SARS-CoV-2 Virus Impact on Astrocytes
SARS-CoV-2 targets astrocytes as its primary target in the brain. It has been proven that SARS-CoV-2 preferentially infects astrocytes over neurons in primary and organoid cortical cultures, causing astrocyte reactivation and non-cell-autonomous neuronal death. Furthermore, it is found that basigin (BSG) also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147) and dipeptidyl-peptidase 4 (DPP4) are significant SARS-CoV-2 infection-related molecular actors in cortical astrocytes (61).
As per a study carried out by Andrews et al., infected astrocytes exhibit heightened reactivity and cellular stress (62). In addition, SARS-CoV-2-infected cultures show non-cell autonomous inflammatory effects such as an increase in reactive microglia and a general loss of neurons due to apoptosis. According to research, astrocytes may have a significant supporting function in the regulation of brain energy, metabolism, and the microenvironment (63). It is interesting to note that BSG/CD147 is important for the astrocyte metabolic pathways that support the energy requirements of neurons (64).
Kriegstein et al. also showed in a preprint published that SARS-CoV-2 preferentially infects astrocytes over other types of brain cells, leading to fatigue, depression and “brain fog”. The virus was introduced to brain organoids, which are tiny, lab-grown structures that resemble the brain. Over all other cells present, astrocytes were almost completely infected by SARS-CoV-2 (65).
Therefore, by inducing inflammation and aberrant brain energy metabolism, SARS-CoV-2 infection in astrocytes may indirectly result in neuronal death.