Tropism of SARS-CoV-2 for human cortical astrocytes

• DOI: 10.1073/pnas.2122236119
• Publication Date: 2022-07-12T18:36:16Z
• Authors: Madeline G. Andrews; Tanzila Mukhtar; Ugomma C. Eze; Camille R. Simoneau; Jayden Ross; Neelroop Parikshak; Shaohui Wang; Li Zhou; Mark Koontz; Dmitry Velmeshev; Clara-Vita Siebert; Kaila M. Gemenes; Takako Tabata; Yonatan Perez; Li Wang; Mohammed A. Mosta...; Martina de Majo; Kevin C. Donohue; David Shin; Jahan Salma; Alex A. Pollen; Tomasz J. Nowakowski; Erik Ullian; G. Renuka Kumar; Ethan A. Winkler; Elizabeth E. Crouch; Melanie Ott; Arnold R. Kriegstein
• Keywords: Organoid; Gliosis; Coronavirus; Cell type; Tissue tropism

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