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

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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. TRIAL REGISTRATION NUMBER: ISRCTN11041050.

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