{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T01:38:56Z","timestamp":1793324336834,"version":"4.5.0"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011866","name":"Colorado Clinical and Translational Sciences Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The emergence of SARS-CoV-2, which causes COVID-19, has led to over 400 million reported cases worldwide. COVID-19 disease ranges from asymptomatic infection to severe disease and may be impacted by individual immune differences.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used multiparameter flow cytometry to compare CD4+ and CD8+ T cell responses in severe (ICU admitted) and non-severe (admitted to observational unit) hospitalized COVID-19 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that patients with severe COVID- 19 had greater frequencies of CD4+ T cells expressing CD62L compared to non-severe patients and greater frequencies of perforin+ CD8+ T cells compared to recovered patients. Furthermore, greater frequencies of CD62L+ CD4+ and CD8+ T cells were seen in severely ill diabetic patients compared to non-severe and non-diabetic patients, and increased CD62L+ CD4+ T cells were also seen in severely ill patients with hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This is the first report to show that CD62L+ T cells and perforin+ T cells are associated with severe COVID-19 illness and are significantly increased in patients with high-risk pre-existing conditions including older age and diabetes. These data provide a potential biological marker for severe COVID-19.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1113932","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T12:26:34Z","timestamp":1675340794000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Severely ill and high-risk COVID-19 patients exhibit increased peripheral circulation of CD62L+ and perforin+ T cells"],"prefix":"10.3389","volume":"14","author":[{"given":"Kelsey E.","family":"Lesteberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Araya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Waugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Chauhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquin M.","family":"Espinosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. David","family":"Beckham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2008-3","article-title":"A new coronavirus associated with human respiratory disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa248","article-title":"Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in wuhan, China","volume":"71","author":"Qin","year":"2020","journal-title":"Clin Infect Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical characteristics of coronavirus disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.2648","article-title":"Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72314 cases from the Chinese center for disease control and prevention","volume":"323","author":"Wu","year":"2020","journal-title":"JAMA"},{"key":"B7","doi-asserted-by":"publisher","first-page":"m1985","DOI":"10.1136\/bmj.m1985","article-title":"Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO clinical characterisation protocol: prospective observational cohort study","volume":"369","author":"Docherty","year":"2020","journal-title":"BMJ"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2020.03.005","article-title":"Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients","volume":"80","author":"Liu","year":"2020","journal-title":"J Infect"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7010e4","article-title":"Body mass index and risk for COVID-19-Related hospitalization, intensive care unit admission, invasive mechanical ventilation, and death - united states, march-December 2020","volume":"70","author":"Kompaniyets","year":"2021","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.20892\/j.issn.2095-3941.2020.0289","article-title":"COVID-19 in cancer patients: risk, clinical features, and management","volume":"17","author":"Liu","year":"2020","journal-title":"Cancer Biol Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1016\/j.annonc.2020.03.296","article-title":"Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within wuhan, China","volume":"31","author":"Zhang","year":"2020","journal-title":"Ann Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(21)00325-8","article-title":"Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: a retrospective cohort study using data from the national COVID cohort collaborative","volume":"4","author":"Andersen","year":"2022","journal-title":"Lancet Rheumatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01441","article-title":"Immune response, inflammation, and the clinical spectrum of COVID-19","volume":"11","author":"Garcia","year":"2020","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2598-9","article-title":"SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19","volume":"587","author":"Braun","year":"2020","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1016\/j.cell.2020.05.015","article-title":"Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals","volume":"181","author":"Grifoni","year":"2020","journal-title":"Cell"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e145476","DOI":"10.1172\/JCI145476","article-title":"SARS-CoV-2-specific