Evidence of Coronavirus (CoV) Pathogenesis and Emerging Pathogen SARS-CoV-2 in the Nervous System: A Review on Neurological Impairments and Manifestations

Abstract

The coronavirus disease 2019 pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities.

Case Report: Behavioral Unresponsiveness in Acute COVID-19 Patients: The Utility of the Motor Behavior Tool-Revised and 18F-FDG PET/CT

“…Our patients presented severe swallowing disorders, facial akinesia, absence of oculomotricity and lack of motor interaction to stimulation, without any structural brain MRI signs of inflammatory, vascular, degenerative, or infectious encephalopathy. The pathogenic mechanism explaining COVID-related neurological disorders and encephalopathy in particular, is the topic of intense discussion (2,(20)(21)(22)(23). Indeed, it remains undetermined whether SARS-CoV-2 causes direct brain damages (possibly by affecting the olfactory nerves and migrating retrogradely) or whether the cause is indirect, due to an excessive inflammatory response (cytokine storm) or the trigger of an autoimmune response by the virus (24), but more evidence suggest a migration to the central nervous system via transfer across the blood-brain barrier (20,23).…”

Immunologically relevant aspects of the new COVID-19 vaccines—an ÖGAI (Austrian Society for Allergology and Immunology) and AeDA (German Society for Applied Allergology) position paper

“…Large studies have reported the development of autoantibodies after COVID-19, which were also shown to be associated with disease severity [ 32 – 34 ]. The observed neurological impairment in COVID-19 [ 35 ] has been linked to both a direct effect of SARS-CoV‑2 on neurons and to autoimmune mechanisms [ 36 ]. A higher number of peripheral neuropathies (Guillain–Barré syndrome) and polyneuropathies with associated muscle denervation are observed in SARS-CoV-2 patients [ 37 ], which could be part of Long-COVID [ 34 , 38 ].…”

Impact of natural selection on global patterns of genetic variation, and association with clinical phenotypes, at genes involved in SARS-CoV-2 infection

“…The extent to which pre-existing chronic liver conditions affect COVID-19 related complications remains to be elucidated. Smell and taste sensations as well as increased incidence of ischemic stroke have been observed in individuals with COVID-19 [14][15][16][17] .…”