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Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections #MMPMID35474751
Chandran A; Rosenheim J; Nageswaran G; Swadling L; Pollara G; Gupta RK; Burton AR; Guerra-Assuncao JA; Woolston A; Ronel T; Pade C; Gibbons JM; Sanz-Magallon Duque De Estrada B; Robert de Massy M; Whelan M; Semper A; Brooks T; Altmann DM; Boyton RJ; McKnight A; Captur G; Manisty C; Treibel TA; Moon JC; Tomlinson GS; Maini MK; Chain BM; Noursadeghi M
Cell Rep Med 2022[Mar]; 3 (3): 100557 PMID35474751show ga
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.