Early de novo T cell expansion following SARS-CoV-2 infection predicts favourable clinical and virological outcomes
Year: 2025
Type: article
Study design: Observational Study
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).
Source: EBioMedicine
Authors: Joe Fenn, Aleksandra Koycheva, Rhia Kundu, Mica Tolosa-Wright, Lulu Wang, Janakan Sam Narean, Emily Conibear, Seran Hakki, Jakob Jonnerby, Samuel Baldwin, Kieran Madon, Sean Nevin, Nieves Derqui, Timesh D. Pillay, Anjna Badhan, Eleanor Parker, Carolina Rosadas, Graham Taylor, Jake Dunning, Ajit Lalvani, Joe Fenn, Kieran Madon, Emily Conibear, Romain Derelle, Sean Nevin, Rhia Kundu, Seran Hakki, Aleksandra Koycheva, Nieves Derqui, Mica Tolosa-Wright, Jakob Jonnerby, Lulu Wang, Samuel Baldwin, Timesh Pillay, Ryan Thwaites, Constanta Luca, Robert Varro, Anjna Badhan, Eleanor Parker, Carolina Rosadas, Myra McClure, Richard Tedder, Graham Taylor, Ajit Lalvani, Janakan Narean, Lucy Mosscrop, Patricia Watber, Jie Zhou, Jack Barnett, Hamish Houston, Anika Singanayagam, Paul Freemont, Neil Ferguson, Maria Zambon, Wendy Barclay, Jake Dunning, Jessica Cutajar, Valerie Quinn, Sarah Hammett, Eimèar McDermott, Kristel Timcang, Jada Samuel, Samuel Bremang, Samuel Evetts, Megan Davies, Chitra Tejpal, Anjeli Ketkar, Giulia Miserocchi, Harriet Catchpole, Simon Dustan, Isaac Day Weber, Federica Marchesin, Alexandra Kondratiuk
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,780
OpenAlex ID: W4411016232