A study carried out by Brazilian researchers has shown how SARS-COV-2 infects brain cells called astrocytes, causing structural changes in the brain. SARS-CoV-2 infection can cause brain alterations and neurocognitive dysfunction, especially in the long-standing COVID-19 syndrome, but the underlying mechanisms are still unknown.
The investigator Daniel Martins-de-Souza, from the University of Campinas (Brazil), and colleagues used MRI to compare the brain structure of 81 study participants recovering from a mild COVID-19 infection and 81 healthy individuals. The authors found that the first group had less cortical thickness, which correlated with cognitive deficits and symptoms such as anxiety and depression.
The authors analyzed brain samples from 26 people who had died from COVID-19, and found that samples from five of these individuals had tissue damage. Further analysis of the damaged brain samples revealed that astrocytes, which are brain cells that support neuronal metabolism, were especially prone to being infected with SARS-CoV-2 and that the virus enters these cells through the NRP1 receptor.
Once infected, the astrocytes had altered levels of the metabolites used to fuel neurons and the production of neurotransmitters, and the infected cells secreted neurotoxic molecules. According to the authors, the findings uncover the structural changes seen in the brains of people with COVID-19.
The importance of the study denotes that neurological symptoms are among the most frequent extrapulmonary complications of COVID-19, affecting more than 30 percent of patients. In this study, they 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.
They also demonstrate that astrocytes are susceptible to SARS-CoV-2 infection through a non-canonical mechanism involving pico-NRP1 interaction and respond to infection by remodeling energy metabolism, which in turn alters plasma levels. of metabolites used to fuel neurons and support neurotransmitter synthesis.
The altered secretory phenotype of infected astrocytes then impairs neuronal viability.. These features could explain the damage and structural changes observed in the brains of COVID-19 patients. Although there is increasing evidence confirming neuropsychiatric manifestations primarily associated with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of the “long COVID-19” syndrome) following mild infection.
The study shows the spectrum of the brain impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in individuals with mild infection (orbitofrontal cortical atrophy, neurocognitive impairment, fatigue and symptoms of anxiety) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via transethmoidal endonasal access) of individuals who died of COVID-19.