{
  "abstract": "Angiotensin-converting enzyme 2 ( ACE2 ) is the cellular receptor for SARS-CoV-2, and its genetic polymorphisms may influence COVID-19 susceptibility. This hospital-based case-control study investigated the association between three ACE2 SNPs (rs2285666, rs4646127, rs971249) and normalized viral load, as well as risk of hospitalization for SARS-CoV-2 infection (comparing hospitalized COVID-19 patients versus hospitalized SARS-CoV-2-negative patients with other severe acute conditions), in 441 participants (226 cases, 215 hospital controls). Genotyping was performed by PCR-RFLP, and viral load was quantified by qRT-PCR and normalized to the RNase P gene. Associations were assessed using sex-stratified logistic regression with Benjamini-Hochberg correction for multiple testing. In females, the rs971249 T allele showed a trend toward higher frequency in controls (48.9% vs. 39.5%; raw p = 0.007), but this association did not remain significant after Benjamini-Hochberg correction (q = 0.12). In males, the T alleles of rs971249 and rs4646127 were associated with reduced infection risk and remained significant after correction for multiple testing (raw p = 0.003, q = 0.048 and raw p = 0.002, q = 0.036, respectively). No significant associations were observed for rs2285666. While no ACE2 polymorphism was significantly associated with normalized viral load after correction for multiple testing (all q > 0.05), rs971249 showed a trend toward higher viral load in heterozygous females that did not reach statistical significance (raw p = 0.052; q = 0.18). For mortality analysis, the reported associations for rs971249 and rs4646127 in females (adjusted OR = 2.54 and 2.73, respectively) are based on covariate-adjusted logistic regression (age, comorbidities, sampling time) but did not undergo Benjamini-Hochberg correction due to the exploratory nature of this subgroup analysis; these findings should be considered hypothesis-generating and are clearly labeled as ‘nominally significant’ in the Results section (raw p < 0.05). However, these findings should be interpreted cautiously due to the limited sample size and the exploratory nature of the subgroup analyses and because the rs971249 variant deviated from Hardy-Weinberg equilibrium in female controls ( p = 0.010). These findings suggest that the rs971249 and rs4646127 T alleles may confer sex-specific protection against hospitalized SARS-CoV-2 infection in this cohort of hospitalized patients. However, because controls were hospitalized patients with severe non-COVID-19 conditions, these associations reflect differences between two hospitalized groups rather than population-level susceptibility. Therefore, large-scale studies with population-based controls and diverse ethnic groups are warranted to validate these sex-specific associations and to clarify the role of ACE2 variants in population-level COVID-19 susceptibility.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Mahnaz Baghershiroodi"
    },
    {
      "name": "Sadegh Fattahi"
    },
    {
      "name": "Arefeh Ebrahimian Shiadeh"
    },
    {
      "name": "Haleh Akhavan-Niaki"
    },
    {
      "name": "Mohammad Hossein Tayefeh-Arbab"
    },
    {
      "name": "Yousef Yahyapour"
    },
    {
      "name": "Farzin Sadeghi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9g4bzm77mwmxn.bib",
  "cited_by": 0,
  "doi": "10.1038/s41598-026-76243-z",
  "fulltext_url": null,
  "id": "9g4bzm77mwmxn",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://www.nature.com/articles/s41598-026-76243-z",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
  ],
  "openalex": "W7223001028",
  "pdf_url": "https://www.nature.com/articles/s41598-026-76243-z_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-20",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/9g4bzm77mwmxn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:31Z",
      "native_id": "10.1038/s41598-026-76243-z",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41598-026-76243-z"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|SARS-CoV-2 and COVID-19 Research",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Sex-specific associations of ACE2 variants with COVID-19 hospitalization, viral load, and mortality: an Iranian hospital-based case-control study",
  "title_text": "Sex-specific associations of ACE2 variants with COVID-19 hospitalization, viral load, and mortality: an Iranian hospital-based case-control study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:31Z",
  "url": "https://research.draconitic.com/paper/9g4bzm77mwmxn",
  "venue": "Scientific Reports",
  "versions": []
}