Non-severe SARS-CoV-2 infection is characterised by very early T cell proliferation independent of type 1 interferon responses and distinct from other acute respiratory viruses.

Chandran, A.; Rosenheim, J.; Nageswaran, G.; Swaddling, L.; Pollara, G.; Gupta, R.; Guerra-Assuncao, J. A.; Woolston, A.; Ronel, T.; Pade, C.; Gibbons, J.; Sanz-Magallon Duque De Estrada, B.; Robert de Massy, M.; Whelan, M.; Semper, A.; Brooks, T.; Altmann, D. M.; Boyton, R. J.; McKnight, A.; Manisty, C.; Treibel, T. A.; Moon, J.; Tomlinson, G. S.; Maini, M. K.; Chain, B. M.; Noursadeghi, M.; investigators, COVIDsortium

The correlates of natural protective immunity to SARS-CoV-2 in the majority who experience asymptomatic infection or non-severe disease are not fully characterised, and remain important as new variants emerge. We addressed this question using blood transcriptomics, multiparameter flow cytometry and T cell receptor (TCR) sequencing spanning the time of incident infection. We identified a type 1 interferon (IFN) response common to other acute respiratory viruses, and a cell proliferation response that discriminated SARS-CoV-2 from other viruses. These responses peaked by the time the virus was first detected, and in some preceded virus detection. Cell proliferation was most evident in CD8 T cells and associated with rapid expansion of SARS-CoV-2 reactive TCRs. We found an equally rapid increase in immunoglobulin transcripts, but circulating virus-specific antibodies lagged by 1-2 weeks. Our data support a protective role for rapid induction of type 1 IFN and CD8 T cell responses to SARS-CoV-2.