Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study

the SIREN Study Group and the Crick COVID Immunity Pipeline Consortium

doi:10.1016/j.jinf.2022.09.004

Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study

the SIREN Study Group and the Crick COVID Immunity Pipeline Consortium

UK Health Security Agency

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

23 Citations (Scopus)

Abstract

Objectives: To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection. Methods: We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models. Results: We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001–0·31) and LV-N Alpha (OR 0·07, CI 0·009–0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03–0·64) and Alpha (0·06, CI 0·008–0·40). Conclusions: Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect.

Original language	English
Pages (from-to)	545-556
Number of pages	12
Journal	Journal of Infection
Volume	85
Issue number	5
DOIs	https://doi.org/10.1016/j.jinf.2022.09.004
Publication status	Published - Nov 2022

Bibliographical note

Funding Information:
Funding: This study was supported by the U.K. Health Security Agency, the U.K. Department of Health and Social Care (with contributions from the governments in Northern Ireland, Wales, and Scotland), the National Institute for Health Research, and grant from the UK Medical Research Council (grant number MR/W02067X/1). This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2087, CC1283), the UK Medical Research Council (CC2087, CC1283), and the Wellcome Trust (CC2087, CC1283). We would like to thank all participants for their continued contribution and commitment to this study, and to all the research teams at 135 sites across the UK for their hard-work and support delivering the study. Thank you all for making this study possible. We are grateful to our colleagues for their support with the reinfection workstream within the SIREN study, in particular Edgar Wellington, Jameel Khawam, Davina Calbraith and Noshin Sajed, as well as Shaun Seaman for his expertise on conditional regression models. We would like to thank Jules Marczak, Gita Mistry, Nicola Bex, Bobbi Clayton and the staff of the Scientific Technology Platforms (STPs) at the Francis Crick Institute. We thank Prof. Wendy Barclay of Imperial College and the wider Genotype to Phenotype consortium for the Alpha strain used in this study, and Max Whiteley and Thushan de Silva at The University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust for providing source material, as well as Dr Laura McCoy of UCL for her original synthesis of the CR3009 protein used in development of the HTS assay.

Funding Information:
Funding: This study was supported by the U.K. Health Security Agency, the U.K. Department of Health and Social Care (with contributions from the governments in Northern Ireland, Wales, and Scotland), the National Institute for Health Research, and grant from the UK Medical Research Council (grant number MR/W02067X/1). This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2087, CC1283), the UK Medical Research Council (CC2087, CC1283), and the Wellcome Trust (CC2087, CC1283).

Publisher Copyright:
© 2022

Keywords

Immunity
Neutralising antibodies
Reinfection
SARS-CoV-2
SARS-CoV-2 serology

UN SDGs

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

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10.1016/j.jinf.2022.09.004

Cite this

@article{b856b52957144afc99e4423199bc6604,

title = "Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study",

abstract = "Objectives: To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection. Methods: We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models. Results: We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001–0·31) and LV-N Alpha (OR 0·07, CI 0·009–0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03–0·64) and Alpha (0·06, CI 0·008–0·40). Conclusions: Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect.",

keywords = "Immunity, Neutralising antibodies, Reinfection, SARS-CoV-2, SARS-CoV-2 serology",

author = "{the SIREN Study Group and the Crick COVID Immunity Pipeline Consortium} and Ana Atti and Ferdinando Insalata and Carr, {Edward J.} and Otter, {Ashley D.} and Javier Castillo-Olivares and Mary Wu and Ruth Harvey and Michael Howell and Andrew Chan and Jonathan Lyall and Nigel Temperton and Diego Cantoni and {da Costa}, Kelly and Angalee Nadesalingam and Andrew Taylor-Kerr and Nipunadi Hettiarachchi and Caio Tranquillini and Jacqueline Hewson and Cole, {Michelle J.} and Sarah Foulkes and Katie Munro and Monk, {Edward J.M.} and Milligan, {Iain D.} and Ezra Linley and Chand, {Meera A.} and Brown, {Colin S.} and Jasmin Islam and Amanda Semper and Andre Charlett and Heeney, {Jonathan L.} and Rupert Beale and Maria Zambon and Susan Hopkins and Tim Brooks and Victoria Hall",

note = "Funding Information: Funding: This study was supported by the U.K. Health Security Agency, the U.K. Department of Health and Social Care (with contributions from the governments in Northern Ireland, Wales, and Scotland), the National Institute for Health Research, and grant from the UK Medical Research Council (grant number MR/W02067X/1). This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2087, CC1283), the UK Medical Research Council (CC2087, CC1283), and the Wellcome Trust (CC2087, CC1283). We would like to thank all participants for their continued contribution and commitment to this study, and to all the research teams at 135 sites across the UK for their hard-work and support delivering the study. Thank you all for making this study possible. We are grateful to our colleagues for their support with the reinfection workstream within the SIREN study, in particular Edgar Wellington, Jameel Khawam, Davina Calbraith and Noshin Sajed, as well as Shaun Seaman for his expertise on conditional regression models. We would like to thank Jules Marczak, Gita Mistry, Nicola Bex, Bobbi Clayton and the staff of the Scientific Technology Platforms (STPs) at the Francis Crick Institute. We thank Prof. Wendy Barclay of Imperial College and the wider Genotype to Phenotype consortium for the Alpha strain used in this study, and Max Whiteley and Thushan de Silva at The University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust for providing source material, as well as Dr Laura McCoy of UCL for her original synthesis of the CR3009 protein used in development of the HTS assay. Funding Information: Funding: This study was supported by the U.K. Health Security Agency, the U.K. Department of Health and Social Care (with contributions from the governments in Northern Ireland, Wales, and Scotland), the National Institute for Health Research, and grant from the UK Medical Research Council (grant number MR/W02067X/1). This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2087, CC1283), the UK Medical Research Council (CC2087, CC1283), and the Wellcome Trust (CC2087, CC1283). Publisher Copyright: {\textcopyright} 2022",

