{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T09:08:50Z","timestamp":1785575330102,"version":"3.56.0"},"reference-count":62,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R35 GM126928"],"award-info":[{"award-number":["R35 GM126928"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,24]]},"abstract":"<jats:p>BACKGROUND. Lymphopenia and failure of lymphocytes to mount an early IFN-\u03b3 response correlate with increased mortality in COVID-19. Given the essential role of CD4 helper and CD8 cytotoxic cells in eliminating viral pathogens, this profound loss in lymphocytes may impair patients\u2019 ability to eliminate the virus. IL-7 is a pleiotropic cytokine that is obligatory for lymphocyte survival and optimal function.<\/jats:p>\n                  <jats:p>METHODS. We conducted a prospective, double-blind, randomized, placebo-controlled trial of CYT107, recombinant human IL-7, in 109 critically ill, patients with lymphopenia who have COVID-19. The primary endpoint was to assess CYT107\u2019s effect on lymphocyte recovery with secondary clinical endpoints including safety, ICU and hospital length-of-stay, incidence of secondary infections, and mortality.<\/jats:p>\n                  <jats:p>RESULTS. CYT107 was well tolerated without precipitating a cytokine storm or worsening pulmonary function. Absolute lymphocyte counts increased in both groups without a significant difference between CYT107 and placebo. Patients with COVID-19 receiving CYT107 but not concomitant antiviral medications, known inducers of lymphopenia, had a final lymphocyte count that was 43% greater than placebo (P = 0.067). There were significantly fewer treatment-emergent adverse events in CYT107 versus placebo-treated patients (P &lt; 0.001), consistent with a beneficial drug effect. Importantly, CYT107-treated patients had 44% fewer hospital-acquired infections versus placebo-treated patients (P = 0.014).<\/jats:p>\n                  <jats:p>CONCLUSION. Given that hospital-acquired infections are responsible for a large percentage of COVID-19 deaths, this effect of CYT107 to decrease nosocomial infections could substantially reduce late morbidity and mortality in this highly lethal disease. The strong safety profile of CYT107 and its excellent tolerability provide support for trials of CYT107 in other potential pandemic respiratory viral infections.<\/jats:p>\n                  <jats:p>TRIAL REGISTRATION. NCT04379076, NCT04426201, NCT04442178, NCT04407689, NCT04927169.<\/jats:p>\n                  <jats:p>FUNDING. Funding for the trial was provided by RevImmune and the Cancer Research Institute.<\/jats:p>","DOI":"10.1172\/jci.insight.189150","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T12:02:28Z","timestamp":1738670548000},"source":"Crossref","is-referenced-by-count":23,"title":["A randomized, double-blind, placebo-controlled trial of IL-7 in critically ill patients with COVID-19"],"prefix":"10.1172","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5338-2538","authenticated-orcid":true,"given":"Manu","family":"Shankar-Hari","sequence":"first","affiliation":[{"name":"Department of Translational Critical Care Medicine, Centre for Inflammation Research, Institute for Regeneration and Repair, The University of Edinburgh, Scotland, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Francois","sequence":"additional","affiliation":[{"name":"Medical-Surgical ICU & Inserm CIC 1435 Centre Hospitalier 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