Neurobiology of COVID-19: how can the virus affect the brain?

Abstract

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), which has been declared a public health emergency of international interest, with confirmed cases in most countries. COVID-19 presents manifestations that can range from asymptomatic or mild infections up to severe manifestations that lead to hospitalization and death. A growing amount of evidence indicates that the virus may cause neuroinvasion. Postmortem brain study findings have included edema, hemorrhage, hydrocephalus, atrophy, encephalitis, infarcts, swollen axons, myelin loss, gliosis, neuronal satellitosis, hypoxic-ischemic damage, arteriolosclerosis, leptomeningeal inflammation, neuronal loss, and axon degeneration. In addition, the COVID-19 pandemic is causing dangerous effects on the mental health of the world population, some of which can be attributed to its social impact (social distancing, financial issues, and quarantine). There is also a concern that environmental stressors, enhanced by psychological factors, are contributing to the emergence of psychiatric outcomes during the pandemic. Although clinical studies and diagnosing SARS-CoV-2-related neurological disease can be challenging, they are necessary to help define the manifestations and burden of COVID-19 in neurological and psychiatric symptoms during and after the pandemic. This review aims to present the neurobiology of coronavirus and postmortem neuropathological hallmarks.

Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis

“…Persistent symptoms may arise from a combination of biological and psychological mechanisms. For example, SARS-CoV-2 RNA may remain in brain tissue long-term, worsening neuronal loss over time [ 4 , [34] , [35] , [36] ]. Moreover, innate immune cell entry secondary to blood brain barrier dysfunction may prolong neuro-inflammation [ 34 , 37 ].…”

Concurrent catatonia and COVID-19 infection – An experiential account of challenges and management of cases from a tertiary care psychiatric hospital in India

“…Here we would like to stress that neurotropic infectious agents are also known to cause catatonia and other neuropsychiatric disorders and the same could also contribute to the presentation of catatonia via direct neuro-invasion by SARS-COV2 (severe acute respiratory syndrome coronavirus 2). Neuro-invasion by the hematogenous route via the altered blood-brain barrier and direct invasion by the virus via the olfactory route have been reported as possible pathways ( Generoso et al, 2021 ). Angiotensin-converting enzyme 2 (ACE 2) receptors are expressed by neurons, glia, and endothelium making them a potential target for viral invasion, potentially contributing to neuropsychiatric manifestations such as catatonia ( Generoso et al, 2021 ).…”

“…Neuro-invasion by the hematogenous route via the altered blood-brain barrier and direct invasion by the virus via the olfactory route have been reported as possible pathways ( Generoso et al, 2021 ). Angiotensin-converting enzyme 2 (ACE 2) receptors are expressed by neurons, glia, and endothelium making them a potential target for viral invasion, potentially contributing to neuropsychiatric manifestations such as catatonia ( Generoso et al, 2021 ). These mechanisms in the context of COVID-19 infection and catatonia are yet to be understood but possibly point towards genetic, immunogenic, metabolic, and/or neurotoxic pathologies.…”

Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

“…The third stage culminates with the release of the viral genetic materials, which is then recognized by pathogen-associated molecular patterns resulting in the activation of pro-inflammatory molecules. These pro-inflammatory mediators then initiate the innate immune response ( 150 ).…”