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Peer-reviewedCC BY 4.0Frontiers in Immunology

Antibody afucosylation and enhanced autoreactive antibody response are associated with thyroid dysfunction during severe SARS-CoV-2 infection

  • Elisa Pesce1,2
  • Andrea Gobbini1
  • Mauro Bombaci1
  • Andrea Favalli1
  • Sara Maioli2
  • Stefano Artin Serapian3
  • Noemi di Marzo4
  • Luca Sorrentino4
  • Mirco Toccafondi4
  • Paola Gruarin1
  • Andrea Lombardi5,6
  • Mirco Armenti2,7
5 more authors
  • Mariangela Lorenzo1
  • Alessandra Bandera5,6
  • Giorgio Colombo3
  • Ilaria Muller2,7
  • Renata M. Grifantini1
7 affiliations
  1. 1Istituto Nazionale di Genetica Molecolare (INGM) “Romeo ed Enrica Invernizzi”
  2. 2Department of Clinical Sciences and Community Health, Department of Excellence 2023-2027, University of Milan
  3. 3Department of Chemistry, University of Pavia
  4. 4CheckmAb SrL
  5. 5Infectious Diseases Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico
  6. 6Department of Pathophysiology and Transplantation, University of Milan
  7. 7Endocrinology Unit, Graves’ Orbitopathy Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
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Abstract

Introduction: SARS-CoV-2 infections causing severe COVID-19 are known to induce or exacerbate thyroid dysfunctions (TD), comprising autoimmune thyroiditis and subacute thyroiditis. Non-thyroidal illness syndrome is also common. Thyroid damage could result from direct viral infection and/or aberrant immuno-inflammatory responses. However, the specific immunological mechanisms contributing to TD in severe COVID-19 are not fully understood.

Methods: We investigated the relationship between severe SARS-CoV-2 infection and TD by analyzing antibody autoreactivity and fucosylation level in 40 COVID-19 patients recruited during the 2020 pandemic wave. Using protein arrays, ELISA, and computational modeling, we compared patients with and without TD to 20 healthy controls and 29 Graves’ disease cases, focusing on the functional impact of the elicited antibodies.

Results: We observed a significant shift in IgG autoreactivity, specifically targeting CD16A and KIR2DL1 in COVID-19 patients, both TD and not-TD, compared to Healthy Controls (HC) or other thyroid disease patients. Anti-Spike IgGs from COVID-19-TD patients exhibited a lower fucosylation state compared with those without TD and were associated with increased NK-cell activation and degranulation. Furthermore, patients’ sera showed increased binding to immortalized human thyroid epithelial cells. Computational analysis identified structural similarities between the SARS-CoV-2 Spike protein and thyroglobulin.

Discussion: Thyroid damage in severe COVID-19 involves a complex interplay of different mechanisms. We proposed a potential role of lowly fucosylated anti-Spike antibodies, which may contribute to heightened NK cell-mediated activation via CD16A, potentially exacerbated by virus-induced autoreactivity. Altered IgG fucosylation and autoreactivity are associated with thyroid dysfunctions in severe COVID-19.

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Cite

BibTeXRIS
BibTeX
@article{pesce2026antibody,
  title = {{Antibody afucosylation and enhanced autoreactive antibody response are associated with thyroid dysfunction during severe SARS-CoV-2 infection}},
  author = {Elisa Pesce and Andrea Gobbini and Mauro Bombaci and Andrea Favalli and Sara Maioli and Stefano Artin Serapian and Noemi di Marzo and Luca Sorrentino and Mirco Toccafondi and Paola Gruarin and Andrea Lombardi and Mirco Armenti and Mariangela Lorenzo and Alessandra Bandera and Giorgio Colombo and Ilaria Muller and Renata M. Grifantini},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1806272},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1806272/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Antibody afucosylation and enhanced autoreactive antibody response are associated with thyroid dysfunction during severe SARS-CoV-2 infection
AU  - Elisa Pesce
AU  - Andrea Gobbini
AU  - Mauro Bombaci
AU  - Andrea Favalli
AU  - Sara Maioli
AU  - Stefano Artin Serapian
AU  - Noemi di Marzo
AU  - Luca Sorrentino
AU  - Mirco Toccafondi
AU  - Paola Gruarin
AU  - Andrea Lombardi
AU  - Mirco Armenti
AU  - Mariangela Lorenzo
AU  - Alessandra Bandera
AU  - Giorgio Colombo
AU  - Ilaria Muller
AU  - Renata M. Grifantini
PY  - 2026
DA  - 2026/10/19
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1806272
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1806272/full
AB  - Introduction: SARS-CoV-2 infections causing severe COVID-19 are known to induce or exacerbate thyroid dysfunctions (TD), comprising autoimmune thyroiditis and subacute thyroiditis. Non-thyroidal illness syndrome is also common. Thyroid damage could result from direct viral infection and/or aberrant immuno-inflammatory responses. However, the specific immunological mechanisms contributing to TD in severe COVID-19 are not fully understood.  Methods: We investigated the relationship between severe SARS-CoV-2 infection and TD by analyzing antibody autoreactivity and fucosylation level in 40 COVID-19 patients recruited during the 2020 pandemic wave. Using protein arrays, ELISA, and computational modeling, we compared patients with and without TD to 20 healthy controls and 29 Graves’ disease cases, focusing on the functional impact of the elicited antibodies.  Results: We observed a significant shift in IgG autoreactivity, specifically targeting CD16A and KIR2DL1 in COVID-19 patients, both TD and not-TD, compared to Healthy Controls (HC) or other thyroid disease patients. Anti-Spike IgGs from COVID-19-TD patients exhibited a lower fucosylation state compared with those without TD and were associated with increased NK-cell activation and degranulation. Furthermore, patients’ sera showed increased binding to immortalized human thyroid epithelial cells. Computational analysis identified structural similarities between the SARS-CoV-2 Spike protein and thyroglobulin.  Discussion: Thyroid damage in severe COVID-19 involves a complex interplay of different mechanisms. We proposed a potential role of lowly fucosylated anti-Spike antibodies, which may contribute to heightened NK cell-mediated activation via CD16A, potentially exacerbated by virus-induced autoreactivity. Altered IgG fucosylation and autoreactivity are associated with thyroid dysfunctions in severe COVID-19.
SN  - 1664-3224
ER  -