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

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, Ana Atti^*, Ferdinando Insalata, Edward J Carr, Ashley D Otter, Javier Castillo-Olivares, Mary Wu, Ruth Harvey, Michael Howell, Andrew Chan, Jonathan Lyall, Nigel Temperton, Diego Cantoni, Kelly da Costa, Angalee Nadesalingam, Andrew Taylor-Kerr, Nipunadi Hettiarachchi, Caio Tranquillini, Jacqueline Hewson, Michelle J ColeSarah Foulkes, Katie Munro, Edward J M Monk, Iain D Milligan, Ezra Linley, Meera A Chand, Colin S Brown, Jasmin Islam, Amanda Semper, Andre Charlett, Jonathan L Heeney, Rupert Beale, Maria Zambon, Susan Hopkins, Tim Brooks, Victoria Hall

^*Corresponding author for this work

School of Medicine

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

23 Citations (Scopus)

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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.

Trial registration number
ISRCTN11041050

Original language	English
Pages (from-to)	545-556
Number of pages	12
Journal	Journal of Infection
Volume	85
Issue number	5
Early online date	13 Oct 2022
DOIs	https://doi.org/10.1016/j.jinf.2022.09.004
Publication status	Published - 1 Nov 2022

Keywords

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

UN SDGs

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

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10.1016/j.jinf.2022.09.004Licence: CC BY

Atti_2022_JI_Antibody_CC
Crown Copyright © 2022 Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Final published version, 3.59 MBLicence: CC BY

Cite this

the SIREN Study Group and the Crick COVID Immunity Pipeline Consortium, Atti, A., Insalata, F., Carr, E. J., Otter, A. D., Castillo-Olivares, J., Wu, M., Harvey, R., Howell, M., Chan, A., Lyall, J., Temperton, N., Cantoni, D., da Costa, K., Nadesalingam, A., Taylor-Kerr, A., Hettiarachchi, N., Tranquillini, C., Hewson, J., ... Hall, V. (2022). Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: a nested case-control within the SIREN study. Journal of Infection, 85(5), 545-556. https://doi.org/10.1016/j.jinf.2022.09.004

@article{1150db558f4545a4ad3cffb2f9955136,

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

abstract = "ObjectivesTo investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection.MethodsWe 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.ResultsWe 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).ConclusionsBefore 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.Trial registration numberISRCTN11041050",

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

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 and Dhasmana, {Devesh J}",

note = "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).",

year = "2022",

month = nov,

day = "1",

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

language = "English",

volume = "85",

pages = "545--556",

journal = "Journal of Infection",

issn = "0163-4453",

publisher = "W.B. Saunders Ltd",

number = "5",

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the SIREN Study Group and the Crick COVID Immunity Pipeline Consortium, Atti, A, Insalata, F, Carr, EJ, Otter, AD, Castillo-Olivares, J, Wu, M, Harvey, R, Howell, M, Chan, A, Lyall, J, Temperton, N, Cantoni, D, da Costa, K, Nadesalingam, A, Taylor-Kerr, A, Hettiarachchi, N, Tranquillini, C, Hewson, J, Cole, MJ, Foulkes, S, Munro, K, Monk, EJM, Milligan, ID, Linley, E, Chand, MA, Brown, CS, Islam, J, Semper, A, Charlett, A, Heeney, JL, Beale, R, Zambon, M, Hopkins, S, Brooks, T & Hall, V 2022, 'Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: a nested case-control within the SIREN study', Journal of Infection, vol. 85, no. 5, pp. 545-556. https://doi.org/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; Atti, Ana; Insalata, Ferdinando et al.
In: Journal of Infection, Vol. 85, No. 5, 01.11.2022, p. 545-556.

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

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

AU - Dhasmana, Devesh J

N1 - 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).

PY - 2022/11/1

Y1 - 2022/11/1

N2 - ObjectivesTo investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection.MethodsWe 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.ResultsWe 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).ConclusionsBefore 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.Trial registration numberISRCTN11041050

AB - ObjectivesTo investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection.MethodsWe 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.ResultsWe 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).ConclusionsBefore 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.Trial registration numberISRCTN11041050

KW - SARS-CoV-2

KW - Neutralising antibodies

KW - SARS-CoV-2 serology

KW - Reinfection

KW - Immunity

U2 - 10.1016/j.jinf.2022.09.004

DO - 10.1016/j.jinf.2022.09.004

M3 - Article

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

Keywords

UN SDGs

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