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@article{Fenn:2025:10.1016/j.ebiom.2025.105795,
author = {Fenn, J and Koycheva, A and Kundu, R and Tolosa-Wright, M and Wang, L and Narean, JS and Conibear, E and Hakki, S and Jonnerby, J and Baldwin, S and Madon, K and Nevin, S and Derqui, N and Pillay, TD and Badhan, A and Parker, E and Rosadas, C and Taylor, G and Dunning, J and Lalvani, A and Fenn, J and Madon, K and Conibear, E and Derelle, R and Nevin, S and Kundu, R and Hakki, S and Koycheva, A and Derqui, N and Tolosa-Wright, M and Jonnerby, J and Wang, L and Baldwin, S and Pillay, T and Thwaites, R and Luca, C and Varro, R and Badhan, A and Parker, E and Rosadas, C and McClure, M and Tedder, R and Taylor, G and Lalvani, A and Narean, J and Mosscrop, L and Watber, P and Zhou, J and Barnett, J and Houston, H and Singanayagam, A and Freemont, P and Ferguson, N and Zambon, M and Barclay, W and Dunning, J and Cutajar, J and Quinn, V and Hammett, S and McDermott, E and Timcang, K and Samuel, J and Bremang, S and Evetts, S and Davies, M and Tejpal, C and Ketkar, A and Miserocchi, G and Catc},
doi = {10.1016/j.ebiom.2025.105795},
journal = {eBioMedicine},
title = {Early de novo T cell expansion following SARS-CoV-2 infection predicts favourable clinical and virological outcomes},
url = {http://dx.doi.org/10.1016/j.ebiom.2025.105795},
volume = {117},
year = {2025}
}
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TY  - JOUR
AB  - BackgroundDe 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.MethodsWe 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.FindingsEarly 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.InterpretationThese findings provide empiric evidence for early antigen-specific T cell expansion being protective against naturally acquired viral infection in humans.FundingThis 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).
AU  - Fenn,J
AU  - Koycheva,A
AU  - Kundu,R
AU  - Tolosa-Wright,M
AU  - Wang,L
AU  - Narean,JS
AU  - Conibear,E
AU  - Hakki,S
AU  - Jonnerby,J
AU  - Baldwin,S
AU  - Madon,K
AU  - Nevin,S
AU  - Derqui,N
AU  - Pillay,TD
AU  - Badhan,A
AU  - Parker,E
AU  - Rosadas,C
AU  - Taylor,G
AU  - Dunning,J
AU  - Lalvani,A
AU  - Fenn,J
AU  - Madon,K
AU  - Conibear,E
AU  - Derelle,R
AU  - Nevin,S
AU  - Kundu,R
AU  - Hakki,S
AU  - Koycheva,A
AU  - Derqui,N
AU  - Tolosa-Wright,M
AU  - Jonnerby,J
AU  - Wang,L
AU  - Baldwin,S
AU  - Pillay,T
AU  - Thwaites,R
AU  - Luca,C
AU  - Varro,R
AU  - Badhan,A
AU  - Parker,E
AU  - Rosadas,C
AU  - McClure,M
AU  - Tedder,R
AU  - Taylor,G
AU  - Lalvani,A
AU  - Narean,J
AU  - Mosscrop,L
AU  - Watber,P
AU  - Zhou,J
AU  - Barnett,J
AU  - Houston,H
AU  - Singanayagam,A
AU  - Freemont,P
AU  - Ferguson,N
AU  - Zambon,M
AU  - Barclay,W
AU  - Dunning,J
AU  - Cutajar,J
AU  - Quinn,V
AU  - Hammett,S
AU  - McDermott,E
AU  - Timcang,K
AU  - Samuel,J
AU  - Bremang,S
AU  - Evetts,S
AU  - Davies,M
AU  - Tejpal,C
AU  - Ketkar,A
AU  - Miserocchi,G
AU  - Catchpole,H
AU  - Dustan,S
AU  - Weber,ID
AU  - Marchesin,F
AU  - Kondratiuk,A
DO  - 10.1016/j.ebiom.2025.105795
PY  - 2025///
SN  - 2352-3964
TI  - Early de novo T cell expansion following SARS-CoV-2 infection predicts favourable clinical and virological outcomes
T2  - eBioMedicine
UR  - http://dx.doi.org/10.1016/j.ebiom.2025.105795
UR  - https://doi.org/10.1016/j.ebiom.2025.105795
VL  - 117
ER  -
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