{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T07:58:16Z","timestamp":1771660696101,"version":"3.50.1"},"reference-count":25,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Fiocruz\/INOVA COVID-19","award":["VPPCB-005-FIO-20"],"award-info":[{"award-number":["VPPCB-005-FIO-20"]}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico do Brasil","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MercoSur Fund for Structural Convergence"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Coronavirus disease 2019 (COVID-19) can progress to severe pneumonia with respiratory failure and is aggravated by the deregulation of the immune system causing an excessive inflammation including the cytokine storm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we report that severe acutely infected patients have high levels of both type-1 and type-2 cytokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results show abnormal cytokine levels upon T-cell stimulation, in a nonpolarized profile. Furthermore, our findings indicate that this hyperactive cytokine response is associated with a significantly increased frequency of late-differentiated T cells with particular phenotype of effector exhausted\/senescent CD28\u2212CD57+ cells. Of note, we demonstrated for the first time an increased frequency of CD3+CD4+CD28\u2212CD57+ T cells with expression of programmed death 1, one of the hallmarks of T-cell exhaustion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings reveal that COVID-19 is associated with acute immunodeficiency, especially within the CD4+ T-cell compartment, and points to possible mechanisms of loss of clonal repertoire and susceptibility to viral relapse and reinfection events.<\/jats:p><\/jats:sec>","DOI":"10.1093\/infdis\/jiab425","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T15:34:13Z","timestamp":1629819253000},"source":"Crossref","is-referenced-by-count":15,"title":["Critically Ill Coronavirus Disease 2019 Patients Exhibit Hyperactive Cytokine Responses Associated With Effector Exhausted Senescent T Cells in Acute Infection"],"prefix":"10.1093","author":[{"given":"Ang\u00e9lica","family":"Arcanjo","sequence":"first","affiliation":[{"name":"Medical Biochemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamila","family":"Guimar\u00e3es Pinto","sequence":"additional","affiliation":[{"name":"Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorgete","family":"Logullo","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo Em\u00edlio Corr\u00eaa","family":"Leite","sequence":"additional","affiliation":[{"name":"Directory of Metrology Applied to Life Sciences \u2013 DIMAV, National Institute of Metrology Quality and Technology \u2013 INMETRO, 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Fiocruz, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvaro","family":"Luiz Bertho","sequence":"additional","affiliation":[{"name":"Immunoparasitology Laboratory, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula Mello","family":"De Luca","sequence":"additional","affiliation":[{"name":"Immunoparasitology Laboratory, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Mauro Granjeiro","sequence":"additional","affiliation":[{"name":"Directory of Metrology Applied to Life Sciences \u2013 DIMAV, National Institute of Metrology Quality and Technology \u2013 INMETRO, Duque de Caxias, Rio de Janeiro, Brazil"},{"name":"Dental School, Fluminense Federal University \u2013 UFF, Niteroi, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shana Priscila","family":"Coutinho Barroso","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory, Institute of Biomedical Research, Marc\u00edlio Dias Naval Hospital, Navy of Brazil, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F\u00e1tima","family":"Concei\u00e7\u00e3o-Silva","sequence":"additional","affiliation":[{"name":"Immunoparasitology Laboratory, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilson","family":"Savino","sequence":"additional","affiliation":[{"name":"Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil"},{"name":"National Institute of Science and Technology on Neuroimmunomodulation - INCT-NIM, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil"},{"name":"Rio de Janeiro Research Network on Neuroinflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio 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