Carotid body dysregulation contributes to the enigma of long COVID

Abstract:

The symptoms of long COVID, which include fatigue, breathlessness, dysregulated breathing, and exercise intolerance, have unknown mechanisms. These symptoms are also observed in heart failure and are partially driven by increased sensitivity of the carotid chemoreflex. As the carotid body has an abundance of ACE2 (the cell entry mechanism for SARS-CoV-2), we investigated whether carotid chemoreflex sensitivity was elevated in participants with long COVID. During cardiopulmonary exercise testing, the VE/VCO2 slope (a measure of breathing efficiency) was higher in the long COVID group than in the controls, indicating excessive hyperventilation.

The hypoxic ventilatory response, which measures carotid chemoreflex sensitivity, was increased in long COVID participants and correlated with the VE/VCO2 slope, suggesting that excessive hyperventilation may be related to carotid body hypersensitivity. Therefore, the carotid chemoreflex is sensitized in long COVID and may explain dysregulated breathing and exercise intolerance in these participants. Tempering carotid body excitability may be a viable treatment option for long COVID patients.

Source: Ahmed El-MedanyZoe H AdamsHazel C BlytheKatrina A HopeAdrian H KendrickAna Paula Abdala SheikhJulian FR PatonAngus K NightingaleEmma C Hart. Carotid body dysregulation contributes to the enigma of long COVID. https://www.medrxiv.org/content/10.1101/2023.05.25.23290513v1.full-text (Full text)

Acupuncture and Moxibustion have Different Effects on Fatigue by Regulating the Autonomic Nervous System: A Pilot Controlled Clinical Trial

Abstract:

In order to investigate the different effects of acupuncture and moxibustion on chronic fatigue syndrome (CFS) and alterations in the autonomic nervous system by measuring heart rate variability (HRV).

Forty-five participants were recruited and randomly divided into 3 groups using a randomization schedule. The control group (CG, n = 15) and the acupuncture group (AG, n = 15) were treated by manipulation acupuncture, and the moxibustion group (MG, n = 15) was treated by indirect moxibustion. Primary outcomes were the scores of the Fatigue Assessment Instrument (FAI). Secondary outcomes were the HRV parameters which can reflect activity of the autonomic nervous system.

This trial considered both instantaneous changes and long-term effectiveness. FAI scores decreased after the 4th and 10th treatments in the 3 groups. The decrease in FAI in the MG was greater than that in the AG. Acupuncture was more effective in instantaneous changes of HRV and moxibustion in long-term aspects. Both acupuncture and moxibustion improved fatigue in CFS patients, but moxibustion was more effective.

The possible mechanism of the intervention may be through activation of the vagus nerve. Moxibustion was more effective than acupuncture in long-term treatment of CFS.

 

Source: Shu Q, Wang H, Litscher D, Wu S, Chen L, Gaischek I, Wang L, He W, Zhou H, Litscher G, Liang F. Acupuncture and Moxibustion have Different Effects on Fatigue by Regulating the Autonomic Nervous System: A Pilot Controlled Clinical Trial. Sci Rep. 2016 Nov 25;6:37846. doi: 10.1038/srep37846. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122953/ (Full article)

 

Variability of postural orthostatic tachycardia in patients with myalgic encephalomyelitis and orthostatic intolerance

Abstract:

Central nervous system dysfunction with myalgic encephalomyelitis (ME) has been suggested as the main cause of chronic fatigue syndrome. Fluctuation of the symptom severity and hierarchy is a characteristic feature in ME patients. The characteristics of the sympathetic activation may differ between the “good days” and “bad days” in them.

Twenty-four ME patients with orthostatic intolerance underwent a conventional 10-min active standing test and echocardiography both on a “good day” and a “bad day”, defined according to the severity of their symptoms. The mean heart rate at rest was significantly higher on the “bad days” than on the “good days”. During the standing test on a “bad day”, 5 patients (21 %) failed to maintain an upright posture for 10 min, whereas on a “good day” all the 24 patients maintained it.

Postural orthostatic tachycardia (POT) (increase in heart rate ≥30 beats/min) or severe POT (heart rate ≥120 beats/min) was observed on the “bad days” in 10 patients (43 %) who did not suffer from the severe tachycardia on the “good days”, suggesting the exaggerated sympathetic nervous activation.

In contrast, POT did not occur or severe POT was attenuated on the “bad days” in 5 patients (21 %) who developed POT or severe POT on the “good days”, suggesting the impaired sympathetic activation. Echocardiography revealed significantly lower mean values of both the left ventricular end-diastolic diameter and stroke volume index on the “bad days” compared with the “good days”.

In conclusion, in ME patients with orthostatic intolerance, the exaggerated activation of the sympathetic nervous system while standing appears to switch to the impaired sympathetic activation after the system is loaded with the additional accentuated stimuli associated with the preload reduction.

 

Source: Miwa K. Variability of postural orthostatic tachycardia in patients with myalgic encephalomyelitis and orthostatic intolerance. Heart Vessels. 2016 Sep;31(9):1522-8. doi: 10.1007/s00380-015-0744-3. Epub 2015 Sep 15. https://www.ncbi.nlm.nih.gov/pubmed/26374335

 

Chronic fatigue syndrome: a hypothesis focusing on the autonomic nervous system

Abstract:

Chronic fatigue syndrome is a debilitating illness of unknown aetiology, with estimated levels of prevalence of up to about 8. 7/100 000 in the U.S.A. Like pain fatigue it is a personal, emotionally rich experience, which may originate from peripheral or central sites (or both). The nature of the symptoms is complex and reflects the interaction of the patient with the environment and cultural milieu. Accordingly the common use of the same terminology for different types of fatigue may be misleading.

Autonomic activation is a key component of both real and simulated physical exercise. Alterations in autonomic nervous system activity are a key component of several physiopathological conditions. In chronic fatigue syndrome disturbances in autonomic activity, and in other homoeostatic mechanisms, such as the hormonal and immune systems, have been reported recently.

In this review we followed the hypothesis that in chronic fatigue syndrome the paradoxical condition of disturbing somatic symptoms in the absence of organic evidence of disease might be addressed by focusing on attending functional correlates. In particular we addressed possible alterations in cardiovascular autonomic control, as can be assessed by spectral analysis of R-R interval and systolic arterial pressure variability.

With this approach, in subjects complaining of unexplained fatigue, we obtained data suggesting a condition of prevailing sympathetic modulation of the sino-atrial node at rest, and reduced responsiveness to excitatory stimuli. Far from considering the issue resolved, we propose that in the context of the multiple physiological and psychological interactions involved in the perception and self-reporting of symptoms, attendant changes in physiological equivalents might furnish a convenient assessment independent from subjective components.

Indices of sympathetic modulation could, accordingly, provide quantifiable signs of the interaction between subject’s efforts and environmental demands, independently of self descriptions, which could provide convenient measurable outcomes, both for diagnosis and treatment titration in chronic fatigue syndrome.

Comment in: Long- and short-term blood pressure and RR-interval variability and psychosomatic distress in chronic fatigue syndrome. [Clin Sci (Lond). 1999]

 

Source: Pagani M, Lucini D. Chronic fatigue syndrome: a hypothesis focusing on the autonomic nervous system. Clin Sci (Lond). 1999 Jan;96(1):117-25. http://www.ncbi.nlm.nih.gov/pubmed/9857114