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; 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; COVIDsortium Investigators; Lauren M. Hickling

doi:10.1016/j.xcrm.2022.100557

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, Blanca Sanz-Magallon Duque De Estrada, Marc Robert de Massy, Matthew Whelan, Amanda Semper, Tim Brooks, Daniel M. Altmann, Rosemary J. Boyton, Áine McKnightGabriella Captur, Charlotte Manisty, Thomas Alexander Treibel, James C. Moon, Gillian S. Tomlinson, Mala K. Maini, Benjamin M. Chain, Mahdad Noursadeghi, COVIDsortium Investigators, Lauren M. Hickling (Consortium member)

Norwich Medical School

Research output: Contribution to journal › Article › peer-review

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 language	English
Article number	100557
Journal	Cell Reports Medicine
Volume	3
Issue number	3
Early online date	4 Mar 2022
DOIs	https://doi.org/10.1016/j.xcrm.2022.100557
Publication status	Published - 15 Mar 2022

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.xcrm.2022.100557Licence: CC BY

Chandran_etal_2022_CellReportsMedicineFinal published version, 3.45 MBLicence: CC BY

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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., ... Hickling, L. M. (2022). Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections. Cell Reports Medicine, 3(3), Article 100557. https://doi.org/10.1016/j.xcrm.2022.100557

@article{00ec0a21749442ccb3baa9ebaedfa28d,

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

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.",

keywords = "CD8 T cells, non-severe SARS-CoV-2 infection, type 1 interferon",

author = "Aneesh Chandran and Joshua Rosenheim and Gayathri Nageswaran and Leo Swadling and Gabriele Pollara and Gupta, {Rishi K.} and Burton, {Alice R.} and Guerra-Assun{\c c}{\~a}o, {Jos{\'e} Afonso} and Annemarie Woolston and Tahel Ronel and Corinna 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 Gabriella Captur and Charlotte Manisty and Treibel, {Thomas Alexander} and Moon, {James C.} and Tomlinson, {Gillian S.} and Maini, {Mala K.} and Chain, {Benjamin M.} and Mahdad Noursadeghi and {COVIDsortium Investigators} and Hickling, {Lauren M.}",

note = "Data and code availability: •Open access to new transcriptional profiling data and essential anonymised metadata is available online through ArrayExpress: E-MTAB-10022 and ArrayExpress: E-MTAB-11345. TCR sequencing data are available at NCBI Short Read Archive: SUB9362448. Requests for access to individual de-identified participant level data will be considered (subject to a data transfer agreement) by an access committee via an online application (https://covid-consortium.com/application-for-samples/), on the basis of availability and scientific merit within the scope of research ethics approvals, participant consent, and data governance. Responses to applications will be made within 4 weeks. •No custom code was generated for the present analysis. •Any additional information required to reanalyze the data reported in this work paper is available from the Lead contact upon request.",

year = "2022",

month = mar,

day = "15",

doi = "10.1016/j.xcrm.2022.100557",

language = "English",

volume = "3",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Elsevier",

number = "3",

}

Chandran, A, Rosenheim, J, Nageswaran, G, Swadling, L, Pollara, G, Gupta, RK, Burton, AR, Guerra-Assunção, 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, Captur, G, Manisty, C, Treibel, TA, Moon, JC, Tomlinson, GS, Maini, MK, Chain, BM, Noursadeghi, M, COVIDsortium Investigators & Hickling, LM 2022, 'Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections', Cell Reports Medicine, vol. 3, no. 3, 100557. https://doi.org/10.1016/j.xcrm.2022.100557

TY - JOUR

T1 - Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections

AU - Chandran, Aneesh

AU - Rosenheim, Joshua

AU - Nageswaran, Gayathri

AU - Swadling, Leo

AU - Pollara, Gabriele

AU - Gupta, Rishi K.

AU - Burton, Alice R.

AU - Guerra-Assunção, José Afonso

AU - Woolston, Annemarie

AU - Ronel, Tahel

AU - Pade, Corinna

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 - Captur, Gabriella

AU - Manisty, Charlotte

AU - Treibel, Thomas Alexander

AU - Moon, James C.

AU - Tomlinson, Gillian S.

AU - Maini, Mala K.

AU - Chain, Benjamin M.

AU - Noursadeghi, Mahdad

AU - COVIDsortium Investigators

A2 - Hickling, Lauren M.

N1 - Data and code availability: •Open access to new transcriptional profiling data and essential anonymised metadata is available online through ArrayExpress: E-MTAB-10022 and ArrayExpress: E-MTAB-11345. TCR sequencing data are available at NCBI Short Read Archive: SUB9362448. Requests for access to individual de-identified participant level data will be considered (subject to a data transfer agreement) by an access committee via an online application (https://covid-consortium.com/application-for-samples/), on the basis of availability and scientific merit within the scope of research ethics approvals, participant consent, and data governance. Responses to applications will be made within 4 weeks. •No custom code was generated for the present analysis. •Any additional information required to reanalyze the data reported in this work paper is available from the Lead contact upon request.

PY - 2022/3/15

Y1 - 2022/3/15

N2 - 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.

AB - 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.

KW - CD8 T cells

KW - non-severe SARS-CoV-2 infection

KW - type 1 interferon

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U2 - 10.1016/j.xcrm.2022.100557

DO - 10.1016/j.xcrm.2022.100557

M3 - Article

C2 - 35474751

AN - SCOPUS:85126319413

SN - 2666-3791

VL - 3

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 3

M1 - 100557

ER -

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

Abstract

Keywords

UN SDGs

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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

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