Acute and chronic neurological disorders in COVID-19: potential mechanisms of disease

Abstract

COVID-19 is a global pandemic caused by SARS-CoV-2 infection and is associated with both acute and chronic disorders affecting the nervous system. Acute neurological disorders affecting patients with COVID-19 range widely from anosmia, stroke, encephalopathy/encephalitis, and seizures to Guillain-Barre Syndrome. Chronic neurological sequelae are less well defined although exercise intolerance, dysautonomia, pain, as well as neurocognitive and psychiatric dysfunctions are commonly reported. Molecular analyses of cerebrospinal fluid and neuropathological studies highlight both vascular and immunologic perturbations. Low levels of viral RNA have been detected in the brains of few acutely ill individuals. Potential pathogenic mechanisms in the acute phase include coagulopathies with associated cerebral hypoxic-ischemic injury, blood-brain barrier abnormalities with endotheliopathy and possibly viral neuroinvasion accompanied by neuro-immune responses. Established diagnostic tools are limited by a lack of clearly defined COVID-19 specific neurological syndromes. Future interventions will require delineation of specific neurological syndromes, diagnostic algorithm development, and uncovering the underlying disease mechanisms that will guide effective therapies.

Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb

“…These virions may remain largely outside cells and not cause inflammation, consistent with the paucity of clinical reports about meningitis in COVID-19 patients. But they may cause neurological sequelae in a subset of patients (Balcom et al, 2021), such as by prompting the generation of autoantibodies against neural antigens (Song et al, 2021a). It is tempting to speculate that this viral RNA presence may contribute to olfactory dysfunction by perturbing signal propagation via the olfactory tract from the OB to the cerebral cortex.…”

Dysautonomia and Implications for Anosmia in Long COVID-19 Disease

“…SARS-CoV-2 can lead to neuronal damages by affecting the nervous system as anosmia and ageusia were among the predominant persisting neurological symptoms described [ 17 ]. Indeed, similarly to other zoonotic coronaviruses, including Middle East respiratory syndrome-related coronavirus and SARS-CoV-1, SARS-CoV-2 possesses the capacity for neurological virulence [ 18 ].…”

TOM70 in Glial Cells as a Potential Target for Treatment of COVID-19

“…Although the respiratory tract is the main target, central nervous system (CNS) involvement has raised special interest since neurological symptoms have been reported in over 30% of hospitalized patients and ∼85% of patients with acute respiratory distress syndrome (Iadecola et al, 2020;Balcom et al, 2021). Acute neurological signs include anosmia, ageusia, headache, altered mental status, seizures, and stroke (Iadecola et al, 2020;Balcom et al, 2021). Interestingly, headache, fatigue, dysgeusia, and anosmia are common in both mild and severe cases (Kanberg et al, 2021).…”

“…Interestingly, headache, fatigue, dysgeusia, and anosmia are common in both mild and severe cases (Kanberg et al, 2021). However, it is yet to be established whether altered mental health is a result from an encephalopathy caused by a systemic inflammatory condition or an encephalitis caused by SARS-CoV-2 neuroinvasion (Iadecola et al, 2020;Balcom et al, 2021). Noteworthy, viral infections may cause neurologic impairment through direct infection of different cells, including neurons, glia or endothelial cells, resulting in acute cell death (Iadecola et al, 2020).…”

“…Despite the evidence reporting various neurological manifestations in COVID-19, it is still uncertain whether SARS-CoV-2 is neurotropic or elicits its effects through the excessive immune response since cytokines can directly pass the blood-brain barrier (BBB) (Iadecola et al, 2020;Balcom et al, 2021). Consistent with the neurotropism hypothesis, previous findings demonstrated that angiotensin-converting enzyme 2 (ACE2) receptor, the protein by which SARS-CoV-2 infects cells, is expressed at relatively high levels in neurons and glial cells of several brain areas as well as in vascular wall cells (Iadecola et al, 2020;Chen et al, 2021).…”