{"doi":"10.1093/clinchem/hvab045","title":"Case-Control Study of Individuals with Discrepant Nucleocapsid and Spike Protein SARS-CoV-2 IgG Results","abstract":"BACKGROUND: Laboratory-based methods for SARS-CoV-2 antibody detection vary widely in performance. However, there are limited prospectively-collected data on assay performance, and minimal clinical information to guide interpretation of discrepant results. METHODS: Over a 2-week period, 1080 consecutive plasma samples submitted for clinical SARS-CoV-2 IgG testing were tested in parallel for anti-nucleocapsid IgG (anti-N, Abbott) and anti-spike IgG (anti-S1, EUROIMMUN). Chart review was conducted for samples testing positive or borderline on either assay, and for an age/sex-matched cohort of samples negative by both assays. CDC surveillance case definitions were used to determine clinical sensitivity/specificity and conduct receiver operating characteristics curve analysis. RESULTS: There were 52 samples positive by both methods, 2 positive for anti-N only, 34 positive for anti-S1 only, and 27 borderline for anti-S1. Of the 34 individuals positive for anti-S1 alone, 8 (24%) had confirmed COVID-19. No anti-S1 borderline cases were positive for anti-N or had confirmed/probable COVID-19. The anti-N assay was less sensitive (84.2% [95% CI 72.1-92.5%] vs 94.7% [95% CI 85.4-98.9%]) but more specific (99.2% [95% CI 95.5-100%] vs 86.9% [95% CI 79.6-92.3%]) than anti-S1. Abbott anti-N sensitivity could be improved to 96.5% with minimal effect on specificity if the index threshold was lowered from 1.4 to 0.6. CONCLUSION: Real-world concordance between different serologic assays may be lower than previously described in retrospective studies. These findings have implications for the interpretation of SARS-CoV-2 IgG results, especially with the advent of spike antigen-targeted vaccination, as a subset of patients with true infection are anti-N negative and anti-S1 positive.","journal":"Clinical Chemistry","year":2021,"id":189826,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8335,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":252914,"name":"Danica Wiredja","orcid":null,"position":1,"is_corresponding":false},{"id":433762,"name":"Lu Yang","orcid":"0000-0001-7965-2674","position":2,"is_corresponding":false},{"id":694939,"name":"Philip L. Bulterys","orcid":"0000-0003-1382-743X","position":3,"is_corresponding":false},{"id":654879,"name":"Cristina Costales","orcid":"0000-0002-9757-366X","position":4,"is_corresponding":false},{"id":226825,"name":"Katharina Röltgen","orcid":"0000-0002-1582-1720","position":5,"is_corresponding":false},{"id":229537,"name":"Justin Manalac","orcid":null,"position":6,"is_corresponding":false},{"id":752655,"name":"Jennifer C. Yee","orcid":"0000-0001-9481-7123","position":7,"is_corresponding":false},{"id":226839,"name":"James L. Zehnder","orcid":"0000-0002-5380-303X","position":8,"is_corresponding":false},{"id":753181,"name":"Run Zhang Shi","orcid":null,"position":9,"is_corresponding":false},{"id":226844,"name":"Scott D. Boyd","orcid":"0000-0003-0963-044X","position":10,"is_corresponding":false},{"id":226843,"name":"Benjamin A. Pinsky","orcid":"0000-0001-8751-4810","position":11,"is_corresponding":false},{"id":226831,"name":"Hannah Wang","orcid":"0000-0002-3712-9188","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:49:18.604374Z","pmid":"33720347","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":[]}