{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:45:53Z","timestamp":1791945953372,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Patients with femur fractures who are concurrently infected with COVID\u201019 face a threefold increase in mortality, likely due to a compounded inflammatory response. Furthermore, sex\u2010specific differences in immune responses to COVID\u201019 are well documented, implicating biological sex as a factor that can modulate disease severity in these comorbid conditions. Understanding the inflammatory interplay underlying this association is critical for the development of effective, targeted therapies to mitigate mortality. In this study, we investigated the systemic, sex\u2010specific inflammatory response in mice that sustain a fracture while infected with a murine coronavirus (MHV), which belongs to the same genus as SARS\u2010CoV\u20102. The combined inflammatory insults of MHV infection and fracture (MHV\u2009+\u2009FX) disrupted systemic immunity in both females and males, producing immune dysregulation characterized by altered cell recruitment and a perturbed inflammatory cascade. In the MHV\u2009+\u2009FX group, females showed recovery toward a cytotoxic T cell dominant profile by Day 7, whereas males exhibited persistent cytotoxic T cell suppression with relatively higher T helper cells. Cytokine patterns were also sexually dimorphic: females displayed sustained increases in IL\u201018 and TNF\u2010\u03b1 in the MHV\u2009+\u2009FX group alone, whereas males showed distinct modulation of IL\u20102\/IL\u20102R and transient changes in chemokines such as CCL7 and IL\u20104 in both the MHV and MHV\u2009+\u2009FX groups. Notably, these differences were minimal or moderate in control or fracture alone groups. Our findings indicate that sex\u2010divergent immune programs under a dual viral\u2010trauma insult, marked by cytotoxic vs helper T\u2010cell biases and distinct cytokine signatures, help explain the heightened risk when COVID\u201019 and fractures coincide. These insights support sex\u2010aware immunomodulatory strategies to improve outcomes for COVID\u201019 patients with musculoskeletal trauma.<\/jats:p>","DOI":"10.1002\/jmv.70654","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T12:57:02Z","timestamp":1761224222000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sexual Dimorphism in Systemic Inflammatory Responses to Femur Fracture in Mice Infected With SARS\u2010CoV\u20102\u2010Like Virus"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8775-5750","authenticated-orcid":false,"given":"Matthew D.","family":"Patrick","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University at Buffalo Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Aneja","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramkumar T.","family":"Annamalai","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University at Buffalo Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"WHO. 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