Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

COVIDsortium investigators; COVIDsortium immune correlates network; Catherine J. Reynolds; Leo Swadling; Joseph M. Gibbons; Corinna Pade; Melanie P. Jensen; Mariana O. Diniz; Nathalie M. Schmidt; David K. Butler; Oliver E. Amin; Sasha N.L. Bailey; Sam M. Murray; Franziska P. Pieper; Stephen Taylor; Jessica Jones; Meleri Jones; Wing Yiu Jason Lee; Joshua Rosenheim; Aneesh Chandran; George Joy; Cecilia Di Genova; Nigel Temperton; Jonathan Lambourne; Teresa Cutino-Moguel; Mervyn Andiapen; Marianna Fontana; Angelique Smit; Amanda Semper; Ben O’Brien; Benjamin Chain; Tim Brooks; Charlotte Manisty; Thomas Treibel; James C. Moon; Mahdad Noursadeghi; Daniel M. Altmann; Mala K. Maini; Áine McKnight; Rosemary J. Boyton

doi:10.1126/SCIIMMUNOL.ABF3698

Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

COVIDsortium investigators, COVIDsortium immune correlates network, Catherine J. Reynolds, Leo Swadling, Joseph M. Gibbons, Corinna Pade, Melanie P. Jensen, Mariana O. Diniz, Nathalie M. Schmidt, David K. Butler, Oliver E. Amin, Sasha N.L. Bailey, Sam M. Murray, Franziska P. Pieper, Stephen Taylor, Jessica Jones, Meleri Jones, Wing Yiu Jason Lee, Joshua Rosenheim, Aneesh ChandranGeorge Joy, Cecilia Di Genova, Nigel Temperton, Jonathan Lambourne, Teresa Cutino-Moguel, Mervyn Andiapen, Marianna Fontana, Angelique Smit, Amanda Semper, Ben O’Brien, Benjamin Chain, Tim Brooks, Charlotte Manisty, Thomas Treibel, James C. Moon, Mahdad Noursadeghi, Daniel M. Altmann, Mala K. Maini, Áine McKnight, Rosemary J. Boyton

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Abstract

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.

Original language	English
Journal	Science immunology
Volume	5
Issue number	54
Early online date	23 Dec 2020
DOIs	https://doi.org/10.1126/SCIIMMUNOL.ABF3698
Publication status	Published - 23 Dec 2020

Bibliographical note

Funding Information: The COVIDsortium is supported by funding 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. Wider support is acknowledged on the COVIDsortium website. Institutional support from Barts Health NHS Trust and Royal Free NHS Foundation Trust facilitated study processes, in partnership with University College London and Queen Mary University London. RJB/DMA are supported by MRC (MR/S019553/1, MR/R02622X/1 and MR/V036939/1), NIHR Imperial Biomedical Research Centre (BRC):ITMAT, Cystic Fibrosis Trust SRC (2019SRC015), and Horizon 2020 Marie Skłodowska-Curie Innovative Training Network (ITN) European Training Network (No 860325). MKM is supported by UKRI/NIHR UK-CIC, Wellcome Trust Investigator Award (214191/Z/18/Z) and CRUK Immunology grant (26603). LS is supported by a Medical Research Foundation fellowship (044-0001). ÁM is supported by Rosetrees Trust, The John Black Charitable Foundation, and Medical College of St Bartholomew’s Hospital Trust. 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. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Open Access: This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material.

Publisher Copyright: Copyright © 2020, American Association for the Advancement of Science.

Citation: C. J. Reynolds et al., Sci. Immunol. 10.1126/sciimmunol.abf3698 (2020).

DOI: 10.1126/sciimmunol.abf3698 (2020).

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COVIDsortium investigators, COVIDsortium immune correlates network, Reynolds, C. J., Swadling, L., Gibbons, J. M., Pade, C., Jensen, M. P., Diniz, M. O., Schmidt, N. M., Butler, D. K., Amin, O. E., Bailey, S. N. L., Murray, S. M., Pieper, F. P., Taylor, S., Jones, J., Jones, M., Lee, W. Y. J., Rosenheim, J., ... Boyton, R. J. (2020). Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection. Science immunology, 5(54). https://doi.org/10.1126/SCIIMMUNOL.ABF3698

@article{3c8e8e99faac4c268fef5aace0febc2a,

title = "Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection",

abstract = "Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.",

author = "{COVIDsortium investigators} and {COVIDsortium immune correlates network} and Reynolds, {Catherine J.} and Leo Swadling and Gibbons, {Joseph M.} and Corinna Pade and Jensen, {Melanie P.} and Diniz, {Mariana O.} and Schmidt, {Nathalie M.} and Butler, {David K.} and Amin, {Oliver E.} and Bailey, {Sasha N.L.} and Murray, {Sam M.} and Pieper, {Franziska P.} and Stephen Taylor and Jessica Jones and Meleri Jones and Lee, {Wing Yiu Jason} and Joshua Rosenheim and Aneesh Chandran and George Joy and Genova, {Cecilia Di} and Nigel Temperton and Jonathan Lambourne and Teresa Cutino-Moguel and Mervyn Andiapen and Marianna Fontana and Angelique Smit and Amanda Semper and Ben O{\textquoteright}Brien and Benjamin Chain and Tim Brooks and Charlotte Manisty and Thomas Treibel and Moon, {James C.} and Mahdad Noursadeghi and Altmann, {Daniel M.} and Maini, {Mala K.} and {\'A}ine McKnight and Boyton, {Rosemary J.}",

