{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T01:56:07Z","timestamp":1780451767790,"version":"3.54.1"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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                      In regions where dengue and COVID-19 co-circulate, cross-reactive antibodies elicited by SARS-CoV-2 may exacerbate dengue severity. This exploratory, cross-sectional, observational pilot study evaluated whether prior SARS-CoV-2 exposure modulated dengue pathogenesis through proteomic profiling and\n                      <jats:italic>in vitro<\/jats:italic>\n                      assays, identifying putative biomarkers and immune pathways for further validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Eighteen participants from Oaxaca, Mexico, were prospectively stratified into four cohorts: healthy controls (CG), dengue with anti-SARS-CoV-2 IgG (NS1\/SARS_IgG), dengue with both anti-SARS-CoV-2 and anti-dengue IgG (NS1\/SARS-DENV_IgG), and dengue with anti-dengue IgG only (NS1\/DENV_IgG). The serum levels of IL-6 and C-reactive protein (CRP) were quantified, and proteomic analysis was performed using label-free Liquid Chromatography-Tandem Mass Spectrometry (LC\u2013MS\/MS).\n                      <jats:italic>In vitro<\/jats:italic>\n                      antibody-dependent enhancement (ADE) assays were performed using the DENV-1 and K562 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The NS1\/DENV_IgG group exhibited the most severe clinical presentation, including 39 \u00b0C fever and 50% thrombocytopenia. In contrast, the NS1\/SARS-DENV_IgG group presented milder symptoms. IL-6 and CRP concentrations peaked in the NS1\/SARS_IgG group (18.3 \u00b1 15.6 pg\/mL and 51.6 \u00b1 29.6 mg\/L, respectively). Proteomic profiling identified 279 high-confidence proteins and 18 differentially expressed proteins (DEPs). The NS1\/SARS-DENV_IgG group showed enrichment in the complement\/coagulation pathways (p = 0.016) and TGF-\u03b2 signaling (p = 0.022). DEPs, including thrombospondin-1 and PRG2, have been implicated in Th2 polarization and ADE-like immune dysregulation. ADE assays confirmed that anti-SARS-CoV-2 serum enhanced DENV replication\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Prior SARS-CoV-2 exposure may potentiate dengue severity via cross-reactive antibody-mediated immune modulation, skewing toward Th2 responses and enhancing viral replication. These findings suggest novel candidate biomarkers for stratifying the dengue risk in co-endemic regions. However, the study\u2019s exploratory nature, small cohort (n = 18), pooled proteomic methodology, and limited clinical characterization necessitate validation in larger longitudinal studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1696179","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T06:35:15Z","timestamp":1767854115000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Pilot proteomic analysis of immune dysregulation in dengue with prior SARS-CoV-2 infection"],"prefix":"10.3389","volume":"16","author":[{"given":"Elizabeth","family":"Cruz-Altamirano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel Angel","family":"Mayoral-Ch\u00e1vez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis 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