{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:30:18Z","timestamp":1776274218228,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T00:00:00Z","timestamp":1695945600000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The outbreak of coronavirus disease 2019 (COVID\u201019) caused by severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) has posed a great threat to human health. Some severe COVID\u201019 patients still carried detectable levels of SARS\u2010CoV\u20102 even after prolonged intensive care unit treatment. However, the immunological features of these COVID\u201019 patients with delayed virus clearance (CDVC) are still unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively reviewed the clinical and immunological data of 13 CDVC cases, who were admitted into one hospital in Wuhan from February to April 2020. These data were also compared to those of perished (<jats:italic>n<\/jats:italic>\u2009=\u20099) and recovered (<jats:italic>n<\/jats:italic>\u2009=\u200952) cases. The expression of the exhaustion marker PD\u20101 on circulating T cells of these patients was measured by flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>High levels of serum interleukin\u20106 (IL\u20106), IL\u20101\u03b2, IL\u20108, as well as other inflammatory mediators, were seen in CDVC cases. Severe lymphopenia was observed in CDVC patients with the counts of total lymphocytes (0.9\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L), CD4<jats:sup>+<\/jats:sup> T cells (0.35\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L), and CD8<jats:sup>+<\/jats:sup> T cells (0.28\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L) below their corresponding lower limits of normal range. Similar to the perished group, CDVC cases have higher percentages of CD25<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup> regulatory T cells (Treg) in circulation. Moreover, enhanced expression of the exhaustion marker PD\u20101 on CCR7<jats:sup>\u2212<\/jats:sup>CD45RA<jats:sup>+<\/jats:sup> effector, CCR7<jats:sup>+<\/jats:sup>CD45RA<jats:sup>\u2212<\/jats:sup> central memory, and CCR7<jats:sup>\u2212<\/jats:sup>CD45RA<jats:sup>\u2212<\/jats:sup> effector memory CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells were also observed in CDVC cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CDVC patients still have SARS\u2010CoV\u20102 and these cases manifest with severe clinical symptoms due to persistent inflammation. Augmentation of the frequency of circulating Treg, severe lymphopenia, and functional exhaustion of T cells might lead to inefficient clearance of SARS\u2010CoV\u20102. Therefore, enhancing lymphocyte counts and reversing T\u2010cell exhaustion might be key methods to boost immune responses and eliminate SARS\u2010CoV\u20102 in CDVC patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.999","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T11:52:54Z","timestamp":1695988374000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The clinical and immunological characteristics of COVID\u201019 patients with delayed SARS\u2010CoV\u20102 virus clearance"],"prefix":"10.1002","volume":"11","author":[{"given":"Jinsong","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Immunology, PLA Army Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6132-4186","authenticated-orcid":false,"given":"Debao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology Medical College of Qingdao University Qingdao Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Tang","sequence":"additional","affiliation":[{"name":"Chongqing International Institute for Immunology Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemin","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Immunology, PLA Army Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjiong","family":"Shi","sequence":"additional","affiliation":[{"name":"Chongqing International Institute for Immunology Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Pingdingshan Medical District the 989th Hospital of the PLA Joint Logistic Support Force Pingdingshan Henan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology the 989th Hospital of the PLA Joint Logistic Support Force Luoyang Henan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzhang","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Immunology, PLA Army Medical University Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Chongqing International Institute for Immunology Chongqing China"},{"name":"School of Pharmacy and Bioengineering Chongqing University of Technology Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinghua","family":"Qiao","sequence":"additional","affiliation":[{"name":"Pingdingshan Medical District the 989th Hospital of the PLA Joint Logistic Support Force Pingdingshan Henan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001017"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30079-5"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30251-8"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30183-5"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000515159"},{"issue":"1","key":"e_1_2_10_7_1","first-page":"20","article-title":"COVID\u201019 pandemic: from origins to outcomes. 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