{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:18:11Z","timestamp":1792091891200,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"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":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Sex\u2010biased differences in COVID\u201019 outcomes in relation to individual SARS\u2010CoV\u20102 variants are not well understood. In this study, lungs and nasal cavities of age\u2010matched female and male K18\u2010hACE2 transgenic mice were collected for dissecting sex\u2010specific differences in pathology after infection of SARS\u2010CoV\u20102 614\u2009G, Delta, or Omicron variant. Overall, Delta infection induced the most severe inflammation and pathology in nasal cavity and lung followed by the 614\u2009G, then Omicron variant. Sex differences in host responses to SARS\u2010CoV\u20102 infection were variant\u2010specific. Delta\u2010infected males showed increased pulmonary infiltration of CD163+ \u201cM2\u201d macrophages, Ly6G+ neutrophils, and NKR\u2010P1C\u2009+\u2009NK cells during early onset of infection, and elevated lung inflammatory cytokines such as IL\u201010, IL\u20106, and IP\u201010 than Delta\u2010infected females. Conversely, females had increased lung CD4\u2009+\u2009T cell recruitment after Omicron infection and significantly elevated lung MCP\u20101 secretion after Delta infection than males. Lung spatial transcriptomics data revealed that Delta\u2010infected females had enriched gene pathways related to humoral immune response and interferon signaling, while males had enriched pathways associated with extracellular matrix production, chemokine signaling, and cell chemotaxis. Taken together, this study highlights the complex infection dynamics with respect to individual SARS\u2010CoV\u20102 variants and underscores the importance of sex as a confounding factor for COVID\u201019 pathology.<\/jats:p>","DOI":"10.1002\/jmv.70506","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T07:55:35Z","timestamp":1753084535000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dissecting Sex\u2010Specific Pathology in K18\u2010hACE2 Transgenic Mice Infected With Different SARS\u2010CoV\u20102 Variants"],"prefix":"10.1002","volume":"97","author":[{"given":"Elysia A.","family":"Masters","sequence":"first","affiliation":[{"name":"Division of Systems Biology, National Center for Toxicological Research United States Food and Drug Administration Jefferson Arkansas 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