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

Hector Huerga Encabo,Venizelos Papayannopoulos,Rachel Ulferts,Manuel Garcia-Albornoz,Rupert Beale,Ghulam Mufti,Iker Valle Aramburu,William Grey,Dominique Bonnet,Austin G Kulasekararaj,Henry Wood

doi:10.1016/j.stemcr.2021.02.001

Hector Huerga Encabo, Venizelos Papayannopoulos + Show 9 more

Open Access

https://doi.org/10.1016/j.stemcr.2021.02.001

Copy DOI

Abstract

SummaryWe 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.

Highlights

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected and spread globally among humans, causing a pandemic crisis
Patients treated for severe COVID-19 at King’s College Hospital (London, UK) show a rapid and profound decline in hemoglobin following admission (Figure 1A)
This is associated with the appearance of circulating nucleated red cells, peaking between 2 and 3 weeks after admission (Figure 1B)

Summary

Introduction

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected and spread globally among humans, causing a pandemic crisis. Further reports demonstrate ACE2 expression in cells from other tissues such as intestinal epithelial cells, hepatocytes, and neurons, making these cells vulnerable to be infected by SARS-CoV-2 (Pellegrini et al, 2020; Sungnak et al, 2020; Wang et al, 2020; Zhang et al, 2020). Disruption of erythropoiesis may be an indirect effect of the systemic hyperinflammation that occurs in intensive care patients Another potential explanation is that direct targeting of hematopoietic stem/progenitor cells (HSPCs) and/or erythroid progenitors (ERP) by SARS-CoV-2 contributes to the hematological features of COVID-19. HSCs from cord blood have been reported to express ACE2, and exposure to the Spike protein can reduce their functionality (Ropa et al, 2020) Despite these observations, the infectivity of SARS-CoV-2 in HSPCs and more in erythroid progenitors has not been characterized. We have studied HSPCs and different erythroid progenitor populations to assess if they can be infected by SARS-CoV-2

Results

Discussion

Conclusion