{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T04:48:18Z","timestamp":1771649298776,"version":"3.50.1"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100022656","name":"Nimes University Hospital","doi-asserted-by":"publisher","award":["NIMAO\/2020\/COVID\/PC_0"],"award-info":[{"award-number":["NIMAO\/2020\/COVID\/PC_0"]}],"id":[{"id":"10.13039\/501100022656","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"ANR","doi-asserted-by":"publisher","award":["216261"],"award-info":[{"award-number":["216261"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Genetic defects in the ability to deliver effective perforin have been reported in patients with hemophagocytic lymphohistiocytosis. We tested the hypothesis that a primary perforin deficiency might also be causal in severe SARS-CoV-2 infection. We recruited 54 volunteers confirmed as being SARS-CoV-2\u2013infected by RT-PCR and admitted to intensive care units or non\u2013intensive care units and age- and sex-matched healthy controls. Compared with healthy controls, the percentage of perforin-expressing CD3\u2212CD56+ NK cells quantified by flow cytometry was low in COVID-19 patients (69.9 \u00b1 17.7 versus 78.6 \u00b1 14.6%, p = 0.026). There was no correlation between the proportions of perforin-positive NK cells and T8 lymphocytes. Moreover, the frequency of NK cells producing perforin was neither linked to disease severity nor predictive of death. Although IL-6 is known to downregulate perforin production in NK cells, we did not find any link between perforin expression and IL-6 plasma level. However, we unveiled a negative correlation between the degranulation marker CD107a and perforin expression in NK cells (r = \u22120.488, p = 10\u22124). PRF1 gene expression and the frequency of NK cells harboring perforin were normal in patients 1 y after acute SARS-CoV-2 infection. A primary perforin defect does not seem to be a driver of COVID-19 because NK perforin expression is 1) linked neither to T8 perforin expression nor to disease severity, 2) inversely correlated with NK degranulation, and 3) normalized at distance from acute infection. Thus, the cause of low frequency of perforin-positive NK cells appears, rather, to be consumption.<\/jats:p>","DOI":"10.4049\/jimmunol.2300359","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T13:52:18Z","timestamp":1707745938000},"page":"1105-1112","source":"Crossref","is-referenced-by-count":2,"title":["Low Percentage of Perforin-Expressing NK Cells during Severe SARS-CoV-2 Infection: Consumption Rather than Primary Deficiency"],"prefix":"10.1093","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3047-930X","authenticated-orcid":false,"given":"Lucy","family":"Kundura","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, UMR9002, CNRS and Montpellier University , Montpellier 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N\u00eemes University Hospital , N\u00eemes ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6463-9386","authenticated-orcid":false,"given":"Albert","family":"Sotto","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, N\u00eemes University Hospital , N\u00eemes ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6587-1876","authenticated-orcid":false,"given":"Tu-Anh","family":"Tran","sequence":"additional","affiliation":[{"name":"Pediatrics Department, N\u00eemes University Hospital , N\u00eemes ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9432-8044","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Estaquier","sequence":"additional","affiliation":[{"name":"INSERM U1124, Universit\u00e9 de Paris , Paris ,","place":["France"]},{"name":"Laval 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