Antibody responses to SARS-CoV2 are distinct in children with MIS-C compared to adults with COVID-19

Weisberg, S. P.; Connors, T.; Zhu, Y.; Baldwin, M.; Lin, W.-H.; Wontakal, S.; Szabo, P. A.; Wells, S. B.; Dogra, P.; Gray, J. I.; Idzikowski, E.; Bovier, F.; Davis-Porada, J.; Matsumoto, R.; Li Poon, M. M.; Chait, M. P.; Mathieu, C.; Horvat, B.; Decimo, D.; Bitan, Z. C.; La Carpia, F.; Ferrara, S. A.; Mace, E.; Milner, J.; Moscona, A.; Hod, E. A.; Porotto, M.; Farber, D. L.

Clinical manifestations of COVID-19 caused by the novel coronavirus SARS-CoV-2 are associated with age. While children are largely spared from severe respiratory disease, they can present with a SARS-CoV-2-associated multisystem inflammatory syndrome (MIS-C) similar to Kawasaki's disease. Here, we show distinct antibody (Ab) responses in children with MIS-C compared to adults with severe COVID-19 causing acute respiratory distress syndrome (ARDS), and those who recovered from mild disease. There was a reduced breadth and specificity of anti-SARS-CoV-2-specific antibodies in MIS-C patients compared to the COVID patient groups; MIS-C predominantly generated IgG Abs specific for the Spike (S) protein but not for the nucleocapsid (N) protein, while both COVID-19 cohorts had anti-S IgG, IgM and IgA Abs, as well as anti-N IgG Abs. Moreover, MIS-C patients had reduced neutralizing activity compared to COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children and adults who develop severe disease, with implications for optimizing treatments based on symptom and age.