The starting point of the project is the hypothesis that SARS-CoV-2 damages the endothelium, the inner lining of the blood vessels. This could expose structures against which the immune system forms autoantibodies. The focus is on autoantibodies against G-protein-coupled receptors (GPCR). The researchers suspect that these antibodies are not merely a consequence of the disease, but actively contribute to its development.
According to this hypothesis, the autoantibodies promote constriction of the blood vessels, encourage remodelling and scarring processes in the heart muscle, and impair the function of the vessel wall. As a result, circulating blood volume could fall and the heart could become stiffer. To compensate for the reduced filling, the heart would have to beat faster. The consequence would be markedly reduced physical capacity – a symptom picture that bears similarities to heart failure with preserved ejection fraction.
For the study, existing blood samples and clinical data from the MYOFLAME-19 study are being analysed. The researchers are examining whether treatment with losartan, which relaxes the blood vessels and is intended to inhibit remodelling processes in the heart muscle, together with low-dose prednisolone, which is intended to dampen the misdirected immune response, lowers the level of GPCR autoantibodies. In addition, the researchers want to clarify whether a decrease in autoantibodies is associated with an improvement in cardiac function and in patients' symptoms.
The results are intended to help improve understanding of the immunological mechanisms of post-COVID ME/CFS. If a link between autoantibodies, cardiac involvement and treatment response can be demonstrated, GPCR autoantibodies could in future serve as biomarkers and open up new starting points for treating the condition.
The project is one of seven projects being funded under the ME/CFS Research Foundation's Research Funding Programme 2026. The foundation is investing a total of €2.4 million in research projects on disease mechanisms, biomarkers and new therapeutic approaches for ME/CFS. The aim of the programme is to strengthen biomedical research into a condition that remains inadequately understood, and to enable progress in diagnostics and disease-modifying treatments.
Project
Myoflame-19 autoimmunity sub-study: GPCR autoantibodies as mechanistic biomarkers for endothelial dysfunction in post-COVID ME/CFS
https://mecfs-research.org/news-researchfunding-projects2026/
Project leads
Prof. Dr Valentina Puntmann and Prof. Dr Eike Nagel, Goethe University Frankfurt
