Postural Orthostatic Tachycardia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID as Neuroimmune Disorders.
Blitshteyn, Svetlana, Doherty, Taylor A, Steinman, Lawrence · ImmunoTargets and therapy · 2026 · DOI
Quick Summary
This editorial argues that three related conditions—POTS, ME/CFS, and Long COVID—should be understood and studied together as disorders affecting both the nervous system and immune system. The authors identify several common problems in these conditions, including heart rate abnormalities when standing, immune system dysfunction, and reduced blood flow to the brain. They believe treating these as a single category of disease could improve how doctors train, research, and care for patients with these serious illnesses.
Why It Matters
This perspective is important because it validates the interconnected nature of conditions that often co-occur or overlap in patients, potentially leading to more integrated research and clinical approaches. If adopted, this framework could improve physician understanding and training, leading to better recognition and management of these disabling conditions that currently lack disease-modifying treatments.
Observed Findings
POTS and ME/CFS are the most common phenotypes of Long COVID
These three conditions share overlapping complex, multi-systemic pathophysiology
Identified mechanistic factors include autonomic dysfunction, immune dysregulation, autoimmunity, mitochondrial dysfunction, cerebral hypoperfusion, and neuroinflammation
These conditions cause significant disability and functional impairment in patients
The exact pathophysiologic mechanisms are still being investigated
Inferred Conclusions
POTS, ME/CFS, and Long COVID should be conceptualized as neuroimmune disorders
These conditions require integration into neuroimmunology subspecialty with dedicated educational curriculum and training pathways
A unified neuroimmunologic framework is key to advancing both basic science and clinical care for this underserved patient population
Current clinical care and research approaches are inadequate for these complex disorders
Remaining Questions
What are the distinct vs. shared mechanisms driving POTS, ME/CFS, and Long COVID in different patient subsets?
What This Study Does Not Prove
This editorial does not provide original experimental data, mechanistic proof, or clinical trials establishing causation for any proposed pathways. It does not demonstrate the prevalence of individual mechanisms across patient populations or prove that reclassification will improve patient outcomes. The piece represents expert opinion rather than empirical evidence of pathophysiology.