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

J Infect Dis. 2024 Jul 25;230(1):45-54. doi: 10.1093/infdis/jiae090.

Abstract

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.

Keywords: COVID-19; SARS-CoV-2 infection; antibodies; correlates of protection.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral* / blood
  • COVID-19 Vaccines / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology
  • Male
  • Middle Aged
  • Outpatients
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus* / immunology
  • United States / epidemiology
  • Vaccine Efficacy
  • Young Adult

Substances

  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • COVID-19 Vaccines
  • Influenza Vaccines