{"doi":"10.1093/clinchem/hvaa213","title":"Ultra-Sensitive Serial Profiling of SARS-CoV-2 Antigens and Antibodies in Plasma to Understand Disease Progression in COVID-19 Patients with Severe Disease","abstract":"BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 21 million people worldwide since August 16, 2020. Compared to PCR and serology tests, SARS-CoV-2 antigen assays are underdeveloped, despite their potential to identify active infection and monitor disease progression. METHODS: We used Single Molecule Array (Simoa) assays to quantitatively detect SARS-CoV-2 spike, S1 subunit, and nucleocapsid antigens in the plasma of patients with coronavirus disease (COVID-19). We studied plasma from 64 patients who were COVID-19 positive, 17 who were COVID-19 negative, and 34 prepandemic patients. Combined with Simoa anti-SARS-CoV-2 serological assays, we quantified changes in 31 SARS-CoV-2 biomarkers in 272 longitudinal plasma samples obtained for 39 patients with COVID-19. Data were analyzed by hierarchical clustering and were compared to longitudinal RT-PCR test results and clinical outcomes. RESULTS: SARS-CoV-2 S1 and N antigens were detectable in 41 out of 64 COVID-19 positive patients. In these patients, full antigen clearance in plasma was observed a mean ± 95% CI of 5 ± 1 days after seroconversion and nasopharyngeal RT-PCR tests reported positive results for 15 ± 5 days after viral-antigen clearance. Correlation between patients with high concentrations of S1 antigen and ICU admission (77%) and time to intubation (within 1 day) was statistically significant. CONCLUSIONS: The reported SARS-CoV-2 Simoa antigen assay is the first to detect viral antigens in the plasma of patients who were COVID-19 positive to date. These data show that SARS-CoV-2 viral antigens in the blood are associated with disease progression, such as respiratory failure, in COVID-19 cases with severe disease.","journal":"Clinical Chemistry","year":2020,"id":50033,"datarank":0.8055957042191495,"base_score":5.3706380281276624,"endowment":5.3706380281276624,"self_citation_contribution":0.8055957042191495,"citation_network_contribution":0.0,"self_endowment_contribution":0.8055957042191495,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":214,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9112,"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":244640,"name":"Adam M. Maley","orcid":"0000-0003-1851-984X","position":1,"is_corresponding":false},{"id":248126,"name":"Connie Wu","orcid":null,"position":2,"is_corresponding":false},{"id":91003,"name":"Tal Gilboa","orcid":"0000-0001-8172-7786","position":3,"is_corresponding":false},{"id":76189,"name":"Maia Norman","orcid":"0000-0002-9654-4904","position":4,"is_corresponding":false},{"id":76191,"name":"Roey Lazarovits","orcid":"0000-0002-4635-9700","position":5,"is_corresponding":false},{"id":248127,"name":"Chih-Ping Mao","orcid":null,"position":6,"is_corresponding":false},{"id":248128,"name":"Gail Newton","orcid":null,"position":7,"is_corresponding":false},{"id":244641,"name":"Matthew Chang","orcid":"0000-0002-7244-997X","position":8,"is_corresponding":false},{"id":244642,"name":"Katrina Nguyen","orcid":"0000-0002-1219-053X","position":9,"is_corresponding":false},{"id":244643,"name":"Maliwan Kamkaew","orcid":"0009-0003-2229-429X","position":10,"is_corresponding":false},{"id":244644,"name":"Quan Zhu","orcid":"0000-0003-1820-4354","position":11,"is_corresponding":false},{"id":244645,"name":"Travis E. Gibson","orcid":"0000-0003-0320-8010","position":12,"is_corresponding":false},{"id":108468,"name":"Edward T. Ryan","orcid":"0009-0005-0169-394X","position":13,"is_corresponding":false},{"id":108258,"name":"Richelle C. Charles","orcid":"0000-0002-8881-1849","position":14,"is_corresponding":false},{"id":244646,"name":"Wayne A. Marasco","orcid":"0000-0003-3764-4611","position":15,"is_corresponding":false},{"id":76195,"name":"David R. Walt","orcid":"0000-0002-5524-7348","position":16,"is_corresponding":false},{"id":244639,"name":"Alana F. Ogata","orcid":"0000-0002-5234-6463","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T20:38:25.860949Z","pmid":"32897389","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":[]}