Pathological Features and Neuroinflammatory Mechanisms of SARS-CoV-2 in the Brain and Potential Therapeutic Approaches

Abstract

The number of deaths has been increased due to COVID-19 infections and uncertain neurological complications associated with the central nervous system. Post-infections and neurological manifestations in neuronal tissues caused by COVID-19 are still unknown and there is a need to explore how brainstorming promoted congenital impairment, dementia, and Alzheimer’s disease. SARS-CoV-2 neuro-invasion studies in vivo are still rare, despite the fact that other beta-coronaviruses have shown similar properties. Neural (olfactory or vagal) and hematogenous (crossing the blood–brain barrier) pathways have been hypothesized in light of new evidence showing the existence of SARS-CoV-2 host cell entry receptors into the specific components of human nerve and vascular tissue. Spike proteins are the primary key and structural component of the COVID-19 that promotes the infection into brain cells. Neurological manifestations and serious neurodegeneration occur through the binding of spike proteins to ACE2 receptor. The emerging evidence reported that, due to the high rate in the immediate wake of viral infection, the olfactory bulb, thalamus, and brain stem are intensely infected through a trans-synaptic transfer of the virus. It also instructs the release of chemokines, cytokines, and inflammatory signals immensely to the blood–brain barrier and infects the astrocytes, which causes neuroinflammation and neuron death; and this induction of excessive inflammation and immune response developed in more neurodegeneration complications. The present review revealed the pathophysiological effects, molecular, and cellular mechanisms of possible entry routes into the brain, pathogenicity of autoantibodies and emerging immunotherapies against COVID-19.

Subjective and Objective Cognitive Impairments in Non-Hospitalized Persons 9 Months after SARS-CoV-2 Infection

“…Of interest is that the regression analysis of the cognitive tests revealed no variables which were consistently and independently associated with cognitive impairments, except poor education level. Since poor education may adversely affect cognition via low cognitive reserves, future studies should be conducted on this specific patient group [ 5 ]. In contrast to the results from Almeria et al [ 40 ], the presence of neurological symptoms was not consistently associated with cognitive functions in the present study.…”

“…The underlying mechanisms by which SARS-CoV-2 affects the brain may include processes related to inflammation, neuroinvasion, microvascular injury, and hypoxia [ 4 ]. Emerging evidence has revealed that the olfactory bulb, thalamus, and brain stem are infected by the virus through a trans-synaptic transfer [ 5 ]. The excessive release of inflammatory signals such as cytokines and chemokines, and infection of the astrocytes induce neuroinflammation and neuronal death and may result in further neurodegenerative complications [ 5 ].…”

The Clinical Observation of Inflammation Theory for Depression: The Initiative of the Formosa Long COVID Multicenter Study (FOCuS)

“…(b) SARS-CoV-2 can directly invade the brain. The neuro-invasion pathway may involve direct brain damage by SARS-CoV-2 and/or the persistence of the coronavirus activating long-lasting inflammation in the brain to cause depression [ 54 , 55 ]. As previously mentioned, depression and other long COVID neuropsychiatric sequelae may share common pathogenic pathways that involve both systemic inflammation and neuroinflammation.…”

Exploring the research landscape of COVID-19-induced olfactory dysfunction: A bibliometric study

“…Najafloo et al (2021) examined the mechanisms associated with olfactory impairment in neocoronary pneumonia, including olfactory cleft syndrome, local inflammation, apoptosis of olfactory cells, and damage to olfactory neurons and stem cells. Sodagar et al (2022) reviewed the pathological features, neuroinflammatory mechanisms, and potential treatments of SARS-CoV-2 in the brain, finding strong infection of the olfactory bulb, thalamus, and brainstem. Karimian et al (2022) explored the molecular mechanism of SARS-CoV-2-induced olfactory deficit, suggesting that OD may be a temporary or long-term complication caused by olfactory neuroepithelial disorders, with the Delta and Omicron strains relying on TMPRSS2 to enter cells and inducing inflammation, apoptosis, and neuronal damage.…”