IgG GLYCOSYLATION PREDICTS COVID-19 DISEASE SEVERITY and VACCINE ANTIBODY RESPONSE

ABSTRACT

Background: Although vaccination efforts have been deployed worldwide over the past 10 months, there are still gaps in our understanding surrounding the immune response to SARS-CoV-2 infection and vaccination, including changes to the antibody repertoire. One way of tracking the immune response over time is through measuring IgG Fc glycosylation, which provides insight into the inflammatory state of an infected individual, antibody effector function, antibody half-life, and more. Therefore we set out to interrogate bulk IgG changes in glycosylation in both natural infection and vaccinated cohorts in order to determine potential insight into protection from severe disease and responsiveness to vaccination. Methods: We evaluated 98 plasma samples from COVID-19 patients with either mild or severe COVID-19. Symptomatic patients were characterized as mild or severe based on hospital admission. We also evaluated plasma from 228 vaccinated individuals (Pfizer-BioNTech). Bulk IgG glycosylation analysis was measured through a quadrupole orbitrap mass spectrometry. Neutralization potential was assessed through a spike pseudotyped neutralization assay. Spike antibody levels were measured using a Luminex assay and ELISA. Results: We found that inflammatory glycans (fucosylated agalactosylated, G0F) on bulk IgG were elevated in hospitalized COVID-19 patients and increased over time in this population when compared to mild infection. Mild patients had an anti-inflammatory glycosylation pattern (afucosylated galactosylated, G2) which increased over time. Siaylation levels were elevated in mild individuals, increased over time, and correlated with increased RBD antibody levels. Interestingly, when we assessed COVID-19 vaccinated individuals with low Spike antibody levels and low neutralization, they had the same glycosylation pattern (G0F) as that of hospitalized COVID-19 patients. Additionally, a small longitudinal vaccinated cohort (out to 8 months) revealed a decrease in G0F associated with peak IgG concentrations and neutralization (Fig 1). Conclusion: Inflammatory glycan signatures, such as an elevation in G0F glycans, can be used as prognostic tools, not only to predict the severity of COVID-19 disease, but also to predict patient responsiveness to COVID-19 vaccines. This is the first report identifying a shift in glycan signature to be associated with COVID-19 disease severity and vaccine responsiveness, which can guide future studies into SARS-CoV-2 protective immunity and vaccine development.