{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:36:28Z","timestamp":1760229388690,"version":"build-2065373602"},"reference-count":86,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["TTU 04.816","SFB1328 A12","SFB841 A6","3U19AI135817-04S1"],"award-info":[{"award-number":["TTU 04.816","SFB1328 A12","SFB841 A6","3U19AI135817-04S1"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TTU 04.816","SFB1328 A12","SFB841 A6","3U19AI135817-04S1"],"award-info":[{"award-number":["TTU 04.816","SFB1328 A12","SFB841 A6","3U19AI135817-04S1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH NIDDK","award":["TTU 04.816","SFB1328 A12","SFB841 A6","3U19AI135817-04S1"],"award-info":[{"award-number":["TTU 04.816","SFB1328 A12","SFB841 A6","3U19AI135817-04S1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Here, we longitudinally assessed the ex vivo frequency and phenotype of SARS-CoV-2 membrane protein (aa145\u2013164) epitope-specific CD4+ T-cells of an anti-CD20-treated patient with prolonged viral positivity in direct comparison to an immunocompetent patient through an MHC class II DRB1*11:01 Tetramer analysis. We detected a high and stable SARS-CoV-2 membrane-specific CD4+ T-cell response in both patients, with higher frequencies of virus-specific CD4+ T-cells in the B-cell-depleted patient. However, we found an altered virus-specific CD4+ T-cell memory phenotype in the B-cell-depleted patient that was skewed towards late differentiated memory T-cells, as well as reduced frequencies of SARS-CoV-2-specific CD4+ T-cells with CD45RA\u2212 CXCR5+ PD-1+ circulating T follicular helper cell (cTFH) phenotype. Furthermore, we observed a delayed contraction of CD127\u2212 virus-specific effector cells. The expression of the co-inhibitory receptors TIGIT and LAG-3 fluctuated on the virus-specific CD4+ T-cells of the patient, but were associated with the inflammation markers IL-6 and CRP. Our findings indicate that, despite B-cell depletion and a lack of B-cell\u2014T-cell interaction, a robust virus-specific CD4+ T-cell response can be primed that helps to control the viral replication, but which is not sufficient to fully abrogate the infection.<\/jats:p>","DOI":"10.3390\/v14061265","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T06:31:59Z","timestamp":1655101919000},"page":"1265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1340-8817","authenticated-orcid":false,"given":"Leon","family":"Cords","sequence":"first","affiliation":[{"name":"Infectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9554-5067","authenticated-orcid":false,"given":"Maximilian","family":"Knapp","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Woost","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophia","family":"Schulte","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silke","family":"Kummer","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christin","family":"Ackermann","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4905-4646","authenticated-orcid":false,"given":"Claudia","family":"Beisel","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Peine","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4779-4648","authenticated-orcid":false,"given":"Alexandra M\u00e4rta","family":"Johansson","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4843-4599","authenticated-orcid":false,"given":"William Wai-Hung","family":"Kwok","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9650-0218","authenticated-orcid":false,"given":"Thomas","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5092-8179","authenticated-orcid":false,"given":"Nicole","family":"Fischer","sequence":"additional","affiliation":[{"name":"German Center for Infection Research (DZIF), Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, 20246 Hamburg, Germany"},{"name":"Leibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany"},{"name":"Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Wittner","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2836-9224","authenticated-orcid":false,"given":"Marylyn Martina","family":"Addo","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9325-8227","authenticated-orcid":false,"given":"Samuel","family":"Huber","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-1938","authenticated-orcid":false,"given":"Julian","family":"Schulze zur Wiesch","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit I, Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1016\/j.jinf.2020.04.021","article-title":"Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis","volume":"81","author":"Zheng","year":"2020","journal-title":"J. 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