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) × 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.
Competing Interests: Potential conflicts of interest. R. K. Z. reports grants from the CDC during the conduct of the study and grants from Sanofi Pasteur outside the submitted work. C. G. G. reports other from the CDC, grants from the National Institutes of Health, other from the Food and Drug Administration, grants and other from the Agency for Healthcare Research and Quality, other from Merck, and other from Syneos Health, outside the submitted work. H. K. T. reports grants from the CDC during the conduct of the study. E. A. B. reports grants from the CDC during the conduct of the study. E. T. M. reports grants from the CDC during the conduct of the study and grants from Merck outside the submitted work. M. G. reports grants from the CDC during the conduct of the study and grants from the CDC, CDC-Vanderbilt, and CDC–Abt Associates, outside the submitted work. M. G. is also cochair of the Infectious Diseases and Immunization Committee, Texas Pediatric Society, Texas Chapter of the American Academy of Pediatrics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
(Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)