{"doi":"10.1093/infdis/jiaa797","title":"SARS-CoV-2 Serologic Assays in Control and Unknown Populations Demonstrate the Necessity of Virus Neutralization Testing","abstract":"BACKGROUND: To determine how serologic antibody testing outcome links with virus neutralization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we evaluated individuals for SARS-CoV-2 antibody level and viral neutralization. METHODS: We compared serum Ig levels across platforms of viral antigens and antibodies with 15 positive and 30 negative SARS-CoV-2 controls followed by viral neutralization assessment. We then applied these platforms to a clinically relevant cohort of 114 individuals with unknown histories of SARS-CoV-2 infection. RESULTS: In controls, the best-performing virus-specific antibody detection platforms were SARS-CoV-2 receptor binding domain (RBD) IgG (sensitivity 87%, specificity 100%, positive predictive value [PPV] 100%, negative predictive value [NPV] 94%), spike IgG3 (sensitivity 93%, specificity 97%, PPV 93%, NPV 97%), and nucleocapsid protein (NP) IgG (sensitivity 93%, specificity 97%, PPV 93%, NPV 97%). Neutralization of positive and negative control sera showed 100% agreement. Twenty individuals with unknown history had detectable SARS-CoV-2 antibodies with 16 demonstrating virus neutralization. Spike IgG3 provided the highest accuracy for predicting serologically positive individuals with virus neutralization activity (misidentified 1/20 unknowns compared to 2/20 for RBD and NP IgG). CONCLUSIONS: The coupling of virus neutralization analysis to a spike IgG3 antibody test is optimal to categorize patients for correlates of SARS-CoV-2 immune protection status.","journal":"The Journal of Infectious Diseases","year":2020,"id":100405,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9439,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":108904,"name":"Emily A. Hemann","orcid":"0000-0002-6398-3492","position":1,"is_corresponding":false},{"id":108903,"name":"Julie Eggenberger","orcid":"0000-0003-1410-4399","position":2,"is_corresponding":false},{"id":294423,"name":"Zhaoqi Li","orcid":"0009-0003-7772-6803","position":3,"is_corresponding":false},{"id":492740,"name":"Megan Knoll","orcid":"0000-0001-8637-7690","position":4,"is_corresponding":false},{"id":108910,"name":"Caleb Stokes","orcid":"0000-0003-3741-0057","position":5,"is_corresponding":false},{"id":245056,"name":"Tien-Ying Hsiang","orcid":"0000-0002-4316-4561","position":6,"is_corresponding":false},{"id":108897,"name":"Jason Netland","orcid":"0000-0003-1173-1709","position":7,"is_corresponding":false},{"id":108902,"name":"Kennidy K. Takehara","orcid":"0000-0002-1990-155X","position":8,"is_corresponding":false},{"id":108919,"name":"Marion Pepper","orcid":"0000-0001-7278-0147","position":9,"is_corresponding":false},{"id":108916,"name":"Michael Gale","orcid":"0000-0002-6332-7436","position":10,"is_corresponding":false},{"id":108909,"name":"Jennifer A. Rathe","orcid":null,"position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T22:38:35.493878Z","pmid":"33367830","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":[]}