{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:32:59Z","timestamp":1792528379283,"version":"4.5.0"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"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":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Systemic reactivation of Epstein\u2013Barr virus (EBV) may occur in novel coronavirus disease 2019 (COVID\u201019) caused by the severe acute respiratory syndrome coronavirus\u20102 (SARS\u2010CoV\u20102). However, the clinical consequences of EBV reactivation remain uncertain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this retrospective study, we screened 1314 patients with confirmed COVID\u201019 who died or were discharged between January 1, 2020 and March 12, 2020, in Wuhan Infectious Disease Hospital, Wuhan, China. Patients who had complete data for EBV serology and cytomegalovirus (CMV) serology were eligible. Serum levels of viral capsid antigen (VCA)\u2010immunoglobulin G (IgG), Epstein\u2013Barr nuclear antigen\u2010IgG, VCA\u2010IgM, early antigen (EA)\u2010IgG, CMV\u2010IgG, and CMV\u2010IgM were compared between survivors and nonsurvivors. Dynamic changes of laboratory tests and outcomes were compared in patients with and without ganciclovir treatment. We used 1:1 matching based on age, gender, and illness severity to balance baseline characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EBV reactivation was present in 55 of 217 patients. EBV reactivation was associated with age (57.91 [13.19] vs. 50.28 [12.66] years, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001), female gender (31 [56%] vs. 60 [37%], <jats:italic>p<\/jats:italic>\u2009=\u2009.02). Patients with EBV reactivation have statistically nonsignificant higher mortality rate (12 [22%] vs. 18 [11%], <jats:italic>p<\/jats:italic>\u2009=\u2009.08). EA\u2010IgG levels were significantly higher in nonsurvivors than in survivors (median difference: \u22120.00005, 95% confidence interval, CI [\u22123.10, 0.00], <jats:italic>p<\/jats:italic>\u2009=\u2009.05). As compared to patients with COVID\u201019 who did not receive ganciclovir therapy, ganciclovir\u2010treated patients had improved survival rate (0.98, 95% CI [0.95, 1.00] vs. 0.88, 95% CI [0.81, 0.95], <jats:italic>p<\/jats:italic>\u2009=\u2009.01). Hemoglobin (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001) and prealbumin (<jats:italic>p<\/jats:italic>\u2009=\u2009.02) levels were significantly higher in ganciclovir\u2010treated patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A high proportion of COVID\u201019 patients had EBV reactivation that may be associated with an increased risk of death. Whether treatment with ganciclovir may decrease the mortality of COVID\u201019 patients complicated with EBV reactivation warrants to be addressed in a placebo\u2010controlled randomized trial in the future.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.597","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T06:21:36Z","timestamp":1646979696000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["COVID\u201019 associated EBV reactivation and effects of ganciclovir treatment"],"prefix":"10.1002","volume":"10","author":[{"given":"Mei","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Dong","sequence":"additional","affiliation":[{"name":"Tuberculosis and Respiratory Department Wuhan Infectious Disease Hospital Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit Shandong Provincial Chest Hospital Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfeng","family":"Deng","sequence":"additional","affiliation":[{"name":"Katharine Hsu International Research Center of Human Infectious Diseases Shandong Provincial Chest Hospital Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhe","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranran","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djillali","family":"Annane","sequence":"additional","affiliation":[{"name":"General Intensive Care Unit, Laboratory of Inflammation and Infection U1173, Raymond Poincar\u00e9 Hospital (APHP) University of Versailles SQY\/INSERM Garches France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Surgical Intensive Care Unit Huadong Hospital Affiliated to Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6589-4151","authenticated-orcid":false,"given":"Dechang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40249-020-00646-x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2002032"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30211-7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30183-5"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30079-5"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-05966-y"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30566-3"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-05991-x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(03)00543-7"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix120"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-1578(10)60642-3"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14020"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2017.10.020"},{"issue":"23","key":"e_1_2_9_15_1","first-page":"2526","article-title":"Acute respiratory distress syndrome: the Berlin definition","volume":"307","author":"Ranieri VM","year":"2012","journal-title":"JAMA"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000339789"},{"issue":"6","key":"e_1_2_9_17_1","first-page":"657","article-title":"Disseminated intravascular coagulation: clinical and biological diagnosis","volume":"73","author":"Touaoussa A","year":"2015","journal-title":"Ann Biol Clin"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-215361"},{"issue":"2","key":"e_1_2_9_20_1","first-page":"88","article-title":"Comparison of the LIAISON\u00aeXL and ARCHITECT IgG, IgM, and IgG avidity assays for the diagnosis of toxoplasma, cytomegalovirus, and rubella virus infections","volume":"42","author":"Genco F","year":"2019","journal-title":"New Microbiol"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099857"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-020-03252-3"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2019-205822"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-800098-4.00006-4"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-021-06094-8"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202003-0543OC"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/v12010021"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.10569"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199609053351007"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0118-9"}],"container-title":["Immunity, Inflammation and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iid3.597","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/iid3.597","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iid3.597","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T19:47:17Z","timestamp":1692992837000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/iid3.597"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,10]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1002\/iid3.597"],"URL":"https:\/\/doi.org\/10.1002\/iid3.597","archive":["Portico"],"relation":{},"ISSN":["2050-4527","2050-4527"],"issn-type":[{"value":"2050-4527","type":"print"},{"value":"2050-4527","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,10]]},"assertion":[{"value":"2021-08-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e597"}}