CD8+ T cell responses in convalescent COVID-19 individuals","volume":"131","author":"Kared","year":"2021","journal-title":"J Clin Invest"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.05.006","article-title":"Airway memory CD4(+) T cells mediate protective immunity against emerging respiratory coronaviruses","volume":"44","author":"Zhao","year":"2016","journal-title":"Immunity"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01049-10","article-title":"T Cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice","volume":"84","author":"Zhao","year":"2010","journal-title":"J Virol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00678","article-title":"The CD8 T cell response to respiratory virus infections","volume":"9","author":"Schmidt","year":"2018","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"523","DOI":"10.3390\/ijms22020523","article-title":"Role of CD4+ T cells in the control of viral infections: Recent advances and open questions","volume":"22","author":"Kervevan","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nri3152","article-title":"Expanding roles for CD4(+) T cells in immunity to viruses","volume":"12","author":"Swain","year":"2012","journal-title":"Nat Rev Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nri1983","article-title":"Perforin-mediated target-cell death and immune homeostasis","volume":"6","author":"Voskoboinik","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.04.002","article-title":"Mechanisms and dynamics of T cell-mediated cytotoxicity in vivo","volume":"38","author":"Halle","year":"2017","journal-title":"Trends Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1111\/imm.13262","article-title":"T-Cell responses and therapies against SARS-CoV-2 infection","volume":"162","author":"Toor","year":"2021","journal-title":"Immunology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1093\/nsr\/nwaa041","article-title":"Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients","volume":"7","author":"Zhou","year":"2020","journal-title":"Natl Sci Rev"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2550-z","article-title":"SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls","volume":"584","author":"Le Bert","year":"2020","journal-title":"Nature"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI140965","article-title":"SARS-CoV-2-specific T cell responses and correlations with COVID-19 patient predisposition","volume":"130","author":"Sattler","year":"2020","journal-title":"J Clin Invest"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.769059","article-title":"Dysregulated immune responses in COVID-19 patients correlating with disease severity and invasive oxygen requirements","volume":"12","author":"Garcia-Gonzalez","year":"2021","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1016\/j.cell.2020.10.001","article-title":"Imbalance of regulatory and cytotoxic SARS-CoV-2-Reactive CD4(+) T cells in COVID-19","volume":"183","author":"Meckiff","year":"2020","journal-title":"Cell"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01949","article-title":"Overview of immune response during SARS-CoV-2 infection: Lessons from the past","volume":"11","author":"Shah","year":"2020","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/j.immuni.2016.05.001","article-title":"Lag-3, Tim-3, and TIGIT: Co-inhibitory receptors with specialized functions in immune regulation","volume":"44","author":"Anderson","year":"2016","journal-title":"Immunity"},{"key":"B32","doi-asserted-by":"publisher","first-page":"101302","DOI":"10.1016\/j.smim.2019.101302","article-title":"Tim-3: A co-receptor with diverse roles in T cell exhaustion and tolerance","volume":"42","author":"Tang","year":"2019","journal-title":"Semin Immunol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1097\/COC.0000000000000239","article-title":"CTLA-4 and PD-1 pathways: Similarities, differences, and implications of their inhibition","volume":"39","author":"Buchbinder","year":"2016","journal-title":"Am J Clin Oncol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.03.014","article-title":"Regulation and function of the PD-L1 checkpoint","volume":"48","author":"Sun","year":"2018","journal-title":"Immunity"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36498","article-title":"CD4+CD25+Foxp3+ tregs resolve experimental lung injury in mice and are present in humans with acute lung injury","volume":"119","author":"D'Alessio","year":"2009","journal-title":"J Clin Invest"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2015.143","article-title":"The role of Th17 and treg responses in the pathogenesis of RSV infection","volume":"78","author":"Mangodt","year":"2015","journal-title":"Pediatr Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01559-10","article-title":"Suppression of innate immune pathology by regulatory T cells during influenza a virus infection of immunodeficient