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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Lymphocytes from 20% to 50% of unexposed donors display significant reactivity to SARS-CoV-2 Ag peptide pools.
“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]
The Introduction (page unavailable) reports cross-reactive memory T cells in approximately 28–50% of people not exposed to SARS-CoV-2, supporting the central finding. It does not report a 20% lower bound or specifically describe significant reactivity to SARS-CoV-2 antigen peptide pools. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThis cross-reactivity largely originates from previous exposure to circulating common cold coronaviruses.
“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]
Cross-protection via adaptive immune responses against endemic coronaviruses might partly explain mild COVID-19 in younger individuals.
“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
At least some individuals are low or negative to commercial IgG assays while retaining detectable SARS-CoV-2 CD4+ T cells, representing 1%-10% of PCR-confirmed SARS-CoV-2 infections.
“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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- 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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