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

Aneesh Chandran; Joshua Rosenheim; Gayathri Nageswaran; Leo Swadling; Gabriele Pollara; Rishi K. Gupta; Jose Afonso Guerra-Assuncao; Annemarie Woolston; Tahel Ronel; Corrina 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; Charlotte Manisty; Thomas Alexander Treibel; James Moon; Gillian S. Tomlinson; Mala K. Maini; Benjamin M. Chain; Mahdad Noursadeghi; COVIDsortium Investigators

doi:10.1101/2021.03.30.21254540

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

Aneesh Chandran (Lead Author), Joshua Rosenheim, Gayathri Nageswaran, Leo Swadling, Gabriele Pollara, Rishi K. Gupta, Jose Afonso Guerra-Assuncao, Annemarie Woolston, Tahel Ronel, Corrina 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, Charlotte ManistyThomas Alexander Treibel, James Moon, Gillian S. Tomlinson, Mala K. Maini, Benjamin M. Chain, Mahdad Noursadeghi, COVIDsortium Investigators

Norwich Medical School

Research output: Working paper › Preprint

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.

Original language	English
Publisher	medRxiv
DOIs	https://doi.org/10.1101/2021.03.30.21254540
Publication status	Published - 1 Apr 2021

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1 Article

Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections
Chandran, A., Rosenheim, J., Nageswaran, G., Swadling, L., Pollara, G., Gupta, R. K., Burton, A. R., Guerra-Assunção, J. A., Woolston, A., Ronel, T., Pade, C., Gibbons, J. M., Sanz-Magallon Duque De Estrada, B., Robert de Massy, M., Whelan, M., Semper, A., Brooks, T., Altmann, D. M., Boyton, R. J., McKnight, Á., & 10 othersCaptur, G., Manisty, C., Treibel, T. A., Moon, J. C., Tomlinson, G. S., Maini, M. K., Chain, B. M., Noursadeghi, M., COVIDsortium Investigators & Hickling, L. M., 15 Mar 2022, In: Cell Reports Medicine. 3, 3, 100557.
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Chandran, A., Rosenheim, J., Nageswaran, G., Swadling, L., Pollara, G., Gupta, R. K., Guerra-Assuncao, J. A., Woolston, A., Ronel, T., Pade, C., Gibbons, J. M., Sanz-Magallon Duque De Estrada, B., Robert de Massy, M., Whelan, M., Semper, A., Brooks, T., Altmann, D. M., Boyton, R. J., McKnight, Á., ... COVIDsortium Investigators (2021). 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. medRxiv. https://doi.org/10.1101/2021.03.30.21254540

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title = "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",

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.",

author = "Aneesh Chandran and Joshua Rosenheim and Gayathri Nageswaran and Leo Swadling and Gabriele Pollara and Gupta, {Rishi K.} and Guerra-Assuncao, {Jose Afonso} and Annemarie Woolston and Tahel Ronel and Corrina Pade and Gibbons, {Joseph M.} and {Sanz-Magallon Duque De Estrada}, Blanca and {Robert de Massy}, Marc and Matthew Whelan and Amanda Semper and Tim Brooks and Altmann, {Daniel M.} and Boyton, {Rosemary J.} and {\'A}ine McKnight and Charlotte Manisty and Treibel, {Thomas Alexander} and James Moon and Tomlinson, {Gillian S.} and Maini, {Mala K.} and Chain, {Benjamin M.} and Mahdad Noursadeghi and {COVIDsortium Investigators} and Hickling, {Lauren M.}",

note = "Now published in Cell Reports Medicine doi: 10.1016/j.xcrm.2022.100557 under the title: Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections",

year = "2021",

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doi = "10.1101/2021.03.30.21254540",

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Chandran, A, Rosenheim, J, Nageswaran, G, Swadling, L, Pollara, G, Gupta, RK, 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, Á, Manisty, C, Treibel, TA, Moon, J, Tomlinson, GS, Maini, MK, Chain, BM, Noursadeghi, M & COVIDsortium Investigators 2021 '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' medRxiv. https://doi.org/10.1101/2021.03.30.21254540

TY - UNPB

T1 - 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

AU - Chandran, Aneesh

AU - Rosenheim, Joshua

AU - Nageswaran, Gayathri

AU - Swadling, Leo

AU - Pollara, Gabriele

AU - Gupta, Rishi K.

AU - Guerra-Assuncao, Jose Afonso

AU - Woolston, Annemarie

AU - Ronel, Tahel

AU - Pade, Corrina

AU - Gibbons, Joseph M.

AU - Sanz-Magallon Duque De Estrada, Blanca

AU - Robert de Massy, Marc

AU - Whelan, Matthew

AU - Semper, Amanda

AU - Brooks, Tim

AU - Altmann, Daniel M.

AU - Boyton, Rosemary J.

AU - McKnight, Áine

AU - Manisty, Charlotte

AU - Treibel, Thomas Alexander

AU - Moon, James

AU - Tomlinson, Gillian S.

AU - Maini, Mala K.

AU - Chain, Benjamin M.

AU - Noursadeghi, Mahdad

AU - COVIDsortium Investigators

AU - Hickling, Lauren M.

N1 - Now published in Cell Reports Medicine doi: 10.1016/j.xcrm.2022.100557 under the title: Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections

PY - 2021/4/1

Y1 - 2021/4/1

N2 - 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.

AB - 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.

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BT - 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

PB - medRxiv

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