The following is a summary of “Antibody Levels from High-Throughput Variant-Specific SARS-CoV-2 Anti-Spike IgG and ACE2 Neutralization Assays Correlate with COVID Infection Risk in a Large Population,” published in the December 2024 issue of Infectious Disease by Jacobs et al. 

SARS-CoV-2 antibody levels were proposed as a correlation of protection from infection, but large-scale prospective studies on cost-effective, scalable antibody measures as predictors of infection in real-world conditions were limited.  

Researchers conducted a retrospective study to determine the antibody levels measured by high-throughput variant-specific SARS-CoV-2 anti-spike immunoglobulin G (IgG) and ACE2-neutralization assays correlated with cell-based neutralizing antibody (NAb) measurements and could serve as a reasonable correlate of protection from SARS-CoV-2 infection.  

They performed a study from January 2022 to March 2023, enrolling 2,513 participants who provided dried blood spot (DBS) samples for anti-spike IgG and ACE2 inhibition assessment using high-throughput assays. Serum samples from 105 participants were used to compare with authentic cell-based SARS-CoV-2  NAb assays. The association between antibody levels and infection risk was also evaluated.  

The results showed a strong correlation between serum and DBS samples, as well as between cell-based neutralizing and high-throughput antibody binding assays, for both anti-spike IgG and ACE2 neutralization, though correlation varied by variant. Longitudinal analysis indicated that both DBS-based IgG and ACE2 inhibition levels were inversely related to infection risk, with ACE2 inhibition and variant-matched measures showing higher sensitivity. Both IgG and ACE2 inhibition levels declined over time, with more sustained responses observed in participants whose most recent priming event was infection rather than vaccination.  

Investigators concluded the variant-specific SARS-CoV-2 antibody levels measured via high-throughput assays on DBS might serve as a useful correlate of protection (CoP) against infection, with potential implications for optimizing vaccination schedules and assessing individual infection risk. 

Source: academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiae622/7925158