Introduction:
Long COVID syndrome, also known as long COVID-19, refers to signs and symptoms that persist or develop for over four weeks following an acute COVID-19 infection. During clinical examination, differential diagnosis and detection of concomitant diseases unrelated to SARS-CoV-2 infection are critical. Cardiovascular autonomic dysfunction, also known as dysautonomia, is characterized by poor autonomic nervous system (ANS) function, which leads to a variety of cardiovascular symptoms. Dysautonomia may be acute, chronic, growing, irreversible, or changeable and can be associated with infectious or non-infectious disorders.
Heart rate variability (HRV) can be measured using linear and non-linear approaches to determine cardiovascular autonomic dysfunction. Autonomic tests can be performed to investigate the potential causative links of dysautonomia in people with long-term COVID-19. The relationship between HRV and different inflammatory indicators influences cardiovascular autonomic regulation. HRV monitoring may also improve illness stratification in patients with long COVID-19. The purpose of this article is to offer information on the long-term cardiovascular autonomic dysfunction among individuals with long-term COVID and its influence on morbidity and mortality in this group of patients.
What Is the Autonomic Pathophysiology of Long COVID?
The persistent neurological difficulties reported in long COVID are most likely caused by injury to the CNS (central nervous system) and the peripheral nervous system (PNS). This could result in complicated pathogenesis, including direct viral neuronal injury, neuroinflammation, blood-brain barrier (BBB) disruption, microvasculitis (a range of diseases or presentations associated with a disease, where there is inflammation of small blood vessels), and hypoxia (low levels of oxygen). SARS-CoV-2 attaches to the nervous system (NS) cells in the cerebral cortex, the choroid plexus, and the ventral or posterior nucleus of the thalamus via the angiotensin-converting enzyme 2 (ACE2). After direct SARS-CoV-2 infection, neurotropic effects play an important role in developing long COVID-19. SARS-CoV-2 could employ ACE2 to penetrate CNS and PNS cells via hematogenous or transsynaptic routes.
Although the neurotropic pathways remain unclear, a virus will likely cross the BBB and cause direct or indirect damage. The SARS-CoV-2 spike proteins (S12) can also harm the integrity of the BBB, either alone or in combination with additional cell mediators. The endothelial cells and the pericytes cause indirect harm, as does the activation of the autoimmune system. Other processes contributing to long COVID include a connection between immune-mediated circulatory dysfunction, thromboembolism, and neuronal dysfunction. A link between SNS (sympathetic nervous system) activity and an increase in catecholamines, followed by a cytokine storm and impairment caused by ANS inflammation, is expected to be established. Autonomic dysfunction in long-term COVID can be produced by SARS-CoV-2's direct viral action or an immunological response that affects the ANS.
What Is the Role of HRV and Inflammatory Markers?
HRV (heart rate variability) could help detect and track early inflammatory responses. Yet, further, HRV research is needed to investigate chronic inflammatory conditions. Inflammatory indicators such as C-reactive protein (c-RP) and white blood cell (WBC) count were associated with lower levels of HRV. These findings point to a connection between inflammation and the ANS, as well as an increase in cardiovascular mortality and morbidity. Autonomic dysfunction may enhance the risk of cardiovascular damage in people who have elevated inflammatory biomarkers. Elevated c-RP levels indicate a chronic inflammatory state, which serves as a peripheral indicator in clinical studies and may be linked to the consequences of illness.
What Are the Cardiovascular Autonomic Dysfunctions in Patients Due to COVID-19?
The variations observed in the HR (heart rate) and BP (blood pressure) variability indices in PCS (post-COVID syndrome) patients indicate autonomic dysfunction with sympathetic predominance. The marked disruption of autonomic regulation over the heart and arteries may increase the risk of life-threatening cardiovascular events.
However, one of the most significant findings of the current study was that patients with PCS who underwent evaluation of the parameters analyzed revealed that the unpleasant effect of the post-COVID condition associated with these findings tends to dissipate over time. Long-term COVID-19 may cause cardiovascular dysautonomia. POTS (postural orthostatic tachycardia syndrome) is the most common kind of CVD (cardiovascular disease), characterized by a sustained rise in heart rate of at least 30 beats per minute while standing (upright). Palpitations, chest discomfort, and fitness or orthostatic intolerance could accompany it. POTS is more common in women and may be caused by viral diseases or severe infections.
What Is the Association of ANS and HRV?
HRV monitoring evaluates the ANS and its interrelated sympathetic and parasympathetic divisions. The autonomic nervous system (ANS) significantly impacts heart rate and rhythm. Parasympathetic activity lowers HR via the vagus nerve, while sympathetic resolution activates β-adrenergic receptors. HRV can be assessed with both linear and nonlinear approaches.
High or low HRV is associated with sympathetic ("escape") and parasympathetic activation ("recovery"), respectively. A high HRV suggests sympathovagal balance and strong ANS flexibility. A lower HRV could imply aberrant ANS control. Activation of the inflammatory reflex has been postulated to interfere with vagal modulation of the HR, as inflammation in the chronic and acute phases alters cardiac function via changes in HRV.
Conclusion:
Patients with post-COVID-19 syndrome have HRV abnormalities, indicating some degree of autonomic nervous system dysfunction and thus impaired parasympathetic function in this population; however, this has also been associated with subtle impairment of left ventricular systolic function. Dysautonomia in long-term COVID patients is multifaceted, and vagal dysfunction can explain many of the autonomic symptoms; however, the parasympathetic and sympathetic interaction involved requires further investigation. Knowing cardiovascular autonomic dysfunction and the significance of its association with biomarkers of inflammation in patients with long COVID-19 can lead to more accurate diagnoses, a better understanding of the clinical presentation of the ANS (autonomic nervous system) pathway in response to an infectious disease, and better prognoses.
