{
  "abstract": "Introduction\n\nSex-related differences in coronavirus disease 2019 (COVID-19) severity suggest an important role for sex steroids in regulating immune and endothelial responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Methods\n\nReceptor expression, inflammatory signaling, and monocyte transendothelial migration were assessed by RT-PCR, immunoblotting, and Boyden chamber assay, respectively. HULEC-5a and primary human immune cells were exposed to in vitro-amplified SARS-CoV-2. Samples were collected between June 2020 and April 2022, with sample sizes based on primary sample availability and independent experiments.Results\n\nSARS-CoV-2 differentially regulates estrogen receptor gene expression, decreasing it in endothelial cells (p<0.05) while increasing it in immune cells (p<0.01). SARS-CoV-2 generally activated inflammatory signaling pathways, including NFκB, STAT3, and p38 MAPK, in THP-1 monocytic cells (up to 1.9-fold). The NFκB response was augmented by the androgen receptor agonist dihydrotestosterone (DHT, 44.6%) and attenuated by the androgen receptor antagonist flutamide (44.1%). In endothelial cells, DHT twice reduced SARS-CoV-2 activation of the p38 MAPK signaling pathway. β-estradiol inhibited (2.2-fold), whereas DHT stimulated (4.9-fold) NFκB signaling pathway in neutrophils isolated from patients with COVID-19. SARS-CoV-2 activation of inflammatory signaling pathways deteriorates over time in monocytes from patients with COVID-19 (p<0.05). Furthermore, DHT significantly increased trans-endothelial migration of monocytes (p<0.001) and detachment of SARS-CoV-2 exposed endothelial cells (p<0.01), suggesting a potential role for androgen-responsive pathways in endothelial dysfunction and immune cell trafficking.Discussion\n\nThese findings elucidate the molecular mechanisms driving male-biased COVID-19 severity and underscore the potential of targeting androgen-responsive pathways as a therapeutic strategy to mitigate severe viral inflammation and endothelial dysfunction.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular Oncology, Clinic of Hematology, University Clinical Center of Serbia, Belgrade, Serbia.",
    "Department of Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.",
    "Department of Molecular Oncology, Institute of Virology, Vaccines and Sera \"Torlak\", Belgrade, Serbia.",
    "Department of Microbiology, University Clinical Centre of Serbia, Belgrade, Serbia."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sandra Bižić-Radulović"
    },
    {
      "affs": [
        1
      ],
      "name": "Tijana Subotički"
    },
    {
      "affs": [
        2
      ],
      "name": "Ana Kovačević"
    },
    {
      "affs": [
        1
      ],
      "name": "Emilija Živković"
    },
    {
      "affs": [
        2
      ],
      "name": "Olga Popović"
    },
    {
      "affs": [
        1
      ],
      "name": "Olivera Mitrović-Ajtić"
    },
    {
      "affs": [
        1
      ],
      "name": "Miloš Diklić"
    },
    {
      "affs": [
        3
      ],
      "name": "Snežana Jovanović"
    },
    {
      "affs": [
        1
      ],
      "name": "Vladan P Čokić"
    },
    {
      "affs": [
        2
      ],
      "name": "Bojana Beleslin-Čokić"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3hmc2nmkwcsck.bib",
  "cited_by": 0,
  "doi": "10.3389/fcimb.2026.1976945",
  "fulltext_url": "https://europepmc.org/articles/PMC13713274",
  "id": "3hmc2nmkwcsck",
  "issns": [
    "2235-2988"
  ],
  "landing_url": "https://europepmc.org/article/MED/42952489",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2725|COVID-19 Clinical Research Studies"
    ]
  ],
  "openalex": "W7221800416",
  "pdf_url": "https://europepmc.org/articles/PMC13713274?pdf=render",
  "pmcid": "PMC13713274",
  "pmid": "42952489",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/3hmc2nmkwcsck.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:34Z",
      "native_id": "MED:42952489",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42952489"
    },
    {
      "first_seen": "2026-10-31T12:23:51Z",
      "native_id": "PMC13713274",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcimb.2026.1976945"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|COVID-19 Clinical Research Studies",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Sex steroids differentially modulate SARS-CoV-2-induced inflammatory responses in endothelial and immune cells.",
  "title_text": "Sex steroids differentially modulate SARS-CoV-2-induced inflammatory responses in endothelial and immune cells.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:20:58Z",
  "url": "https://research.draconitic.com/paper/3hmc2nmkwcsck",
  "venue": "Frontiers in cellular and infection microbiology",
  "versions": []
}