{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:22Z","timestamp":1792787602964,"version":"4.5.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases","award":["AI173035"],"award-info":[{"award-number":["AI173035"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NHLBI Division of Intramural Research","award":["HL160661"],"award-info":[{"award-number":["HL160661"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND.<\/jats:bold>\n                    Long-COVID, or post-acute sequelae of COVID-19 (PASC), leads to debilitating physical and cognitive deficits. No PASC molecular signature present in patients with diverse symptoms has been described. While PASC engages pathways regulating pro-fibrotic programs, no comparison of PASC with fibrosis-associated epigenetic landscapes has been reported at the bulk or single-cell level. We hypothesize that a subset of DNA methylation changes are present in PASC patients from multiple cohorts, predominate in specific immune or inflammatory cell-types, and overlap with the epigenetic profile of patients at risk of pulmonary fibrosis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>METHODS.<\/jats:bold>\n                    Two distinct prospective cohorts, in 2021 and in 2022-24, involving 203 patients with PASC underwent bulk whole genome methylation sequencing (WGMS). Single-cell WGMS data was generated from an independent PASC cohort. Sixty-eight pre-pandemic patients with conditions elevating risk of pulmonary fibrosis development were compared with PASC.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS.<\/jats:bold>\n                    Sixteen differentially methylated regions distinguished PASC versus multiple independent, healthy controls. Single-cell analysis of these regions indicated trending relative hypermethylation at multiple cell types, with T4 lymphocytes eliciting hypermethylation at most of the sequences identified to be PASC-specific DMRs in the bulk analysis. Patients at risk of pulmonary fibrosis development elicited DNA methylation changes overlapping PASC.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSION.<\/jats:bold>\n                    In two independent prospective cohorts, blood WGMS identifies differentially methylated regions associated with PASC. Hypermethylation of these regions is predominantly, although not exclusively, associated with T4 lymphocytes and overlap with changes present in pre-pandemic pulmonary fibrosis at-risk patients.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>FUNDING.<\/jats:bold>\n                    National Institutes of Health award HL160661 (AJ); and AI173035 (AJ and RSA).\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.210824","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:00:41Z","timestamp":1790697641000},"source":"Crossref","is-referenced-by-count":0,"title":["Whole-genome methylation sequencing uncovers PASC signature elicited by T4 lymphocytes, shared with pulmonary fibrosis risk"],"prefix":"10.1172","author":[{"given":"Andy","family":"Madrid","sequence":"first","affiliation":[{"name":"Hackensack Meridian Health, Center for Discovery and Innovation, Nutley, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Balnis","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Drake","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupama","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vraj J.","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Feustel","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Experimental Therapeutics, Albany Medical Center, Albany, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Statistics, Medical Sciences Center, University of Wisconsin, Madison, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-0922","authenticated-orcid":true,"given":"S\u00fcnd\u00fcz","family":"Kele\u015f","sequence":"additional","affiliation":[{"name":"Department of Statistics, Medical Sciences Center, University of Wisconsin, Madison, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangxiu","family":"Xu","sequence":"additional","affiliation":[{"name":"Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign, Champaign, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris L.","family":"Wright","sequence":"additional","affiliation":[{"name":"Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign, Champaign, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro G.","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign, Champaign, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Recai","family":"Yucel","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Temple University, Philadelphia, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Judson","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold A.","family":"Singer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Albany Medical Center, Albany, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reid S.","family":"Alisch","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Wisconsin, Madison, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4714-2260","authenticated-orcid":true,"given":"Ariel","family":"Jaitovich","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,9,29]]},"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/insight.jci.org\/articles\/view\/210824\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:00:42Z","timestamp":1790697642000},"score":1,"resource":{"primary":{"URL":"http:\/\/insight.jci.org\/articles\/view\/210824"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":0,"alternative-id":["10.1172\/jci.insight.210824"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.210824","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]}}}