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., Dunning J., Lalvani A., INSTINCT Study Investigators None.
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).