MYOFLAME-19 Autoimmune Substudy: GPCR Autoantibodies as Mechanistic Biomarkers of Endothelial Dysfunction in Post-COVID ME/CFS

The investigators hypothesise that the initiating event in post-COVID ME/CFS is damage to the inner lining of blood vessels (endothelium): once the virus attaches to the blood vessel walls, it disrupts their protective barrier, exposing signalling proteins on the vessel surface to the immune system. They further hypothesise that the immune system, in attempting to respond, generates antibodies that mistakenly target these proteins — and that these G-protein coupled receptor (GPCR) autoantibodies are not innocent bystanders but active drivers of cardiovascular injury. By causing blood vessels to constrict, promoting scarring of the heart muscle, and making vessel walls leaky, they reduce the volume of blood circulating in the body and stiffen the heart. The heart compensates by beating faster, but its capacity to respond to physical effort becomes critically limited — a pattern similar to a form of heart failure in which the muscle is stiff rather than weak.

The MYOFLAME-19 trial tested whether this cascade could be interrupted using two complementary treatments: losartan, to relax blood vessels and reduce scarring, and low-dose prednisolone, to calm the immune response driving antibody production. With the results of MYOFLAME-19 still being processed, this new project asks, for the first time in a context of controlled clinical trial, whether the treatment reduced the levels of these self-targeting antibodies and whether any such reduction explains the improvements in symptoms and heart function seen in patients who received active treatment. Using blood samples already collected from all MYOFLAME-19 participants, this study — as a sub-study to MYOFLAME-19 — will aim to provide direct evidence linking targeted treatment to a reduction in these harmful antibodies: a meaningful step forward in understanding and treating the immune underpinnings of ME/CFS with heart involvement.

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