Investigating the possible mechanisms of autonomic dysfunction post-COVID-19

Maya Jammoul; Judith Naddour; Amir Madi; Mohammad Amine Reslan; Firas Hatoum; Jana Zeineddine; Wassim Abou-Kheir; Nada Lawand

doi:10.1016/j.autneu.2022.103071

Investigating the possible mechanisms of autonomic dysfunction post-COVID-19

Auton Neurosci. 2023 Mar:245:103071. doi: 10.1016/j.autneu.2022.103071. Epub 2022 Dec 24.

Authors

Maya Jammoul¹, Judith Naddour¹, Amir Madi², Mohammad Amine Reslan³, Firas Hatoum⁴, Jana Zeineddine⁴, Wassim Abou-Kheir¹, Nada Lawand⁵

Affiliations

¹ Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Lebanon.
² Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy.
³ Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
⁴ Faculty of Medicine, American University of Beirut, Lebanon.
⁵ Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Lebanon; Department of Neurology, Faculty of Medicine, American University of Beirut, Lebanon. Electronic address: Alchaer@sbcglobal.net.

Abstract

Patients with long COVID suffer from many neurological manifestations that persist for 3 months following infection by SARS-CoV-2. Autonomic dysfunction (AD) or dysautonomia is one complication of long COVID that causes patients to experience fatigue, dizziness, syncope, dyspnea, orthostatic intolerance, nausea, vomiting, and heart palpitations. The pathophysiology behind AD onset post-COVID is largely unknown. As such, this review aims to highlight the potential mechanisms by which AD occurs in patients with long COVID. The first proposed mechanism includes the direct invasion of the hypothalamus or the medulla by SARS-CoV-2. Entry to these autonomic centers may occur through the neuronal or hematogenous routes. However, evidence so far indicates that neurological manifestations such as AD are caused indirectly. Another mechanism is autoimmunity whereby autoantibodies against different receptors and glycoproteins expressed on cellular membranes are produced. Additionally, persistent inflammation and hypoxia can work separately or together to promote sympathetic overactivation in a bidirectional interaction. Renin-angiotensin system imbalance can also drive AD in long COVID through the downregulation of relevant receptors and formation of autoantibodies. Understanding the pathophysiology of AD post-COVID-19 may help provide early diagnosis and better therapy for patients.

Keywords: Autonomic dysfunction; Autonomic nervous system; COVID-19; Dysautonomia; Long COVID; Post-COVID.

Publication types

Review

MeSH terms

Autonomic Nervous System Diseases* / etiology
COVID-19* / complications
Humans
Orthostatic Intolerance*
Post-Acute COVID-19 Syndrome
SARS-CoV-2