year = "2022",

month = nov,

doi = "10.1016/j.jinf.2022.09.004",

language = "English",

volume = "85",

pages = "545--556",

journal = "Journal of Infection",

issn = "0163-4453",

publisher = "British Infection Society",

number = "5",

}

TY - JOUR

T1 - Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination

T2 - A nested case-control within the SIREN study

AU - the SIREN Study Group and the Crick COVID Immunity Pipeline Consortium

AU - Atti, Ana

AU - Insalata, Ferdinando

AU - Carr, Edward J.

AU - Otter, Ashley D.

AU - Castillo-Olivares, Javier

AU - Wu, Mary

AU - Harvey, Ruth

AU - Howell, Michael

AU - Chan, Andrew

AU - Lyall, Jonathan

AU - Temperton, Nigel

AU - Cantoni, Diego

AU - da Costa, Kelly

AU - Nadesalingam, Angalee

AU - Taylor-Kerr, Andrew

AU - Hettiarachchi, Nipunadi

AU - Tranquillini, Caio

AU - Hewson, Jacqueline

AU - Cole, Michelle J.

AU - Foulkes, Sarah

AU - Munro, Katie

AU - Monk, Edward J.M.

AU - Milligan, Iain D.

AU - Linley, Ezra

AU - Chand, Meera A.

AU - Brown, Colin S.

AU - Islam, Jasmin

AU - Semper, Amanda

AU - Charlett, Andre

AU - Heeney, Jonathan L.

AU - Beale, Rupert

AU - Zambon, Maria

AU - Hopkins, Susan

AU - Brooks, Tim

AU - Hall, Victoria

N1 - Funding Information: Funding: This study was supported by the U.K. Health Security Agency, the U.K. Department of Health and Social Care (with contributions from the governments in Northern Ireland, Wales, and Scotland), the National Institute for Health Research, and grant from the UK Medical Research Council (grant number MR/W02067X/1). This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2087, CC1283), the UK Medical Research Council (CC2087, CC1283), and the Wellcome Trust (CC2087, CC1283). We would like to thank all participants for their continued contribution and commitment to this study, and to all the research teams at 135 sites across the UK for their hard-work and support delivering the study. Thank you all for making this study possible. We are grateful to our colleagues for their support with the reinfection workstream within the SIREN study, in particular Edgar Wellington, Jameel Khawam, Davina Calbraith and Noshin Sajed, as well as Shaun Seaman for his expertise on conditional regression models. We would like to thank Jules Marczak, Gita Mistry, Nicola Bex, Bobbi Clayton and the staff of the Scientific Technology Platforms (STPs) at the Francis Crick Institute. We thank Prof. Wendy Barclay of Imperial College and the wider Genotype to Phenotype consortium for the Alpha strain used in this study, and Max Whiteley and Thushan de Silva at The University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust for providing source material, as well as Dr Laura McCoy of UCL for her original synthesis of the CR3009 protein used in development of the HTS assay. Funding Information: Funding: This study was supported by the U.K. Health Security Agency, the U.K. Department of Health and Social Care (with contributions from the governments in Northern Ireland, Wales, and Scotland), the National Institute for Health Research, and grant from the UK Medical Research Council (grant number MR/W02067X/1). This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2087, CC1283), the UK Medical Research Council (CC2087, CC1283), and the Wellcome Trust (CC2087, CC1283). Publisher Copyright: © 2022

PY - 2022/11

Y1 - 2022/11

N2 - Objectives: To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection. Methods: We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models. Results: We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001–0·31) and LV-N Alpha (OR 0·07, CI 0·009–0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03–0·64) and Alpha (0·06, CI 0·008–0·40). Conclusions: Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect.

AB - Objectives: To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection. Methods: We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models. Results: We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001–0·31) and LV-N Alpha (OR 0·07, CI 0·009–0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03–0·64) and Alpha (0·06, CI 0·008–0·40). Conclusions: Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect.

KW - Immunity

KW - Neutralising antibodies

KW - Reinfection

KW - SARS-CoV-2

KW - SARS-CoV-2 serology

UR - http://www.scopus.com/inward/record.url?scp=85138830002&partnerID=8YFLogxK

U2 - 10.1016/j.jinf.2022.09.004

DO - 10.1016/j.jinf.2022.09.004

M3 - Article

AN - SCOPUS:85138830002

SN - 0163-4453

VL - 85

SP - 545

EP - 556

JO - Journal of Infection

JF - Journal of Infection

IS - 5

ER -

Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study

Abstract

Bibliographical note

Keywords

UN SDGs

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