{
  "abstract": "Host genetic variation influencing interferon-γ (IFN-γ) regulation is a critical determinant of immune heterogeneity in COVID-19. We investigated the functional IFNG +874T/A polymorphism (rs2430561), a key regulator of IFN-γ transcription, in 255 PCR-confirmed COVID-19 patients stratified as Outpatient (n = 103), Severe (n = 84), and Critical (n = 68). In parallel, systems-level transcriptomic analyses were conducted using publicly available GEO datasets, including pseudobulk RNA-sequencing of 406 peripheral blood mononuclear cell (PBMC) samples from GSE196198, GSE221066, and GSE300696, categorized into Outpatient (n = 162), Mild–Moderate (n = 140), and Severe–Critical (n = 104) groups, as well as single-nucleus RNA-sequencing of lung tissue from 20 COVID-19 decedents and 7 controls (GSE171524). Genotype-based analyses revealed no significant differences across clinical severity groups under multiple inheritance models. However, the IFNG +874T/A polymorphism showed significant associations with erythrocyte sedimentation rate under the co-dominant model (p = 0.03) and with hematological parameters, including an increased risk of leukopenia associated with the A allele (p = 0.006) and the AA genotype (p = 0.015). At the systemic level, PBMC-derived transcriptomes from Severe–Critical patients demonstrated coordinated upregulation of IFNG, its regulatory antisense transcript IFNG-AS1, and both IFN-γ receptor subunits (IFNGR1 and IFNGR2), indicating preserved transcriptional competence of the IFN-γ signaling axis as disease severity increased. In contrast, lung tissue transcriptomes from COVID-19 decedents did not exhibit parallel activation of the IFN-γ pathway and instead showed modest downregulation of IFNGR1, suggesting impaired tissue-level responsiveness to IFN-γ in advanced disease.",
  "abstract_shown": true,
  "affiliations": [
    "Departments of Internal Medicine, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences",
    "Medical Genetics Center, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences",
    "Biotechnology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences",
    "Hematology and Oncology Research Center, Non-Communicable Diseases Research Institut, e, Shahid Sadoughi University of Medical Sciences"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mohammad Samet"
    },
    {
      "affs": [
        0
      ],
      "name": "Faezeh Niknam"
    },
    {
      "affs": [
        1
      ],
      "name": "Masoud Tajamolian"
    },
    {
      "affs": [
        1
      ],
      "name": "Maryam Karimipanah"
    },
    {
      "affs": [
        0
      ],
      "name": "Mehran Yazdi"
    },
    {
      "affs": [
        2
      ],
      "name": "Panteha Abessi"
    },
    {
      "affs": [
        2
      ],
      "name": "Alireza Nematollahi"
    },
    {
      "affs": [
        3
      ],
      "name": "Seyed Mehdi Hoseini"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cb2k1v3q0vvrb.bib",
  "cited_by": 0,
  "doi": "10.1038/s41598-026-63412-3",
  "fulltext_url": "https://doi.org/10.1038/s41598-026-63412-3",
  "id": "cb2k1v3q0vvrb",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://doi.org/10.1038/s41598-026-63412-3",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "Q"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "2725|COVID-19 Clinical Research Studies"
    ]
  ],
  "openalex": "W7170293281",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/cb2k1v3q0vvrb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:45:56Z",
      "native_id": "11cc0858dae94659ad7e10cb02475ff1",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41598-026-63412-3"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|COVID-19 Clinical Research Studies",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Genetic and transcriptomic evidence linking IFNG +874T/A and IFN-γ signaling to COVID-19 severity",
  "title_text": "Genetic and transcriptomic evidence linking IFNG +874T/A and IFN-γ signaling to COVID-19 severity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T14:20:44Z",
  "url": "https://research.draconitic.com/paper/cb2k1v3q0vvrb",
  "venue": "Scientific Reports",
  "versions": []
}