Fucosylated N-glycans as early biomarkers of COVID-19 severity

Front Immunol. 2023 Jun 5:14:1204661. doi: 10.3389/fimmu.2023.1204661. eCollection 2023.


Background: The pathological mechanisms of SARS-CoV-2 in humans remain unclear and the unpredictability of COVID-19 progression may be attributed to the absence of biomarkers that contribute to the prognosis of this disease. Therefore, the discovery of biomarkers is needed for reliable risk stratification and to identify patients who are more likely to progress to a critical stage.

Methods: Aiming to identify new biomarkers we analysed N-glycan traits in plasma from 196 patients with COVID-19. Samples were classified into three groups according to their severity (mild, severe and critical) and obtained at diagnosis (baseline) and at 4 weeks of follow-up (postdiagnosis), to evaluate their behaviour through disease progression. N-glycans were released with PNGase F and labelled with Rapifluor-MS, followed by their analysis by LC-MS/MS. The Simglycan structural identification tool and Glycostore database were employed to predict the structure of glycans.

Results: We determined that plasma from SARS-CoV-2-infected patients display different N-glycosylation profiles depending on the disease severity. Specifically, levels of fucosylation and galactosylation decreased with increasing severity and Fuc1Hex5HexNAc5 was identified as the most suitable biomarker to stratify patients at diagnosis and distinguish mild from critical outcomes.

Conclusion: In this study we explored the global plasma glycosignature, reflecting the inflammatory state of the organs during the infectious disease. Our findings show the promising potential of glycans as biomarkers of COVID-19 severity.

Keywords: COVID-19; LC-MS/MS; N-glycosylation; biomarker; fucosylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • COVID-19* / diagnosis
  • Chromatography, Liquid
  • Glycosylation
  • Humans
  • Polysaccharides / chemistry
  • SARS-CoV-2
  • Tandem Mass Spectrometry*


  • Biomarkers
  • Polysaccharides

Grants and funding

BP is supported by a fellowship from the Vicente Lopez Program (Eurecat). This work was financially supported by the Catalan Government through the funding grant ACCIÓ-Eurecat (Project PRIV-COVIDOMICS), and also by the COVIDOMICS’ project supported by Direcció General de Recerca i Innovació en Salut (DGRIS), Departament de Salut, Generalitat de Catalunya (PoC-6-17). The research was also supported by the Programa de Suport als Grups de Recerca AGAUR (2021SGR01404), the SPANISH AIDS Research Network [RD16/0025/0006]-ISCIII-FEDER (Spain) and the CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB21/13/00020, CB21/13/00063), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU. AR is supported by a grant from IISPV through the project “2019/IISPV/05” (Boosting Young Talent), by GeSIDA through the “III Premio para Jóvenes Investigadores 2019” and by the Instituto de Salud Carlos III (ISCIII) under grant agreement “CP19/00146” through the Miguel Servet Program.