{
  "abstract": "The COVID-19 (C19) pandemic caused significant mortality often due to lung injury and systemic inflammation, but there is significant heterogeneity in severity, and the pathobiology is not well understood. We examined C19-induced pulmonary and inflammatory sequelae using a murine noninfectious model to further define the model’s utility and to also understand the role of mediators such as heme oxgenase-1 (HO-1). K18-hACE2 male mice oropharyngeally aspirated C19-spike protein(SP) or equal volume control. After 72 h, pulmonary mechanics, bronchoalveolar lavage (BAL), plasma, snap-frozen right lung, and fixed/stained left lung for histologic injury assessment (Qupath) was collected. Cytokine elaboration in BAL and plasma was quantified (Luminex), and lung homogenates were probed for HO-1 and NLRP3 (Western). Statistical (SPSS and R) and pathways comparisons (Ingenuity Pathway Analysis) were made between control and C19-SP. C19-SP exposure significantly reduced inspiratory capacity and static lung compliance; tissue elastance and airway bronchoconstriction were increased. C19-SP exposure caused significant inflammation and thickened alveolar septae on histology. C19-SP exposure also led to inflammatory response in BAL and plasma with simultaneous activation of Type 1 and Type 2 pathways. NLRP3 and HO-1 protein expression is significantly increased after C19-SP. A noninfectious C19-SP murine model showed worsened lung parameters and increased inflammation. Increased expression of HO-1 and NLRP3 were associated with the inflammatory process after exposure to C19, consistent with findings in human cohorts. Further studies may focus on targeted knock in/knock down experiments and dose/time-course studies that probe the mechanistic relationship of HO-1 and NLRP3 in C19-related disease.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-58934-9.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University Grossman School of Medicine (NYUGSoM), 462 1st Avenue, New York, NY 10016 USA",
    "Division of Environmental Medicine, Department of Medicine, NYUGSoM, New York, NY 10010 USA",
    "Division of Biostatistics, Department of Population Health, NYUGSoM, New York, NY USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sophia Kwon",
      "orcid": "0000-0003-3639-5107"
    },
    {
      "affs": [
        0
      ],
      "name": "Joanna Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Jamie Antelo Rivero",
      "orcid": "0009-0001-1840-9352"
    },
    {
      "affs": [
        0
      ],
      "name": "Hailey Bernier",
      "orcid": "0009-0002-9712-6891"
    },
    {
      "affs": [
        1
      ],
      "name": "Arul Veerappan"
    },
    {
      "affs": [
        2
      ],
      "name": "Mengling Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Gabriele Grunig"
    },
    {
      "affs": [
        0
      ],
      "name": "George Crowley",
      "orcid": "0000-0002-0473-6934"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Anna Nolan",
      "orcid": "0000-0002-0631-1171"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7w3cdk3msz3z0.bib",
  "cited_by": 0,
  "doi": "10.1038/s41598-026-58934-9",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13724262/",
  "id": "7w3cdk3msz3z0",
  "issns": [
    "2045-2322"
  ],
  "landing_url": "https://doi.org/10.1038/s41598-026-58934-9",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2725|COVID-19 Clinical Research Studies"
    ]
  ],
  "openalex": "W7172109080",
  "pdf_url": "https://www.nature.com/articles/s41598-026-58934-9_reference.pdf",
  "pmcid": "PMC13724262",
  "pmid": null,
  "published": "2026-08-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7w3cdk3msz3z0.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:22:52Z",
      "native_id": "PMC13724262",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41598-026-58934-9"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|COVID-19 Clinical Research Studies",
      "subfield": "infectious-disease"
    }
  ],
  "title": "HO-1 and NLRP3-associated lung dysfunction and systemic inflammation in a noninfectious COVID-19 spike protein murine model",
  "title_text": "HO-1 and NLRP3-associated lung dysfunction and systemic inflammation in a noninfectious COVID-19 spike protein murine model",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:20:48Z",
  "url": "https://research.draconitic.com/paper/7w3cdk3msz3z0",
  "venue": "Scientific Reports",
  "versions": []
}