Antibody Correlates of Protection from SARS-CoV-2 Reinfection Prior to Vaccination: A Nested Case-Control Within the SIREN Study.

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 individ-uals 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 microneutral-isation (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; re -infections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were sig-nificantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0 middot63, CI 0 middot47-0 middot85), but no association for anti-N levels (OR 0 middot88, CI 0 middot73-1 middot05). Titres > 40 were correlated with protection against reinfection for LV-N Wuhan (OR 0 middot02, CI 0 middot001-0 middot31) and LV-N Alpha (OR 0 middot07, CI 0 middot009-0 middot62). For PV-N, titres > 100 were associated with protection against Wuhan (OR 0 middot14, CI 0 middot03-0 middot64) and Alpha (0 middot06, CI 0 middot008-0 middot40).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: ISRCTN11041050Crown Copyright (c) 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/ )