Exploring DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVID
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 malais...
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2025-02-01
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| Online Access: | https://doi.org/10.1186/s12916-025-03881-x |
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| author | 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 |
| author_facet | 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 |
| author_sort | Andrea Polli |
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| description | 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. |
| format | Article |
| id | doaj-art-de9680111ee84558b6af4a30c9005066 |
| institution | Kabale University |
| issn | 1741-7015 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj-art-de9680111ee84558b6af4a30c90050662025-02-09T12:40:54ZengBMCBMC Medicine1741-70152025-02-0123111210.1186/s12916-025-03881-xExploring DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVIDAndrea Polli0Lode Godderis1Dries S. Martens2Madhura Shekhar Patil3Jolien Hendrix4Arne Wyns5Jente Van Campenhout6Emma Richter7Lara Fanning8Olivia Vandekerckhove9Eveline Claeys10Wim Janssens11Natalie Lorent12Department of Public Health and Primary Care, Centre for Environment & Health, KU LeuvenDepartment of Public Health and Primary Care, Centre for Environment & Health, KU LeuvenCentre for Environmental Sciences, Hasselt UniversityDepartment of Public Health and Primary Care, Centre for Environment & Health, KU LeuvenDepartment of Public Health and Primary Care, Centre for Environment & Health, KU LeuvenPain in Motion (PiM) International Research Group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Rehabilitation Sciences & Physiotherapy, Vrije Universiteit BrusselPain in Motion (PiM) International Research Group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Rehabilitation Sciences & Physiotherapy, Vrije Universiteit BrusselDepartment of Public Health and Primary Care, Centre for Environment & Health, KU LeuvenDepartment of Public Health and Primary Care, Centre for Environment & Health, KU LeuvenDepartment of Respiratory Diseases, University Hospital LeuvenDepartment of Respiratory Diseases, University Hospital LeuvenDepartment of Respiratory Diseases, University Hospital LeuvenDepartment of Respiratory Diseases, University Hospital LeuvenAbstract 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.https://doi.org/10.1186/s12916-025-03881-xLong-COVIDPost-acute COVID-19 syndromePACSTelomere lengthImmune system |
| spellingShingle | 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 Exploring DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVID BMC Medicine Long-COVID Post-acute COVID-19 syndrome PACS Telomere length Immune system |
| title | Exploring DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVID |
| title_full | Exploring DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVID |
| title_fullStr | Exploring DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVID |
| title_full_unstemmed | Exploring DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVID |
| title_short | Exploring DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVID |
| title_sort | exploring dna methylation telomere length mitochondrial dna and immune function in patients with long covid |
| topic | Long-COVID Post-acute COVID-19 syndrome PACS Telomere length Immune system |
| url | https://doi.org/10.1186/s12916-025-03881-x |
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