ABSTRACT
We document here that intensive care COVID19 patients suffer a profound decline in hemoglobin levels but show an increase of circulating nucleated red cells, suggesting that SARS-CoV-2 infection either directly or indirectly induces stress erythropoiesis. However, the impact of SARS-CoV-2 on erythropoiesis has not been well investigated. We show that ACE2 expression peaks during erythropoiesis and renders erythroid progenitors vulnerable to infection by SARS-CoV-2. In particular, we characterize two erythroid progenitor populations as primary targets for the virus. Early erythroid progenitors, defined as CD34-CD117+CD71+CD235a-, show the highest levels of ACE2 and constitute the primary target cell to be infected during erythropoiesis. In addition, SARS-CoV-2 can also bind and infect mid-late erythroid precursors, defined as CD34-CD117-CD71+CD235a+. Our findings constitute the first report of SARS-CoV-2 infectivity in erythroid progenitor cells and can contribute to understanding both the clinical symptoms of severe COVID19 patients and how the virus can spread through the circulation to produce local inflammation in tissues, including the bone marrow.Funding: This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001045), the UK Medical Research Council (FC001045) and the Wellcome Trust (FC001045) to DB.Conflict of Interest: The authors declare no competing interests.Ethical Approval: Peripheral blood was isolated from consenting unscreened healthy adult volunteers following approved protocols by the ethics board of the Francis Crick Institute and the regulations of the Human Tissue act 2004. Peripheral blood mononuclear cells (PBMCs) were isolated by centrifugation over a Histopaque-1119 gradient (Sigma-Aldrich 11191).