Sympathetic Neural Overdrive, Vascular Dysfunction and Diminished Exercise Capacity in [LC]: A Long-Term Study of Cardiovascular Sequelae, 2025, Ono+

[SNT Gatchaman]

Sympathetic Neural Overdrive, Vascular Dysfunction and Diminished Exercise Capacity in Long COVID-19 Patients: A Long-Term Study of Cardiovascular Sequelae
Bruna E. Ono; João E. Izaias; Artur O. Sales; Thais S. Rodrigues; Camila S. Nunes; Jessica F. Niec; Natalia G. Rocha; Helena N.M. Rocha; Gabriel F. Teixeira; Amanda G Rodrigues; Carlos E Negrão; Maria C.C. Irigoyen; Fernanda M.C. Colombo; Antonio Viana Nascimento-Filho; Katia De Angelis; Robson A.S. Santos; Andreia M. Porcari; Katelyn R. Ludwig; Daniel H. Craighead; Matthew J. Rossman; Renata Moll-Bernardes; Douglas R. Seals; Allan R.K Sales

BACKGROUND
We have recently showed that severe COVID patients have neurovascular dysfunction, cardiac morpho-functional alterations, and attenuated exercise capacity. However, whether these alterations persist over time is unknown. Here, we tested the hypothesis that Long COVID patients, even 2 years after SARS-COV-2 infection, exhibit sympathetic overdrive, aortic stiffening, endothelium-dependent dysfunction, cardiac morpho-functional changes, and diminished exercise capacity.

METHODS
Eighteen Long COVID patients and 19 well-matched controls were studied. Muscle sympathetic nerve activity (MSNA; microneurography), brachial artery flow-mediated dilation (BAFMD; ultrasound-Doppler), carotid-femoral pulse wave velocity (CFPWV; tonometry), heart rate (HR; EKG), E/A ratio, left ventricular ejection fraction and global longitudinal strain (LVEF, LVGLS; echocardiography), and peak oxygen uptake (Peak VO2, cardiopulmonary exercise testing) were assessed ⁓2 years after hospital discharge. Circulating angiotensin II (Ang II, mass spectrometry), endothelial cell-derived extracellular vesicles (endothelial cell-derived EVs, flow cytometry), and oxidative stress were also evaluated.

RESULTS
Long COVID patients had higher MSNA, CFPWV, HR and lower E/A ratio, LVEF, LVGLS and Peak VO2 than controls. Endothelial cell-derived EVs and carbonyls were higher in Long COVID patients than controls, whereas superoxide dismutase (SOD) was lower. No difference was observed in Ang II. Peak VO2 was inversely associated with MSNA, LVGLS and carbonyls, and directly associated with BAFMD and SOD.

CONCLUSIONS
Our findings reveal that Long COVID patients, 2 years after acute illness, exhibit persistent sympathetic overactivation, vascular and cardiac impairments, reduced exercise capacity, and increased endothelial cell-derived EVs and oxidative stress. As such, strategies that can resolve these persistent cardiovascular sequelae are urgently needed.

Link | PDF (American Journal of Physiology-Regulatory, Integrative and Comparative Physiology) [Open Access]

 

[SNT Gatchaman]

(Hospitalised, with severe acute COVID)

 

[Eleanor]

Goes on to promote exercise rehabilitation, inevitably.

[...]effective treatments, including non-pharmacological strategies (e.g., antioxidant supplementation, neuromodulation, and exercise rehabilitation)56 that can restore or alleviate cardiovascular sequelae in patients suffering from long COVID-19 are needed. 77 Recent studies have observed that a new exercise model, resistance muscle strength training (IMST), performed at home by 6 weeks (5 min/day, 6 times/week), decreases sympathetic neural outflow, improves endothelial function associated with elevation in NO bioavailability and reduction in ROS, decreases blood pressure, increases cerebrovascular reactive, and improves exercise tolerance in different populations.78–81 Most importantly, this exercise paradigm is safe and well tolerated by the patients, and their adherence is high (~93%). 77,79 Therefore, IMST appears to be a promising intervention to restore cardiovascular health in patients with long COVID. A double-blind, randomized, sham-controlled trial (NTC06091384) from our group is ongoing to confirm this hypothesis.