Multiple Neuroinvasive Pathways in COVID-19

Abstract

COVID-19 is a highly infectious viral disease caused by the novel coronavirus SARS-CoV-2. While it was initially regarded as a strictly respiratory illness, the impact of COVID-19 on multiple organs is increasingly recognized. The brain is among the targets of COVID-19, and it can be impacted in multiple ways, both directly and indirectly. Direct brain infection by SARS-CoV-2 may occur via axonal transport via the olfactory nerve, eventually infecting the olfactory cortex and other structures in the temporal lobe, and potentially the brain stem. A hematogenous route, which involves viral crossing of blood-brain barrier, is also possible. Secondary mechanisms involve hypoxia due to respiratory failure, as well as aberrant immune response leading to various forms of encephalopathy, white matter damage, and abnormal blood clotting resulting in stroke. Multiple neurological symptoms of COVID-19 have been described. These involve anosmia/ageusia, headaches, seizures, mental confusion and delirium, and coma. There is a growing concern that in a number of patients, long-term or perhaps even permanent cognitive impairment will persist well after the recovery from acute illness. Furthermore, COVID-19 survivors may be at increased risk for developing neurodegenerative diseases years or decades later. Since COVID-19 is a new disease, it will take months or even years to characterize the exact nature, scope, and temporal extent of its long-term neurocognitive sequelae. To that end, rigorous and systematic longitudinal follow-up will be required. For this effort to succeed, appropriate protocols and patient registries should be developed and put in place without delay now.

Cardiovascular protective properties of oxytocin against COVID-19

“…The olfactory bulb involvement is supported by the high rates of anosmia or hyposmia in patients with COVID-19 [ 81 ] and by neural connections between the olfactory bulb and SON [ 82 ]. Alternatively, SARS-CoV-2 in the blood can enter the hypothalamus and pituitary through fenestrated capillaries of blood-brain barrier around the third ventricle and pituitary [ 83 ]. Direct evaluation of plasma OXT levels and examination of hypothalamic histology of COVID-19 patients are needed to further clarify this association.…”

SARS-CoV-2 invasion of the central nervous: a brief review

“…Retrospective studies of 214 COVID-19 patients revealed that patients exhibited symptoms ( Figure 1 ) such as dizziness (17%), confusion (9%), impaired consciousness (8%), hypogeusia (6%), anosmia (6%), acute cerebrovascular diseases (3%) (80% ischemic stroke and 20% cerebral hemorrhage), epilepsy (1%), ataxia (1%), and neuralgia [ 28 , 29 ], further confirming the involvement of CNS, although some symptoms, such as dizziness, might be a secondary effect of inflammation or fever. Hypogeusia and anosmia are controlled by the parietal lobe in the brain and dizziness is linked to the parietal cortex [ 30 , 31 ], which suggests that the parietal lobe might be affected by SARS-CoV-2 since the abnormalities were reported in the parietal lobes of COVID-19 patients [ 32 , 33 ]. Four scenarios have been proposed for development of anosmia in SARS-CoV-2 patients, namely nasal obstruction and rhinorrhea, damage of support cells in the olfactory epithelium, brain infiltration affecting olfactory centers, and loss of olfactory receptor neurons [ 34 ].…”

Geospatial Analysis of Environmental Atmospheric Risk Factors in Neurodegenerative Diseases: A Systematic Review

“…This last pathway is similar to one of the atmospheric pollutants reaching the CNS, raising the hypothesis that this virus may pose a higher potential for neuroinflammation and neurodegeneration [ 39 ]. The concept of Neuro-COVID-19 is, thus, being increasingly used in current research [ 40 ].…”