Cardiovascular and haematological pathology in ME/CFS: a role for viruses

“The circulatory system (also called the cardiovascular system) is the body system that moves blood around the body. It consists of the heart and blood vessels. The blood carries various materials that the body needs, and takes away waste and harmful substances.” Wiki

Researchers Nunes, Kell and Pretorius say: Prompted by the overlap between Long COVID and ME/CFS, in this review, we sought to summarize the cardiovascular and haematological findings associated with ME/CFS.

“Haematology is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to blood.” Wiki

The influence of microbes on the coagulation system

Practice points

• The evidence presented in this review resonates with the notion that ME/CFS is characterized by physiological pathology, and not psychosomatic illness. This is a biologically-driven disease characterized by vascular (including haematological) pathology.
• Assessment of cardiovascular (specifically cardiac functioning) and haematological health are necessary steps in the clinical evaluation of ME/CFS patients.
• Deconditioning does not seem to be responsible for the symptoms of ME/CFS.
• The coagulation system and endothelium is becoming more and more implicated in ME/CFS; perhaps these systems are more involved in ME/CFS than previously suspected.
• Viruses are heavily involved in ME/CFS pathology, and their role in causing in ME/CFS seems more likely when scrutinizing the etiology of the similarly-presenting Long COVID – elucidation of the mechanisms of how SARS-CoV-2 leads to Long COVID may advance ME/CFS knowledge.

“The endothelium is a thin membrane that lines the inside of the heart and blood vessels. Endothelial cells release substances that control vascular relaxation and contraction as well as enzymes that control blood clotting, immune function and platelet (a colorless substance in the blood) adhesion. Cedars

Research agenda

• Future studies need to expand on the involvement of the cardiovascular and haematological system in ME/CFS pathology, and determine to what extent these systems and dysfunction thereof contributes to symptom manifestation.
• The cardiac and vascular dysfunction observed in ME/CFS individuals is atypical in the sense that it is non-atherosclerotic heart disease; it seems that neurological (autonomic) dysfunction underlies these abnormalities – mechanisms need to be unveiled, and therapeutics trialled in this neurological context, especially since orthostatic symptoms greatly affect the functional capabilities of patients.
• Given the complexity of ME/CFS, research and clinical efforts will require collaborative multidisciplinary involvement, that include virologists, cardiologists, neurologists, and haematologists.
• There is an urgent need for biomarker establishment in ME/CFS; further investigation of the physiological systems discussed in this review may help aid in this quest, especially since these systems (or aspects thereof) are becoming more and more implicated in ME/CFS research.

In conclusion: “This review highlights the potential of studying cardiac functioning, the vasculature, and coagulation system in ME/CFS.”

Cardiovascular and haematological pathology in ME/CFS: a role for viruses, by Jean M Nunes, Douglas B Kell, Etheresia Pretorius in Blood Reviews Mar 2023 [doi.org/10.1016/j.blre.2023.101075]

Review abstract:

ME/CFS is a debilitating chronic condition that often develops after viral or bacterial infection.

Insight from the study of Long COVID/Post Acute Sequelae of COVID-19 (PASC), the post-viral syndrome associated with SARS-CoV-2 infection, might prove to be useful for understanding pathophysiological mechanisms of ME/CFS.

Disease presentation is similar between the two conditions, and a subset of Long COVID patients meet the diagnostic criteria for ME/CFS. Since Long COVID is characterized by significant vascular pathology – including endothelial dysfunction, coagulopathy, and vascular dysregulation – the question of whether or not the same biological abnormalities are of significance in ME/CFS arises.

Cardiac abnormalities have for a while now been documented in ME/CFS cohorts, with recent studies demonstrating major deficits in cerebral blood flow, and hence vascular dysregulation. A growing body of research is demonstrating that ME/CFS is accompanied by platelet hyperactivation, anomalous clotting, a procoagulant phenotype, and endothelial dysfunction.

Endothelial damage and dysregulated clotting can impair substance exchange between blood and tissues, and result in hypoperfusion, which may contribute to the manifestation of certain ME/CFS symptoms.

Here we review the ME/CFS literature to summarize cardiovascular and haematological findings documented in patients with the condition, and, in this context, briefly discuss the potential role of previously-implicated pathogens.

Overall, cardiac and haematological abnormalities are present within ME/CFS cohorts. While atherosclerotic heart disease is not significantly associated with ME/CFS, suboptimal cardiovascular function defined by reduced cardiac output, impaired cerebral blood flow, and vascular dysregulation are, and these abnormalities do not appear to be influenced by deconditioning. Rather, these cardiac abnormalities may result from dysfunction in the (autonomic) nervous system.

Plenty of recently published studies are demonstrating significant platelet hyperactivity and endothelial dysfunction in ME/CFS, as well as anomalous clotting processes. It is of particular importance to determine to what extent these cardiovascular and haematological abnormalities contribute to symptom severity, and if these two systems can be targeted for therapeutic purposes. Viral reservoirs of herpesviruses exist in ME/CFS, and most likely contribute to cardiovascular and haematological dysfunction directly or indirectly.

This review highlights the potential of studying cardiac functioning, the vasculature, and coagulation system in ME/CFS.