Early de novo T cell expansion following SARS-CoV-2 infection predicts favourable clinical and virological outcomes

Fenn, J; Koycheva, A; Kundu, R; Tolosa-Wright, M; Wang, L; Narean, JS; Conibear, E; Hakki, S; Jonnerby, J; Baldwin, S; Madon, K; Nevin, S; Derqui, N; Pillay, TD; Badhan, A; Parker, E; Rosadas, C; Taylor, G; McClure, M; Dunning, J; Lalvani, A

COVID-19 Collection

Journal article

Early de novo T cell expansion following SARS-CoV-2 infection predicts favourable clinical and virological outcomes

Abstract:: Background
De novo T cell expansion to a novel viral infection is assumed to confer protection, but empirical evidence in humans is limited. The SARS-CoV-2 pandemic provided a unique opportunity to investigate de novo T cell-mediated protection in antigen-naïve individuals without the confounding effects of preexisting immune memory.
Methods
We leveraged a prospective household contact study to recruit new COVID-19 cases a median of 4 days post-SARS-CoV-2 exposure. We longitudinally enumerated SARS-CoV-2 antigen-specific functional T cell subsets using dual IFN-γ/IL-2 fluorescence-linked immunospot (FLISpot) assays. We then correlated T cell dynamics with detailed clinical and virological outcomes derived from longitudinal measurement of symptom burden and viral load.
Findings
Early expansion (day 0-7) of SARS-CoV-2-specific IFN-γ-secreting T cells correlated with lower peak viral load and symptom burden. Conversely, late T cell expansion (day 7-28) correlated with higher symptom burden. Neither pre-existing cross-reactive T cells nor early antibody induction correlated with virological outcomes.
Interpretation
These findings provide empiric evidence for early antigen-specific T cell expansion being protective against naturally acquired viral infection in humans.
Funding
This work is supported by the NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London in partnership with the UK Health Security Agency (Grant number: NIHR200927; AL) and the Medical Research Council (Grant number: MR/X004058/1).

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Fenn, J., Koycheva, A., Kundu, R., Tolosa-Wright, M., Wang, L., Narean, J. S., Conibear, E., Hakki, S., Jonnerby, J., Baldwin, S., Madon, K., Nevin, S., Derqui, N., Pillay, T. D., Badhan, A., Parker, E., Rosadas, C., Taylor, G., McClure, M., … Lalvani, A. (2025). Early de novo T cell expansion following SARS-CoV-2 infection predicts favourable clinical and virological outcomes. EBioMedicine, 117.

MLA Style

Fenn, J, et al. “Early De Novo T Cell Expansion Following SARS-CoV-2 Infection Predicts Favourable Clinical and Virological Outcomes.” EBioMedicine, vol. 117, 2025.

Chicago Style

Fenn, J, A Koycheva, R Kundu, et al. 2025. “Early De Novo T Cell Expansion Following SARS-CoV-2 Infection Predicts Favourable Clinical and Virological Outcomes.” EBioMedicine 117.
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