{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:10:43Z","timestamp":1788844243462,"version":"build-2803163510"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Obesity is a major risk factor for severe COVID-19, yet the immunological mechanisms by which it modifies disease progression remain incompletely characterized. We aimed to dissect the independent and interactive contributions of obesity and COVID-19 severity on circulating adipokines, cytokines, and immune cell populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sixty patients with confirmed SARS-CoV-2 infection were stratified by disease severity (Mild\/Moderate, n = 8; Severe, n = 30; Critical, n = 22) and obesity status (persons without obesity [PwoO], n = 30; persons with obesity [PwO], n = 30; BMI threshold 30 kg\/m\u00b2). Serum TNF-\u03b1, resistin, IL-1\u03b2, IL-8, and NETs-ISG15 complexes were measured alongside circulating Th1, Th2, Th17, CD8 Treg, CD8 Tcm, intermediate monocytes, and low-density granulocytes (LDGs). Statistical analysis used Aligned Rank Transform ANOVA (ART-ANOVA), followed by Kruskal\u2013Wallis and Dunn\u2019s\n                      <jats:italic>post-hoc<\/jats:italic>\n                      test with Holm adjustment within each obesity stratum.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ART-ANOVA identified three distinct immunological patterns. First, TNF-\u03b1 and resistin were significantly elevated by obesity as independent main effects (p = 0.012 and p = 0.026), with resistin additionally driven by severity (p = 0.0001). Second, IL-1\u03b2, IL-8, and NETs-ISG15 complexes were governed by disease severity (p = 0.0003, p = 0.0003, p = 0.002); IL-1\u03b2 showed a symmetric Severe-to-Critical elevation across obesity strata, whereas IL-8 and NETs-ISG15 were selectively amplified in PwO at the critical stage (Severe vs. Critical: IL-8 p = 0.0002; NETs-ISG15 p = 0.015). Third, CD8 Treg cells and LDGs showed the largest severity-driven effects (both p &amp;lt; 0.0001), with symmetric depletion and expansion across obesity strata, identifying them as severity biomarkers independent of metabolic background. Th17 cells were suppressed by obesity (p = 0.001) and severity (p = 0.021). CD8 Tcm exhibited a unique obesity \u00d7 severity interaction (p = 0.009), with a paradoxical expansion in critical PwO patients, absent in PwoO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Obesity and COVID-19 severity exert distinct, non-interacting effects on the immune landscape, with three exceptions: TNF-\u03b1 and IL-8\/NETs-ISG15 show obesity-conditional amplification of severity, and CD8 Tcm undergoes an obesity-specific expansion at the critical stage. These findings provide a mechanistic framework for obesity-modified immune responses in COVID-19 and identify candidate biomarkers for severity stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1890251","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:27:02Z","timestamp":1788841622000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Obesity and COVID-19 severity independently shape adipokine dysregulation and immune cell remodeling"],"prefix":"10.3389","volume":"17","author":[{"given":"Karla Jimena","family":"Basilio-Aguilar","sequence":"first","affiliation":[{"name":"Red Medicina para la Educaci\u00f3n, el Desarrollo y la Investigaci\u00f3n Cient\u00edfica de Iztacala (MEDICI), Carrera de M\u00e9dico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Tlalnepantla de 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