Cardiovascular, Autonomic, and Vascular Research
1 MCAM Multi-Site Autonomic Dysfunction Study
Principal Investigator:: Elizabeth Unger and collaborators
Institution:: CDC / multi-site (USA)
Contact/URL:: https://doi.org/10.3390/jcm14176269
Funder:: CDC
Status:: Published 2025
Phase:: Observational (multi-site clinical assessment)
Cohort:: ME/CFS patients from the MCAM (Multi-Site Clinical Assessment of ME/CFS) programme
Mechanism/Focus:: Characterised autonomic dysfunction using COMPASS-31 scores and the NASA lean test. Demonstrated high prevalence of autonomic symptoms across ME/CFS cohorts regardless of recruitment site.
Primary Outcomes:: Autonomic dysfunction symptoms are pervasive in ME/CFS; COMPASS-31 scores significantly elevated versus controls
Estimated Completion:: Published
Publication Medium:: Journal of Clinical Medicine
Document Relevance:: Ch. 10 (cardiovascular), Ch. 8 (neurological dysfunction—autonomic)
The MCAM study’s multi-site design strengthens generalisability: autonomic dysfunction is not an artefact of specialist referral patterns but a consistent feature across diverse clinical settings (Issa et al. 2025). The NASA lean test used here is simpler than head-up tilt, making it a practical screening tool for primary care.
2 Small Fibre Neuropathy in ME/CFS and Post-COVID
Principal Investigator:: Naia Azcue and collaborators
Institution:: Multi-centre (Spain)
Contact/URL:: https://doi.org/10.1111/ene.70016
Funder:: Institutional
Status:: Published 2025
Phase:: Observational (case-control)
Cohort:: ME/CFS patients, post-COVID patients, and healthy controls
Mechanism/Focus:: Assessed small fibre neuropathy using electrochemical skin conductance, nerve reaction times to temperature stimuli, and corneal confocal microscopy. Both ME/CFS and post-COVID patients showed significantly higher autonomic and neuropathic symptom burden than controls.
Primary Outcomes:: SFN features present in both ME/CFS and post-COVID; corneal nerve fibre density reduced
Estimated Completion:: Published
Publication Medium:: European Journal of Neurology
Document Relevance:: Ch. 8 (neurological dysfunction), Ch. 10 (cardiovascular—perfusion), Ch. 14 Speculative Cross-Disease Connections
Small fibre neuropathy provides an objective, quantifiable marker for a symptom—neuropathic pain and dysautonomia—that is otherwise self-reported (Azcue et al. 2025). The corneal confocal microscopy approach is non-invasive and could serve as a bedside diagnostic. The shared SFN phenotype between ME/CFS and post-COVID strengthens the case for common neurovascular pathology.
3 Microvascular Remodelling and Endothelial Dysfunction
Principal Investigator:: Multiple groups
Institution:: Multi-centre (Europe)
Contact/URL:: https://doi.org/10.64898/2026.01.22.26344661
Funder:: Institutional
Status:: Preprint January 2026
Phase:: Observational (case-control)
Cohort:: Post-COVID and ME/CFS patients versus healthy controls
Mechanism/Focus:: Used retinal vessel analysis as a non-invasive measure of systemic microvascular health. Identified reduced venular flicker-induced dilation in patients, indicating ongoing endothelial dysfunction even in clinically stable individuals.
Primary Outcomes:: Endothelial dysfunction detectable via retinal imaging; reduced venular reactivity in ME/CFS and post-COVID
Estimated Completion:: Preprint published; peer review pending
Publication Medium:: medRxiv
Document Relevance:: Ch. 10 (cardiovascular), Ch. 13 (integrative models)
Retinal vessel analysis offers a window into systemic microvascular health without invasive procedures (2026). The persistent endothelial dysfunction in clinically stable patients suggests ongoing vascular injury that may underlie fatigue and cognitive symptoms even when patients report partial recovery. This complements the microclot findings (Nunes et al. 2022) and the coagulation proteomics data (2024).
4 POTS Autonomic Profiling Across Aetiologies
Principal Investigator:: Multiple groups
Institution:: Multi-centre
Status:: Published 2025
Phase:: Observational (comparative)
Cohort:: POTS patients from syncope, CFS, and post-COVID-19 populations
Mechanism/Focus:: Identified distinct autonomic profiles: syncope-related POTS showed baroreceptor dysfunction and sympathetic predominance, whereas CFS-related POTS was characterised by parasympathetic impairment and impaired short-term baroreflex regulation.
Primary Outcomes:: CFS-related POTS has a distinct autonomic signature from syncope-related and post-COVID POTS
Estimated Completion:: Published
Document Relevance:: Ch. 10 (cardiovascular), Ch. 8 (neurological dysfunction—autonomic)
The distinction between CFS-related and syncope-related POTS autonomic profiles has therapeutic implications: parasympathetic impairment in CFS-related POTS suggests vagal tone-targeting interventions (e.g., tVNS, Section Clinical Trials (Interventional)) may be more appropriate than the beta-blockade used for hyperadrenergic POTS (2025).