Detection of erythroid progenitors and erythrocytopathies in patients with severe COVID-19 disease.

OBJECTIVES: To assess the effect of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on erythropoiesis and red blood cells (RBC) surface markers by evaluating erythroid progenitor cells (CD [cluster of differentiation]71+/CD235a+) and RBC surface markers (CD235a and CD36), together with various hematological parameters. METHODS: This case-control study includes 47 participants recruited in the study: 30 patients with coronavirus disease 2019 (COVID-19) and 17 healthy individuals. The COVID-19 patients were recruited from the intensive care unit (ICU) of various hospitals in Makkah, Saudi Arabia. Blood samples were collected during July and September 2021. Red blood cells indices were measured using a CBC analyzer. The expression of CD235a, CD71, and CD36 was obtained using flow cytometry technique. The unpaired t-test was conducted to evaluate the differences in these markers in COVID-19 patients and healthy individuals. RESULTS: The data showed that more than half of the COVID-19 patients were anemic (64%). Expansion of erythroid progenitors (CD71+/CD235a+) was detected in the COVID-19 patients. Analysis of the expression of RBC surface markers, such as CD235a and CD36, showed that SARS-CoV-2 was associated with significantly higher expression of these markers in COVID-19 patients. CONCLUSION: Severe acute respiratory syndrome coronavirus-2 promoted the expansion of erythroid progenitors in the peripheral blood of COVID-19 patients. In addition, the expression of RBC surface markers was higher in COVID-19 patients. The expansion of erythroid progenitors and alteration of RBC surface markers can contribute to erythrocytopathies observed in severe COVID-19 patients and can therefore be used as prognostic factors.

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.