Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study - 13/10/22

Doi : 10.1016/j.jinf.2022.09.004

Ana Atti ^a,^⁎ , Ferdinando Insalata ^a, Edward J Carr ^b, Ashley D Otter ^c, Javier Castillo-Olivares ^d, Mary Wu ^b, Ruth Harvey ^b, Michael Howell ^b, Andrew Chan ^d, Jonathan Lyall ^d, Nigel Temperton ^e, Diego Cantoni ^e, Kelly da Costa ^e, Angalee Nadesalingam ^d, Andrew Taylor-Kerr ^a, Nipunadi Hettiarachchi ^a, Caio Tranquillini ^a, Jacqueline Hewson ^c, Michelle J Cole ^a, Sarah Foulkes ^a, Katie Munro ^a, Edward J M Monk ^a, Iain D Milligan ^a, Ezra Linley ^f, Meera A Chand ^a, Colin S Brown ^a,^g, Jasmin Islam ^a, Amanda Semper ^a, Andre Charlett ^a,^h,ⁱ, Jonathan L Heeney ^c, Rupert Beale ^b, Maria Zambon ^a, Susan Hopkins ^a,^g, Tim Brooks ^a,^{^{1
These authors contributed equally to this work.}}, Victoria Hall ^a,^g,^{^{1
These authors contributed equally to this work.}}
the SIREN Study Group and the Crick COVID Immunity Pipeline Consortium^a,^²
SIREN study group and Crick COVID Immunity Pipeline Consortium names provided in supplementary material.
^a UK Health Security Agency, Smith Square, London SW1P, UK
^b The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK
^c UK Health Security Agency, Porton Down, Salisbury SP4 0JG, UK
^d Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge University, Madingley Road, Cambridge CB3 0ES, UK
^e Viral Pseudotype Unit, Medway School of Pharmacy, Universities of Greenwich and Kent at Medway, Central Ave, Gillingham, Chatham ME4 4BF, UK
^f Manchester Royal Infirmary, UK Health Security Agency, Oxford Road, Manchester M139WL, UK
^g The National Institute for Health Research Health Protection Research (NIHR) Unit in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford, Old Road Campus, Headington, Oxford OX3 7BN, UK
^h NIHR Health Protection Research Unit in Behavioural Science and Evaluation at University of Bristol in partnership with Public Health England, Queens Road, Bristol BS8 1QU, UK
ⁱ NIHR Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England, Keppel St, London WC1E 7HT, UK

^⁎Corresponding author.

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Summary

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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Keywords : SARS-CoV-2, Neutralising antibodies, SARS-CoV-2 serology, Reinfection, Immunity

Plan

Introduction

Methods

Study population and design

Conditional logistic model

Correlation between assays

Results

Comparing antibodies between cases and controls

Correlation between assays

Role of the funding source

Discussion

Conclusions

Data sharing

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Vol 85 - N° 5

P. 545-556 - novembre 2022 Retour au numéro

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Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study - 13/10/22

Summary

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Methods

Results

Conclusions

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