mice","volume":"84","author":"Antunes","year":"2010","journal-title":"J Virol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.immuni.2020.12.002","article-title":"PD-1-Expressing SARS-CoV-2-Specific CD8(+) T cells are not exhausted, but functional in patients with COVID-19","volume":"54","author":"Rha","year":"2021","journal-title":"Immunity"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00827","article-title":"Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19)","volume":"11","author":"Diao","year":"2020","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"eabe4782","DOI":"10.1126\/sciimmunol.abe4782","article-title":"Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8(+) T cells","volume":"6","author":"Kusnadi","year":"2021","journal-title":"Sci Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e02243-20","DOI":"10.1128\/mBio.02243-20","article-title":"Impaired cytotoxic CD8(+) T cell response in elderly COVID-19 patients","volume":"11","author":"Westmeier","year":"2020","journal-title":"mBio"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0401-3","article-title":"Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients","volume":"17","author":"Zheng","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(94)90076-0","article-title":"Lymphocyte homing and leukocyte rolling and migration are impaired in l-selectin-deficient mice","volume":"1","author":"Arbones","year":"1994","journal-title":"Immunity"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20052205","article-title":"Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially l-selectin dependent","volume":"203","author":"Galkina","year":"2006","journal-title":"J Exp Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.12.090","article-title":"L-selectin is essential for delivery of activated CD8(+) T cells to virus-infected organs for protective immunity","volume":"14","author":"Mohammed","year":"2016","journal-title":"Cell Rep"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1101\/2021.06.14.21258910","article-title":"A multi-center, prospective, observational-cohort controlled study of clinical outcomes following COVID-19 convalescent plasma therapy in hospitalized COVID-19 patients","volume":"75","author":"Chauhan","year":"2021","journal-title":"Clin Infect Dis"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/cpmc.100","article-title":"SARS-CoV-2 seroconversion in humans: A detailed protocol for a serological assay, antigen production, and test setup","volume":"57","author":"Stadlbauer","year":"2020","journal-title":"Curr Protoc Microbiol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-021-00504-9","article-title":"Multicentre performance evaluation of the elecsys anti-SARS-CoV-2 immunoassay as an aid in determining previous exposure to SARS-CoV-2","volume":"10","author":"Riester","year":"2021","journal-title":"Infect Dis Ther"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa666","article-title":"Prolonged severe acute respiratory syndrome coronavirus 2 replication in an immunocompromised patient","volume":"223","author":"Baang","year":"2021","journal-title":"J Infect Dis"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab996","article-title":"Host predictors of broadly cross-reactive antibodies against SARS-CoV-2 variants of concern differ between infection and vaccination","volume":"75","author":"Tang","year":"2021","journal-title":"Clin Infect Dis"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01068","article-title":"L-selectin: A major regulator of leukocyte adhesion, migration and signaling","volume":"10","author":"Ivetic","year":"2019","journal-title":"Front Immunol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"eabe8063","DOI":"10.1126\/sciimmunol.abe8063","article-title":"The known unknowns of T cell immunity to COVID-19","volume":"5","author":"Karlsson","year":"2020","journal-title":"Sci Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0819-2","article-title":"Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19","volume":"26","author":"Thevarajan","year":"2020","journal-title":"Nat Med"},{"key":"B54","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.cell.2020.08.017","article-title":"Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19","volume":"183","author":"Sekine","year":"2020","journal-title":"Cell"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-016-1803-z","article-title":"CD57 in human natural killer cells and T-lymphocytes","volume":"65","author":"Kared","year":"2016","journal-title":"Cancer Immunol Immunother"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/nri1866","article-title":"The descent of memory T-cell subsets","volume":"6","author":"Lefrancois","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13531","article-title":"Different subsets of haematopoietic cells and immune cells in bone marrow between young and older donors","volume":"203","author":"Yao","year":"2021","journal-title":"Clin Exp Immunol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-020-00762-2","article-title":"A human circulating immune cell landscape in aging and COVID-19","volume":"11","author":"Zheng","year":"2020","journal-title":"Protein