Washington: A study shows how SARS-CoV-2 infects brain cells called astrocytes, causing structural changes in the brain. SARS-CoV-2 infection can lead to brain changes and neurocognitive dysfunction, especially in the prolonged COVID-19 syndrome, but the underlying mechanisms are elusive.
Daniel Martins-D-Souza and his colleagues used MRI to compare brain structure in 81 study participants and 81 healthy individuals recovering from mild COVID-19 infection. The authors found that the former group exhibited less cortical thickness, which was related to cognitive impairment and symptoms such as anxiety and depression.
The authors analyzed brain samples from 26 people who died of COVID-19, finding that samples from five of these individuals exhibited tissue damage.
Further analysis of the damaged brain samples revealed that astrocytes, which are brain cells that maintain neuronal metabolism, were particularly likely to be infected with SARS-CoV-2 and that the virus acts through the NRP1 receptor. enters these cells.
Once infected, astrocytes exhibited altered levels of metabolites used to promote neurons and neurotransmitter production, and infected cells secreted neurotoxic molecules. According to the authors, the findings highlight structural changes observed in the brains of people with COVID-19.
The importance of the study reflects the neurological symptoms that are most prevalent among the extrapulmonary 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) is found 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 that involves the spike-NRP1 interaction and respond to infection by remodeling energy metabolism, which This, 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 observed in the brains of COVID-19 patients.
Although increasing evidence primarily confirms neuropsychiatric manifestations associated with severe COVID-19 infection, prolonged neuropsychiatric dysfunction (recently characterized as part of the “long COVID-19” syndrome) is frequently observed following mild infection. has gone.
The study shows the spectrum of brain effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from mild to severe long-term changes in infected individuals (symptoms of orbitofrontal cortical atrophy, neurocognitive impairment, extreme fatigue and anxiety). Happens till. Acute damage was confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) of individuals who died of COVID-19.
In an independent cohort of 26 individuals who died of COVID-19, we used the histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that 5 of those individuals showed symptoms. demonstrated, all of them were genetic. Virus content in the brain.
Brain tissue samples from these five patients demonstrated foci of SARS-CoV-2 infection and replication exclusively in astrocytes. Supporting the hypothesis of astrocyte infection, in vitro neural stem cell-derived human astrocytes are susceptible to SARS-CoV-2 infection through a non-canonical mechanism that involves the spike-NRP1 interaction.
SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites that fuel neurons, as well as changes in the biogenesis of neurotransmitters. Furthermore, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability.
Study Outcomes Cognitive impairment and neuropsychiatric symptoms Correlation with Altered Cerebral Cortical Thickness in Convalescent COVID-19 Patients. A cortical surface-based morphometry analysis (using a high-resolution 3T 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 presented in SI Appendix,
The analysis was performed within a mean (SD) interval of 57 (26) d after the detection of SARS-CoV-2 by qRT-PCR, and the subjects were compared to 81 healthy volunteers scanned during the COVID-19 pandemic (without of neuropsychiatric comorbidities). (balanced for age [P = 0.97] more sex [P = 0.3]) The COVID-19 group presented higher levels of anxiety and symptoms of depression, fatigue, and excessive daytime sleepiness (SI Appendix, Table S1 shows epidemiological and clinical data).
Analysis of cortical thickness (adjusted for multiple comparisons using the Holm–Bonferroni method) revealed areas of particularly low cortical thickness in the left hemisphere, including the left gyrus rectus (p = 0.01), the superior temporal gyrus (p = 0.01). 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.