The antibody response to the glycan α-Gal correlates with COVID-19 disease symptoms

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide. Characterization of the immunological mechanisms involved in disease symptomatology and protective response is important to progress in disease control and prevention. Humans evolved by losing the capacity to synthesize the glycan Gal alpha 1-3Gal beta 1-(3)4GlcNAc-R (alpha-Gal), which resulted in the development of a protective response against pathogenic viruses and other microorganisms containing this modification on membrane proteins mediated by anti-alpha-Gal immunoglobulin M (IgM)/IgG antibodies produced in response to bacterial microbiota. In addition to anti-alpha-Gal antibody-mediated pathogen opsonization, this glycan induces various immune mechanisms that have shown protection in animal models against infectious diseases without inflammatory responses. In this study, we hypothesized that the immune response to alpha-Gal may contribute to the control of COVID-19. To address this hypothesis, we characterized the antibody response to alpha-Gal in patients at different stages of COVID-19 and in comparison with healthy control individuals. The results showed that while the inflammatory response and the anti-SARS-CoV-2 (Spike) IgG antibody titers increased, reduction in anti-alpha-Gal IgE, IgM, and IgG antibody titers and alteration of anti-alpha-Gal antibody isotype composition correlated with COVID-19 severity. The results suggested that the inhibition of the alpha-Gal-induced immune response may translate into more aggressive viremia and severe disease inflammatory symptoms. These results support the proposal of developing interventions such as probiotics based on commensal bacteria with alpha-Gal epitopes to modify the microbiota and increase alpha-Gal-induced protective immune response and reduce severity of COVID-19.