The cellular immune response to COVID-19 deciphered by single cell multi-omics across three UK centres-猫眼课题宝

DOI：

10.1101/2021.01.13.21249725

发表时间：

2021-01

期刊：

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Emily Stephenson;Gary Reynolds;R. Botting;F. Calero-Nieto;Michael Morgan;Z. Tuong;Karsten Bach;W. Sungnak;Kaylee B. Worlock;M. Yoshida;Natsuhiko Kumasaka;Katarzyna Kania;J. Engelbert;B. Olabi;J. Spegarova;Nicola K Wilson;N. Mende;Laura Jardine;Louis C. S. Gardner;Issac Goh;Dave Horsfall;J. McGrath;S. Webb;M. Mather;Rik G. H. Lindeboom;Emma Dann;N. Huang;K. Polański;E. Prigmore;F. Gothe;Jonathan Scott;R. Payne;K. Baker;Aidan T. Hanrath;Ina Schim van der Loeff;Andrew S Barr;A. Sánchez-González;L. Bergamaschi;F. Mescia;Josephine L. Barnes;E. Kilich;A. de Wilton;Anita Saigal;Aarash Saleh;Sam M. Janes;Claire M. Smith;N. Gopee;Caroline Wilson;P. Coupland;J.M Coxhead;Vladimir Y Kiselev;Stijn van Dongen;Jaume Bacardit;Hamish W. King;A. Rostron;A. J. Simpson;S. Hambleton;E. Laurenti;Paul A. Lyons;Kerstin B. Meyer;Marko Z Nikolić;Christopher J A Duncan;Kenneth G. C. Smith;Sarah A. Teichmann;M. Clatworthy;J. Marioni;Berthold Gottgens;M. Haniffa

由SARS冠状病毒2 （SARS- cov -2）引起的COVID-19大流行导致了过高的发病率和死亡率以及经济衰退。为了描述宿主对SARS-CoV-2的系统性免疫反应，我们进行了单细胞rna测序和细胞表面蛋白分析，提供了来自130名COVID-19患者的80多万个外周血单个核细胞的分子谱。我们的队列来自三个英国中心，跨越了临床表现和疾病严重程度的范围，从无症状到危急。包括三个对照组：健康志愿者、患有非covid -19严重呼吸道疾病的患者和静脉注射脂多糖以模拟急性炎症反应的健康个体。完整的单细胞转录组结合188种细胞表面蛋白以及T和B淋巴细胞抗原受体谱的定量分析，为COVID-19提供了几点见解：1。一种新的非经典单核细胞状态，隔离血小板并补充肺泡巨噬细胞池；2. 血小板激活伴随着未成熟造血干细胞/祖细胞早期巨核形成的启动和巨核细胞启动祖细胞的扩增；3. CD8+效应记忆T细胞、CD4+和CD8+ T细胞在病情更严重的患者中扩增增加；和4。在无症状阶段，随着疾病严重程度的增加，IgA浆母细胞的相对增加，转变为IgG浆母细胞和浆细胞的增加，并伴随着BCR共享的更高发生率。所有的数据和分析结果都可以通过一个直观的门户网站进行查询和数据挖掘。总之，这些数据详细描述了COVID-19急性免疫反应期间外周血中存在的细胞过程，并作为跨多个中心的多组学单细胞数据整合的模板，以快速构建强大的资源，帮助抗击COVID-19等疾病。

The COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well as economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling of over 800,000 peripheral blood mononuclear cells from a cohort of 130 patients with COVID-19. Our cohort, from three UK centres, spans the spectrum of clinical presentations and disease severities ranging from asymptomatic to critical. Three control groups were included: healthy volunteers, patients suffering from a non-COVID-19 severe respiratory illness and healthy individuals administered with intravenous lipopolysaccharide to model an acute inflammatory response. Full single cell transcriptomes coupled with quantification of 188 cell surface proteins, and T and B lymphocyte antigen receptor repertoires have provided several insights into COVID-19: 1. a new non-classical monocyte state that sequesters platelets and replenishes the alveolar macrophage pool; 2. platelet activation accompanied by early priming towards megakaryopoiesis in immature haematopoietic stem/progenitor cells and expansion of megakaryocyte-primed progenitors; 3. increased clonally expanded CD8+ effector:effector memory T cells, and proliferating CD4+ and CD8+ T cells in patients with more severe disease; and 4. relative increase of IgA plasmablasts in asymptomatic stages that switches to expansion of IgG plasmablasts and plasma cells, accompanied with higher incidence of BCR sharing, as disease severity increases. All data and analysis results are available for interrogation and data mining through an intuitive web portal. Together, these data detail the cellular processes present in peripheral blood during an acute immune response to COVID-19, and serve as a template for multi-omic single cell data integration across multiple centers to rapidly build powerful resources to help combat diseases such as COVID-19.

The cellular immune response to COVID-19 deciphered by single cell multi-omics across three UK centres

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