Cell"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1111\/all.14657","article-title":"Risk factors for severe and critically ill COVID-19 patients: A review","volume":"76","author":"Gao","year":"2021","journal-title":"Allergy"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.7202","article-title":"Characteristics of hospitalized adults with COVID-19 in an integrated health care system in California","volume":"323","author":"Myers","year":"2020","journal-title":"JAMA"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.4161\/hv.24480","article-title":"Age is an important determinant in humoral and T cell responses to immunization with hepatitis b surface antigen","volume":"9","author":"Rosenberg","year":"2013","journal-title":"Hum Vaccin Immunother"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112148-20200220-00105","article-title":"[Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV]","volume":"48","author":"Peng","year":"2020","journal-title":"Zhonghua Xin Xue Guan Bing Za Zhi"},{"key":"B63","doi-asserted-by":"publisher","first-page":"m1966","DOI":"10.1136\/bmj.m1966","article-title":"Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in new York city: prospective cohort study","volume":"369","author":"Petrilli","year":"2020","journal-title":"BMJ"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22831","article-title":"High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation","volume":"28","author":"Simonnet","year":"2020","journal-title":"Obes (Silver Spring)"},{"key":"B65","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.celrep.2019.03.030","article-title":"Obesity expands a distinct population of T cells in adipose tissue and increases vulnerability to infection","volume":"27","author":"Misumi","year":"2019","journal-title":"Cell Rep"},{"key":"B66","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/s41574-021-00575-1","article-title":"Adaptive immune cells shape obesity-associated type 2 diabetes mellitus and less prominent comorbidities","volume":"18","author":"SantaCruz-Calvo","year":"2022","journal-title":"Nat Rev Endocrinol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0244-2","article-title":"The global epidemiology of hypertension","volume":"16","author":"Mills","year":"2020","journal-title":"Nat Rev Nephrol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.2991\/jegh.k.191028.001","article-title":"Epidemiology of type 2 diabetes - global burden of disease and forecasted trends","volume":"10","author":"Khan","year":"2020","journal-title":"J Epidemiol Glob Health"},{"key":"B69","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/s41574-020-00435-4","article-title":"COVID-19 and diabetes mellitus: from pathophysiology to clinical management","volume":"17","author":"Lim","year":"2021","journal-title":"Nat Rev Endocrinol"},{"key":"B70","doi-asserted-by":"publisher","first-page":"193","DOI":"10.2147\/IJGM.S59902","article-title":"A review of the epidemiological and clinical aspects of West Nile virus","volume":"7","author":"Gray","year":"2014","journal-title":"Int J Gen Med"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2015.1007043","article-title":"Risk factors for West Nile virus infection and disease in populations and individuals","volume":"13","author":"Montgomery","year":"2015","journal-title":"Expert Rev Anti Infect Ther"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2020.04.004","article-title":"Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations","volume":"14","author":"Singh","year":"2020","journal-title":"Diabetes Metab Syndr"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1086\/431587","article-title":"Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus","volume":"41","author":"Muller","year":"2005","journal-title":"Clin Infect Dis"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.22.10494","article-title":"Inhibition of insulitis and prevention of diabetes in nonobese diabetic mice by blocking l-selectin and very late antigen 4 adhesion receptors","volume":"90","author":"Yang","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830250605","article-title":"Lack of l-selectin expression by cells transferring diabetes in NOD mice: insights into the mechanisms involved in diabetes prevention by Mel-14 antibody treatment","volume":"25","author":"Lepault","year":"1995","journal-title":"Eur J Immunol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.6.2659","article-title":"L-selectin is not required for T cell-mediated autoimmune diabetes","volume":"168","author":"Friedline","year":"2002","journal-title":"J Immunol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02692","article-title":"Defining memory CD8 T cell","volume":"9","author":"Martin","year":"2018","journal-title":"Front Immunol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1038\/44385","article-title":"Two subsets of memory T lymphocytes with distinct homing potentials and effector functions","volume":"401","author":"Sallusto","year":"1999","journal-title":"Nature"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2006.03.007","article-title":"T-Cell