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Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19
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Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is causing a global pandemic, and cases continue to rise. Most infected individuals experience mildly symptomatic coronavirus disease 2019 (COVID-19), but it is unknown whether this can induce persistent immune memory that could contribute to immunity. We performed a longitudinal assessment of individuals recovered from mild COVID-19 to determine whether they develop and sustain multifaceted SARS-CoV-2-specific immunological memory. Recovered individuals developed SARS-CoV-2-specific immunoglobulin (IgG) antibodies, neutralizing plasma, and memory B and memory T cells that persisted for at least 3 months. Our data further reveal that SARS-CoV-2-specific IgG memory B cells increased over time. Additionally, SARS-CoV-2-specific memory lymphocytes exhibited characteristics associated with potent antiviral function: memory T cells secreted cytokines and expanded upon antigen re-encounter, whereas memory B cells expressed receptors capable of neutralizing virus when expressed as monoclonal antibodies. Therefore, mild COVID-19 elicits memory lymphocytes that persist and display functional hallmarks of antiviral immunity.
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“Among cytokine profiles of spike-responsive memory T cells, production was dominated by the expression of IL-2 and IFN-γ that were highly expressed by CCR6− subsets.32, 33”
From Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial (2022) · cites this paper as [33]
In the citing paper
“However, neutralizing antibody responses decay rapidly in early convalescence9,14–17.”
From Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection (2021) · cites this paper as [9]
In the citing paper
“We and others have shown that SARS-CoV-2-specific memory B cells accumulate over the first few months after initial infection2,3,8,9,28 (Fig. 1a)”
From Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection (2021) · cites this paper as [9]
In the citing paper
“The observations that frequencies of circulating memory B cells continue to increase for several months after recovery from COVID-19 (refs2,3,8,9,28), when most other responses are declining (Fig. 1a), suggest that recall of B cell memory may provide a mechanism to extend the duration of antibody-dependent protection in the face of waning serological titres.”
From Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection (2021) · cites this paper as [9]
In the citing paper
“SARS-CoV-2 infection rapidly elicits nAbs (16, 21–24) that decline, but remain detectable, over several months (25–29).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [26]
In the citing paper
“SARS-CoV-2 infection can induce the production of neutralizing antibodies, and these antibodies are believed to contribute to protection from reinfection (Rodda et al., 2020; Wajnberg et al., 2020).”
From SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies (2021) · cites this paper as Rodda et al., 2020
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Khoury, D. S., Cromer, D., Reynaldi, A., Schlub, T. E., Wheatley, A. K., Juno, J. A., Subbarao, K., Kent, S. J., Triccas, J. A., & Davenport, M. P. (2021) · Nature Medicine · doi:10.1038/s41591-021-01377-8 · Cited by 3,742
Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection.
Dan, J. M., Mateus, J., Kato, Y., Hastie, K. M., Yu, E. D., Faliti, C. E., Grifoni, A., Ramirez, S. I., Haupt, S., Frazier, A., et al. (2021) · Science · doi:10.1126/science.abf4063 · Cited by 2,656
Adaptive immunity to SARS-CoV-2 and COVID-19
Sette, A., & Crotty, S. (2021) · Cell · doi:10.1016/j.cell.2021.01.007 · Cited by 1,860
Evolution of antibody immunity to SARS-CoV-2
Gaebler, C., Wang, Z., Lorenzi, J. C. C., Muecksch, F., Finkin, S., Tokuyama, M., Cho, A., Jankovic, M., Schaefer-Babajew, D., Oliveira, T. Y., et al. (2021) · Nature · doi:10.1038/s41586-021-03207-w · Cited by 1,674
Seow, J., Graham, C., Merrick, B., Acors, S., Pickering, S., Steel, K. J. A., Hemmings, O., O’Byrne, A., Kouphou, N., Galao, R. P., et al. (2020) · Nature Microbiology · doi:10.1038/s41564-020-00813-8 · Cited by 1,419
Metadata
- Authors
- Rodda, L. B., Netland, J., Shehata, L., Pruner, K. B., Morawski, P. A., Thouvenel, C. D., Takehara, K. K., Eggenberger, J., Hemann, E. A., Waterman, H. R., Fahning, M. L., Chen, Y., Hale, M., Rathe, J., Stokes, C., Wrenn, S., Fiala, B., Carter, L., Hamerman, J. A., King, N. P., Gale, M., Campbell, D. J., Rawlings, D. J., & Pepper, M.
- Affiliations
- University of Washington (US)
- Benaroya Research Institute (US)
- Corresponding author
- Pepper, Marion
- ORCID
- Rodda, Lauren B.
- Netland, Jason
- Shehata, Laila
- Pruner, Kurt B.
- Morawski, Peter A.
- Thouvenel, Christopher D.
- Takehara, Kennidy K.
- Eggenberger, Julie
- Hemann, Emily A.
- Waterman, Hayley R.
- Fahning, Mitchell L.
- Chen, Yu
- Hale, Malika
- Stokes, Caleb
- Wrenn, Samuel
- Fiala, Brooke
- Carter, Lauren
- Hamerman, Jessica A.
- King, Neil P.
- Gale, Michael
- Campbell, Daniel J.
- Rawlings, David J.
- Pepper, Marion
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 184
- Issue
- 1
- Pages
- 169-183.e17
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7682481
- OpenAlex
- W3107730772
- Cited by
- 647
- References
- 80
- Citations by year
- 2026: 10 · 2025: 30 · 2024: 46 · 2023: 85 · 2022: 171 · 2021: 278
- FWCI
- 18.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Institutes of Health
- Burroughs Wellcome Fund
- 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, mild COVID-19, immunological memory, memory B cells, memory T cells, neutralizing antibodies, IgG, long-term immunity, cytokine production, monoclonal antibodies, antiviral immunity
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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