{
  "schema_version": "2.0.0",
  "id": "appelman-2024-lc-muscle",
  "name": "Amsterdam Long COVID muscle-biopsy PEM cohort (Appelman)",
  "aliases": [
    "Amsterdam UMC long COVID exercise/biopsy study"
  ],
  "outbreak_event": "COVID-19 pandemic",
  "pathogen_id": "sars-cov-2",
  "pathogen_class": "virus",
  "exposure_ascertainment": "mixed",
  "design": "case_control",
  "denominator_defined": "no",
  "denominator_method": null,
  "recruitment_source": "outpatient_clinic",
  "time_zero_definition": "Established long COVID with exertion-triggered post-exertional malaise; assessed before and after an exercise challenge",
  "time_zero_precision": "undefined",
  "control_group": "healthy_convenience",
  "control_matching_variables": [
    "age",
    "sex"
  ],
  "n_source_population": null,
  "n_enrolled": 46,
  "n_analysed": 46,
  "followups": [],
  "max_followup_months": null,
  "instruments": [],
  "case_definition": "author_defined",
  "pem_assessed": "yes_validated_instrument",
  "objective_measures": [
    "cpet_two_day",
    "muscle_biopsy",
    "lab_panel"
  ],
  "specimens_collected": true,
  "specimen_types": [
    "muscle_tissue",
    "whole_blood",
    "serum"
  ],
  "acute_phase_specimens": "no",
  "storage": null,
  "biobank_status": "unknown",
  "consent_future_use": "unknown",
  "external_access": "collaboration_only",
  "contact": null,
  "registration_id": "NCT05225688",
  "funders": [
    "Amsterdam UMC",
    "Stichting Long COVID"
  ],
  "conflicts": null,
  "data_availability": null,
  "notes": "Small longitudinal case-control study (25 long COVID patients with PEM vs 21 healthy controls) and the only cohort in this database with tissue-level objective measures: a two-day cardiopulmonary exercise test to induce post-exertional malaise, with skeletal muscle biopsies before and after. It documented exercise-induced myopathy, metabolic disturbance, and amyloid-containing deposits that worsened after PEM. Included for the objective-measures and PEM-assessment gap matrices rather than for symptom prevalence; not denominator-defined for prevalence estimation.",
  "symptom_inventory_scope": "single_domain",
  "n_symptoms_queried": null,
  "symptom_instrument_note": "Selected specifically for post-exertional malaise; not a general symptom-prevalence survey.",
  "related_cohorts": [],
  "last_verified": "2026-07-20",
  "verified_by": "OSMF research-tracker (web-verified against source)",
  "publications": [
    {
      "id": "appelman-2024",
      "title": "Muscle abnormalities worsen after post-exertional malaise in long COVID",
      "authors": "Appelman B, Charlton BT, Goulding RP, et al.",
      "year": 2024,
      "journal": "Nature Communications",
      "doi": "10.1038/s41467-023-44432-3",
      "pmid": "38177128",
      "url": "https://pubmed.ncbi.nlm.nih.gov/38177128/",
      "open_access": true,
      "is_primary_cohort_paper": true
    }
  ],
  "harmonisation_ruleset": "pais-harmony-v1",
  "observations": [
    {
      "id": "appelman-myopathy-postpem",
      "cohort_id": "appelman-2024-lc-muscle",
      "publication_id": "appelman-2024",
      "schema_version": "2.0.0",
      "measure_id": "physio:skeletal-muscle-pathology",
      "measure_verbatim": "exercise-induced myopathy, metabolic disturbance and amyloid-containing deposits in skeletal muscle, worsening after post-exertional malaise",
      "population": { "scope": "whole_cohort", "stratum": null, "denominator_basis": "assessed_at_timepoint", "n_assessed": 25 },
      "timing": { "timepoint_months": null, "timepoint_band": "unspecified", "reference_period": "not_applicable", "is_cumulative": false },
      "method": { "ascertainment": "physiologic_test", "instrument_id": null, "severity_threshold": null, "blinded_assessment": "not_reported" },
      "value": { "type": "qualitative", "text": "Muscle biopsies after a two-day CPET-induced post-exertional malaise showed severe exercise-induced myopathy (atrophic fibres, focal necrosis), local and systemic metabolic disturbance, and amyloid-containing deposits; abnormalities were worse post-PEM than at baseline. No prevalence is reported — this is a mechanistic tissue finding.", "n_supporting": 25 },
      "comparator": { "group": "healthy_convenience", "value": { "status": "measured_not_reported" }, "effect": null },
      "harmonised": null,
      "provenance": { "source_locator": "Abstract / Results (muscle biopsy pre/post exercise)", "extracted_by": null, "extracted_on": null, "verified_by": "OSMF research-tracker (web-verified against source)", "verified_on": "2026-07-20", "extraction_method": "manual" }
    }
  ]
}