Non-severe SARS-CoV-2 infection characterised by very early T cell proliferation

 --independent of type 1 interferon responses and distinct from other acute respiratory viruses

Aneesh Chandran, Joshua Rosenheim, Gayathrie Nageswaran, Leo Swaddling, Gabriele Pollara, Rishi Gupta, Jose Afonso Guerra-Assuncao, Annemarie Woolston, Tahel Ronel, Corrina Pade, Joseph Gibbons, Blanca Sanz-Magallon Duque De Estrada, Marc Robert de Massy, Matthew Whelan, Amanda Semper, Tim Brooks, Daniel M Altmann, Rosemary J Boyton, Aine McKnight, Charlotte Manisty, Thomas Alexander Treibel, James Moon, Gillian S Tomlinson, Mala K Maini, Benjamin M Chain, Mahdad Noursadeghi, COVIDsortium investigators

doi: https://doi.org/10.1101/2021.03.30.21254540

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.03.30.21254540v1.full.pdf

Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Funding for COVIDsortium was donated by individuals, charitable Trusts, and corporations including Goldman Sachs, Citadel and Citadel Securities, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from UCLH Charity. RKG is funded by National Institute for Health Research (DRF-2018-11-ST2-004). JCM, CM, and TAT are directly and indirectly supported by the University College London Hospitals (UCLH) and Barts NIHR Biomedical Research Centres, and through the British Heart Foundation (BHF) Accelerator Award (AA/18/6/34223). TAT is funded by a BHF Intermediate Research Fellowship (FS/19/35/34374). MN is supported by the Wellcome Trust (207511/Z/17/Z) and by NIHR Biomedical Research Funding to UCL and UCLH. RJB/DMA are supported by UKRI/MRC Newton (MR/S019553/1, MR/R02622X/1, MR/V036939/1MR/S019553/1, and MR/R02622X/1), NIHR Imperial Biomedical Research Centre (BRC):ITMAT, Cystic Fibrosis Trust SRC, and Horizon 2020 Marie Curie Actions. MKM is supported by the UKRI/NIHR UK-CIC grant, a Wellcome Trust Investigator Award (214191/Z/18/Z), and a CRUK Immunology grant (26603) AM is supported by Rosetrees Trust, The John Black Charitable Foundation, and Medical College of St Bartholomew Hospital Trust. Funders had no role in study design, data collection, data analysis, data interpretation, writing of the report, or decision to submit for publication. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

https://www.medrxiv.org/content/10.1101/2021.03.30.21254540v1