{
  "abstract": "Objective and designTo test whether the hypoxia-inducible factor 1-alpha (HIF1A) axis links transcriptional, cellular, biomarker and host-genetic features of severe COVID-19, in a retrospective multi-scale observational study of public cohorts and one hospital cohort.\n\nMaterial or subjects35,268 hospitalized patients (Mexican national registry); 1,100 samples from five bulk RNA-seq cohorts; 25,773 peripheral neutrophils from six individuals; 326 hospitalized patients (Sao Paulo, Brazil); 93 hospitalized patients (University Clinical Center Kragujevac, Serbia).\n\nTreatmentNone.\n\nMethodsWithin-cohort effect sizes for a 10-gene HIF1A panel; single-cell pathway scoring; logistic regression and gradient boosting with SHAP; TaqMan genotyping of HIF1A rs11549465 and rs41508050; cross-validation with bootstrap confidence intervals.\n\nResultsHIF1A (mean Cohens d +0.39) and LDHA (+0.76) were higher in severe disease in all five cohorts. Neutrophils of all three patients who failed extubation scored higher than those of both weaned patients and over-expressed S100A8/A9. C-reactive protein dominated ICU prediction; laboratory variables raised the AUC from 0.636 to 0.794. In Kragujevac, a clinical model predicted severe outcome (AUC 0.84, 95% CI 0.75-0.92). rs11549465 CT/TT carriers had lower mortality (1/11 vs 28/78; p = 0.095).\n\nConclusionsHIF1A pathway activation is reproducible across cohorts and localizes to an alarmin-rich neutrophil state; host-genetic effects require larger cohorts.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Information Technologies Kragujevac, University of Kragujevac"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "M. N. Zivanovic"
    },
    {
      "name": "I. Rakovic"
    },
    {
      "name": "A. Miric"
    },
    {
      "name": "M. Z. Milosavljevic"
    },
    {
      "name": "N. Milivojevic Dimitrijevic"
    },
    {
      "name": "N. Filipovic"
    },
    {
      "name": "J. Kosaric"
    },
    {
      "name": "K. Virijevic"
    },
    {
      "name": "M. Brankovic"
    },
    {
      "name": "T. Mladenovic"
    },
    {
      "name": "B. Popovska Jovicic"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cst4zy2e7ea5j.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.23.26366304",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.23.26366304v1.full",
  "id": "cst4zy2e7ea5j",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.23.26366304v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "infectious diseases"
    ],
    [
      "openalex",
      "2725|COVID-19 Clinical Research Studies"
    ]
  ],
  "openalex": "W7223651469",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.23.26366304v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cst4zy2e7ea5j.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:47Z",
      "native_id": "10.64898/2026.10.23.26366304",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.23.26366304v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:infectious diseases",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Multi-scale analysis of the HIF1A hypoxia-inflammation axis in severe COVID-19",
  "title_text": "Multi-scale analysis of the HIF1A hypoxia-inflammation axis in severe COVID-19",
  "type": "preprint",
  "updated_at": "2026-10-30T12:21:47Z",
  "url": "https://research.draconitic.com/paper/cst4zy2e7ea5j",
  "venue": "medRxiv",
  "versions": []
}