SARS-CoV-2 Infection in the Central and Peripheral Nervous System-Associated Morbidities and Their Potential Mechanism

Abstract

The recent outbreak of SARS-CoV-2 infections that causes coronavirus-induced disease of 2019 (COVID-19) is the defining and unprecedented global health crisis of our time in both the scale and magnitude. Although the respiratory tract is the primary target of SARS-CoV-2, accumulating evidence suggests that the virus may also invade both the central nervous system (CNS) and the peripheral nervous system (PNS) leading to numerous neurological issues including some serious complications such as seizures, encephalitis, and loss of consciousness. Here, we present a comprehensive review of the currently known role of SARS-CoV-2 and identify all the neurological problems reported among the COVID-19 case reports throughout the world. The virus might gain entry into the CNS either through the trans-synaptic route via the olfactory neurons or through the damaged endothelium in the brain microvasculature using the ACE2 receptor potentiated by neuropilin-1 (NRP-1). The most critical of all symptoms appear to be the spontaneous loss of breathing in some COVID-19 patients. This might be indicative of a dysfunction within the cardiopulmonary regulatory centers in the brainstem. These pioneering studies, thus, lay a strong foundation for more in-depth basic and clinical research required to confirm the role of SARS-CoV-2 infection in neurodegeneration of critical brain regulatory centers. Keywords ACE1. ACE2. Brain. COVID-19. Coronavirus. Headache. Loss of consciousness. Loss of smell. Loss of taste. Neuropilin-1. Nervous system. SARS-CoV-2. Seizures. Stroke Abbreviations ACE2 Angiotensin-converting enzyme 2 ARDS Acute respiratory distress syndrome BBB Blood-brain barrier BNB Blood-nerve barrier BSCB Blood-spinal cord barriers CMAP Compound muscle action potential CNS Central nervous system CTSL Cathepsin L GBS Guillain-Barré syndrome

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

“…Autopsy, animal, and organoid model studies show that, like SARS-CoV, SARS-CoV-2 is able to reach and infect cells of the CNS, infect neurons, and produce neuroinflammation ( Matschke et al, 2020 ; Song et al, 2020 ; Song et al, 2021 ). Indeed, SARS-CoV-2 may be capable of transport up and down nerves and neuronal axons ( Lima et al, 2020 ; Rangon et al, 2020 ; Song et al, 2020 ; Karuppan et al, 2021 ).…”

COVID-19 is a systemic vascular hemopathy: insight for mechanistic and clinical aspects

“…Until then, models of SARS-CoV2 damage of ECs should consider direct infection via ACE2 as a hypothesis to be confirmed. Finally, ACE2 is not the only possible endothelial receptor for viral entry: other molecules including neuropilin-1, as well as integrings, have been suggested as possible receptors for the virus as well [ 155 – 158 ], but their role in supporting SARS-CoV-2 infection of ECs remains to be demonstrated.…”

A Review of Neurological Involvement in Patients with SARS-CoV-2 Infection

“…In a few cases of Miller-Fisher syndrome concomitant with COVID-19, commonly reported manifestations included perioral paresthesia, ataxia, impaired vision, ophthalmoplegia, and generalized areflexia [ 74 ]. Fortunately, two-thirds of patients showed improvement after administration of immunoglobulin [ 75 ].…”

“…There is a growing concern regarding the long-term sequelae of COVID-19, particularly involving the nervous system, as cases of patients recovering from initial symptoms while beginning to present new neurological manifestations are now emerging. It was demonstrated that some patients had double vision, hallucinations, disorientation, and impaired attention, quadriplegia, facial paralysis, and hypogeusia even 6 months after infection [ 75 ]. A prospective cohort study in France assessed the clinical status of COVID-19 patients 4 months after discharge.…”