About this Research Topic
The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or coronavirus disease (COVID-19), has dramatically impacted global society. Globally ~5.5 million cases have been reported with ~350,000 deaths to date. More than 100,000 deaths have occurred in the USA alone. SARS-CoV-2 in particular affects older adults (>60yrs); those with diabetes, hypertension, obesity, heart and/or lung disease, are in nursing home facilities or are immunocompromised. Patients with cognitive impairment and/or age associated neurodegenerative diseases are a particularly vulnerable population. Among this older adult population altered mental status or delirium is much more likely to be presenting clinical manifestations. This is in contrast to the more typical COVID-19 symptoms of fever, cough and dyspnea.
Neurological complications, are common with more severe infection, that disproportionately affect older adults, including impaired consciousness, stroke, and seizures. Though the pathogenesis of neurological complications in COVID-19 are still being elucidated, possibilities include direct neuronal invasion, thrombosis and/or microangiopathy with subsequent stroke or intracranial hemorrhage, sequelae of critical illness including hypoxic brain injury, critical illness neuropathy or myopathy, or post-infectious molecular mimicry syndromes such as Guillain Barre Syndrome or necrotizing encephalomyelitis. This is likely due, in part, to the fact that the COVID-19 virus is now known to target the central nervous system (CNS).
Host-virus interactions in the CNS, or neurotropism, may relate to levels of expression of angiotensin-converting enzyme 2 (ACE2) and TMPRSS 2 in neurological tissue. The COVID-19 virus exploits the ACE2 receptor to enter into cells. Direct invasion of the brain and into vascular endothelial cells are likely contributors to what is now recognized to be a myriad of neurological manifestations in both the acute phase of COVID-19 and in those who have recovered from infection. Neurotropic and neuroinvasive capabilities may be through ACE2 which has been demonstrated to be expressed in neurons, as well as brain endothelial and arterial smooth muscle cells. The neuroinvasive potential of the COVID-19 virus may also play a direct role in the respiratory abnormalities of patients through spread within synapse-connected routes to medullary cardiorespiratory centers, from the mechanoreceptors and chemoreceptors in the lung/ lower respiratory airways. In this older population it is expected that a significant percentage of COVID patients will also have preclinical AD, which may also predispose them to neurological symptoms related to reduced neuronal reserve and/or associated blood-brain-barrier (BBB) dysfunction. Interestingly, recent data suggest that inheritance of the apolipoprotein E4 allele, the major genetic risk factor for AD, is also associated with more severe COVID-19 disease, independent of the presence of dementia.
In this Research Topic, experts on the neurological and neuroscientific evidence in aged COVID-19 patients will contribute articles to better understand the pathogenesis of infection and factors that predispose to more severe disease and/or neurological complications, in particular in aged populations, as well as potential pharmacological and non-pharmacological therapeutic approaches.
Neurological complications, are common with more severe infection, that disproportionately affect older adults, including impaired consciousness, stroke, and seizures. Though the pathogenesis of neurological complications in COVID-19 are still being elucidated, possibilities include direct neuronal invasion, thrombosis and/or microangiopathy with subsequent stroke or intracranial hemorrhage, sequelae of critical illness including hypoxic brain injury, critical illness neuropathy or myopathy, or post-infectious molecular mimicry syndromes such as Guillain Barre Syndrome or necrotizing encephalomyelitis. This is likely due, in part, to the fact that the COVID-19 virus is now known to target the central nervous system (CNS).
Host-virus interactions in the CNS, or neurotropism, may relate to levels of expression of angiotensin-converting enzyme 2 (ACE2) and TMPRSS 2 in neurological tissue. The COVID-19 virus exploits the ACE2 receptor to enter into cells. Direct invasion of the brain and into vascular endothelial cells are likely contributors to what is now recognized to be a myriad of neurological manifestations in both the acute phase of COVID-19 and in those who have recovered from infection. Neurotropic and neuroinvasive capabilities may be through ACE2 which has been demonstrated to be expressed in neurons, as well as brain endothelial and arterial smooth muscle cells. The neuroinvasive potential of the COVID-19 virus may also play a direct role in the respiratory abnormalities of patients through spread within synapse-connected routes to medullary cardiorespiratory centers, from the mechanoreceptors and chemoreceptors in the lung/ lower respiratory airways. In this older population it is expected that a significant percentage of COVID patients will also have preclinical AD, which may also predispose them to neurological symptoms related to reduced neuronal reserve and/or associated blood-brain-barrier (BBB) dysfunction. Interestingly, recent data suggest that inheritance of the apolipoprotein E4 allele, the major genetic risk factor for AD, is also associated with more severe COVID-19 disease, independent of the presence of dementia.
In this Research Topic, experts on the neurological and neuroscientific evidence in aged COVID-19 patients will contribute articles to better understand the pathogenesis of infection and factors that predispose to more severe disease and/or neurological complications, in particular in aged populations, as well as potential pharmacological and non-pharmacological therapeutic approaches.
Keywords: COVID-19, Neurotropism, Neurological Complications, SARS-CoV-2
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