Serum N-glycomic profiling may provide potential signatures for surveillance of COVID-19

Abstract

Disease development and progression are often associated with aberrant glycosylation, indicating that changes in biological fluid glycome may potentially serve as disease signatures. The corona virus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a significant threat to global human health. However, the effect of SARS-CoV-2 infection on the overall serum N-glycomic profile has been largely unexplored. Here, we extended our 96-well-plate-based high-throughput, high-sensitivity N-glycan profiling platform further with the aim of elucidating potential COVID-19-associated serum N-glycomic alterations. Use of this platform revealed both similarities and differences between the serum N-glycomic fingerprints of COVID-19 positive and control cohorts. Although there were no specific glycan peaks exclusively present or absent in COVID-19 positive cohort, this cohort showed significantly higher levels of glycans and variability. On the contrary, the overall N-glycomic profiles for healthy controls were well-contained within a narrow range. From the serum glycomic analysis, we were able to deduce changes in different glycan subclasses sharing certain structural features. Of significance was the hyperbranched and hypersialylated glycans and their derived glycan subclass traits. T-distributed stochastic neighbour embedding (tSNE) and hierarchical heatmap clustering analysis were performed to identify 13 serum glycomic variables that potentially distinguished the COVID-19 positive from healthy controls. Such serum N-glycomic changes described herein may indicate or correlate to the changes in serum glycoproteins upon COVID-19 infection. Furthermore, mapping the serum N-glycome following SARS-CoV-2 infection may help us better understand the disease and enable “Long-COVID” surveillance to capture the full spectrum of persistent symptoms.

The Alterations of Serum N-glycome in Response to SARS-CoV-2 Vaccination

“…The presented results are in agreement with previous reports, where increased levels of mono-, bi-, tri- and tetra-sialylation and also higher fucosylation were found in COVID-19-positive patients compared to healthy controls [ 15 ]. Beimdiek et al reported an elevation in the level of sialylated bi-antennary glycans supporting our results, although they have also found increased level of oligomannose structures, which was not significantly altered and rather decreased in our results.…”

“…The changes in serum N-glycosylation have also been identified in several infectious diseases including tuberculosis, HIV, influenza, ebola and viral hepatitis [ 14 ]. Recent studies suggest that serum glycosylation can be significantly altered in patients after SARS-CoV-2 infection, and the analysis of serum N-glycome might be significant in the surveillance of COVID-19 [ 15 , 16 ].…”

Complex changes in serum protein levels in COVID-19 convalescents

“…The three peptides originated from albumin (ALB) and immunoglobulin heavy constant alpha 1 (IGHA1); these two proteins did not show significantly differential levels across the two cohorts. Our results were consistent with extensive serum glycosylation observed in COVID-19 patients 23,24 . Other modifications affected only a few peptides in our data.…”

Complex changes in serum protein levels in COVID-19 convalescents

“…The three peptides originated from albumin (ALB) and immunoglobulin heavy constant alpha 1 (IGHA1); these two proteins did not show significantly differential levels across the two cohorts. Our results were consistent with extensive serum glycosylation observed in COVID-19 patients 20,21 .…”

“…Figure 1A shows the experimental outline; Supplementary Table S1 describes the cohort demographics. Participant age ranged from 22 to 61 years, with a median (interquartile range, IQR) of 44 (20) years. The male to female ratio was 1.2:1.…”