Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections
Aneesh Chandran, Joshua Rosenheim, Gayathri Nageswaran, Leo Swadling, Gabriele Pollara, Rishi K Gupta, Alice R. Burton, José Afonso Guerra‐Assunção, Annemarie Woolston, Tahel Ronel, Corinna Pade, Joseph M. Gibbons, B. Estrada, Marc Robert de Massy, Matthew V. X. Whelan, Amanda Semper, Tim Brooks, Daniel M. Altmann, Rosemary J. Boyton, Áine McKnight, Gabriella Captur, Charlotte Manisty, Thomas A. Treibel, James Moon, Gillian S. Tomlinson, Mala K. Maini, Benny Chain, Mahdad Noursadeghi
Abstract
Effective control of SARS-CoV-2 infection on primary exposure may reveal correlates of protective immunity to future variants, but we lack insights into immune responses before or at the time virus is first detected. We use blood transcriptomics, multiparameter flow cytometry, and T cell receptor (TCR) sequencing spanning the time of incident non-severe infection in unvaccinated virus-naive individuals to identify rapid type 1 interferon (IFN) responses common to other acute respiratory viruses and cell proliferation responses that discriminate SARS-CoV-2 from other viruses. These peak by the time the virus is first detected and sometimes precede virus detection. Cell proliferation is most evident in CD8 T cells and associated with specific expansion of SARS-CoV-2-reactive TCRs, in contrast to virus-specific antibodies, which lag by 1-2 weeks. Our data support a protective role for early type 1 IFN and CD8 T cell responses, with implications for development of universal T cell vaccines.