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.
“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]
Neutralizing antibody responses decay rapidly in early convalescence.
“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]
SARS-CoV-2-specific memory B cells accumulate over the first few months after initial infection.
“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]
Frequencies of circulating memory B cells continue to increase for several months after recovery from COVID-19 when most other responses decline, suggesting recall of B cell memory may extend antibody-dependent protection despite waning serological titres.
“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]
SARS-CoV-2 infection rapidly elicits nAbs that decline, but remain detectable, over several months.
“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]
SARS-CoV-2 infection can induce production of neutralizing antibodies, and these antibodies are believed to contribute to protection from reinfection.
“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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Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV
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A COVID-19 Vaccine: Big Strides Come with Big Challenges
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Self-citationFull Spectrum Flow Cytometry as a Powerful Technology for Cancer Immunotherapy Research
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Self-citationB-cell and antibody responses to SARS-CoV-2: infection, vaccination, and hybrid immunity
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Durable SARS-CoV-2 B cell immunity after mild or severe disease
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SARS-CoV-2 mutations acquired in mink reduce antibody-mediated neutralization
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Follow-up study on COVID-19 survivors one year after discharge from hospital
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Cognitive dysfunction in post‐COVID‐19 condition: Mechanisms, management, and rehabilitation
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Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses
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Overview of Neutralizing Antibodies and Their Potential in COVID-19
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COVID-19—Lessons Learned and Questions Remaining
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- 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 · 2020: 27
- 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
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