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Publications

Journal Article Epublish

PubMed: 39901177 DOI: 10.1186/s12916-025-03881-x

Exploring DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVID.

BMC Med 23(1):60

Authors: Andrea Polli, Lode Godderis, Dries S Martens, Madhura Shekhar Patil, Jolien Hendrix, Arne Wyns, Jente Van Campenhout, Emma Richter, Lara Fanning, Olivia Vandekerckhove, Eveline Claeys, Wim Janssens, Natalie Lorent

Affiliations

  • Department of Public Health and Primary Care, Centre for Environment & Health, KU Leuven, O&N5 Herestraat 49, Leuven, Belgium.
  • Pain in Motion (PiM) International Research Group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Rehabilitation Sciences & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.
  • Flanders Research Foundation - FWO, Brussels, Belgium.
  • Department of Public Health and Primary Care, Centre for Environment & Health, KU Leuven, O&N5 Herestraat 49, Leuven, Belgium.
  • External Service for Prevention and Protection at Work, IDEWE, Heverlee, Belgium.
  • Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium.
  • Pain in Motion (PiM) International Research Group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Rehabilitation Sciences & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.
  • Flanders Research Foundation - FWO, Brussels, Belgium.
  • Department of Respiratory Diseases, University Hospital Leuven, Leuven, Belgium.
  • Department of Chronic Diseases, Metabolism and Aging (CHROMETA)-BREATHE Laboratory, KU Leuven, Leuven, Belgium.

Abstract

BACKGROUND

Long-COVID is defined as the persistency or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. Common persistent symptoms are fatigue, sleep disturbances, post-exertional malaise (PEM), pain, and cognitive problems. Long-COVID is estimated to be present in about 65 million people. We aimed to explore clinical and biological factors that might contribute to Long-COVID.

METHODS

Prospective longitudinal cohort study including patients infected with SARS-CoV-2 between March 2020 and March 2022. Patients were assessed between 4 and 12 months after infection at the COVID follow-up clinic at UZ Leuven. We performed a comprehensive clinical assessment (including questionnaires and the 6-min walking test) and biological measures (global DNA methylation, telomere length, mitochondrial DNA copy number, inflammatory cytokines, and serological markers such as C-reactive protein, D-dimer, troponin T).

RESULTS

Of the 358 participants, 328 were hospitalised, of which 130 had severe symptoms requiring intensive care admission; 30 patients were ambulatory referrals. Based on their clinical presentation, we could identify 6 main clusters. One-hundred and twenty-seven patients (35.4%) belonged to at least one cluster. The bigger cluster included PEM, fatigue, sleep disturbances, and pain (n = 57). Troponin T and telomere shortening were the two main markers predicting Long-COVID and PEM-fatigue symptoms.

CONCLUSIONS

Long-COVID is not just one entity. Different clinical presentations can be identified. Cardiac involvement (as measured by troponin T levels) and telomere shortening might be a relevant risk factor for developing PEM-fatigue symptoms and deserve further exploring.

MeSH

Pain, Telomere Shortening, Sleep, Troponin, Signs And Symptoms, Dna Methylation, Dna, Mitochondrial, Fatigue, Dna, Telomere, Infections, Post-Acute Covid-19 Syndrome

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