Disequilibrium, Rather than Postural Orthostatic Tachycardia Syndrome, Is the Primary Determinant of Orthostatic Intolerance in Patients with Long COVID. — CFSMEATLAS
Disequilibrium, Rather than Postural Orthostatic Tachycardia Syndrome, Is the Primary Determinant of Orthostatic Intolerance in Patients with Long COVID.
Miwa, Kunihisa · Journal of clinical medicine · 2026 · DOI
Quick Summary
Many long COVID patients experience dizziness and difficulty standing (orthostatic intolerance), but researchers found this is not usually caused by the heart racing when standing up (POTS). Instead, balance problems detected by simple standing tests were the main cause in these patients. When treated with an antibiotic or brain stimulation therapy, most patients with balance-related standing problems improved.
Why It Matters
This study challenges the widely-held assumption that POTS is the primary cause of standing intolerance in long COVID, suggesting instead that balance dysfunction is the key driver. This finding could redirect treatment approaches toward vestibular and neurological rehabilitation rather than cardiovascular interventions alone, potentially improving outcomes for patients with orthostatic symptoms.
Observed Findings
Of 7 patients with orthostatic intolerance, 0 had POTS but 6 (86%) had disequilibrium on testing.
Of 8 patients with POTS, 0 had orthostatic intolerance.
Disequilibrium was present in 9 patients total (28% of cohort), with 6 of these 9 (67%) meeting OI criteria.
Multiple regression showed disequilibrium positively associated with OI (r=0.64, p<0.001) and POTS inversely associated (r=-0.38, p<0.05).
Five of six treated patients showed recovery of OI symptoms and resolution of disequilibrium after minocycline ± rTMS therapy.
Inferred Conclusions
Disequilibrium (postural instability) is the primary determinant of orthostatic intolerance in long COVID, not POTS.
POTS and OI appear to be largely independent phenomena in long COVID, suggesting different underlying pathophysiologies.
Minocycline and/or repetitive transcranial magnetic stimulation may be effective treatments for OI driven by disequilibrium in long COVID.
Remaining Questions
What is the mechanism by which disequilibrium causes orthostatic intolerance in long COVID—is it vestibular, proprioceptive, cerebellar, or multifactorial?
Why do some patients develop POTS while others develop disequilibrium, and what are the different underlying pathophysiologies?
What This Study Does Not Prove
This study does not establish causation between disequilibrium and orthostatic intolerance—the cross-sectional design only shows association. The small sample size (n=32, with only 7 OI cases) limits generalizability to the broader long COVID population. The treatment response in a subset of patients suggests potential therapeutic options but does not prove the underlying mechanism of how disequilibrium causes OI.
Tags
Symptom:Orthostatic Intolerance
Phenotype:Long COVID Overlap
Method Flag:Weak Case DefinitionNo ControlsSmall Sample
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
How do minocycline and rTMS treatments resolve disequilibrium-related OI, and are these durable long-term improvements?
How do these findings in this small cohort generalize to the broader long COVID population, and what proportion have disequilibrium-driven versus other OI mechanisms?