Sars-Cov-2 Spike Protein Induces Cellular Changes in Primitive and Mature Hematopoietic Cells

The devastating effects of SARS-CoV-2 infection (which causes COVID-19) highlight the need for a deeper understanding of the virus, host response, and the tissues affected by infection, including the hematopoietic stem cells (HSC), hematopoietic progenitors (HPC), and more mature blood cells including immune cells. While other coronavirus infections have been associated with hematopoietic or immune cell complications (Chu et al., J Infect Dis 2016), the effects of SARS-CoV-2 infection on HSC/HPC and mature immune cells are not yet understood. We performed studies to examine the potential susceptibility of HSC/HPC subpopulations and immune cells to infection and functional studies to explore if exposure to SARS-CoV-2 proteins impacts these cells. The most well-studied receptor for SARS-CoV-2 is ACE2 (Hoffmann et al., Cell 2020), a cell surface protein to which SARS-CoV-2 spike protein (S protein) binds to facilitate viral entry to host cells. We explored expression of ACE2 in primitive and mature blood cells. We demonstrated using RT-qPCR as well as western blotting that ACE2 is expressed at both the mRNA and protein levels in pooled low-density peripheral blood cells (PB) from healthy donors (n=5); pooled CD34+ cells from cord blood (CB) enriched for HSC/HPC (n=7); lineage+ (lin+) low density CB cells (n=7), and high density polymorphonuclear leukocytes (PMN) from CB (n=3). We then determined ACE2 expression on specific subpopulations of HSC/HPC and immune cells. Flow cytometry analysis (FACS) demonstrated that ACE2 is expressed on the cell surface of small subpopulations of PB immune cells, including 1-2% of T-cells, 2-4% of B-cells, and Disclosures No relevant conflicts of interest to declare.