Putative mechanism of neurological damage in COVID-19 infection

Abstract

The recent pandemic of the coronavirus infectious disease 2019 (COVID-19) has affected around 192 countries, and projections have shown that around 40% to 70% of world population could be infected in the next months. COVID-19 is caused by the virus SARS-CoV-2, it enters the cells through the ACE2 receptor (angiotensin converting enzyme 2). It is well known that SARS-CoV-2 could develop mild, moderate, and severe respiratory symptoms that could lead to death. The virus receptor is expressed in different organs such as the lungs, kidney, intestine, and brain, among others. In the lung could cause pneumonia and severe acute respiratory syndrome (SARS). The brain can be directly affected by cellular damage due to viral invasion, which can lead to an inflammatory response, by the decrease in the enzymatic activity of ACE2 that regulates neuroprotective, neuro-immunomodulatory and neutralizing functions of oxidative stress. Another severe damage is hypoxemia in patients that do not receive adequate respiratory support. The neurological symptoms that the patient presents, will depend on factors that condition the expression of ACE2 in the brain such as age and sex, as well as the mechanism of neuronal invasion, the immune response and the general state of the patient. Clinical and histopathological studies have described neurological alterations in human patients with COVID-19. These conditions could have a possible contribution to the morbidity and mortality caused by this disease and may even represent the onset of neurodegenerative activity in recovered patients.

Evaluation of cognitive functions in adult individuals with COVID-19

“…These findings have also been supported by the results that hippocampal damage can be observed at the cellular level after infection in studies on animals [7]. It is also stated that hypercoagulatory and hyperinflammatory states that can be observed in severe COVID-19 cases may contribute to delirium and possible cognitive deficits in the future [7].…”

“…It is not known how much of the ischemic damage occurs secondary to cardiorespiratory disease through direct effects of the virus on the CNS. However, cerebral white matter affection, which is sensitive to ischemia, is stated to contribute to cognitive deficits such as attention problems, and impairments in verbal memory and executive functions [ 6 , 7 ]. These findings have also been supported by the results that hippocampal damage can be observed at the cellular level after infection in studies on animals [ 7 ].…”

“…However, cerebral white matter affection, which is sensitive to ischemia, is stated to contribute to cognitive deficits such as attention problems, and impairments in verbal memory and executive functions [ 6 , 7 ]. These findings have also been supported by the results that hippocampal damage can be observed at the cellular level after infection in studies on animals [ 7 ]. It is also stated that hypercoagulatory and hyperinflammatory states that can be observed in severe COVID-19 cases may contribute to delirium and possible cognitive deficits in the future [ 7 ].…”

Changes in cognitive functioning after COVID‐19: A systematic review and meta‐analysis

“…The pathological mechanisms that might underlie the potential cognitive impairment associated with COVID‐19 are still unclear, but may include the direct effects of cellular damage due to viral invasion, secondary inflammatory responses, decreased angiotensin‐converting enzyme 2 (ACE2) activity that regulates neuroprotective and neuro‐immunomodulatory functions; oxidative stress 38 ; and hypoxia, sepsis, and/or multi‐organ damage related to severe COVID‐19. Cognitive impairment in ARDS survivors ranges from 70% to 100% at hospital discharge, 46% to 80% at 1 year, and 20% at 5 years 39 .…”

Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review

“…There is a myriad of symptoms comprehending long COVID ranging from hair loss, breathlessness, chronic coughing [ 7 ], to symptoms characteristic of the central [ 9 ] (CNS) and peripheral nervous systems (PNS) such as headache [ 10 ], memory impairment [ 11 ], attention deficit [ 12 ], generalized chronic pain [ 10 ] and fatigue [ 13 ]. These last ones have been attributed to an invasion if the virus to the nervous system [ 14 ], and two hypotheses of how this may happen exist: retrograde axonal transport and invasion of infected leukocytes through the blood–brain barrier [ 14 , 15 , 16 ], however, controversy still remains around this subject.…”