Robust SARS-CoV-2-specific T cell immunity is maintained at 6 months following primary infection
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Abstract
The immune response to SARS-CoV-2 is critical in controlling disease, but there is concern that waning immunity may predispose to reinfection. We analyzed the magnitude and phenotype of the SARS-CoV-2-specific T cell response in 100 donors at 6 months following infection. T cell responses were present by ELISPOT and/or intracellular cytokine staining analysis in all donors and characterized by predominant CD4+ T cell responses with strong interleukin (IL)-2 cytokine expression. Median T cell responses were 50% higher in donors who had experienced a symptomatic infection, indicating that the severity of primary infection establishes a 'set point' for cellular immunity. T cell responses to spike and nucleoprotein/membrane proteins were correlated with peak antibody levels. Furthermore, higher levels of nucleoprotein-specific T cells were associated with preservation of nucleoprotein-specific antibody level although no such correlation was observed in relation to spike-specific responses. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T cell responses are retained at 6 months following infection.
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Using HLA class I and II predicted peptide megapools, circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in COVID-19 acute, mild and convalescent patients.
“Using HLA class I and II predicted peptide “megapools,” circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in COVID-19 acute, mild and convalescent patients [110, 118-125].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [124]
The Results (IL-2 production dominates SARS-CoV-2-specific T cell responses; page unavailable) identify SARS-CoV-2-specific CD4+ and CD8+ T cells. But Materials and Methods (Synthetic peptides) describes overlapping 15-mer peptide pools, not HLA class I- and II-predicted megapools; the cohort comprised convalescent donors sampled six months after infection, not patients sampled during acute illness (Results, Characteristics of enrolled donors; page unavailable). (LLM, conf=0.88)
Experimental — accuracy not yet measuredDocumented reinfection and short-lived immunity to endemic human coronaviruses raise the prospect that protective immunity after SARS-CoV-2 infection may last months rather than years.
“documented examples of SARS-CoV-2 reinfection as well as evidence of short-lived immunity to endemic human coronavirus (hCoV) infections raise the prospect that protective immunity after SARS-CoV-2 infection may last for months instead of years.”
From Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection (2021) · cites this paper as [10]
Cellular immune responses to SARS-CoV-2 infection are generally more stable than antibody responses.
“Cellular responses to infection seem to be generally more stable3,8,10 (Fig. 1) but their role in immune protection is not yet clear”
From Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection (2021) · cites this paper as [10]
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SARS-CoV-2–specific B- and T-cell immunity in a population-based study of young Swedish adults
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T cell perturbations persist for at least 6 months following hospitalization for COVID-19
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Antibiotic resistance during and beyond COVID-19
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SARS-CoV-2—The Role of Natural Immunity: A Narrative Review
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Impact of SARS-CoV-2 exposure history on the T cell and IgG response
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Immune Responses to SARS-CoV-2 in Solid Organ Transplant Recipients
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Mechanistic Insights Into the Immune Pathophysiology of COVID-19; An In-Depth Review
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Recovering or Persisting: The Immunopathological Features of SARS-CoV-2 Infection in Children
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- Authors
- Zuo, J., Dowell, A. C., Pearce, H., Verma, K., Long, H. M., Begum, J., Aiano, F., Amin-Chowdhury, Z., Hoschler, K., Brooks, T., Taylor, S., Hewson, J., Hallis, B., Stapley, L., Borrow, R., Linley, E., Ahmad, S., Parker, B., Horsley, A., Amirthalingam, G., Brown, K., Ramsay, M. E., Ladhani, S., & Moss, P.
- Affiliations
- University of Birmingham (GB)
- Manchester Royal Infirmary (GB)
- Manchester Academic Health Science Centre (GB)
- Manchester University NHS Foundation Trust (GB)
- University of Manchester (GB)
- St George's, University of London (GB)
- Corresponding author
- Ladhani, Shamez
- Moss, Paul
- ORCID
- Venue
- Nature Immunology
- Published
- 2021-03-05
- Volume
- 22
- Issue
- 5
- Pages
- 620-626
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC7610739
- OpenAlex
- W3134099704
- Cited by
- 392
- References
- 39
- Citations by year
- 2026: 10 · 2025: 31 · 2024: 37 · 2023: 56 · 2022: 115 · 2021: 137 · 2020: 6
- FWCI
- 27.48
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-05-20)
- Open access
- bronze
- doi.org
- Locations
- Nature Immunology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Research Explorer (The University of Manchester) (submittedVersion, cc-by-nd)
- Research Explorer (The University of Manchester) (submittedVersion, other-oa)
- Funders
- RCUK | Medical Research Council (MR/R011230/1)
- Bloodwise (17009)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- SARS-CoV-2, COVID-19 pandemic, T cell immunity, CD4+ T cells, waning immunity, reinfection, interleukin-2, spike protein, nucleocapsid protein, membrane proteins, antibody kinetics, symptomatic infection, set point
- MeSH terms
- COVID-19, SARS-CoV-2, Adult, Aged, Antibodies, Viral, Antigens, Viral, Female, Humans, Immunity, Cellular, Interleukin-2, Male, Middle Aged, Phenotype, Time Factors, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Host-Pathogen Interactions, Young Adult
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