Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections

COVIDsortium investigators, 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, Blanca Sanz-Magallon Duque De Estrada, Marc Robert de Massy, Matthew Whelan, Amanda Semper, Tim Brooks, Daniel M. Altmann, Rosemary J. BoytonÁine McKnight, Gabriella Captur, Charlotte Manisty, Thomas Alexander Treibel, James C. Moon, Gillian S. Tomlinson, Mala K. Maini, Benjamin M. Chain, Mahdad Noursadeghi*

*Corresponding author for this work

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30 Citations (Scopus)
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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.

Original languageEnglish
Article number100557
JournalCell Reports Medicine
Volume3
Issue number3
Early online date4 Mar 2022
DOIs
Publication statusPublished - 15 Mar 2022

Bibliographical note

Funding Information: Funding for COVIDsortium was donated by individuals, charitable Trusts, and corporations, including Goldman Sachs, Kenneth C. Griffin, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from UCLH Charity. R.K.G. is funded by the National Institute for Health Research (DRF-2018-11-ST2-004). J.C.M., C.M., and T.A.T. are directly and indirectly supported by the University College London Hospitals NHS Foundation Trust (UCLH) and Barts NIHR Biomedical Research Centers and through the British Heart Foundation (BHF) Accelerator Award (AA/18/6/34223). T.A.T. is funded by a BHF Intermediate Research Fellowship (FS/19/35/34374). M.N. is supported by the Wellcome Trust (207511/Z/17/Z) and by NIHR Biomedical Research Funding to UCL and UCLH. M.K.M. is supported by UKRI/NIHR UK-CIC and Wellcome Trust (214191/Z/18/Z). G.S.T. is supported by a UK Medical Research Council Clinician Scientist Fellowship (MR/N007727/1). R.J.B. and D.M.A. are supported by UKRI/MRC Newton (MR/S019553/1, MR/R02622X/1, MR/V036939/1, MR/W020610/1), NIHR Imperial Biomedical Research Center (BRC): ITMAT, Cystic Fibrosis Trust SRC (2019SRC015), NIHR EME Fast Track (NIHR134607), NIHR Long Covid (COV-LT2-0027), Innovate Uk (SBRI 10008614), and Horizon 2020 Marie Skłodowska-Curie Innovative Training Network (ITN) European Training Network (no. 860325). A.M. is supported by Rosetrees Trust, The John Black Charitable Foundation, and Medical College of St Bartholomew’s Hospital Trust. B.M.C. is supported by the Rosetrees Trust and the NIHR UCLH BRC.

The authors declare no competing interests.

Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Publisher Copyright: © 2022 The Authors

Citation: 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, Blanca Sanz-Magallon Duque De Estrada, Marc Robert de Massy, Matthew Whelan, Amanda Semper, Tim Brooks, Daniel M. Altmann, Rosemary J. Boyton, Áine McKnight, Gabriella Captur, Charlotte Manisty, Thomas Alexander Treibel, James C. Moon, Gillian S. Tomlinson, Mala K. Maini, Benjamin M. Chain, Mahdad Noursadeghi, Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections, Cell Reports Medicine,
Volume 3, Issue 3, 2022, 100557, ISSN 2666-3791,

DOI: https://doi.org/10.1016/j.xcrm.2022.100557.

Keywords

  • CD8 T cells
  • non-severe SARS-CoV-2 infection
  • type 1 interferon

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