{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T03:53:39Z","timestamp":1777953219346,"version":"3.51.4"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020884","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>\n                      Glucose metabolism disorders (GMDs) are established risk factors for severe COVID-19, but increasing evidence indicates that they may also develop\n                      <jats:italic>de novo<\/jats:italic>\n                      after SARS-CoV-2 infection. Neutrophil extracellular trap formation (NETosis) plays a central role in immunothrombosis, and because neutrophils rely predominantly on glycolysis, they are particularly sensitive to systemic metabolic disturbances. However, the impact of post-COVID-19 GMDs on NETosis remains poorly understood. This study aimed to characterize the emergence of GMDs after COVID-19 and to determine their effect on neutrophil NETosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixty COVID-19 patients were stratified according to the presence or absence of GMDs before infection and at four months post-infection. Demographic, clinical, metabolic, and inflammatory parameters were assessed. Vital NETosis was quantified by flow cytometry. In addition, the capacity of patient plasma to induce NETosis was evaluated using live-cell imaging of healthy neutrophils as biosensors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among patients without pre-existing GMDs, 24 of 36 developed insulin resistance (IR) four months after COVID-19. Neutrophils from these patients exhibited increased basal NETosis but showed impaired NETosis in response to TLR7\/8 agonists, key sensors of viral single-stranded RNA, compared with control groups. In contrast, NETosis responses to IL-6 and TNF-\u03b1 were preserved, excluding an intrinsic neutrophil defect. Plasma from IR patients significantly enhanced NETosis, and\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments demonstrated that insulin enhances NETosis independently of glucose concentrations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>De novo<\/jats:italic>\n                      IR following COVID-19 dysregulates NETosis primarily through an insulin-enhancing effect. Post-viral control of glucose metabolism disorders may be critical to limit pathological NETosis and its thrombo-inflammatory consequences.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1787799","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T14:36:01Z","timestamp":1777905361000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["De novo COVID-19-associated insulin resistance drives dysregulated neutrophil extracellular trap formation (NETosis) four months after infection"],"prefix":"10.3389","volume":"17","author":[{"given":"Sergio","family":"Sanhueza","sequence":"first","affiliation":[{"name":"Molecular and Translational Immunology laboratory, Department of Clinical Biochemistry and Immunology, Pharmacy Faculty, University of Concepcion","place":["Concepcion, 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