Nearly Two-Thirds of Patients With Long COVID Meet Diagnostic Criteria for POTS

Almost two-thirds (62.5%) of patients with long COVID in a small Australian study met formal diagnostic criteria for postural orthostatic tachycardia syndrome (POTS), according to findings published in the Journal of the American Heart Association. The investigators said the overlap supports routine autonomic assessment in patients with persistent postviral illness.^1,2

POTS is a form of autonomic dysfunction defined by a sustained heart rate increase of at least 30 beats per minute (bpm) within 10 minutes of standing, without orthostatic hypotension, along with orthostatic symptoms lasting at least 3 months. Because it affects the system that governs heart rate, breathing, and digestion, POTS can produce a wide range of seemingly unrelated symptoms, making it challenging to diagnose.^2-4

Study Compared Autonomic Function and Immune Markers Across 3 Groups

In the cross-sectional study, conducted between August 2021 and December 2022, investigators from Adelaide University, the South Australian Health and Medical Research Institute, and the University of Oklahoma Health Sciences Center enrolled 24 patients with POTS, 24 patients with postacute sequelae of COVID-19 (PASC, or long COVID), and 19 healthy controls. The 67 participants had a mean age of 32.4 years, and 71% were women.¹

Participants underwent 10-minute active stand testing and 24-hour Holter monitoring, along with serum cytokine and adrenergic autoantibody assays. Patient-reported outcomes were collected electronically. According to Adelaide University, the study is believed to be the first to examine autonomic symptoms, heart rate response, inflammatory markers, and autoantibodies across all 3 groups.^1,2

Standing Heart Rate Response Mirrored POTS in Many Patients With Long COVID

On standing, heart rate rose by a mean of 46.3 bpm in the POTS group and 34.6 bpm in the PASC group, compared with 12.7 bpm in controls (P < .001). The difference between the POTS and PASC groups was also significant (P = .005). Among participants with PASC, 62.5% met formal POTS criteria.¹

“What’s striking in this study is just how similar the two groups were,” said lead researcher Marie-Claire Seeley, of the Rosemary Bryant AO Research Centre at Adelaide University, in a news release.²

Seeley noted that POTS can be assessed with a relatively simple standing test, but that its overlap with other conditions complicates diagnosis. She added that recognizing the link could give clinicians another avenue for investigation and help patients reach targeted treatment sooner.²

Both Conditions Carried a Substantial Functional Burden

Compared with controls, participants with POTS and those with PASC reported greater fatigue, orthostatic intolerance, and autonomic symptom burden, as well as reduced health-related quality of life. Nearly 6 in 10 participants with long COVID (58.3%) had been unable to return to work after their infection, and only 4.2% of participants with POTS were engaged in full-time work or education.^1,2

Inflammatory Signals Emerged, but No Diagnostic Biomarker

Cytokine analysis showed lower IL-2 and higher IL-8 levels in patients with POTS versus controls, and participants who met POTS criteria had elevated tumor necrosis factor-α compared with those who did not. However, adrenergic autoantibody activation did not differ significantly among groups, and multivariate biomarker models lacked predictive value for a POTS diagnosis.¹

The authors concluded that the changes suggest a possible cytokine-linked or compartmentalized immune contribution, but that cytokine and autoantibody measures alone cannot predict POTS.¹

Treatment Options Remain Off-Label and Understudied

For pharmacists, the findings highlight a persistent treatment gap, as POTS lacks approved pharmacologic therapies. A 2025 systematic review of 21 randomized clinical trials, including 750 patients, found no well-powered trials to guide treatment. Most trial evidence exists for propranolol and midodrine, with more limited evidence for ivabradine, pyridostigmine, desmopressin, compression garments, and increased dietary salt.^4,5

More recently, a randomized, placebo-controlled crossover trial in 28 women with POTS compared ivabradine and propranolol across three 4-week treatment phases. Peak heart rate during head-up tilt testing was 99 bpm with ivabradine and 100 bpm with propranolol, vs 118 bpm with placebo (P < .001 for both). Ivabradine also raised systolic blood pressure more than propranolol, which the authors said supports personalized drug selection.⁴

Because dizziness, fatigue, and palpitations are common complaints in long COVID, pharmacists may be well positioned to flag patients who could benefit from referral for autonomic evaluation. The JAHA investigators called for routine autonomic assessment in persistent postviral illness, as well as larger longitudinal, multimodal studies.¹

REFERENCES

1. Seeley MC, Gallagher C, Wilson G, et al. Comparative analysis of circulating cytokines and adrenergic autoantibodies in postural orthostatic tachycardia syndrome, postacute sequelae of SARS-CoV-2, and healthy controls. J Am Heart Assoc. 2026;15(11):e048615. doi:10.1161/JAHA.125.048615

2. New clues link long COVID and POTS. News release. EurekAlert! September 16, 2026. Accessed September 25, 2026. https://www.eurekalert.org/news-releases/1144192

3. Gunning WT 3rd, Spatafore JW, Morran MP, et al. Plasma cytokine and caspase-1p20 profiles in pre-pandemic and long COVID-associated postural orthostatic tachycardia syndrome. Biomedicines. 2026;14(7):1605. doi:10.3390/biomedicines14071605

4. Uppal J, Deol P, Giri P, et al. A randomized crossover trial of ivabradine, propranolol, and placebo in postural orthostatic tachycardia syndrome: a detailed description. JACC Adv. 2026;5. doi:10.1016/j.jacadv.2026.102795

5. Kwok CS, Lee S, Hall M, et al. The evidence for treatments for postural orthostatic tachycardia syndrome: a systematic review of randomized trials. Trends Cardiovasc Med. 2025. https://www.sciencedirect.com/science/article/abs/pii/S1050173825000933