Role Of Retroelements In The Development Of COVID-19 Neurological Consequences

Abstract

Retroelements play a key role in brain functioning in humans and other animals, since they represent dynamic regulatory elements controlling the expression of specific neuron types. The activity of retroelements in the brain is impaired under the influence of SARS-CoV-2, penetrating the blood-brain barrier. We propose a new concept, according to which the neurological complications of COVID-19 and their long-term effects are caused by modified expression of retroelements in neurons due to viral effect. This effect is implemented in several ways: a direct effect of the virus on the promoter regions of retroelement-encoding genes, virus interaction with miRNAs causing silencing of transposons, and an effect of the viral RNA on the products of retroelement transcription. Aging-related physiological activation of retroelements in the elderly is responsible for more severe course of COVID-19. The associations of multiple sclerosis, Parkinson’s disease, Guillain-Barré syndrome, acute disseminated encephalomyelitis with coronavirus lesions also indicate the role of retroelements in such complications, because retroelements are involved in the mechanisms of the development of these diseases. According to meta-analyses, COVID-19-caused neurological complications ranged 36.4-73%. The neuropsychiatric consequences of COVID-19 are observed in patients over a long period after recovery, and their prevalence may exceed those during the acute phase of the disease. Even 12 months after recovery, unmotivated fatigue, headache, mental disorders, and neurocognitive impairment were observed in 82%, 60%, 26.2-45%, and 16.2-46.8% of patients, correspondingly. These manifestations are explained by the role of retroelements in the integration of SARS-CoV-2 into the human genome using their reverse transcriptase and endonuclease, which results in a long-term viral persistence. The research on the role of specific retroelements in these changes can become the basis for developing targeted therapy for neurological consequences of COVID-19 using miRNAs, since epigenetic changes in the functioning of the genome in neurons, affected by transposons, are reversible.

Host Genetic Variants Linked to COVID-19 Neurological Complications and Susceptibility in Young Adults—A Preliminary Analysis

“…The TMPRSS2 gene, which is responsible for SARS-CoV-2 penetration into the cell [ 3 ], has been repeatedly implicated in COVID-19-related outcomes [ 10 , 24 , 32 ]. Nevertheless, in the present study we observed a combined effect of TMPRSS2 rs4290734 with NR1H2 rs1405655 on accompanying neurological complications.…”

“…The effect of the SARS-CoV-2 virus on the respiratory system, cardiovascular system, and gastrointestinal tract has been repeatedly demonstrated [ 1 , 2 ]. Together with epidemiological data on disease severity related to anthropometric parameters and concomitant chronic pathology [ 1 ], the role of genetic factors in COVID-19 illness and disease severity has been reported (for review, see [ 2 , 3 , 4 ]). Twin studies have elucidated a substantial genetic influence for predicted COVID-19, with a concordance rate of 80% in MZ twins [ 4 ].…”

“…Together with the well-established negative effects of SARS-CoV-2 on the pulmonary system, gastrointestinal tract, and cardiovascular system, the virus can also penetrate the blood–brain barrier, affect both neurons and glial cells, and cause neurological complications [ 3 ]. Different pathomechanisms underlie the development of neurological impairments, including post-COVID-19 syndrome, such as chronic fatigue, cognitive dysfunction, mood and sleep disorders, pain syndromes, and smell and taste impairments [ 2 ].…”