{"doi":"10.1093/infdis/jiae622","title":"Antibody Levels From High-Throughput Variant-Specific SARS-CoV-2 Anti-Spike Immunoglobulin G and Angiotensin-Converting Enzyme 2 Neutralization Assays Correlate With COVID-19 Infection Risk in a Large Population","abstract":"BACKGROUND: SARS-CoV-2 antibody levels have been proposed as a correlate of protection from infection. Yet, large-scale prospective studies of cost-effective scalable antibody measures as predictors of infection under real-world conditions are limited. We examined whether antibody levels measured by high-throughput variant-specific SARS-CoV-2 anti-spike immunoglobulin G (IgG) and angiotensin-converting enzyme 2 (ACE2) neutralization assays correlate with cell-based neutralizing antibody measurements and whether they can serve as a reasonable correlate of protection from SARS-CoV-2 infection. METHODS: We conducted a large institutional cohort study between January 2022 and March 2023. Participants (N = 2513) provided dried blood spot (DBS) samples for assessment of anti-spike IgG and ACE2 inhibition levels through high-throughput assays. Comparison with authentic cell-based SARS-CoV-2 neutralizing antibody assays was conducted with serum samples (n = 105). Associations between antibody levels and risk of infection were evaluated. RESULTS: Correlation between serum and DBS sampling and between cell-based neutralizing and high-throughput antibody binding assays was high for anti-spike IgG and ACE2 neutralization, though the degree of correlation varied by variant. Longitudinal evaluation suggested that DBS-based IgG and ACE2 inhibition levels were anticorrelated with infection risk, with higher sensitivity noted for ACE2 inhibition and variant-matched measures. IgG and ACE2 inhibition levels decreased over time, with more durable responses observed in participants whose most recent priming event was infection vs vaccination. CONCLUSIONS: Findings suggest that variant-specific SARS-CoV-2 antibody levels may be a useful correlate of protection for infection, which has important implications for vaccination recommendations and evaluating infection risk. High-throughput assays measured via DBS may have utility in timing of boosters at the population or individual level.","journal":"The Journal of Infectious Diseases","year":2024,"id":474796,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":249772,"name":"Alex E. Clark","orcid":"0000-0003-1687-416X","position":1,"is_corresponding":false},{"id":1297976,"name":"Nicole H. Goldhaber","orcid":"0000-0002-3847-3634","position":2,"is_corresponding":false},{"id":803894,"name":"Holly Valentine","orcid":"0000-0002-5400-6374","position":3,"is_corresponding":false},{"id":1036945,"name":"Andrea Rivera","orcid":"0009-0003-7972-0616","position":4,"is_corresponding":false},{"id":1311266,"name":"Toan Van Ngo","orcid":"0009-0003-4746-6772","position":5,"is_corresponding":false},{"id":1311267,"name":"Tom Barber","orcid":"0000-0002-6729-5232","position":6,"is_corresponding":false},{"id":1085447,"name":"Jacqueline Holmes","orcid":null,"position":7,"is_corresponding":false},{"id":1311718,"name":"Brittany Manfredi","orcid":null,"position":8,"is_corresponding":false},{"id":106549,"name":"Aaron F. Garretson","orcid":"0000-0003-3855-4482","position":9,"is_corresponding":false},{"id":635097,"name":"William Bray","orcid":"0000-0003-2414-0190","position":10,"is_corresponding":false},{"id":3554,"name":"Rob Knight","orcid":"0000-0002-0975-9019","position":11,"is_corresponding":false},{"id":74541,"name":"Chris Longhurst","orcid":"0000-0003-4908-6856","position":12,"is_corresponding":false},{"id":103778,"name":"Aaron F. Carlin","orcid":"0000-0002-1669-8066","position":13,"is_corresponding":false},{"id":886856,"name":"Peter De Hoff","orcid":"0000-0002-0163-7535","position":14,"is_corresponding":false},{"id":105299,"name":"Louise C. Laurent","orcid":"0000-0002-2095-7534","position":15,"is_corresponding":false},{"id":243154,"name":"Marni Jacobs","orcid":"0000-0001-6649-6692","position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:06:13.042906Z","pmid":"39676529","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}