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Despite lower intracellular viral loads than the ancestral strain, Omicron elicits enhanced T-cell apoptosis largely through a bystander mechanism. Omicron-stimulated epithelial cells secrete GDF15, which upregulates the pro-apoptotic protein BCL2L13 in T cells and thereby remotely accelerates apoptosis in uninfected bystanders. Functionally, recombinant GDF15 increases BCL2L13 and apoptosis, while genetic dampening of BCL2L13 blunts Omicron-specific high-intensity bystander death. In clinical samples, plasma GDF15 associates with mortality, SOFA scores, and lower lymphocyte counts, bridging the epithelial\u2013immune axis to patient outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data delineate a two-track model of Omicron immune injury\u2014CD63-enabled T-cell entry plus GDF15\u2013BCL2L13-driven bystander apoptosis\u2014that reconciles lower epithelial cytopathicity with deeper T-cell depletion in critical disease. These findings nominate the GDF15\u2013BCL2L13 axis as a mechanistic marker and potential point of intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41420-026-03079-x","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:04:47Z","timestamp":1774656287000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Variant-divergent death: Omicron intensifies bystander T-cell apoptosis via GDF15\u2013BCL2L13"],"prefix":"10.1038","volume":"12","author":[{"given":"Chao","family":"Gao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanbing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Chi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinxing","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahuang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9526-9613","authenticated-orcid":false,"given":"Ying","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruixuan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6097-9172","authenticated-orcid":false,"given":"Jianfeng","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibo","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7800-3557","authenticated-orcid":false,"given":"Jie","family":"Chao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4857-4532","authenticated-orcid":false,"given":"Shufeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"3079_CR1","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/s41392-022-00919-x","volume":"7","author":"XR Shen","year":"2022","unstructured":"Shen XR, Geng R, Li Q, Chen Y, Li SF, Wang Q, et al. 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