The DOI matches its Crossref record; 49 of the 52 references it cites were found in a registry or an index, and 2 are not checked yet.
Cross-reactive memory T cells and herd immunity to SARS-CoV-2
Open accessAbstract
Immunity is a multifaceted phenomenon. For T cell-mediated memory responses to SARS-CoV-2, it is relevant to consider their impact both on COVID-19 disease severity and on viral spread in a population. Here, we reflect on the immunological and epidemiological aspects and implications of pre-existing cross-reactive immune memory to SARS-CoV-2, which largely originates from previous exposure to circulating common cold coronaviruses. We propose four immunological scenarios for the impact of cross-reactive CD4+ memory T cells on COVID-19 severity and viral transmission. For each scenario, we discuss its implications for the dynamics of herd immunity and on projections of the global impact of SARS-CoV-2 on the human population, and assess its plausibility. In sum, we argue that key potential impacts of cross-reactive T cell memory are already incorporated into epidemiological models based on data of transmission dynamics, particularly with regard to their implications for herd immunity. The implications of immunological processes on other aspects of SARS-CoV-2 epidemiology are worthy of future study.
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“at least some individuals are low or negative to commercial IgG assays, while retaining detectable SARS-CoV-2 CD4+ T cells. Current estimates are these individuals represent 1%–10% of PCR-confirmed SARS-CoV-2 infections (Gudbjartsson et al., 2020; Lipsitch et al., 2020; Nelde et al., 2021; Schwarzkopf et al., 2021; Sekine et al., 2020).”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Lipsitch et al., 2020
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In the citing paper
“lymphocytes from 20% to 50% of unexposed donors display significant reactivity to SARS-CoV-2 Ag peptide pools (Figure 6).”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [111]
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“This cross-reactivity largely originates from previous exposure to circulating common cold coronaviruses [110-116].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [111]
In the citing paper
“It is possible that cross-protection via adaptive immune responses against endemic coronaviruses might be in part responsible for mild disease courses in younger individuals (Lipsitch et al., 2020).”
From COVID-19 and the human innate immune system (2021) · cites this paper as Lipsitch et al., 2020
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Temporal dynamics in viral shedding and transmissibility of COVID-19
He, X., Lau, E. H. Y., Wu, P., Deng, X., Wang, J., Hao, X., Lau, Y. C., Wong, J. Y., Guan, Y., Tan, X., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0869-5 · Cited by 4,300
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Self-citationClinical and immunological assessment of asymptomatic SARS-CoV-2 infections
Long, Q.-X., Tang, X.-J., Shi, Q.-L., Li, Q., Deng, H.-J., Yuan, J., Hu, J.-L., Xu, W., Zhang, Y., Lv, F.-J., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0965-6 · Cited by 2,686
Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period
Kissler, S. M., Tedijanto, C., Goldstein, E., Grad, Y. H., & Lipsitch, M. (2020) · Science · doi:10.1126/science.abb5793 · Cited by 2,611
Self-citationSuperspreading and the effect of individual variation on disease emergence
Lloyd-Smith, J. O., Schreiber, S. J., Kopp, P. E., & Getz, W. M. (2005) · Nature · doi:10.1038/nature04153 · Cited by 2,514
SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls
Le Bert, N., Tan, A. T., Kunasegaran, K., Tham, C. Y. L., Hafezi, M., Chia, A., Chng, M. H. Y., Lin, M., Tan, N., Linster, M., et al. (2020) · Nature · doi:10.1038/s41586-020-2550-z · Cited by 1,887
Rydyznski Moderbacher, C., Ramirez, S. I., Dan, J. M., Grifoni, A., Hastie, K. M., Weiskopf, D., Belanger, S., Abbott, R. K., Kim, C., Choi, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.038 · Cited by 1,790
Self-citationRobust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19
Sekine, T., Perez-Potti, A., Rivera-Ballesteros, O., Strålin, K., Gorin, J.-B., Olsson, A., Llewellyn-Lacey, S., Kamal, H., Bogdanovic, G., Muschiol, S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.017 · Cited by 1,788
A serological assay to detect SARS-CoV-2 seroconversion in humans
Amanat, F., Stadlbauer, D., Strohmeier, S., Nguyen, T. H. O., Chromikova, V., McMahon, M., Jiang, K., Arunkumar, G. A., Jurczyszak, D., Polanco, J., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0913-5 · Cited by 1,769
Cited by
Sorted by citations
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
Self-citationChen, R. E., Zhang, X., Case, J. B., Winkler, E. S., Liu, Y., VanBlargan, L. A., Liu, J., Errico, J. M., Xie, X., Suryadevara, N., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01294-w · Cited by 881
COVID-19 and the human innate immune system
Schultze, J. L., & Aschenbrenner, A. C. (2021) · Cell · doi:10.1016/j.cell.2021.02.029 · Cited by 714
“It is possible that cross-protection via adaptive immune responses against endemic coronaviruses might be in part responsible for mild disease courses in younger individuals (Lipsitch et al., 2020).”
BackgroundTarke, A., Sidney, J., Methot, N., Yu, E. D., Zhang, Y., Dan, J. M., Goodwin, B., Rubiro, P., Sutherland, A., Wang, E., et al. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100355 · Cited by 706
Self-citationImmune determinants of COVID-19 disease presentation and severity
Brodin, P. (2021) · Nature Medicine · doi:10.1038/s41591-020-01202-8 · Cited by 670
Metadata
- Authors
- Lipsitch, M., Grad, Y. H., Sette, A., & Crotty, S.
- Affiliations
- Harvard University (US)
- La Jolla Institute for Immunology (US)
- Corresponding author
- Lipsitch, Marc
- Grad, Yonatan H.
- Sette, Alessandro
- Crotty, Shane
- Venue
- Nature Reviews Immunology
- Published
- 2020-10-06
- Volume
- 20
- Issue
- 11
- Pages
- 709-713
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC7537578
- OpenAlex
- W3091791643
- Cited by
- 260
- References
- 48
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 12 · 2023: 29 · 2022: 59 · 2021: 129 · 2020: 9
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (75N9301900065)
- National Institute of Allergy and Infectious Diseases (U19 AI42742, 75N9301900065, AI42742, U19AI142742)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- SARS-CoV-2, cross-reactive T cells, memory CD4+ T cells, herd immunity threshold, COVID-19 severity, common cold coronaviruses, pre-existing immunity, virus transmission, epidemic modeling, COVID-19 pandemic
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Antibodies, Viral, Coronaviridae, Coronaviridae Infections, Cross Reactions, Humans, Immunologic Memory, Pneumonia, Viral, Rhinovirus, Viral Vaccines, CD4-Positive T-Lymphocytes, Coronavirus Infections, Immunity, Herd, Adaptive Immunity, Pandemics
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