Anti-SARS-CoV-2 antibodies from severe COVID-19 individuals or S2 immunizations do not worsen disease in hamsters
Severe COVID-19 associates with humoral immune response dysregulation. While antibodies confer protection against SARS-CoV-2, evidence also support their putative contribution to disease severity. Our study demonstrates that higher levels of S2-IgG, and S2-, RBD-, and Nucleocapsid-IgA differentiate severe and non-severe cases. However, no major antibody functional differences are found between both COVID-19 manifestations. Enhanced Fc-dependent functions in severe cases are primarily driven by increased antibody titers. No differences in antibody avidity are found between severe and non-severe cases, but a gradation in binding strength across specificities suggests that early anti-RBD, -S2, and -Nucleocapsid antibodies may originate from different pathways. In golden Syrian hamsters, S2 immunization or transfer of RBD-depleted antibodies isolated from severe and non-severe cases promote a faster clinical recovery after SARS-CoV-2 challenge, despite a transient initial weight loss. These findings indicate that antibodies are not major determinants of COVID-19 severity and suggest additional factors influencing disease outcomes.
Authors
- José Moltó (ORCID: https://orcid.org/0000-0003-4564-1963)
- Nuria Izquierdo‐Useros (ORCID: https://orcid.org/0000-0002-1039-1821)
- Jorge Abad (ORCID: https://orcid.org/0000-0002-8129-7859)
- Ferran Tarrés-Freixas (ORCID: https://orcid.org/0000-0002-1569-0126)
- Bonaventura Clotet (ORCID: https://orcid.org/0000-0003-3232-4598)
- Lourdes Mateu (ORCID: https://orcid.org/0000-0001-7223-7611)
- Boris Revollo (ORCID: https://orcid.org/0000-0001-9245-2183)
- Beatriz Mothe (ORCID: https://orcid.org/0000-0001-9975-407X)
- Carla Usai (ORCID: https://orcid.org/0000-0002-6373-2765)
- Núria Roca (ORCID: https://orcid.org/0009-0009-7743-7458)
- Dàlia Raϊch‐Regué (ORCID: https://orcid.org/0000-0001-7656-5700)
- Maria Luisa Rodrı́guez de la Concepción (ORCID: https://orcid.org/0000-0002-6944-3462)
- Julieta Carabelli (ORCID: https://orcid.org/0000-0003-2329-3996)
- Carlos Ávila‐Nieto
- Edwards Pradenas (ORCID: https://orcid.org/0000-0001-5162-8920)
- Núria Pedreño-López (ORCID: https://orcid.org/0000-0001-6927-2301)
- Marta Massanella (ORCID: https://orcid.org/0000-0002-3326-151X)
- Erola Ainsua‐Enrich (ORCID: https://orcid.org/0000-0001-7901-5798)
- Joaquím Segalés (ORCID: https://orcid.org/0000-0002-1539-7261)
- Júlia Vergara‐Alert (ORCID: https://orcid.org/0000-0001-7484-444X)
- Julià Blanco (ORCID: https://orcid.org/0000-0002-2225-0217)
- Guillermo Cantero (ORCID: https://orcid.org/0000-0003-4200-503X)
- Susana Benet (ORCID: https://orcid.org/0000-0002-2219-8826)
- Jorge Carrillo (ORCID: https://orcid.org/0000-0003-0221-5948)
- Mónica Pérez
- Marina Matilla
- A Hernández (ORCID: https://orcid.org/0009-0007-2985-2644)
Institutions
- Universitat de Vic - Universitat Central de Catalunya (ES)
- Universitat Autònoma de Barcelona (ES)
- IrsiCaixa (ES)
- Centre de Recerca en Sanitat Animal (ES)
- Centro de Investigación Biomédica en Red (ES)
- Fundació ACE (ES)
- Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES)
- Hospital Universitari Germans Trias i Pujol (ES)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-11-24
- DOI
- https://doi.org/10.1038/s42003-025-09034-3
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Centres de Recerca de Catalunya
- Agenția Națională pentru Cercetare și Dezvoltare
- Generalitat de Catalunya
- Ministerio de Ciencia e Innovación
- Agencia Nacional de Investigación y Desarrollo
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Agencia Estatal de Investigación
- Direcció General de Recerca, Generalitat de Catalunya
- CHIST-ERA