Abnormal antibodies to self-carbohydrates in SARS-CoV-2-infected patients

Our immune system is critical for preventing and treating SARS-CoV-2 infections, but aberrant immune responses can have deleterious effects. While antibodies to glycans could recognize the virus and influence the clinical outcome, little is known about their roles. Using a carbohydrate antigen microarray, we profiled serum antibodies in healthy control subjects and COVID-19 patients from two separate cohorts. COVID-19 patients had numerous autoantibodies to self-glycans, including antiganglioside antibodies that can cause neurological disorders. Additionally, nearly all antiglycan IgM signals were lower in COVID-19 patients, indicating a global dysregulation of this class of antibodies. Autoantibodies to certain N-linked glycans correlated with more severe disease, as did low levels of antibodies to the Forssman antigen and ovalbumin. Collectively, this study indicates that expanded testing for antiglycan antibodies could be beneficial for clinical analysis of COVID-19 patients and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses. Significance Statement: Antibody responses induced by SARS-CoV-2 infection can provide protection, but aberrant responses can be harmful. Since the surface of the virus is heavily glycosylated, glycan-binding antibodies can be induced and may affect disease severity and clinical outcome. To evaluate their roles, we used a glycan microarray to profile serum antiglycan antibodies in COVID-19 patients and healthy control subjects. Overall, we uncovered striking differences, including global dysregulation of antiglycan IgM and induction of numerous autoantibodies to glycans in COVID-19 patients, including some that cause neurological problems. The results provide a deeper understanding of antibody responses, illustrate the importance of evaluating antibody responses to glycans, and indicate that assessment of antiglycan antibodies could aid the clinical analysis of COVID-19 patients.