COVID-19: infection and neurological complications

Abstract

The issues of neurological complications after coronavirus disease 2019 (COVID-19) are highlighted, since coronaviruses affect not only the respiratory system but also other organs and systems of the body, notably they can cause neurological disorders and diseases. There is little evidence for a direct mechanism of SARS-CoV-2 virus neuroinvasiveness and neurotoxicity. Various mechanisms of coronavirus invasion into the brain are discussed - anterograde and retrograde, neuronal spread, transcriptional and hematogenous pathways. Retrograde / anterograde transport and transsynaptic transmission of the virus have been confirmed by in vitro studies, notably SARS-CoV-2 can enter the central nervous system through olfactory nerve receptor cells. Once in the olfactory bulb, the coronavirus can spread to the cortex and other brain structures, in particular the hippocampus and spinal cord. Invasion of the virus into the central nervous system is also possible by spreading along peripheral nerves, such as along the vagus nerve, which innervates the lungs and intestines. The virus invasion into the central nervous system through the blood-brain barrier is considered to be one of the most frequent routes. There are several possible mechanisms for the spread of SARS-CoV-2 across the blood-brain barrier (circulation of viral particles in the bloodstream, viral transcytosis through vascular and capillary endothelial cells, infection of leukocytes with viruses and their transmission of viruses across the blood-brain barrier ("Trojan horse")). However, there is no robust evidence of CNS infection with SARS-CoV-2. Hypoxia induced by the cytokine storm and respiratory distress lead to the impairment of brain metabolism and neurological complications development. There is an ongoing debate as to whether neurological disorders are primary neurological symptoms or secondary consequences of acute respiratory distress syndrome and inflammation. Among the large number of disorders of the nervous system, there are five main types with long-term neurological complications associated with COVID-19: 1) encephalopathy with delirium / psychosis, 2) inflammatory syndromes of the central nervous system, including encephalitis, myelitis, acute disseminated encephalomyelitis, 3) ischemic strokes (half of them with pulmonary embolism), 4) peripheral neuropathies, Guillain-Barré syndrome and brachial plexopathies, 5) other disorders of the central nervous system. Incompleteness or inconsistency of statistical data on neurological complications after infection was noted. Further study is required of all early and long-term manifestations of neurological disorders and diseases in mild and asymptomatic manifestations of infection, acute and long COVID-19 and after vaccination.