Anti-SARS-CoV-2 Antibody Levels Associated With COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu Vaccine Effectiveness Network, October 2021-June 2022

Background. We assessed associations between binding antibody (bAb) concentration <5 days from symptom onset and testing positive for COVID-19 among patients in a test-negative study. Methods. From October 2021 to June 2022, study sites in 7 states enrolled patients aged >= 6 months presenting with acute respiratory illness. Respiratory specimens were tested for SARS-CoV-2. In blood specimens, we measured concentrations of anti-SARS-CoV-2 antibodies against the spike protein receptor binding domain (RBD) and nucleocapsid antigens from the ancestral strain in standardized bAb units (BAU). Percentage change in odds of COVID-19 by increasing anti-RBD bAb was estimated via logistic regression as (1 - adjusted odds ratio of COVID-19) x 100, adjusting for COVID-19 mRNA vaccine doses, age, site, and high-risk exposure. Results Out of 2018 symptomatic patients, 662 (33%) tested positive for acute SARS-CoV-2 infection. Geometric mean RBD bAb levels were lower among COVID-19 cases than SARS-CoV-2 test-negative controls during the Delta-predominant period (112 vs 498 BAU/mL) and Omicron-predominant period (823 vs 1189 BAU/mL). Acute-phase ancestral spike RBD bAb levels associated with 50% lower odds of COVID-19 were 1968 BAU/mL against Delta and 3375 BAU/mL against Omicron; thresholds may differ in other laboratories. Conclusions During acute illness, antibody concentrations against ancestral spike RBD were associated with protection against COVID-19.