Low-Avidity CD4+ T Cell Responses to SARS-CoV-2 in Unexposed Individuals and Humans with Severe COVID-19
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Abstract
CD4+ T cells reactive against SARS-CoV-2 can be found in unexposed individuals, and these are suggested to arise in response to common cold coronavirus (CCCoV) infection. Here, we utilized SARS-CoV-2-reactive CD4+ T cell enrichment to examine the antigen avidity and clonality of these cells, as well as the relative contribution of CCCoV cross-reactivity. SARS-CoV-2-reactive CD4+ memory T cells were present in virtually all unexposed individuals examined, displaying low functional avidity and multiple, highly variable cross-reactivities that were not restricted to CCCoVs. SARS-CoV-2-reactive CD4+ T cells from COVID-19 patients lacked cross-reactivity to CCCoVs, irrespective of strong memory T cell responses against CCCoV in all donors analyzed. In severe but not mild COVID-19, SARS-CoV-2-specific T cells displayed low functional avidity and clonality, despite increased frequencies. Our findings identify low-avidity CD4+ T cell responses as a hallmark of severe COVID-19 and argue against a protective role for CCCoV-reactive T cells in SARS-CoV-2 infection.
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Healthy adults commonly show CD4+ T cell memory against hCoVs.
“several studies indicate the presence of widespread CD4+ T cell memory to hCoVs among healthy adults32,79–81.”
From Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection (2021) · cites this paper as [79]
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Self-citation
- Authors
- Bacher, P., Rosati, E., Esser, D., Martini, G. R., Saggau, C., Schiminsky, E., Dargvainiene, J., Schröder, I., Wieters, I., Khodamoradi, Y., Eberhardt, F., Vehreschild, M. J. G. T., Neb, H., Sonntagbauer, M., Conrad, C., Tran, F., Rosenstiel, P., Markewitz, R., Wandinger, K.-P., Augustin, M., Rybniker, J., Kochanek, M., Leypoldt, F., Cornely, O. A., Koehler, P., Franke, A., & Scheffold, A.
- Affiliations
- Christian-Albrechts-Universität zu Kiel (DE)
- University Hospital Schleswig-Holstein (DE)
- Goethe University Frankfurt (DE)
- University Hospital Frankfurt (DE)
- Klinik Preetz (DE)
- University of Cologne (DE)
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 53
- Issue
- 6
- Pages
- 1258-1271.e5
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC7689350
- OpenAlex
- W3108728530
- Cited by
- 314
- References
- 44
- Citations by year
- 2026: 13 · 2025: 27 · 2024: 43 · 2023: 41 · 2022: 84 · 2021: 101 · 2020: 4
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Publikationsdatenbank der Fraunhofer-Gesellschaft (Fraunhofer-Gesellschaft) (submittedVersion)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- Funders
- Shionogi
- Novartis
- Roche
- Bayer
- Miltenyi Biotec
- Meso Scale Diagnostics
- Astellas Pharma
- Deutsche Forschungsgemeinschaft (DFG 433038070, DFG 4096610003, RU5042-miTarget)
- Teva Pharmaceutical Industries
- Biogen
- Basilea Pharmaceutica
- 3M
- Universität zu Köln
- Merck KGaA
- Bundesministerium für Bildung und Forschung (01GM1908A, LE3064/2-1, 03ZZ0838B, 01KX2021)
- Gilead Sciences
- Ferring Pharmaceuticals
- Paul Scherrer Institut
- Pfizer
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, CD4+ T cells, T cell avidity, T cell clonality, cross-reactivity, memory T cells, severe COVID-19, T cell response
- MeSH terms
- COVID-19, SARS-CoV-2, Antigens, Viral, Cells, Cultured, Cross Reactions, Environmental Exposure, Humans, Immunologic Memory, Lymphocyte Activation, Protein Binding, Receptors, Antigen, T-Cell, Rhinovirus, Severity of Illness Index, CD4-Positive T-Lymphocytes, Disease Progression, T-Cell Antigen Receptor Specificity
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