{
  "abstract": "Introduction: Despite extensive studies, many questions remain regarding the pathology and mechanisms behind Coronavirus disease 2019 (COVID-19), and particularly on post-acute sequelae of COVID-19 (PASC).\n\nMethods: Because existing mouse models cannot recapitulate human immune responses, we developed a human immune system (HIS) mouse model with physiologic expression of hACE2.\n\nResults and discussion: After intranasal infection, persistent viral RNA was observed in multiple organs for 8 weeks, despite the generation of human SARS-CoV-2-specific T cell responses. Human immune cells increased the presence of viral RNA in the lung and non-pulmonary tissues. COVID-19-related pathology was recapitulated in the lungs, with fibrosis peaking at 14 days post-infection. Immune activation was detected in the lungs, hearts, intestines and brains of acutely infected mice and persisted at 8 weeks in the heart and lungs. The presence of human T cells correlated with attenuated innate antiviral transcriptional signatures in the lung, where a persisting cytotoxic mature CD4+ T cell population with JAK-STAT activation was enriched in infected mice. Thus, human T cells mount an antigen-specific but ultimately dysfunctional response, while paradoxically suppressing the innate interferon response, permitting chronic interferon activation and long-term persistence of viral RNA, recapitulating several immunologic and histopathologic features associated with PASC. This model will uniquely facilitate understanding of virus-human immune dynamics and therapeutic approaches to PASC-related immunological features.",
  "abstract_shown": true,
  "affiliations": [
    "Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, Columbia University",
    "Department of Microbiology and Immunology, Columbia University Medical Center, Columbia University",
    "Institute of Comparative Medicine, Columbia University Medical Center, Columbia University",
    "Department of Pathology and Cell Biology, Columbia University Medical Center, Columbia University",
    "Aaron Diamond AIDS Research Center, Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, Columbia University",
    "Department of Surgery, Columbia University Medical Center, Columbia University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Amber Wolabaugh"
    },
    {
      "affs": [
        0
      ],
      "name": "Vrushali V. Agashe"
    },
    {
      "affs": [
        0
      ],
      "name": "Zicheng Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Nichole M. Danzl"
    },
    {
      "affs": [
        0
      ],
      "name": "Christopher A. Parks"
    },
    {
      "affs": [
        0
      ],
      "name": "Mohsen Khosravi-Maharlooei"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaolan Ding"
    },
    {
      "affs": [
        0
      ],
      "name": "Hao Wei Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Candace Castagna"
    },
    {
      "affs": [
        0
      ],
      "name": "Giorgia Zanetti"
    },
    {
      "affs": [
        0
      ],
      "name": "Katherine D. Long"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yasmeen S. Saad"
    },
    {
      "affs": [
        3
      ],
      "name": "Anjali Saqi"
    },
    {
      "affs": [
        4
      ],
      "name": "Moriya Tsuji"
    },
    {
      "affs": [
        0,
        1,
        5
      ],
      "name": "Megan Sykes"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1z8aad32ykh8v.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1951246",
  "fulltext_url": null,
  "id": "1z8aad32ykh8v",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1951246/full",
  "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": "W7223173774",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1951246/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/1z8aad32ykh8v.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1951246",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1951246/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|SARS-CoV-2 and COVID-19 Research",
      "subfield": "infectious-disease"
    }
  ],
  "title": "A novel model demonstrating that human immune cells promote multiorgan SARS-CoV-2 dissemination and human T cells limit anti-viral innate immunity",
  "title_text": "A novel model demonstrating that human immune cells promote multiorgan SARS-CoV-2 dissemination and human T cells limit anti-viral innate immunity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:17Z",
  "url": "https://research.draconitic.com/paper/1z8aad32ykh8v",
  "venue": "Frontiers in Immunology",
  "versions": []
}