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Lymphopenia occurs in up to ~52% of patients with sepsis and is associated with a higher mortality at both 30 and 100\u2009days. In COVID\u201019, the presence of lymphopenia correlates with intensive care unit admission, acute respiratory distress syndrome and death. The mechanisms underpinning lymphopenic sepsis remain unknown, and while high rates of lymphocyte apoptosis have been implicated, the relative contributions of cellular trafficking to inflamed tissues and reduction in lymphopoiesis require investigation. Further delineation of these underlying mechanisms holds the potential to open new avenues for the development of host\u2010directed therapies in lymphopenic sepsis. These may include recombinant cytokines (e.g. interleukin\u20107), monoclonal antibodies (e.g. anti\u2010interleukin\u20101, anti\u2010programmed cell death protein 1) and small interfering RNA (e.g. targeting interleukin\u201010, transforming growth factor beta). Applying the frontier tools of translational cellular and genomic medicine to understand lymphopenia in the setting of critical infections holds the potential to significantly reduce the excessive global burden of sepsis.<\/jats:p>","DOI":"10.1111\/imcb.12611","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T08:27:39Z","timestamp":1670228859000},"page":"535-544","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Lymphopenia in sepsis\u2014an acquired immunodeficiency?"],"prefix":"10.1111","volume":"101","author":[{"given":"Simon","family":"Finfer","sequence":"first","affiliation":[{"name":"Critical Care Division, The George Institute University of New South Wales  Sydney NSW Australia"},{"name":"School of Public Health, Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balasubramanian","family":"Venkatesh","sequence":"additional","affiliation":[{"name":"Critical Care Division, The George Institute University of New South Wales  Sydney NSW Australia"},{"name":"Princess Alexandria and Wesley Hospitals  Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S","family":"Hotchkiss","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology, Medicine, and Surgery Washington University School of Medicine  St Louis MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C","family":"Sasson","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Immunopathology Westmead Hospital Sydney  Sydney NSW Australia"},{"name":"The Kirby Institute, University of New South Wales  Sydney NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-06169-1"},{"key":"e_1_2_5_4_1","unstructured":"FinferS.Stopping sepsis: National Action Plan. 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