AI Article Synopsis

  • SARS-CoV-2 can infect a variety of cell types, severely affecting respiratory function and causing neurological symptoms in about one-third of COVID-19 cases.
  • Research using stem-cell-derived cortical organoids and human cortical tissue revealed that SARS-CoV-2 predominantly infects astrocytes in the brain, leading to increased inflammation and cellular stress.
  • Despite the lack of ACE2 expression in astrocytes, the presence of coreceptors CD147 and DPP4 is linked to the infection's severity, indicating that manipulating these coreceptors could influence the infection rate.

Article Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. Neurological symptoms, which range in severity, accompany as many as one-third of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized stem-cell-derived cortical organoids as well as primary human cortical tissue, both from developmental and adult stages. We find significant and predominant infection in cortical astrocytes in both primary tissue and organoid cultures, with minimal infection of other cortical populations. Infected and bystander astrocytes have a corresponding increase in inflammatory gene expression, reactivity characteristics, increased cytokine and growth factor signaling, and cellular stress. Although human cortical cells, particularly astrocytes, have no observable ACE2 expression, we find high levels of coronavirus coreceptors in infected astrocytes, including CD147 and DPP4. Decreasing coreceptor abundance and activity reduces overall infection rate, and increasing expression is sufficient to promote infection. Thus, we find tropism of SARS-CoV-2 for human astrocytes resulting in inflammatory gliosis-type injury that is dependent on coronavirus coreceptors.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335272PMC
http://dx.doi.org/10.1073/pnas.2122236119DOI Listing

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