The cellular immune response to B.1.1.7 variant COVID-19 deciphered by single cell multi-omics

单细胞多组学破译对 B.1.1.7 变体 COVID-19 的细胞免疫反应

• 批准号: MR/W014556/1
• 负责人: Berthold Gottgens
• 金额: $ 4.75万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW014556%2F1
• 关键词: cellular; immune; response; B.1.1.7; variant

Regardless of rapid vaccination programs, the coronavirus SARS-CoV2 is likely to remain a concern for the foreseeable future, because viral pathogens evolve, and acquire mutations that may alter severity of the disease or render current vaccines ineffective. During the 1st wave of coronavirus, we have analysed over 800,000 blood and immune cells from more than 100 patients treated in Cambridge, Newcastle and London. This work provides the largest reference dataset available anywhere to interrogate how blood and immune cells are affected by the infection, and may contribute to fighting it. Given the recent emergence of a more aggressive strain (the so-called UK or Kent variant), there is an urgent need to investigate whether this new variant causes the same changes in blood and immune cells as the original strain. Such information is vital to know whether current therapies need to be amended, and whether there are opportunities to develop new treatments. We propose to answer these important questions by studying 30 patients of the current wave, where the majority are infected with the new variant. Because of time sensitivity, our results will be made available to the wider scientific community as soon as is practicable.

不管快速的疫苗接种计划如何，在可预见的未来，冠状病毒 SARS-CoV2 可能仍然是一个令人担忧的问题，因为病毒病原体会进化，并发生突变，可能会改变疾病的严重程度或使当前的疫苗失效。在第一波冠状病毒爆发期间，我们分析了来自剑桥、纽卡斯尔和伦敦接受治疗的 100 多名患者的超过 800,000 个血液和免疫细胞。这项工作提供了最大的参考数据集，可用于探究血液和免疫细胞如何受到感染的影响，并可能有助于对抗感染。鉴于最近出现了一种更具攻击性的菌株（所谓的英国或肯特变种），迫切需要研究这种新变种是否会引起与原始菌株相同的血液和免疫细胞变化。这些信息对于了解当前的疗法是否需要修改以及是否有机会开发新的疗法至关重要。我们建议通过研究当前浪潮中的 30 名患者来回答这些重要问题，其中大多数患者感染了新变种。由于时间敏感性，我们的结果将尽快向更广泛的科学界提供。

项目成果

Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease.

纵向分析表明，旁观者 CD8 T 细胞激活延迟和早期免疫病理学可区分严重的 COVID-19 和轻度疾病。

• DOI: http://dx.10.1016/j.immuni.2021.05.010
• 发表时间: 2021
• 期刊: Immunity
• 影响因子: 32.4
• 作者: Bergamaschi L

The impact of hypoxia on B cells in COVID-19.

缺氧对 COVID-19 中 B 细胞的影响。

• DOI: http://dx.10.17863/cam.82829
• 发表时间: 2022
• 作者: Kotagiri P

Unique molecular and functional features of extramedullary hematopoietic stem and progenitor cell reservoirs in humans

人类髓外造血干细胞和祖细胞库的独特分子和功能特征

• DOI: http://dx.10.17863/cam.79902
• 发表时间: 2022
• 作者: Laurenti E

Single-Cell Protein Analysis - Methods and Protocols

单细胞蛋白质分析 - 方法和实验方案

• DOI: http://dx.10.1007/978-1-0716-1771-7_13
• 发表时间: 2022
• 作者: Mende N

Local and systemic responses to SARS-CoV-2 infection in children and adults

儿童和成人对 SARS-CoV-2 感染的局部和全身反应

• DOI: 10.1038/s41586-021-04345-x
• 发表时间: 2021-12-22
• 期刊: Nature
• 影响因子: 64.8
• 作者: Masahiro Yoshida;Kaylee B. Worlock;N. Huang;Rik G. H. Lindeboom;C. Butler;Natsuhiko Kumasaka;C. Domínguez Conde;L. Mamanova;L. Bolt;L. Richardson;K. Polański;E. Madissoon;Josephine L. Barnes;J. Allen;E. Kilich;B. Jones;A. de Wilton;A. Wilbrey;W. Sungnak;J. P. Pett;Juliane Weller;E. Prigmore;H. Yung;P. Mehta;Aarash Saleh;A. Saigal;Vivian Chu;Jonathan M. Cohen;C. Cane;A. Iordanidou;Soichi Shibuya;Ann;I. Herczeg;A. Argento;R. Wunderink;Sean B. Smith;T. Poor;C. Gao;J. Dematte;G. R. S. H. K. N. S. Z. Budinger Donnelly Markov Lu;G. S. Budinger;H. Donnelly;N. Markov;Ziyan Lu;G. Reynolds;M. Haniffa;Georgina S. Bowyer;M. Coates;M. Clatworthy;F. Calero;B. Göttgens;C. O’Callaghan;N. Sebire;C. Jolly;P. de Coppi;C. Smith;A. Misharin;S. Janes;S. Teichmann;M. Nikolić;K. Meyer
• 通讯作者: K. Meyer