To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection.


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.


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).


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.


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/).

Cite as

Consortium, T., Atti, A., Insalata, F., Carr, E., Otter, A., 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, M., Foulkes, S., Munro, K., Monk, E., Milligan, I., Linley, E., Chand, M., Brown, C., Islam, J., Semper, A., Charlett, A., Heeney, J., 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, 85(5), pp. 545-556. https://doi.org/10.1016/j.jinf.2022.09.004

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Last updated: 27 October 2022
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