Human Erythroid Progenitors Are Directly Infected by SARS-CoV-2: Implications for Emerging Erythropoiesis in Severe COVID-19 Patients.
Human Erythroid Progenitors Are Directly Infected by SARS-CoV-2: Implications for Emerging Erythropoiesis in Severe COVID-19 Patients.
复制标题
人类红细胞祖细胞直接被SARS-COV-2感染：严重的Covid-19患者对新兴的红细胞生成的影响。
DOI：
10.1016/j.stemcr.2021.02.001
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发表时间：
2021-03-09
影响因子：
5.9
通讯作者：
Bonnet D
中科院分区：
文献类型：
--
作者：
Huerga Encabo H;Grey W;Garcia-Albornoz M;Wood H;Ulferts R;Aramburu IV;Kulasekararaj AG;Mufti G;Papayannopoulos V;Beale R;Bonnet D
我们在这里记录了重症监护COVID-19患者的血红蛋白水平严重下降，但循环有核红细胞增加，表明SARS-CoV-2感染直接或间接诱导应激性红细胞生成。我们发现ACE 2表达在红细胞生成过程中达到峰值，并使红系祖细胞易受SARS-CoV-2感染。早期红系祖细胞，定义为CD 34 − CD 117 + CD 71 + CD 235 a −，显示出最高水平的ACE 2，并构成红细胞生成过程中被感染的主要靶细胞。SARS-CoV-2引起红系祖细胞集落形成的扩增，并且在初始感染2周后可以在这些细胞中检测到。我们的研究结果构成了SARS-CoV-2在红系祖细胞中感染性的第一份报告，有助于理解严重COVID-19患者的临床症状以及病毒如何通过循环传播以在组织中产生局部炎症，包括骨髓。COVID-19重症患者表现为严重贫血和有核红细胞增加红系祖细胞共表达ACE 2和TMPRSS 2早期和中晚期红系祖细胞可被SARS-CoV-2感染SARS-CoV-2在首次感染H. Huerga Encabo及其同事证明，SARS-CoV-2可以感染红系祖细胞而不损害其功能，而是导致可以检测到病毒的菌落扩张。这些发现揭示了患有严重COVID-19的患者，他们患有异常增加的有核红细胞，同时伴有血红蛋白水平降低。
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. COVID19 severe patients show severe anemia and increase in nucleated red blood cells Erythroid progenitors co-express ACE2 and TMPRSS2 Early and mid-late erythroid progenitors could be infected by SARS-CoV-2 SARS-CoV-2 can be detected in erythroid colonies 14 days after the initial infection H. Huerga Encabo and colleagues demonstrate that SARS-CoV-2 can infect erythroid progenitors without impairing their functionality, rather causing an expansion of colonies where the virus can be detected. These findings shed light into the patients with severe COVID-19 who suffer from an aberrant increase of nucleated red blood cells concomitant with reduced levels of hemoglobin.
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