{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:42:33Z","timestamp":1790199753535,"version":"4.1.0"},"reference-count":56,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T00:00:00Z","timestamp":1653264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016796","name":"Adaptive Biotechnologies","doi-asserted-by":"crossref","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"10.13039\/100016796","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012728","name":"Frederick National Laboratory for Cancer Research","doi-asserted-by":"crossref","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"10.13039\/100012728","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["NIAID contract 75N91019D00024"],"award-info":[{"award-number":["NIAID contract 75N91019D00024"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["NIAID contract 75N93019C0063"],"award-info":[{"award-number":["NIAID contract 75N93019C0063"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["NIAID contract HHSN272201800013C"],"award-info":[{"award-number":["NIAID contract HHSN272201800013C"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Laulima Government Solutions, LLC","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}]},{"name":"Fred Hutchinson Joel Meyers Endowment","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}]},{"DOI":"10.13039\/100016127","name":"Fast-Grants","doi-asserted-by":"crossref","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"10.13039\/100016127","id-type":"DOI","asserted-by":"crossref"}]},{"name":"American Society for Transplantation and Cell Therapy","award":["New Investigator Award"],"award-info":[{"award-number":["New Investigator Award"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,23]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Measuring the immune response to SARS-CoV-2 enables assessment of past infection and protective immunity. SARS-CoV-2 infection induces humoral and T cell responses, but these responses vary with disease severity and individual characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A T cell receptor (TCR) immunosequencing assay was conducted using small-volume blood samples from 302 individuals recovered from COVID-19. Correlations between the magnitude of the T cell response and neutralizing antibody (nAb) titers or indicators of disease severity were evaluated. Sensitivity of T cell testing was assessed and compared with serologic testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>SARS-CoV-2\u2013specific T cell responses were significantly correlated with nAb titers and clinical indicators of disease severity, including hospitalization, fever, and difficulty breathing. Despite modest declines in depth and breadth of T cell responses during convalescence, high sensitivity was observed until at least 6 months after infection, with overall sensitivity ~5% greater than serology tests for identifying prior SARS-CoV-2 infection. Improved performance of T cell testing was most apparent in recovered, nonhospitalized individuals sampled &gt; 150 days after initial illness, suggesting greater sensitivity than serology at later time points and in individuals with less severe disease. T cell testing identified SARS-CoV-2 infection in 68% (55 of 81) of samples with undetectable nAb titers (&lt;1:40) and in 37% (13 of 35) of samples classified as negative by 3 antibody assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>These results support TCR-based testing as a scalable, reliable measure of past SARS-CoV-2 infection with clinical value beyond serology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>Specimens were accrued under trial NCT04338360 accessible at clinicaltrials.gov.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>This work was funded by Adaptive Biotechnologies, Frederick National Laboratory for Cancer Research, NIAID, Fred Hutchinson Joel Meyers Endowment, Fast Grants, and American Society for Transplantation and Cell Therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.150070","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T12:08:05Z","timestamp":1650370085000},"source":"Crossref","is-referenced-by-count":44,"title":["T cell receptor sequencing identifies prior SARS-CoV-2 infection and correlates with neutralizing antibodies and disease severity"],"prefix":"10.1172","volume":"7","author":[{"given":"Rebecca","family":"Elyanow","sequence":"first","affiliation":[{"name":"Adaptive Biotechnologies, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7256-7821","authenticated-orcid":true,"given":"Thomas M.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Adaptive Biotechnologies, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeb C.","family":"Dalai","sequence":"additional","affiliation":[{"name":"Adaptive Biotechnologies, Seattle, Washington, USA."},{"name":"Stanford University School of Medicine, Stanford, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3202-6582","authenticated-orcid":true,"given":"Rachel M.","family":"Gittelman","sequence":"additional","affiliation":[{"name":"Adaptive Biotechnologies, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5858-2662","authenticated-orcid":true,"given":"Jim","family":"Boonyaratanakornkit","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, Washington, USA."},{"name":"Fred Hutchinson Cancer Research Center, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3486-6438","authenticated-orcid":true,"given":"Anna","family":"Wald","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, Washington, USA."},{"name":"Fred Hutchinson Cancer Research Center, Seattle, Washington, USA."