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.