homing specificity and plasticity: new concepts and future challenges","volume":"27","author":"Mora","year":"2006","journal-title":"Trends Immunol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.834862","article-title":"Comparison of lung-homing receptor expression and activation profiles on NK cell and T cell subsets in COVID-19 and influenza","volume":"13","author":"Brownlie","year":"2022","journal-title":"Front Immunol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0602-4","article-title":"COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis","volume":"38","author":"Chua","year":"2020","journal-title":"Nat Biotechnol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0224-6","article-title":"TIM3 comes of age as an inhibitory receptor","volume":"20","author":"Wolf","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02474-07","article-title":"High level of PD-1 expression on hepatitis c virus (HCV)-specific CD8+ and CD4+ T cells during acute HCV infection, irrespective of clinical outcome","volume":"82","author":"Kasprowicz","year":"2008","journal-title":"J Virol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1053\/j.gastro.2008.03.037","article-title":"Dynamic programmed death 1 expression by virus-specific CD8 T cells correlates with the outcome of acute hepatitis b","volume":"134","author":"Zhang","year":"2008","journal-title":"Gastroenterology"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.897995","article-title":"In vitro exposure of primary human T cells and monocytes to polyclonal stimuli reveals a basal susceptibility to display an impaired cellular immune response and develop severe COVID-19","volume":"13","author":"Viurcos-Sanabria","year":"2022","journal-title":"Front Immunol"},{"key":"B86","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1046\/j.1600-6143.2003.00293.x","article-title":"CD4+ CD25+ CD62+ T-regulatory cell subset has optimal suppressive and proliferative potential","volume":"4","author":"Fu","year":"2004","journal-title":"Am J Transpl"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-05-2044","article-title":"Only the CD62L+ subpopulation of CD4+CD25+ regulatory T cells protects from lethal acute GVHD","volume":"105","author":"Ermann","year":"2005","journal-title":"Blood"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1259","article-title":"Characteristics of T-cell responses in COVID-19 patients with prolonged SARS-CoV-2 positivity - a cohort study","volume":"10","author":"Yang","year":"2021","journal-title":"Clin Transl Immunol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.2.179","article-title":"Mortality associated with influenza and respiratory syncytial virus in the united states","volume":"289","author":"Thompson","year":"2003","journal-title":"JAMA"},{"key":"B90","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/cei.12863","article-title":"Age-related alterations in immune responses to West Nile virus infection","volume":"187","author":"Montgomery","year":"2017","journal-title":"Clin Exp Immunol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.529","article-title":"The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection","volume":"18","author":"Haynes","year":"2000","journal-title":"Annu Rev Immunol"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2007.00891.x","article-title":"Immunosenescence: deficits in adaptive immunity in the elderly","volume":"70","author":"Hakim","year":"2007","journal-title":"Tissue Antigens"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2021.09.017","article-title":"Understanding T cell aging to improve anti-viral immunity","volume":"51","author":"Zhang","year":"2021","journal-title":"Curr Opin Virol"},{"key":"B94","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.exger.2017.10.024","article-title":"Age and immunity: What is \"immunosenescence\"","volume":"105","author":"Pawelec","year":"2018","journal-title":"Exp Gerontol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1029006","article-title":"Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID","volume":"13","author":"Kundura","year":"2022","journal-title":"Front Immunol"},{"key":"B96","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1016\/j.immuni.2022.01.017","article-title":"Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease","volume":"55","author":"Vijayakumar","year":"2022","journal-title":"Immunity"},{"key":"B97","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.cell.2021.12.040","article-title":"Complement activation induces excessive T cell cytotoxicity in severe COVID-19","volume":"185","author":"Georg","year":"2022","journal-title":"Cell"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1113932\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T12:26:41Z","timestamp":1675340801000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1113932\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,2]]},"references-count":97,"alternative-id":["10.3389\/fimmu.2023.1113932"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1113932","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,2]]},"article-number":"1113932"}}