Neurological Complications of COVID-19: Underlying Mechanisms and Management

Abstract

COVID-19 is a severe respiratory disease caused by the newly identified human coronavirus (HCoV) Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The virus was discovered in December 2019, and in March 2020, the disease was declared a global pandemic by the World Health Organization (WHO) due to a high number of cases. Although SARS-CoV-2 primarily affects the respiratory system, several studies have reported neurological complications in COVID-19 patients. Headache, dizziness, loss of taste and smell, encephalitis, encephalopathy, and cerebrovascular diseases are the most common neurological complications that are associated with COVID-19. In addition, seizures, neuromuscular junctions' disorders, and Guillain-Barré syndrome were reported as complications of COVID-19, as well as neurodegenerative and demyelinating disorders. However, the management of these conditions remains a challenge. In this review, we discuss the prevalence, pathogenesis, and mechanisms of these neurological sequelae that are secondary to SARS-CoV-2 infection. We aim to update neurologists and healthcare workers on the possible neurological complications associated with COVID-19 and the management of these disease conditions.

Keywords: COVID-19; Guillain–Barré syndrome; SARS-CoV-2; cerebrovascular; dizziness; encephalitis; encephalopathy; headache; management; myalgia; neurological; seizures; stroke.

Figure 1

Mechanisms of SARS-CoV-2 invasion of the CNS. (A) Hematogenous route: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) invasion of CNS from the bloodstream is mediated by three mechanisms; 1. Transcellular migration which involves binding of the virus to its receptors; ACE2, basigin (BSG), or neuropilin-1 (NRP-1), on brain microvasculature endothelial cells then crossing endothelial cells via transcytosis, 2. Infecting immune cells which then carry the virus across the blood–brain barrier (BBB) endothelial cells into the CNS (Trojan Horse mechanism), and 3. Paracellular route by disrupting endothelial cells’ tight junctions. (B) SARS-CoV-2 infects olfactory epithelium and reaches the CNS via the olfactory neurons. This figure was created with BioRender.com.

Figure 2

Mechanisms of COVID-19 neurological complications. Lung infection by SARS-CoV-2 results in severe inflammation, acute respiratory distress syndrome (ARDS), and hypoxia. This leads to hypoxia- and inflammation-induced encephalopathy and seizures. Brain damage due to viral replication may lead to encephalitis. Severe systemic inflammation could result in hypercoagulability which may eventually lead to stroke. Nonspecific symptoms due to nervous system affections include headache, dizziness, loss of taste and smell, and myalgia. Usage of ACE2 receptor; by SARS-CoV-2, to infect target cells, including endothelial cells, would deplete the receptor resulting in the accumulation of angiotensin II (AngII). High levels of AngII promote vasoconstriction, fluid retention, inflammation, and blood coagulation, which could result in ischemic or hemorrhagic stroke. This figure was created with BioRender.com.