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

Atti, Ana, Insalata, Ferdinando, Carr, Edward J, Otter, Ashley D, Castillo-Olivares, Javier, Wu, Mary, Harvey, Ruth, Howell, Michael, Chan, Andrew, Lyall, Jonathan, and others. (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). pp. 545-556. ISSN 0163-4453. E-ISSN 1532-2742. (doi:10.1016/j.jinf.2022.09.004) (KAR id:96858)

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DOI for this version: 10.22024/UniKent/01.02.96858.3276738

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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.

Item Type: Article
DOI/Identification number: 10.1016/j.jinf.2022.09.004
Projects: 23196
Additional information: For the purpose of open access, the author has applied a CC BY public copyright licence (where permitted by UKRI, an Open Government Licence or CC BY ND public copyright licence may be used instead) to any Author Accepted Manuscript version arising.
Uncontrolled keywords: SARS-CoV-2; Neutralising Antibodies; SARS-CoV-2 serology; Reinfection; Immunity
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Funders: UK Health Security Agency (
Department of Health and Social Care (
National Institute for Health Research (
Medical Research Council (
Depositing User: Nigel Temperton
Date Deposited: 11 Sep 2022 15:21 UTC
Last Modified: 04 Jul 2023 14:00 UTC
Resource URI: (The current URI for this page, for reference purposes)

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