Human Erythroid Progenitors Are Directly Infected by SARS-CoV-2: Implications for Emerging Erythropoiesis in Severe COVID-19 Patients

We document here that intensive care COVID-19 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. We show that ACE2 expression peaks during erythropoiesis and renders erythroid progenitors vulnerable to infection by SARS-CoV-2. 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. SARS-CoV-2 causes the expansion of colony formation by erythroid progenitors and can be detected in these cells after 2 weeks of the initial infection. 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 COVID-19 patients and how the virus can spread through the circulation to produce local inflammation in tissues, including the bone marrow.

Automated summary

This study demonstrates that severe COVID-19 patients in intensive care experience a significant decline in hemoglobin levels but an increase in circulating nucleated red cells, indicating a possible induction of stress erythropoiesis by SARS-CoV-2 infection. The research also shows that ACE2 expression peaks during erythropoiesis, making erythroid progenitors susceptible to infection by the virus. Furthermore, the study identifies early erythroid progenitors as the primary target cells for SARS-CoV-2 infection during erythropoiesis, highlighting how the virus can impact the clinical symptoms of severe COVID-19 patients.