{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T20:08:42Z","timestamp":1779912522907,"version":"3.53.1"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"24","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","award":["RF-2016-02362512"],"award-info":[{"award-number":["RF-2016-02362512"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,22]]},"abstract":"<jats:p>\n                    A substantial proportion of patients who have recovered from coronavirus disease-2019 (COVID-19) experience COVID-19\u2013related symptoms even months after hospital discharge. We extensively immunologically characterized patients who recovered from COVID-19. In these patients, T cells were exhausted, with increased PD-1\n                    <jats:sup>+<\/jats:sup>\n                    T cells, as compared with healthy controls. Plasma levels of IL-1\n                    <jats:bold>\u03b2<\/jats:bold>\n                    , IL-1RA, and IL-8, among others, were also increased in patients who recovered from COVID-19. This altered immunophenotype was mirrored by a reduced ex vivo T cell response to both nonspecific and specific stimulation, revealing a dysfunctional status of T cells, including a poor response to SARS-CoV-2 antigens. Altered levels of plasma soluble PD-L1, as well as of\n                    <jats:italic>PD1<\/jats:italic>\n                    promoter methylation and\n                    <jats:italic>PD1<\/jats:italic>\n                    -targeting miR\u201315-5p, in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells were also observed, suggesting abnormal function of the PD-1\/PD-L1 immune checkpoint axis. Notably, ex vivo blockade of PD-1 nearly normalized the aforementioned immunophenotype and restored T cell function, reverting the observed post\u2013COVID-19 immune abnormalities; indeed, we also noted an increased T cell\u2013mediated response to SARS-CoV-2 peptides. Finally, in a neutralization assay, PD-1 blockade did not alter the ability of T cells to neutralize SARS-CoV-2 spike pseudotyped lentivirus infection. Immune checkpoint blockade ameliorates post\u2013COVID-19 immune abnormalities and stimulates an anti\u2013SARS-CoV-2 immune response.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.146701","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T12:01:37Z","timestamp":1637064097000},"source":"Crossref","is-referenced-by-count":76,"title":["PD-1 blockade counteracts post\u2013COVID-19 immune abnormalities and stimulates the anti\u2013SARS-CoV-2 immune response"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7583-8540","authenticated-orcid":true,"given":"Cristian","family":"Loretelli","sequence":"first","affiliation":[{"name":"International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Sciences \u201cL. Sacco\u201d, University of Milan, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Abdelsalam","sequence":"additional","affiliation":[{"name":"International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Sciences \u201cL. Sacco\u201d, University of Milan, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0345-0694","authenticated-orcid":true,"given":"Francesca","family":"D\u2019Addio","sequence":"additional","affiliation":[{"name":"International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Sciences \u201cL. Sacco\u201d, University of Milan, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moufida","family":"Ben Nasr","sequence":"additional","affiliation":[{"name":"International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Sciences \u201cL. Sacco\u201d, University of Milan, Milan, Italy."},{"name":"Nephrology Division, Boston Children\u2019s Hospital, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Assi","sequence":"additional","affiliation":[{"name":"International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Sciences \u201cL. 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Sacco\u201d, University of Milan, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4211-5485","authenticated-orcid":true,"given":"Andy Joe","family":"Seelam","sequence":"additional","affiliation":[{"name":"International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Sciences \u201cL. Sacco\u201d, University of Milan, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3770-7205","authenticated-orcid":true,"given":"Elio","family":"Ippolito","sequence":"additional","affiliation":[{"name":"International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Sciences \u201cL. 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