New US research funded by Dysautonomia International
Long-COVID Postural Tachycardia Syndrome: A deep phenotyping study
https://www.medrxiv.org/content/10.1101/2025.04.28.25326587v1
"An unexpected finding of our study was that 8.7% of LC-POTS participants exhibited aggregates of P-syn on skin biopsy"
#POTS @pots #dysautonomia @dysautonomia @longcovid
#LongCovid #PwLC #PostCovidSyndrome #LC #PASC #postcovid
#CovidBrain
medRxiv · Long-COVID Postural Tachycardia Syndrome: A deep phenotyping studyBackground: Postural tachycardia syndrome (POTS) has emerged as one of the most common autonomic complications of Long-COVID (LC). However, disease mechanisms remain incompletely understood. Objectives: To evaluate the frequency and severity of autonomic dysfunction in a subset of carefully phenotyped, previously healthy patients with LC-POTS using a detailed protocol of autonomic, cerebrovascular, respiratory, blood, and tissue analyses. Methods: Participants in this study completed a battery of autonomic function tests, including measures of sudomotor, cardiovagal, and sympathetic adrenergic function, and head-up tilt (HUT) with transcranial Doppler measures of cerebral blood flow velocity (CBFv), end-tidal CO2 (ETCO2), cerebral and skeletal muscle near-infrared spectroscopy (NIRS) and plasma catecholamines. Skin biopsy was performed at proximal and distal sites and analyzed for intraepidermal nerve fiber density (IENFD) and phosphorylated α-synuclein (P-Syn). Results were compared to healthy controls (HC) ≥ 3 months post-COVID infection with no lasting sequelae. Results: LC-POTS participants (n=24) exhibited a greater increase in heart rate on HUT (31.1±20.3, p=0.01), and 38% exhibited elevated upright norepinephrine levels consistent with a hyperadrenergic response. CBFv did not significantly differ between LC-POTS and HC (n=10). EtCO2 and NIRS were also similar between groups. Twenty-two percent of LC-POTS and 38% of HC had decreased IENFD on skin biopsy, while 8.7% LC-POTS had dermal P-Syn aggregation on skin biopsy, compared to none of HC. Conclusions: LC-POTS was associated with widespread autonomic dysfunction, including orthostatic tachycardia, sympathetic adrenergic hyperactivity, small fiber neuropathy, and dermal P-Syn deposition. Our findings support the concept of multiple pathophysiological mechanisms in most patients with POTS triggered by SARS-CoV-2.
### Competing Interest Statement
Dr. Larsen, Jannika Machnik, Jordan Seliger, and Ruba Shaik have nothing to disclose. Dr. Gibbons has received grant funding from the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institutes of Health (NIH) and has stock options in CND Life Sciences outside the submitted work. Dr. Utz has recieved grant funding from the National Institutes of Health outside of the submitted work. Dr. Lansberg has received consulting fees from Genentech, Biogen, and Novo Nordisk and royalties from a health-related publication. Dr. Muppidi has reported receiving consulting fees from Alexion, Argenx, UCB/Ra Pharma, and Horizont Pharma and royalties from a health-related publication. Dr. Jaradeh reported consulting fees from Alnylam, Akcea, and has received grant funding from Alnylam, outside of the submittedwork. Dr. Miglis has received consulting fees from 2nd MD, Infinite MD, and Jazz Pharmaceuticals, royalties from a health care publication, and grant funding from Ono Pharmaceuticals, the Agency for Healthcare Research and Quality (AHRQ), the National Institutes of Health, and Dysautonomia International, outside the submitted work.
### Funding Statement
The study was funded by Dysautonomia International (East Moriches, New York)
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
IRB of Stanford University gave ethical approval for this work.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
Yes
All data produced in the present study are available upon reasonable request to the authors.
![You got some nerves
well no shit
[pic of the whole human nervous system]](https://files.mastodon.social/media_attachments/files/114/421/652/130/516/707/original/aeff0161aa67c855.jpg "You got some nerves
well no shit
[pic of the whole human nervous system]")
