{"doi":"10.1101/2022.01.23.22269354","title":"Nucleocapsid antigenemia is a marker of acute SARS-CoV-2 infection","abstract":"Abstract Background Reliable detection of SARS-CoV-2 infection is essential for diagnosis and treatment of disease as well as infection control and prevention during the ongoing COVID-19 pandemic. Existing nucleic acid tests do not reliably distinguish acute from resolved infection, as residual RNA is frequently detected in the absence of replication-competent virus. We hypothesized that viral nucleocapsid in serum or plasma may be a specific biomarker of acute infection that could enhance isolation and treatment strategies at an individualized level. Methods Samples were obtained from a retrospective serological survey using a convenience sampling method from adult inpatient and outpatient encounters from January through March 2021. Samples were categorized along a timeline of infection (e.g. acute, late presenting, convalescent) based on timing of available SARS-CoV-2 testing and symptomatology. Nucleocapsid was quantified by digital immunoassay on the Quanterix HD-X platform. Results In a large sample of 1860 specimens from 1607 patients, the highest level and frequency of antigenemia were observed in samples obtained during acute SARS-CoV-2 infection. Levels of antigenemia were highest in samples from seronegative individuals and in those with more severe disease. Using ROC analysis, we found that antigenemia exhibited up to 85.8% sensitivity and 98.6% specificity as a biomarker for acute COVID-19. Conclusions Nucleocapsid antigenemia is a sensitive and specific biomarker for acute SARS-CoV-2 infection and may aid in individualized assessment of SARS-CoV-2 infection resolution or persistence, although interpretation is limited by absence of a diagnostic gold standard for active infection.","journal":"medRxiv","year":2022,"id":300873,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9673,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":681966,"name":"Gregory L. Damhorst","orcid":"0000-0002-2237-1713","position":1,"is_corresponding":false},{"id":795287,"name":"Daniel S. Graciaa","orcid":"0000-0002-9484-8488","position":2,"is_corresponding":false},{"id":899615,"name":"Kaleb McLendon","orcid":"0000-0002-6040-1346","position":3,"is_corresponding":false},{"id":899616,"name":"William O’Sick","orcid":"0000-0002-6289-6311","position":4,"is_corresponding":false},{"id":485175,"name":"Chad Robichaux","orcid":"0009-0002-8403-5499","position":5,"is_corresponding":false},{"id":558767,"name":"Narayanaiah Cheedarla","orcid":"0000-0001-6072-4383","position":6,"is_corresponding":false},{"id":580956,"name":"Sindhu Potlapalli","orcid":null,"position":7,"is_corresponding":false},{"id":693546,"name":"Shang‐Chuen Wu","orcid":"0000-0002-5284-5596","position":8,"is_corresponding":false},{"id":755021,"name":"Kristin R V Harrington","orcid":"0000-0002-9306-4980","position":9,"is_corresponding":false},{"id":768476,"name":"Andrew S Webster","orcid":null,"position":10,"is_corresponding":false},{"id":109934,"name":"Colleen S. Kraft","orcid":"0000-0003-1757-8477","position":11,"is_corresponding":false},{"id":94488,"name":"Christina A. Rostad","orcid":"0000-0001-8439-0592","position":12,"is_corresponding":false},{"id":168177,"name":"Jesse J. Waggoner","orcid":"0000-0002-0244-5957","position":13,"is_corresponding":false},{"id":308895,"name":"Neel R. Gandhi","orcid":"0000-0002-1665-299X","position":14,"is_corresponding":false},{"id":226161,"name":"Jeannette Guarner","orcid":"0000-0001-5610-3541","position":15,"is_corresponding":false},{"id":433638,"name":"Sara C. Auld","orcid":"0000-0002-8972-3736","position":16,"is_corresponding":false},{"id":226168,"name":"Andrew S. Neish","orcid":"0000-0002-7090-0237","position":17,"is_corresponding":false},{"id":226173,"name":"John D. Roback","orcid":"0000-0001-9952-2252","position":18,"is_corresponding":false},{"id":337554,"name":"Wilbur A. Lam","orcid":"0000-0002-0325-7990","position":19,"is_corresponding":false},{"id":431025,"name":"Neha Shah","orcid":"0000-0002-9575-9161","position":20,"is_corresponding":false},{"id":226169,"name":"Sean R. Stowell","orcid":"0000-0002-1130-9551","position":21,"is_corresponding":false},{"id":226159,"name":"Hans Verkerke","orcid":"0000-0002-5152-0095","position":0,"is_corresponding":true}],"reference_count":27,"raw_metadata":null,"created_at":"2026-07-19T00:31:57.812980Z","pmid":null,"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":[]}