{
  "abstract": "Introduction: Long COVID (LC) is characterized by persistent and, often, disabling symptoms, yet its biological basis remains unclear. Multiple mechanisms, including immune dysregulation, endothelial dysfunction, and persistence of SARS-CoV-2 components, have been proposed, although it is unknown whether these define distinct biological subtypes or overlapping processes.\n\nMethods: We conducted a cross-sectional analysis of 312 individuals, including 139 people with LC (PWLC), 99 COVID-19-recovered controls (both groups sampled a median of 8 months after primary SARS-CoV-2 infection), and 74 uninfected controls, from an unvaccinated population, thereby minimizing major sources of biological and epidemiological variability. Circulating immune and endothelial biomarkers and plasma SARS-CoV-2 RNA were assessed, together with serological signatures associated with herpesvirus reactivation and SARS-CoV-2-specific humoral responses. Associations with symptom persistence were analyzed using multivariable models and machine learning approaches.\n\nResults: Most soluble biomarker differences primarily distinguished previously infected individuals from uninfected controls rather than PWLC from recovered participants. Increased IL-1 receptor antagonist (IL-1RA) levels, together with reduced IL-1β/IL-1RA ratios, were the immune alterations most strongly associated with LC, while P-selectin was the endothelial marker showing a suggestive association with symptom persistence. Plasma SARS-CoV-2 RNA was detected at low and comparable frequencies in PWLC and recovered individuals, while Ct values tended to be lower among RNA-positive PWLC not reaching statistical difference. Epstein-Barr virus serological profiles were characterized by lower latency- and higher reactivation-associated responses in PWLC, whereas SARS-CoV-2-specific antibody levels were comparable between groups. Integrated biomarker profiles discriminated prior infection more effectively than LC status, and expansion to multimodal predictors did not clearly improve discrimination between PWLC and recovered participants.\n\nDiscussion: Overall, LC was associated with overlapping immune, endothelial, and virological alterations rather than discrete biomarker-defined subtypes.",
  "abstract_shown": true,
  "affiliations": [
    "IrsiCaixa",
    "ISGlobal",
    "Faculty of Medicine and Health Sciences, Universitat de Barcelona (UB)",
    "Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII)",
    "Germans Trias i Pujol Research Institute (IGTP)",
    "Facultad de Ciencias, Universidad San Sebastián",
    "Biomedicine Doctoral Programme, Faculty of Biology, University of Barcelona (UB)",
    "Infectious Diseases Department, Germans Trias i Pujol Hospital",
    "Fight Against Infections Foundation",
    "Chair in Infectious Diseases and Immunity, Centre for Health and Social Care Research (CESS), Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC)",
    "Spanish Long COVID Research Network (REiCOP)",
    "Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)",
    "Center for Global Health and Diseases, Department of Pathology, Case Western Reserve University School of Medicine",
    "Department of Infectious Diseases and Immunity, University of Vic-Central University of Catalonia (UVic-UCC)",
    "CaixaResearch Institute, “la Caixa” Foundation"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 27,
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    {
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        0
      ],
      "name": "Francisco Muñoz-López"
    },
    {
      "affs": [
        0
      ],
      "name": "Marissa Flores-Santamaría"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Rebeca Santano"
    },
    {
      "affs": [
        0
      ],
      "name": "Macedonia Trigueros"
    },
    {
      "affs": [
        0
      ],
      "name": "Eva Riveira-Muñoz"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Sara Cabrero de las Heras"
    },
    {
      "affs": [
        0
      ],
      "name": "Gooya Banaei"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Edwards Pradenas"
    },
    {
      "affs": [
        0
      ],
      "name": "Benjamin Trinité"
    },
    {
      "affs": [
        0
      ],
      "name": "Silvia Marfil"
    },
    {
      "affs": [
        0
      ],
      "name": "Ana Gervassi"
    },
    {
      "affs": [
        0
      ],
      "name": "Víctor Urrea"
    },
    {
      "affs": [
        0,
        4,
        6
      ],
      "name": "Jon Izquierdo-Pujol"
    },
    {
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        7,
        8,
        9
      ],
      "name": "Cora Loste"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "José Ramón Santos"
    },
    {
      "affs": [
        7,
        8,
        10
      ],
      "name": "Gemma Lladós"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Tomasso Francesco Aiello"
    },
    {
      "affs": [
        8
      ],
      "name": "Anna Chamorro"
    },
    {
      "affs": [
        1,
        11
      ],
      "name": "Alfons Jiménez"
    },
    {
      "affs": [
        1
      ],
      "name": "Carlota Dobaño"
    },
    {
      "affs": [
        0,
        3,
        7,
        8,
        12
      ],
      "name": "Roger Paredes"
    },
    {
      "affs": [
        0,
        3,
        4,
        13
      ],
      "name": "Julià Blanco"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Ester Ballana"
    },
    {
      "affs": [
        1,
        2,
        3,
        14
      ],
      "name": "Gemma Moncunill"
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    {
      "affs": [
        7,
        8,
        9,
        10
      ],
      "name": "Lourdes Mateu"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Nevot"
    },
    {
      "affs": [
        0,
        3,
        10
      ],
      "name": "Marta Massanella"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6myb7r3vt3hx9.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1957339",
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  "metadata_licence": null,
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      "2728|Long-Term Effects of COVID-19"
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  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1957339/pdf",
  "pmcid": "PMC13724367",
  "pmid": "42973492",
  "published": "2026-10-19",
  "publisher": "Frontiers Media SA",
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      "origin": "openalex:2728|Long-Term Effects of COVID-19",
      "subfield": "neurology"
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  "title": "Long COVID shows IL-1 pathway dysregulation without a discrete circulating biomarker signature",
  "title_text": "Long COVID shows IL-1 pathway dysregulation without a discrete circulating biomarker signature",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:21:08Z",
  "url": "https://research.draconitic.com/paper/6myb7r3vt3hx9",
  "venue": "Frontiers in Immunology",
  "versions": []
}