When energy fails

Mr. Westermeier, what exactly is chronic fatigue syndrome (CFS)?

Francisco Westermeier: ME/CFS is a chronic, debilitating, and multisystem disease that affects more women than men. It often results in a drastic loss of functional capacity – about 75% of ME/CFS patients are unable to work, and a significant proportion are housebound or bedridden. Although the exact cause remains unclear, most patients report a preceding infectious episode.

The condition affects the nervous, immune, and cardiovascular systems, among others, and presents with a wide range of symptoms. The most characteristic is post-exertional malaise (PEM – a worsening of symptoms after even minor physical or mental activity, lasting for days or weeks. Other common symptoms include concentration difficulties, “brain fog,” sleep disturbances, dizziness, and discomfort in an upright position, although symptom patterns vary and may also involve gastrointestinal or musculoskeletal systems.

You’re a cardiovascular expert. What aspects does your ME/CFS research focus on?

Westermeier: I became interested in this disease because, at the time we began our research, there was very limited information available regarding cardiovascular alterations in ME/CFS. Given my background in cardiovascular physiology, I saw a need to explore this area further.

One key component of the cardiovascular system is the endothelium – the thin layer of cells that lines the inside of blood vessels. These endothelial cells play a vital role in regulating blood flow, delivering oxygen and nutrients to tissues, and removing waste products. When the endothelium is not functioning properly – a condition known as endothelial dysfunction – these processes are impaired, which may contribute to many of the symptoms observed in ME/CFS and long COVID. Our research focuses on how endothelial cells are affected in this context, particularly in terms of their ability to maintain vascular function when exposed to plasma from affected individuals.

How are you proceeding?

Westermeier: Building on previous work, we are currently investigating the effects of patient plasma on endothelial cells. In collaboration with Eva Untersmayr-Elsenhuber at the Medical University of Vienna, we obtained samples from an Austrian cohort including individuals diagnosed with either ME/CFS or long COVID. We incubate endothelial cells in vitro with this plasma to mimic aspects of the in vivo environment.

One key function of endothelial cells is the production of nitric oxide, a signaling molecule that supports blood flow and nutrient delivery. Our research focuses on the metabolic pathways involved in nitric oxide synthesis. Recently, we observed that plasma from ME/CFS patients reduces the ability of endothelial cells to produce nitric oxide, suggesting the presence of endothelial dysfunction at a cellular level.

What is the difference between long Covid and ME/CFS?

Westermeier: At this stage, we can’t say for certain. Although the symptoms are often similar, there appear to be differences between patient subgroups. In our analyses, we take into account relevant factors such as sex and age. However, we must be cautious when comparing conditions like ME/CFS and long COVID, as robust comparisons require well-matched cohorts, standardized diagnostic criteria, and sufficient sample sizes to account for biological and clinical heterogeneity.

What can you tell us about high-risk groups?

Westermeier: So far, women appear to be affected more frequently than men, with an estimated ratio of about 3 to 1. However, whether this reflects a true biological risk factor or differences in immune response, hormone levels, or diagnostic patterns is still under investigation. In a recent study, we explored the potential role of steroid hormones, but more research is needed to establish any causal links. Age may also influence symptom presentation, but ME/CFS and long COVID affect individuals across the lifespan, including many young adults and adolescents.

Are people with chronic illnesses more at risk?

Westermeier: This is an important and complex question. While there is currently no conclusive evidence that pre-existing chronic conditions increase the risk of developing ME/CFS or long COVID, comorbidities play a crucial role in how these illnesses are diagnosed, studied, and managed. Individuals with other chronic diseases often face delayed or missed diagnoses, in part due to overlapping symptoms and the absence of standardized diagnostic criteria.

From a research perspective, comorbidities introduce additional layers of complexity but also reflect the real-world clinical context. These coexisting conditions may influence long-term outcomes, symptom burden, and treatment responses. Therefore, it is essential to include individuals with comorbidities in studies to better capture disease variability and improve the applicability of findings. Addressing these challenges requires international collaboration and the integration of diverse areas of expertise.

What is the status of ME/CFS research on an international level?

Westermeier: The COVID-19 pandemic has acted as a catalyst for ME/CFS research. While the pandemic itself posed immense challenges, it also brought renewed attention to post-viral syndromes, accelerating interest and funding in this field. In the past five years, we’ve seen meaningful progress: biobanks are being established, large-scale clinical data are becoming available, and collaborative research networks have been strengthened.

A key focus now is the identification of reliable biomarkers and the stratification of patients into biologically defined subgroups. This is essential for improving diagnostics, understanding disease mechanisms, and developing targeted interventions. In several countries around the world, established research groups are actively addressing these priorities.

Despite this progress, major challenges remain—including the lack of standardized diagnostic criteria, limited treatment options, and the need for validated models to study disease mechanisms. Still, I am optimistic that these coordinated efforts will lead to significant breakthroughs in the coming years.