19; Multisystem inflammatory syndrome in children (MIS-C); antibody effector functions; multiplex assays