{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:52:22Z","timestamp":1772139142194,"version":"3.50.1"},"reference-count":15,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21jk0210034h0002"],"award-info":[{"award-number":["21jk0210034h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Clinical observations have shown that there is a relationship between coronavirus disease 2019 (COVID-19) and atypical lymphocytes in the peripheral blood; however, knowledge about the time course of the changes in atypical lymphocytes and the association with the clinical course of COVID-19 is limited.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>Our purposes were to investigate the dynamics of atypical lymphocytes in COVID-19 patients and to estimate their clinical significance for diagnosis and monitoring disease course.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>We retrospectively identified 98 inpatients in a general ward at Kashiwa Municipal Hospital from May 1st, 2020, to October 31st, 2020. We extracted data on patient demographics, symptoms, comorbidities, blood test results, radiographic findings, treatment after admission and clinical course. We compared clinical findings between patients with and without atypical lymphocytes, investigated the behavior of atypical lymphocytes throughout the clinical course of COVID-19, and determined the relationships among the development of pneumonia, the use of supplemental oxygen and the presence of atypical lymphocytes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Patients with atypical lymphocytes had a significantly higher prevalence of pneumonia (80.4% vs. 42.6%, p &lt; 0.0001) and the use of supplemental oxygen (25.5% vs. 4.3%, p = 0.0042). The median time to the appearance of atypical lymphocytes after disease onset was eight days, and atypical lymphocytes were observed in 16\/98 (16.3%) patients at the first visit. Atypical lymphocytes appeared after the confirmation of lung infiltrates in 31\/41 (75.6%) patients. Of the 13 oxygen-treated patients with atypical lymphocytes, approximately two-thirds had a stable or improved clinical course after the appearance of atypical lymphocytes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Atypical lymphocytes frequently appeared in the peripheral blood of COVID-19 patients one week after disease onset. Patients with atypical lymphocytes were more likely to have pneumonia and to need supplemental oxygen; however, two-thirds of them showed clinical improvement after the appearance of atypical lymphocytes.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0259910","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T18:32:47Z","timestamp":1636741967000},"page":"e0259910","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Atypical lymphocytes in the peripheral blood of COVID-19 patients: A prognostic factor for the clinical course of COVID-19"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9372-9671","authenticated-orcid":true,"given":"Jun","family":"Sugihara","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sho","family":"Shibata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Doi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4947-0049","authenticated-orcid":true,"given":"Takuya","family":"Shimmura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichiro","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayaka","family":"Makino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasunari","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"pone.0259910.ref001","volume-title":"WHO Coronavirus Disease (COVID-19)","author":"WHO","year":"2021"},{"key":"pone.0259910.ref002","volume-title":"Harrison\u2019s Principles of Internal Medicine.","author":"AS Fauci","year":"2008","edition":"17"},{"issue":"5","key":"pone.0259910.ref003","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1111\/bjh.16690","article-title":"Reactive lymphocytes in patients with COVID-19","volume":"189","author":"VCL Chong","year":"2020","journal-title":"Br J Haematol"},{"issue":"9","key":"pone.0259910.ref004","doi-asserted-by":"crossref","first-page":"153063","DOI":"10.1016\/j.prp.2020.153063","article-title":"Atypical lymphocyte morphology in SARS-CoV-2 infection.","volume":"216","author":"SM El Jamal","year":"2020","journal-title":"Pathol Res Pract"},{"issue":"1","key":"pone.0259910.ref005","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/bjh.16848","article-title":"Atypical lymphocytes in peripheral blood of patients with COVID-19","volume":"190","author":"SE Weinberg","year":"2020","journal-title":"Br J Haematol"},{"key":"pone.0259910.ref006","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.humpath.2021.04.010","article-title":"Comprehensive evaluation of bronchoalveolar lavage from patients with severe COVID-19 and correlation with clinical outcomes.","volume":"113","author":"I Gelarden","year":"2021","journal-title":"Hum Pathol"},{"issue":"2","key":"pone.0259910.ref007","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1620\/tjem.252.109","article-title":"Differential Diagnosis of COVID-19: Importance of Measuring Blood Lymphocytes, Serum Electrolytes, and Olfactory and Taste Functions","volume":"252","author":"H Nakanishi","year":"2020","journal-title":"Tohoku J Exp Med"},{"issue":"3","key":"pone.0259910.ref008","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1093\/ajcp\/aqaa231","article-title":"Clinical Significance of CBC and WBC Morphology in the Diagnosis and Clinical Course of COVID-19 Infection","volume":"155","author":"O Pozdnyakova","year":"2020","journal-title":"Am J Clin Pathol"},{"issue":"9","key":"pone.0259910.ref009","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1007\/s10096-016-2675-z","article-title":"Are atypical lymphocytes present with viral influenza-like illnesses (ILIs) in hospitalized adults?","volume":"35","author":"BA Cunha","year":"2016","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"20","key":"pone.0259910.ref010","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1056\/NEJMoa030685","article-title":"A major outbreak of severe acute respiratory syndrome in Hong Kong","volume":"348","author":"N Lee","year":"2003","journal-title":"N Engl J Med"},{"issue":"1","key":"pone.0259910.ref011","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1365-2257.2004.00652.x","article-title":"Haematological parameters in severe acute respiratory syndrome.","volume":"27","author":"WJ Chng","year":"2005","journal-title":"Clin Lab Haematol"},{"key":"pone.0259910.ref012","article-title":"Atypical lymphoid cells circulating in blood in COVID-19 infection: morphology, immunophenotype and prognosis value","author":"A Merino","year":"2020","journal-title":"J Clin Pathol"},{"key":"pone.0259910.ref013","doi-asserted-by":"crossref","first-page":"102763","DOI":"10.1016\/j.ebiom.2020.102763","article-title":"Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients.","volume":"55","author":"J Liu","year":"2020","journal-title":"EBioMedicine"},{"key":"pone.0259910.ref014","doi-asserted-by":"crossref","first-page":"104361","DOI":"10.1016\/j.jcv.2020.104361","article-title":"The clinical course and its correlated immune status in COVID-19 pneumonia.","volume":"127","author":"R He","year":"2020","journal-title":"J Clin Virol"},{"issue":"11","key":"pone.0259910.ref015","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1093\/infdis\/jiaa150","article-title":"Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia.","volume":"221","author":"F Wang","year":"2020","journal-title":"J Infect Dis"}],"container-title":["PLOS 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