The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Single-cell analysis of healthy- and
The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Single-cell analysis of healthy- and SARS-CoV-2-infected tissues offers a unique lens to identify these mechanisms. In an international integrated analysis of the Human Cell Atlas Lung Biological Network–which spans more than 100 single-cell and single-nucleus RNA-Seq datasets previously collected from healthy tissues and includes many previously unpublished studies–we identified the cell types throughout the body most likely to be susceptible to viral entry. In line with epidemiological observations, we also identified increased expression of key mediators of SARS-CoV-2 cellular entry associated with increasing age, male gender, and smoking. In addition, we identified a gene program shared by these cells that includes genes that may mediate viral entry and play key immune roles, such as IL6 and its receptor and co-receptor, IL1R; TNF-response pathways; and complement genes. Following these studies, as the pandemic reached our local Boston community, we have adapted existing sample-processing pipelines with our collaborators in Boston hospitals and are using single-cell and spatial genomics techniques to procure, process, and analyze blood and post-mortem tissue from COVID-19 patients. We are using these pipelines to examine the tissue and immune cellular response to COVID-19, particularly to understand the factors underlying its severity in some individuals, and will share our preliminary results.
(Wednesday) 3:00 pm - 4:00 pm