{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:25:00Z","timestamp":1772173500819,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1013170","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000}}],"reference-count":96,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005242","name":"Universit\u00e9 de Montr\u00e9al","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005242","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003151","name":"Fonds de recherche du Qu\u00e9bec \u2013 Nature et technologies","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003151","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["AI170115"],"award-info":[{"award-number":["AI170115"]}]},{"name":"Natural Sciences and Engineering Research Council (NSERC) of Canada and the Public Health Agency of Canada","award":["OMNI-REUNIS"],"award-info":[{"award-number":["OMNI-REUNIS"]}]},{"name":"Natural Sciences and Engineering Research Council (NSERC) of Canada and the Public Health Agency of Canada","award":["OMNI-REUNIS"],"award-info":[{"award-number":["OMNI-REUNIS"]}]},{"name":"Natural Sciences and Engineering Research Council (NSERC) DISCOVERY","award":["RGPIN-2018-04546"],"award-info":[{"award-number":["RGPIN-2018-04546"]}]},{"name":"COVID-19 immunity task force and the Canadian Institute of Health research","award":["VR2-173203"],"award-info":[{"award-number":["VR2-173203"]}]},{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canada Research Chair in Computational Immunology"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in millions of deaths globally. Adults with immunosuppression (e.g., solid organ transplant recipients) and those undergoing active cancer treatments experience worse infections and more severe COVID-19. It is difficult to conduct clinical studies in these populations, resulting in a restricted amount of data that can be used to relate mechanisms of immune dysfunction to COVID-19 outcomes in these vulnerable groups. To study immune dynamics after infection with SARS-CoV-2 and to investigate drivers of COVID-19 severity in individuals with cancer and immunosuppression, we adapted our mathematical model of the immune response during COVID-19 and generated virtual patient cohorts of cancer and immunosuppressed patients. The cohorts of plausible patients recapitulated available longitudinal clinical data collected from patients in Montr\u00e9al, Canada area hospitals. Our model predicted that both cancer and immunosuppressed virtual patients with severe COVID-19 had decreased CD8\u2009+\u2009T cells, elevated interleukin-6 concentrations, and delayed type I interferon peaks compared to those with mild COVID-19 outcomes. Additionally, our results suggest that cancer patients experience higher viral loads (however, with no direct relation with severity), likely because of decreased initial neutrophil counts (i.e., neutropenia), a frequent toxic side effect of anti-cancer therapy. Furthermore, severe cancer and immunosuppressed virtual patients suffered a high degree of tissue damage associated with elevated neutrophils. Lastly, parameter values associated with monocyte recruitment by infected cells were found to be elevated in severe cancer and immunosuppressed patients with respect to the COVID-19 reference group. Together, our study highlights that dysfunctions in type I interferon and CD8\u2009+\u2009T cells are key drivers of immune dysregulation in COVID-19, particularly in cancer patients and immunosuppressed individuals.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1013170","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T13:58:50Z","timestamp":1749477530000},"page":"e1013170","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Using virtual patient cohorts to uncover immune response differences in cancer and immunosuppressed COVID-19 patients"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6972-243X","authenticated-orcid":true,"given":"Sonia 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