Research shows how SARS-COV-2 infects brain cells called astrocytes, causing structural changes in the brain. SARS-CoV-2 infection can cause brain changes and neurocognitive dysfunction, especially in the long-term COVID-19 syndrome, but the underlying mechanisms are elusive.

Daniel Martins de Souza and colleagues used MRI to compare brain structure in 81 study participants recovering from mild COVID-19 infection and 81 healthy individuals.

The authors found that the first group showed reduced cortical thickness, which correlated with cognitive impairment and symptoms such as anxiety and depression.

The authors analyzed brain samples from 26 people who died of COVID-19, finding that the samples from five of those people showed tissue damage.

Further analysis of damaged brain samples showed that astrocytes, which are brain cells that support neuronal metabolism, are particularly likely to be infected by SARS-CoV-2 and that the virus enters these cells through the NRP1 receptor.

After infection, astrocytes exhibited altered levels of metabolites used to fuel neurons and produce neurotransmitters, and infected cells secreted neurotoxic molecules. According to the authors, the results reveal structural changes seen in the brains of people with COVID-19.

The significance of the study points to neurological symptoms, which are among the most common non-pulmonary complications of COVID-19, affecting more than 30 percent of patients. In this study, we provide evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resides in the human brain, where it infects astrocytes and, to a lesser extent, neurons.

We also show that astrocytes are susceptible to SARS-CoV-2 infection through a non-canonical mechanism involving spike-NRP1 interaction and respond to infection by remodeling energy metabolism, which in turn alters the levels of metabolites used to fuel neurons and support neurotransmitters synthesis. The altered secretory phenotype of infected astrocytes then impairs neuronal viability. These features may explain the damage and structural changes seen in the brains of patients with COVID-19.

Although increasing evidence supports neuropsychiatric manifestations associated primarily with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently described as part of the “long-term COVID-19” syndrome) is often seen after mild infection.

The study shows a spectrum of cerebral effects of coronavirus 2 (SARS-CoV-2) infection in severe acute respiratory syndrome, from long-lasting changes in individuals with mild infection (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute injury confirmed in brain tissue samples taken from the fronto-orbital region (via endonasal transethmoidal access) in individuals who died of COVID-19.

In an independent cohort of 26 people who died of COVID-19, we used histopathological features of brain damage as a marker for possible brain infection with SARS-CoV-2 and found that among the 5 people who showed these features, all had genetic material virus in the brain.

Brain tissue samples from these five patients also revealed foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the astrocyte infection hypothesis, human astrocytes derived from neural stem cells in vitro are susceptible to SARS-CoV-2 infection through a non-canonical mechanism involving spike-NRP1 interaction.

Astrocytes infected with SARS-CoV-2 showed changes in energy metabolism and in key proteins and metabolites used to feed neurons, as well as in the biogenesis of neurotransmitters. Moreover, infection of human astrocytes induces a secretory phenotype that reduces neuronal viability.

The results of the study show that cognitive impairment and neuropsychiatric symptoms in convalescent patients with COVID-19 are correlated with changes in the thickness of the cerebral cortex. Analysis of cortical surface morphometry based (using 3T high-resolution MRI) on 81 subjects diagnosed with mild COVID-19 infection (62 self-reported anosmia or dysgeusia) who did not require oxygen support (methodological details and patient demographics are provided in the Appendix SI).

Analyzes were performed at a mean (SD) interval of 57 (26) days after detection of SARS-CoV-2 by qRT-PCR, and subjects were compared with 81 healthy volunteers (without neuropsychiatric disease) examined during the COVID-19 pandemic ( balanced by age [P = 0.97] and sex [P = 0.3]). The COVID-19 group showed higher levels of symptoms of anxiety and depression, fatigue, and excessive daytime sleepiness ( SI Appendix , Table S1 shows epidemiological and clinical data).

Analysis of cerebral cortical thickness (with multiple comparisons using the Holm-Banferroni method) revealed areas of reduced cortical thickness exclusively in the left hemisphere, including the left rectus gyrus (P = 0.01), superior temporal gyrus (P = 0.036), inferior temporal sulcus (P = 0.02) and posterior transverse collateral sulcus (P = 0.003) (Fig. 1A). No increase in cortical thickness was observed.


Source: ANI

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