Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19
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Abstract
Abstract The durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4 + and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG + memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.
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Better responses with a larger interval before boosting are consistent with an observed increase in the number of memory B cells within the first months after infection.
“Better responses with a larger interval before boosting are consistent with an observed increase in the number of memory B cells within the first months after infection.35”
From Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis (2022) · cites this paper as [35]
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Self-citation
- Authors
- Wheatley, A. K., Juno, J. A., Wang, J. J., Selva, K. J., Reynaldi, A., Tan, H.-X., Lee, W. S., Wragg, K. M., Kelly, H. G., Esterbauer, R., Davis, S. K., Kent, H. E., Mordant, F. L., Schlub, T. E., Gordon, D. L., Khoury, D. S., Subbarao, K., Cromer, D., Gordon, T. P., Chung, A. W., Davenport, M. P., & Kent, S. J.
- Affiliations
- Australian Research Council (AU)
- The University of Melbourne (AU)
- Flinders University (AU)
- UNSW Sydney (AU)
- The University of Sydney (AU)
- South Australia Pathology (AU)
- Corresponding author
- Kent, Stephen J.
- ORCID
- Wheatley, Adam K.
- Juno, Jennifer A.
- Wang, Jing J.
- Selva, Kevin J.
- Reynaldi, Arnold
- Tan, Hyon-Xhi
- Lee, Wen Shi
- Kelly, Hannah G.
- Esterbauer, Robyn
- Davis, Samantha K.
- Mordant, Francesca L.
- Schlub, Timothy E.
- Gordon, David L.
- Khoury, David S.
- Subbarao, Kanta
- Cromer, Deborah
- Gordon, Tom P.
- Chung, Amy W.
- Davenport, Miles P.
- Kent, Stephen J.
- Venue
- Nature Communications
- Published
- 2021-02-19
- Volume
- 12
- Issue
- 1
- Pages
- 1162-1162
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7896046
- OpenAlex
- W3131938123
- Cited by
- 351
- References
- 59
- Citations by year
- 2026: 8 · 2025: 25 · 2024: 26 · 2023: 61 · 2022: 142 · 2021: 86 · 2020: 3
- FWCI
- 25.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- The Sydney eScholarship Repository (The University of Sydney) (submittedVersion)
- Funders
- Department of Health | National Health and Medical Research Council (APP1149990)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, immune response dynamics, antibody waning, neutralizing antibodies, memory B cells, T follicular helper cells, CD4+ T cells, reinfection, convalescent patients, spike protein
- MeSH terms
- COVID-19, Antibodies, Viral, Antibody Formation, B-Lymphocytes, T-Lymphocytes, Helper-Inducer, Humans, Immunoglobulin G, Immunity, Cellular, Immunologic Memory, Longitudinal Studies, Models, Theoretical, Neutralization Tests, CD4-Positive T-Lymphocytes, Antibodies, Neutralizing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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