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

Abstract

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 anti-ganglioside antibodies that can cause neurological disorders. Additionally, nearly all anti-glycan 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 anti-glycan 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.

Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19

“…This is coupled with the fact that bacterial models are widely used in subunit vaccine production due to their simplicity of implementation and substantial cost reduction. Even more, unglycosylated antigens could avoid the auto-antibodies production against host carbohydrates produced in SARS-CoV-2 infection [ 109 ]. However, impurities from E. coli , like endotoxins (lipopolysaccharides or Lipid A), are responsible for triggering proinflammatory cytokine production, which is important in the design of vaccines administrated parenterally [ 110 , 111 ].…”

Guillain−Barré syndrome and SARS‐CoV‐2 infection: a systematic review and meta‐analysis on a debated issue and evidence for the ‘Italian factor’

“…Anti‐ganglioside antibodies were found in 17.6% of patients. The surface of the SARS‐CoV‐2 spike protein is heavily glycosylated and in 40 sera of COVID‐19 patients high levels of antibodies to numerous self‐glycans, even non‐human, were described [54]. Specifically, antibodies to gangliosides reported in GBS were found in 15% of sera but it is not stated if these patients actually had GBS.…”

Antibody-Dependent Enhancement with a Focus on SARS-CoV-2 and Anti-Glycan Antibodies

“…Viruses 2023, 15, 1584 2 of 20 by antibody-dependent enhancement (ADE) [1,2]; this phenomenon was found in patients with SARS-CoV and MERS-CoV, respiratory syncytial virus (RSV), dengue [3,4], influenza [5], HIV, and viral diseases in animals [2,6]. It is difficult to specify whether severe COVID-19 is caused by ADE or other factors.…”

“…The transmembrane S-protein is extensively glycosylated with a total of 22 potential sites of N-glycosylation and several O-linked glycosylation sites which mediate infectivity and immune escape [ 12 , 13 , 14 ]. Pre-existing antibodies to glycans recognize the virus and potentially influence disease progression [ 15 ]. In some infections [ 16 , 17 , 18 ], natural anti-glycan antibodies (AGA) were found to contribute to the disease development.…”

“…In some infections [ 16 , 17 , 18 ], natural anti-glycan antibodies (AGA) were found to contribute to the disease development. A previously studied AGA profile in patients with COVID-19 indicates that the abnormally high IgG and IgM antibodies observed against number of self-glycans may help explain some of the unusual and prolonged symptoms observed in severe COVID-19 patients [ 15 ]. The natural AGAs are also associated with activation of the antiviral immune response [ 19 ].…”