Specific thresholds of circulating antibody titers predict against infection and reduced disease severity in SARS-CoV-2 close contacts
Higher circulating SARS-CoV-2 IgG titers correlate with SARS-CoV-2 ex vivo viral neutralization, but how well this translates to clinical protection in the real-world setting is unclear. In a prospective cohort study, we enrolled 44 SARS-CoV-2 negative, confirmed SARS-CoV-2 close contacts. Receptor-binding domain (RBD) and full-spike IgG and SARS-CoV-2 memory B-cell frequencies were measured at exposure, and participants were serially tested for incident infection over 14 days. Those who developed SARS-CoV-2 infection had significantly lower RBD titers, but not memory B-cell frequencies. An RBD IgG titer >6321 BAU/ml was associated with a reduced SARS-CoV-2 acquisition risk (HR 0.32, 95% CI 0.13-0.81), while an RBD IgG titer >456 BAU/ml was associated with a reduced moderate or severe COVID-19 risk (HR 0.15, 95% CI 0.03-0.81), identifying this threshold as a correlate of protection.
Authors
- Peter Doran (ORCID: https://orcid.org/0000-0003-2064-5335)
- Gurvin Saini (ORCID: https://orcid.org/0000-0002-1746-4579)
- Jane A. O’Halloran (ORCID: https://orcid.org/0000-0001-8265-9471)
- Alan Landay (ORCID: https://orcid.org/0000-0001-9645-1356)
- Patrick Mallon (ORCID: https://orcid.org/0000-0002-4337-6222)
- Mary M. Horgan (ORCID: https://orcid.org/0000-0003-0288-4455)
- Eoin R. Feeney (ORCID: https://orcid.org/0000-0003-4118-4945)
- Virginie Gautier (ORCID: https://orcid.org/0000-0003-1862-2644)
- Siobhan O’Regan (ORCID: https://orcid.org/0000-0002-4071-9517)
- Orlaith Casey
- Joanne Byrne (ORCID: https://orcid.org/0000-0002-0184-0947)
- Colette Marie Gaillard
- Corinna Sadlier (ORCID: https://orcid.org/0000-0002-8415-2022)
- Dana Alalwan
- A. Léon (ORCID: https://orcid.org/0009-0003-7696-8800)
- Tessa O’Gorman
- Lili Gu (ORCID: https://orcid.org/0009-0001-7116-6062)
- Aoife G. Cotter (ORCID: https://orcid.org/0000-0001-7712-3533)
- Eoghan de Barra (ORCID: https://orcid.org/0000-0001-7679-5565)
- Grace Kenny (ORCID: https://orcid.org/0000-0002-9646-7910)
Institutions
- University College Dublin (IE)
- Royal College of Surgeons in Ireland (IE)
- Beaumont Hospital (IE)
- Cork University Hospital (IE)
- Mater Misericordiae University Hospital (IE)
- St. Vincent's University Hospital (IE)
- The University of Texas Medical Branch at Galveston (US)
Publication Details
- Journal
- The Journal of Immunology
- Published
- 2025-05-22
- DOI
- https://doi.org/10.1093/jimmun/vkaf101
- Citations
- 1
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 1.40
Funders
- Science Foundation Ireland