Disequilibrium, Rather than Postural Orthostatic Tachycardia Syndrome, Is the Primary Determinant of Orthostatic Intolerance in Patients with Long COVID

<b>Background</b>: Orthostatic intolerance (OI) is an important factor affecting daily functional capacity in patients with long COVID. Traditionally, most OI symptoms have been attributed to exaggerated sympathetic nervous system activation associated with postural orthostatic tachycardia syndrome (POTS). Disequilibrium, also referred to as postural instability, may contribute to the development of OI in patients with long COVID. <b>Methods</b>: This study evaluated 32 patients with long COVID using neurological examinations and the active 10-min standing test. Disequilibrium was assessed using the Romberg and tandem gait tests. OI was defined as the inability to complete the active 10-min standing test. <b>Results</b>: Seven patients (22%) were diagnosed with OI. None of them had POTS, whereas six (86%) demonstrated disequilibrium, as detected by the Romberg and/or tandem gait test. POTS was observed in eight patients (25%), none of whom had OI. Disequilibrium was observed in nine patients (28%), six of whom (67%) had OI. Multiple regression analysis revealed that disequilibrium was positively associated with OI (r = 0.64, <i>p</i> < 0.001), whereas POTS was inversely associated (r = -0.38, <i>p</i> < 0.05). After 6 weeks of oral minocycline treatment in six patients and 2 weeks of repetitive transcranial magnetic stimulation therapy following minocycline in the other one patient, symptom amelioration was reported in six patients with OI. OI concomitant with disequilibrium recovered in five of the six patients treated and tested, although one patient who experienced symptom recovery failed to undergo the repeated standing test. <b>Conclusions</b>: Disequilibrium, rather than POTS, was the primary determinant of OI in patients with long COVID.