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FGL-1 affects T-cell function by interacting with lymphocyte-activation gene 3 (LAG-3), and blocking this interaction can enhance T-cell activity, making it a potential therapeutic target. In coronavirus disease 2019 (COVID-19), the upregulation of immune checkpoints on T cells, particularly LAG-3, is associated with disease severity. Liver inflammation and damage are well-known features of COVID-19 pathogenesis; however, little is known about FGL-1 expression patterns in COVID-19 and other infectious diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a cohort of 65 patients with COVID-19 and 33 healthy donors, plasma FGL-1 levels were measured, and their correlations with clinical parameters and the course of the disease were evaluated. Additionally, both bulk and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-specific T-cell immune phenotypes, as well as SARS-CoV-2-specific immune responses were comprehensively characterized and measured using multicolor flow cytometry and pMHC multimer technology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Plasma FGL-1 levels were elevated in patients with COVID-19 and correlated with IL-6 and disease severity. LAG-3 was significantly upregulated on bulk and COVID-19-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and was co-expressed with T-cell activation markers (CD38, HLA-DR) and inhibitory receptors (PD-1, TIGIT).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest a role for FGL-1 in the pathogenesis of COVID-19, potentially through modulation of T-cell activation and function via LAG-3, and may also be relevant in other hyperinflammatory conditions where immune modulation plays a role.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s43856-026-01775-4","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:45:11Z","timestamp":1785501911000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FGL-1 plasma levels correlate with markers of inflammation and severe disease during SARS-CoV-2 infection"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6876-9655","authenticated-orcid":false,"given":"Sophia","family":"Cichutek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1340-8817","authenticated-orcid":false,"given":"Leon","family":"Cords","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3382-0171","authenticated-orcid":false,"given":"Kilian","family":"Keetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liz J.","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Woost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schmiedel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansgar W.","family":"Lohse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Bokemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9789-5776","authenticated-orcid":false,"given":"Christoph","family":"Schulthei\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2836-9224","authenticated-orcid":false,"given":"Marylyn M.","family":"Addo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0275-8803","authenticated-orcid":false,"given":"Walter","family":"Fiedler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mascha","family":"Binder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-1938","authenticated-orcid":false,"given":"Julian","family":"Schulze zur Wiesch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"1775_CR1","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1002\/jmv.25757","volume":"92","author":"LQ Li","year":"2020","unstructured":"Li, L. 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