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Research on Fatigue in Long-COVID

20th January 2023

The chronic exhaustion syndrome "fatigue" not only severely limits the quality of life of cancer patients, but also frequently occurs as a consequence of surviving COVID-19 infection. By studying a total of 100 patients, researchers from three scientific institutions in Baden-Württemberg want to gain new insights into fatigue to identify new targets for the therapy of fatigue associated with long-COVID.

The collaborative project "Multimodal Characterization of Liquor-Specific Signatures in Long-COVID" is one of a total of 12 projects statewide funded by the Baden-Württemberg Ministry of Science, Research and the Arts over a period of two years as part of the special funding measure for research into long-COVID.

"Fatigue and exhaustion reduce the resilience as well as the quality of life of many Long-COVID patients. To be able to help those affected as quickly as possible, the underlying mechanisms of this fatigue syndrome must be investigated. The new collaborative project has the potential to identify diagnostic as well as therapeutic approaches - and ultimately to help fatigue sufferers back into life", says Petra Olschowski, Baden-Württemberg's Minister of Science.

Fatigue refers to a permanent, chronic state of exhaustion as a result of a disease, which occurs independently of physical or mental stress and can hardly be alleviated by rest or sleep. Fatigue is primarily associated with cancer, but comparable symptoms also occur in other diseases such as multiple sclerosis, Parkinson's disease or rheumatism - and in long-COVID. Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) should also be mentioned in this context.

In the cooperation project, the Neurological Clinics of the University Medical Center Mannheim (Prof. Dr. Lucas Schirmer) and the University Hospital Ulm (Prof. Dr. Hayrettin Tumani) as well as the Department of Psychiatry and Psychotherapy of the Central Institute of Mental Health in Mannheim (Dr. Claudia Schilling) are contributing their respective expertise to better understand the mechanisms underlying fatigue in long COVID and to identify new biomarkers and targets for the detection and treatment of COVID-19 associated fatigue syndrome.

The patients to be studied are divided into four cohorts of equal size: long-COVID patients with fatigue and three control groups. Two of these control groups show comparable fatigue symptoms: patients with multiple sclerosis and patients after brain inflammation (encephalitis) due to survived infection with a virus other than SARS-CoV-2. The fourth cohort includes patients with non-inflammatory headaches.

"We suspect that inflammatory responses in the central nervous system occur in the three disease entities associated with fatigue. Therefore, we focus on a compartment close to the central nervous system, the cerebrospinal fluid", explains project leader Lucas Schirmer.

In the search for dysregulated parameters that are common to fatigue or specific to the particular disease entity, the researchers analyze the patients' cerebrospinal fluid multimodally: at the level of RNA transcripts (transcriptome), proteins (proteome) and metabolic products (metabolome).

The investigations in the laboratory are followed by complex computer-assisted bioinformatic analyses via a platform established by Lucas Schirmer. In parallel, neuropsychological and magnetic resonance imaging examinations will be performed in order to compare the identified markers with clinical parameters and to draw conclusions about their function.

By the end of the project, the scientists should have identified a repertoire of markers that can subsequently be validated in clinical studies.

The project

"Multimodal characterization of liquor-specific signatures in long-COVID." Supported by the Ministry of Science, Research and the Arts Baden-Württemberg

Project Lead:
Prof. Dr. Lucas Schirmer
Department of Neurology
Medical Faculty Mannheim of the University of Heidelberg

Cooperation partner:
Prof. Dr. Hayrettin Tumani
Neurological Clinic
University Hospital Ulm

Dr. Claudia Schilling
Department of Psychiatry and Psychotherapy
Central Institute for Mental Health in Mannheim

Press release at the Medical Faculty Mannheim (German language)
20.01.2023 Erforschung von Fatigue bei Long-COVID