The extended autonomic system, dyshomeostasis, and COVID-19

Abstract

The pandemic viral illness COVID-19 is especially life-threatening in the elderly and in those with any of a variety of chronic medical conditions. This essay explores the possibility that the heightened risk may involve activation of the "extended autonomic system" (EAS). Traditionally, the autonomic nervous system has been viewed as consisting of the sympathetic nervous system, the parasympathetic nervous system, and the enteric nervous system. Over the past century, however, neuroendocrine and neuroimmune systems have come to the fore, justifying expansion of the meaning of "autonomic." Additional facets include the sympathetic adrenergic system, for which adrenaline is the key effector; the hypothalamic-pituitary-adrenocortical axis; arginine vasopressin (synonymous with anti-diuretic hormone); the renin-angiotensin-aldosterone system, with angiotensin II and aldosterone the main effectors; and cholinergic anti-inflammatory and sympathetic inflammasomal pathways. A hierarchical brain network-the "central autonomic network"-regulates these systems; embedded within it are components of the Chrousos/Gold "stress system." Acute, coordinated alterations in homeostatic settings (allostasis) can be crucial for surviving stressors such as traumatic hemorrhage, asphyxiation, and sepsis, which throughout human evolution have threatened homeostasis; however, intense or long-term EAS activation may cause harm. While required for appropriate responses in emergencies, EAS activation in the setting of chronically decreased homeostatic efficiencies (dyshomeostasis) may reduce thresholds for induction of destabilizing, lethal vicious cycles. Testable hypotheses derived from these concepts are that biomarkers of EAS activation correlate with clinical and pathophysiologic data and predict outcome in COVID-19 and that treatments targeting specific abnormalities identified in individual patients may be beneficial.

Three decades of Clinical Autonomic Research and beyond

“…Despite the many difficulties associated with the global COVID-19 pandemic, the year 2020 was a good one for Clinical Autonomic Research, and the prospects for 2021 are even better. During 2020, the journal published special issues and articles on the autonomic aspects related to COVID-19 [ 2 , 5 , 7 , 10 , 12 , 13 ]. All COVID-19-related manuscripts are Open Access immediately upon publication.…”

Autonomic function test during the COVID-19 pandemic: is it safe and sound?

“…Autonomic function testing is essential for detection, quantification, and localization of autonomic dysfunction of several medical conditions, and are relevant to diagnosis, prognosis, and clinical management of patients to improve their quality of life [ 1 ]. Furthermore, some have hypothesized that the autonomic nervous system is involved in the pathophysiology of COVID-19 [ 4 , 5 ], and that autonomic dysfunction could be part of the spectrum of long-term sequelae in survivors, known as “long-haul COVID” [ 8 ]. If this is true, referral for autonomic testing would be expected to rise soon.…”

Hydroelectrolytic Disorder in COVID-19 patients: Evidence Supporting the Involvement of Subfornical Organ and Paraventricular Nucleus of the Hypothalamus

“…SARS-CoV-2 infection can increase sympathetic activity via changes in blood gases and immunoinflammatory factors ( Porzionato et al, 2020 ). Autonomic activation has direct adrenergic effects on RAAS, which increases aldosterone secretion and contributes to the loss of K + ( Darbar et al, 1996 ; Goldstein, 2020 ; Gordon et al, 1967 ; Nayyar et al, 2017 ). One study also showed a relationship between the mortality of COVID-19 patients with increased plasma cortisol levels ( Tan et al, 2020 ).…”