},{"name":"Department of Epidemiology,"},{"name":"Department of Laboratory Medicine and Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy","family":"Selke","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8304-6957","authenticated-orcid":true,"given":"Mark H.","family":"Wener","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, Washington, USA."},{"name":"Department of Laboratory Medicine and Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5330-9464","authenticated-orcid":true,"given":"Chihiro","family":"Morishima","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7443-0527","authenticated-orcid":true,"given":"Alexander L.","family":"Greninger","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6332-7436","authenticated-orcid":true,"suffix":"Jr.","given":"Michael","family":"Gale","sequence":"additional","affiliation":[{"name":"Department of Immunology,"},{"name":"Department of Microbiology, and"},{"name":"Department of Global Health, University of Washington, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4316-4561","authenticated-orcid":true,"given":"Tien-Ying","family":"Hsiang","sequence":"additional","affiliation":[{"name":"Department of Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lichen","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0824-2667","authenticated-orcid":true,"given":"Michael R.","family":"Holbrook","sequence":"additional","affiliation":[{"name":"National Institute of Allergy and Infectious Diseases (NIAID) Integrated Research Facility, Frederick, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Adaptive Biotechnologies, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Jabran","family":"Zahid","sequence":"additional","affiliation":[{"name":"Microsoft Research, Redmond, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6902-3153","authenticated-orcid":true,"given":"Damon H.","family":"May","sequence":"additional","affiliation":[{"name":"Adaptive Biotechnologies, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6618-3653","authenticated-orcid":true,"given":"Jonathan M.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Microsoft Research, Redmond, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9136-0663","authenticated-orcid":true,"given":"Lance","family":"Baldo","sequence":"additional","affiliation":[{"name":"Adaptive Biotechnologies, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Manley","sequence":"additional","affiliation":[{"name":"Adaptive Biotechnologies, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harlan S.","family":"Robins","sequence":"additional","affiliation":[{"name":"Adaptive Biotechnologies, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1255-9023","authenticated-orcid":true,"given":"David M.","family":"Koelle","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, Washington, USA."},{"name":"Fred Hutchinson Cancer Research Center, Seattle, Washington, USA."},{"name":"Department of Laboratory Medicine and Pathology,"},{"name":"Department of Global Health, University of Washington, Seattle, Washington, USA."},{"name":"Benaroya Research Institute, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,5,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe2028079"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf4063"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00902-8"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2026116"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-01194-5"},{"key":"B6","article-title":"Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: a preliminary report of an open-label, phase 1 clinical trial","volume":"31","author":"Tebas","year":"2020","journal-title":"EClinicalMedicine"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.11.007"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf6950"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100355"},{"key":"B10","doi-asserted-by":"crossref","unstructured":"Wu K, et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants [preprint]. https:\/\/doi.org\/10.1101\/2021.01.25.427948 Posted on bioRxiv January 25, 2021","DOI":"10.1101\/2021.01.25.427948"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03324-6"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31483-5"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvaa211"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2020.11.002"},{"issue":"11","key":"B15","doi-asserted-by":"crossref","first-page":"e02107","DOI":"10.1128\/JCM.02107-20","article-title":"Neutralizing antibodies correlate with protection from SARS-CoV-2 in humans during a fishery vessel outbreak with a high attack rate","volume":"58","author":"Addetia","year":"2020","journal-title":"J Clin Microbiol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21111-9"},{"key":"B17","doi-asserted-by":"crossref","unstructured":"Snyder MT, et al. Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels [preprint]. https:\/\/doi.org\/10.1101\/2020.07.31.20165647 Posted on medRxiv September 17, 2020","DOI":"10.1101\/2020.07.31.20165647"},{"key":"B18","doi-asserted-by":"crossref","unstructured":"Dalai SC, et al. Clinical validation of a novel T-cell receptor sequencing assay for identification of recent or prior SARS-CoV-2 infection [preprint]. https:\/\/doi.org\/10.1101\/2021.01.06.21249345 Posted on medRxiv January 8, 2021","DOI":"10.1101\/2021.01.06.21249345"},{"issue":"47","key":"B19","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3001442","article-title":"Overlap and effective size of the human CD8+ T cell receptor repertoire","volume":"2","author":"Robins","year":"2010","journal-title":"Sci Transl Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0249484"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3822"},{"key":"B22","doi-asserted-by":"crossref","unstructured":"Greissl J, et al. Immunosequencing of the T-cell receptor repertoire reveals signatures specific for diagnosis and characterization of early Lyme disease [preprint]. https:\/\/doi.org\/10.1101\/2021.07.30.21261353 Posted on medRxiv August 2, 2021","DOI":"10.1101\/2021.07.30.21261353"},{"key":"B23","doi-asserted-by":"crossref","unstructured":"Gittelman RM, et al. Diagnosis and tracking of SARS-CoV-2 infection by T-cell receptor sequencing [preprint]. https:\/\/doi.org\/10.1101\/2020.11.09.20228023 Posted on medRxiv February 10, 2021","DOI":"10.1101\/2020.11.09.20228023"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI144930"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0141561"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.7326\/M20-3742"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.017"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0965-6"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048908"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3201\/eid2701.203611"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.08.001"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00625-9"},{"key":"B33","unstructured":"US Food and Drug Administration. Emergency Use Authorization for Vaccines to Prevent COVID-19: Guidance for Industry. https:\/\/www.fda.gov\/media\/142749\/download Accessed April 18, 2022"},{"key":"B34","unstructured":"Snyder TM, et al. Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection and vaccination. Paper presented at: IDWeek 2021; September 29\u2013October 3, 2021; Virtual. https:\/\/idweek.org\/events\/idweek2021\/ Accessed April 18, 2022"},{"key":"B35","unstructured":"May DH, et al. Omicron variant partially escapes the T-cell response induced by SARS-CoV-2 vaccines. https:\/\/www.adaptivebiotech.com\/wp-content\/uploads\/2021\/12\/omicron_t_cell_impact.pdf Accessed April 18, 2022"},{"key":"B36","doi-asserted-by":"crossref","unstructured":"Redd AD, et al. Minimal cross-over between mutations associated with Omicron variant of SARS-CoV-2 and CD8+ T cell epitopes identified in COVID-19 convalescent individuals [preprint]. https:\/\/doi.org\/10.1101\/2021.12.06.471446 Posted on bioRxiv December 9, 2021","DOI":"10.1101\/2021.12.06.471446"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj5365"},{"key":"B38","unstructured":"Centers for Disease Control and Prevention. COVID Data Tracker: Trends in Number of COVID-19 Cases and Deaths in the US Reported to CDC, by State\/Territory. https:\/\/covid.cdc.gov\/covid-data-tracker\/#trends_dailytrendscases. Accessed April 18, 2022"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100354"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24938-4"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30243-7"},{"issue":"9","key":"B42","doi-asserted-by":"crossref","DOI":"10.1002\/cti2.1340","article-title":"Landscape of T-cell repertoires with public COVID-19-associated T-cell receptors in pre-pandemic risk cohorts","volume":"10","author":"Simnica","year":"2021","journal-title":"Clin Transl Immunology"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.38358"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1944"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20202617"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00902-8"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2021.1905525"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-04-217604"},{"issue":"1\u20132","key":"B49","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jim.2011.09.001","article-title":"Ultra-sensitive detection of rare T cell clones","volume":"375","author":"Robins","year":"2012","journal-title":"J Immunol Methods"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3680"},{"issue":"6","key":"B51","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.158126","article-title":"T cell response to intact SARS-CoV-2 includes coronavirus cross-reactive and variant-specific components","volume":"7","author":"Jing","year":"2022","journal-title":"JCI Insight"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60556"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3390\/v13050893"},{"key":"B54","doi-asserted-by":"crossref","unstructured":"Nolan S, et al. A large-scale database of T-cell receptor beta (TCR\u03b2) sequences and binding associations from natural and synthetic exposure to SARS-CoV-2 [preprint]. https:\/\/doi.org\/10.21203\/rs.3.rs-51964\/v1 Posted on Research Square August 4, 2020","DOI":"10.21203\/rs.3.rs-51964\/v1"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01026"},{"issue":"1","key":"B56","doi-asserted-by":"crossref","DOI":"10.2307\/2683591","article-title":"LOWESS: a program for smoothing scatterplots by robust locally weighted regression","volume":"35","author":"Cleveland","year":"1981","journal-title":"Am Stat"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/150070\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:34:02Z","timestamp":1779147242000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/150070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,23]]},"references-count":56,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,5,23]]},"published-print":{"date-parts":[[2022,5,23]]}},"alternative-id":["10.1172\/jci.insight.150070"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.150070","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.03.19.21251426","asserted-by":"object"}]},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,23]]},"article-number":"e150070"}}