{
  "abstract": "Introduction: Vaccination and natural infection with Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) confer immune protection through distinct mechanisms, however, their effects on Natural Killer (NK) cell responses remain poorly understood, particularly in relation to COVID-19 disease severity. NK cells, key mediators of anti-viral immunity, have been implicated in coronavirus disease 2019 (COVID-19) pathogenesis, where severe disease is associated with hyperactivated yet dysfunctional NK-cell states that likely impair viral control and contribute to tissue damage.\n\nMethods: To define how vaccination and infection shape NK-cell biology, we performed longitudinal single-cell RNA sequencing (scRNA-seq) of NK cells from SARS-CoV-2-naïve individuals receiving two doses of the BNT162b2mRNA vaccine. These longitudinal vaccine profiles were integrated with cross-sectional scRNA-seq datasets from unvaccinated patients with acute COVID-19 and from independent convalescent individuals, all enrolled before vaccine introduction.\n\nResults: We identified distinct NK cell transcriptional programs associated with vaccination, acute infection and convalescence, with the most pronounced infection-related alterations observed in the severe form of the disease. These diverging transcriptional signatures correlate with differences in NK-cell subset composition and activation markers between vaccinated and infected individuals.\n\nConclusions: Taken together, these findings provide a rationale for future studies examining whether vaccine-associated NK-cell transcriptional programs contribute to durable immune protection.",
  "abstract_shown": true,
  "affiliations": [
    "Unit of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital",
    "Department of Medical Biotechnology and Translational Medicine, University of Milan",
    "Department of Biomedical Sciences, Humanitas University, Pieve Emanuele",
    "Luigi Sacco Department of Biomedical and Clinical Sciences DIBIC, University of Milan",
    "Human Technopole",
    "Institute of Genetics and Biomedical Research, UoS of Milan, National Research Council",
    "Department of Infectious Diseases, Luigi Sacco University Hospital, ASST Fatebenefratelli Sacco",
    "Department of Oncology and Hemato-Oncology, University of Milan",
    "Department of Biomedical Unit, IRCCS Humanitas Research Hospital"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Alessandro Frigo"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Sara Terzoli"
    },
    {
      "affs": [
        0
      ],
      "name": "Paolo Marzano"
    },
    {
      "affs": [
        0
      ],
      "name": "Nicolò Coianiz"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Michela Calvi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lara Orlandi"
    },
    {
      "affs": [
        0
      ],
      "name": "Simone Balin"
    },
    {
      "affs": [
        0
      ],
      "name": "Valentina Cazzetta"
    },
    {
      "affs": [
        0
      ],
      "name": "Anna Carletti"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Silvia Della Bella"
    },
    {
      "affs": [
        0
      ],
      "name": "Joanna Mikulak"
    },
    {
      "affs": [
        3
      ],
      "name": "Maciej Tarkowski"
    },
    {
      "affs": [
        4
      ],
      "name": "Matteo Bonfanti"
    },
    {
      "affs": [
        4
      ],
      "name": "Paolo Ferrari"
    },
    {
      "affs": [
        4
      ],
      "name": "Eugenia Ricciardelli"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Clelia Peano"
    },
    {
      "affs": [
        3,
        6
      ],
      "name": "Agostino Riva"
    },
    {
      "affs": [
        4,
        7
      ],
      "name": "Giuseppe Testa"
    },
    {
      "affs": [
        2,
        8
      ],
      "name": "Antonio Voza"
    },
    {
      "affs": [
        0
      ],
      "name": "Francesca Calcaterra"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Clara Di Vito"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Domenico Mavilio"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d3x6b7a1kc9xk.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1972608",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727542/?tool=EBI",
  "id": "d3x6b7a1kc9xk",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1972608/full",
  "language": "eng",
  "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": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2403|Immune Cell Function and Interaction"
    ]
  ],
  "openalex": "W7214666874",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1972608/pdf",
  "pmcid": "PMC13727542",
  "pmid": "42978614",
  "published": "2026-10-20",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/d3x6b7a1kc9xk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1972608",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1972608/full"
    },
    {
      "first_seen": "2026-11-04T15:20:46Z",
      "native_id": "PMC:PMC13727542",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13727542"
    },
    {
      "first_seen": "2026-11-06T12:23:24Z",
      "native_id": "PMC13727542",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1972608"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune Cell Function and Interaction",
      "subfield": "immunology"
    }
  ],
  "title": "Single-cell profiling of dysfunctional NK cells in COVID-19: from immunization to acute infection and beyond",
  "title_text": "Single-cell profiling of dysfunctional NK cells in COVID-19: from immunization to acute infection and beyond",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:20:42Z",
  "url": "https://research.draconitic.com/paper/d3x6b7a1kc9xk",
  "venue": "Frontiers in Immunology",
  "versions": []
}