Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells
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Abstract
Ending the COVID-19 pandemic will require long-lived immunity to SARS-CoV-2. Here, we evaluate 254 COVID-19 patients longitudinally up to 8 months and find durable broad-based immune responses. SARS-CoV-2 spike binding and neutralizing antibodies exhibit a bi-phasic decay with an extended half-life of >200 days suggesting the generation of longer-lived plasma cells. SARS-CoV-2 infection also boosts antibody titers to SARS-CoV-1 and common betacoronaviruses. In addition, spike-specific IgG+ memory B cells persist, which bodes well for a rapid antibody response upon virus re-exposure or vaccination. Virus-specific CD4+ and CD8+ T cells are polyfunctional and maintained with an estimated half-life of 200 days. Interestingly, CD4+ T cell responses equally target several SARS-CoV-2 proteins, whereas the CD8+ T cell responses preferentially target the nucleoprotein, highlighting the potential importance of including the nucleoprotein in future vaccines. Taken together, these results suggest that broad and effective immunity may persist long-term in recovered COVID-19 patients.
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The model with waning indicates a protection half-life of 229 days (95% CI 150-389 days), in line with the time scale of antibody waning described in other studies.
“The model with waning also indicates a protection”
From Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa (2023) · cites this paper as [18]
Memory B and T cell responses persist for at least 8 months after SARS-CoV-2 symptom onset.
“Immunological studies of SARS-CoV-2 infection show that memory B and T cell responses appear to persist for at least 8 months after symptom onset (28, 29).”
From mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (2021) · cites this paper as [29]
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- Authors
- Cohen, K. W., Linderman, S. L., Moodie, Z., Czartoski, J., Lai, L., Mantus, G., Norwood, C., Nyhoff, L. E., Edara, V. V., Floyd, K., De Rosa, S. C., Ahmed, H., Whaley, R., Patel, S. N., Prigmore, B., Lemos, M. P., Davis, C. W., Furth, S., O’Keefe, J. B., Gharpure, M. P., Gunisetty, S., Stephens, K., Antia, R., Zarnitsyna, V. I., Stephens, D. S., Edupuganti, S., Rouphael, N., Anderson, E. J., Mehta, A. K., Wrammert, J., Suthar, M. S., Ahmed, R., & McElrath, M. J.
- Affiliations
- Fred Hutch Cancer Center (US)
- Emory University (US)
- University of Washington (US)
- Corresponding author
- Ahmed, Rafi
- McElrath, M. Juliana
- ORCID
- Cohen, Kristen W.
- Linderman, Susanne L.
- Moodie, Zoe
- Czartoski, Julie
- Lai, Lilin
- Mantus, Grace
- Norwood, Carson
- Nyhoff, Lindsay E.
- Edara, Venkata Viswanadh
- Floyd, Katharine
- Whaley, Rachael
- Lemos, Maria P.
- Davis, Carl W.
- Furth, Sarah
- O’Keefe, James B.
- Gunisetty, Sivaram
- Antia, Rustom
- Zarnitsyna, Veronika I.
- Stephens, David S.
- Edupuganti, Srilatha
- Rouphael, Nadine
- Anderson, Evan J.
- Mehta, Aneesh K.
- Wrammert, Jens
- Suthar, Mehul S.
- Ahmed, Rafi
- McElrath, M. Juliana
- Venue
- Cell Reports Medicine
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 2
- Issue
- 7
- Pages
- 100354
- ISSN
- 2666-3791 (ISSN-L)
- PMC
- PMC8253687
- OpenAlex
- W3178772652
- Cited by
- 441
- References
- 44
- Citations by year
- 2026: 12 · 2025: 52 · 2024: 57 · 2023: 112 · 2022: 159 · 2021: 49
- FWCI
- 29.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports Medicine (publishedVersion, cc-by-nc-nd)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- ImmPort
- Funders
- Georgia Research Alliance
- National Institutes of Health (U19AI090023, 1U54CA260563, UM1AI069481-14S1, UM1AI068618-14S1, ORIP/OD P51OD011132, U19AI057266-17S1, T32AI074492, UM1A057266-S1)
- Children's Healthcare of Atlanta
- Paul G Allen Family Foundation (12931)
- National Institute of Allergy and Infectious Diseases
- 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, immunological memory, neutralizing antibodies, spike protein, antibody half-life, plasma cells, memory B cells, memory T cells, CD4+ T cells, CD8+ T cells, cross-reactive antibodies, SARS-CoV-1, betacoronaviruses, nucleocapsid protein, vaccine design, long-term immunity
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