note = "Funding Information: The COVIDsortium is supported by funding 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. Wider support is acknowledged on the COVIDsortium website. Institutional support from Barts Health NHS Trust and Royal Free NHS Foundation Trust facilitated study processes, in partnership with University College London and Queen Mary University London. RJB/DMA are supported by MRC (MR/S019553/1, MR/R02622X/1 and MR/V036939/1), NIHR Imperial Biomedical Research Centre (BRC):ITMAT, Cystic Fibrosis Trust SRC (2019SRC015), and Horizon 2020 Marie Sk{\l}odowska-Curie Innovative Training Network (ITN) European Training Network (No 860325). MKM is supported by UKRI/NIHR UK-CIC, Wellcome Trust Investigator Award (214191/Z/18/Z) and CRUK Immunology grant (26603). LS is supported by a Medical Research Foundation fellowship (044-0001). {\'A}M is supported by Rosetrees Trust, The John Black Charitable Foundation, and Medical College of St Bartholomew{\textquoteright}s Hospital Trust. 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. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Open Access: This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material. Publisher Copyright: Copyright {\textcopyright} 2020, American Association for the Advancement of Science. Citation: C. J. Reynolds et al., Sci. Immunol. 10.1126/sciimmunol.abf3698 (2020). DOI: 10.1126/sciimmunol.abf3698 (2020).",

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doi = "10.1126/SCIIMMUNOL.ABF3698",

language = "English",

volume = "5",

journal = "Science immunology",

issn = "2470-9468",

publisher = "American Association for the Advancement of Science",

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COVIDsortium investigators, COVIDsortium immune correlates network, Reynolds, CJ, Swadling, L, Gibbons, JM, Pade, C, Jensen, MP, Diniz, MO, Schmidt, NM, Butler, DK, Amin, OE, Bailey, SNL, Murray, SM, Pieper, FP, Taylor, S, Jones, J, Jones, M, Lee, WYJ, Rosenheim, J, Chandran, A, Joy, G, Genova, CD, Temperton, N, Lambourne, J, Cutino-Moguel, T, Andiapen, M, Fontana, M, Smit, A, Semper, A, O’Brien, B, Chain, B, Brooks, T, Manisty, C, Treibel, T, Moon, JC, Noursadeghi, M, Altmann, DM, Maini, MK, McKnight, Á & Boyton, RJ 2020, 'Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection', Science immunology, vol. 5, no. 54. https://doi.org/10.1126/SCIIMMUNOL.ABF3698

TY - JOUR

T1 - Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

AU - COVIDsortium investigators

AU - COVIDsortium immune correlates network

AU - Reynolds, Catherine J.

AU - Swadling, Leo

AU - Gibbons, Joseph M.

AU - Pade, Corinna

AU - Jensen, Melanie P.

AU - Diniz, Mariana O.

AU - Schmidt, Nathalie M.

AU - Butler, David K.

AU - Amin, Oliver E.

AU - Bailey, Sasha N.L.

AU - Murray, Sam M.

AU - Pieper, Franziska P.

AU - Taylor, Stephen

AU - Jones, Jessica

AU - Jones, Meleri

AU - Lee, Wing Yiu Jason

AU - Rosenheim, Joshua

AU - Chandran, Aneesh

AU - Joy, George

AU - Genova, Cecilia Di

AU - Temperton, Nigel

AU - Lambourne, Jonathan

AU - Cutino-Moguel, Teresa

AU - Andiapen, Mervyn

AU - Fontana, Marianna

AU - Smit, Angelique

AU - Semper, Amanda

AU - O’Brien, Ben

AU - Chain, Benjamin

AU - Brooks, Tim

AU - Manisty, Charlotte

AU - Treibel, Thomas

AU - Moon, James C.

AU - Noursadeghi, Mahdad

AU - Altmann, Daniel M.

AU - Maini, Mala K.

AU - McKnight, Áine

AU - Boyton, Rosemary J.

N1 - Funding Information: The COVIDsortium is supported by funding 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. Wider support is acknowledged on the COVIDsortium website. Institutional support from Barts Health NHS Trust and Royal Free NHS Foundation Trust facilitated study processes, in partnership with University College London and Queen Mary University London. RJB/DMA are supported by MRC (MR/S019553/1, MR/R02622X/1 and MR/V036939/1), NIHR Imperial Biomedical Research Centre (BRC):ITMAT, Cystic Fibrosis Trust SRC (2019SRC015), and Horizon 2020 Marie Skłodowska-Curie Innovative Training Network (ITN) European Training Network (No 860325). MKM is supported by UKRI/NIHR UK-CIC, Wellcome Trust Investigator Award (214191/Z/18/Z) and CRUK Immunology grant (26603). LS is supported by a Medical Research Foundation fellowship (044-0001). ÁM is supported by Rosetrees Trust, The John Black Charitable Foundation, and Medical College of St Bartholomew’s Hospital Trust. 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. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Open Access: This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material. Publisher Copyright: Copyright © 2020, American Association for the Advancement of Science. Citation: C. J. Reynolds et al., Sci. Immunol. 10.1126/sciimmunol.abf3698 (2020). DOI: 10.1126/sciimmunol.abf3698 (2020).

PY - 2020/12/23

Y1 - 2020/12/23

N2 - Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.

AB - Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.

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U2 - 10.1126/SCIIMMUNOL.ABF3698

DO - 10.1126/SCIIMMUNOL.ABF3698

M3 - Article

C2 - 33361161

AN - SCOPUS:85099074025

SN - 2470-9468

VL - 5

JO - Science immunology

JF - Science immunology

IS - 54

ER -

Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection

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