Toward Understanding COVID-19 Infection, Transmission, and Pathogenesis at Single-Cell Resolution with the Human Cell Atlas

About this Class

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single-cell and single-nucleus RNA-Seq datasets previously collected from healthy tissues and includes many previously unpublished studies--we identified the cell types throughout the body most likely to be susceptible to viral entry.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.