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Longitudinal analyses reveal immunological misfiring in severe COVID-19

机译：纵向分析揭示了严重Covid-19中的免疫误导

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摘要

Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)(1-4). However, the longitudinal immunological correlates of disease outcome remain unclear. Here we serially analysed immune responses in 113 patients with moderate or severe COVID-19. Immune profiling revealed an overall increase in innate cell lineages, with a concomitant reduction in T cell number. An early elevation in cytokine levels was associated with worse disease outcomes. Following an early increase in cytokines, patients with moderate COVID-19 displayed a progressive reduction in type 1 (antiviral) and type 3 (antifungal) responses. By contrast, patients with severe COVID-19 maintained these elevated responses throughout the course of the disease. Moreover, severe COVID-19 was accompanied by an increase in multiple type 2 (anti-helminths) effectors, including interleukin-5 (IL-5), IL-13, immunoglobulin E and eosinophils. Unsupervised clustering analysis identified four immune signatures, representing growth factors (A), type-2/3 cytokines (B), mixed type-1/2/3 cytokines (C), and chemokines (D) that correlated with three distinct disease trajectories. The immune profiles of patients who recovered from moderate COVID-19 were enriched in tissue reparative growth factor signature A, whereas the profiles of those with who developed severe disease had elevated levels of all four signatures. Thus, we have identified a maladapted immune response profile associated with severe COVID-19 and poor clinical outcome, as well as early immune signatures that correlate with divergent disease trajectories.
机译：最近的研究已经为2019年（Covid-19）（1-4）的冠状病毒疾病发病机制提供了见解。然而，疾病结果的纵向免疫相关仍然不清楚。在这里，我们在113例中度或严重的Covid-19患者中串联分析了免疫应答。免疫分析显示先天细胞谱系的总体增加，伴随着T细胞数。细胞因子水平的早期升高与疾病成果更严重。在细胞因子早期增加后，中度Covid-19的患者展示了1型（抗病毒）和3型（抗真菌）反应的逐渐减少。相比之下，严重Covid-19患者在疾病过程中保持了这些效应。此外，严重的Covid-19伴随着多种2型（抗HelmintHs）效应的增加，包括白细胞介素-5（IL-5），IL-13，免疫球蛋白E和嗜酸性粒细胞。未经监督的聚类分析确定了四种免疫签名，代表生长因子（a），2/3型细胞因子（b），混合型-1 / 2/3细胞因子（c），以及与三种不同的疾病轨迹相关的趋化因子（d） 。从中度Covid-19恢复的患者的免疫谱富集于组织重复生长因子签名A中，而开发严重疾病的人的谱具有所有四种签名的水平升高。因此，我们已经确定了与严重的Covid-19和临床结果不良相关的不良免疫反应谱，以及与发散疾病轨迹相关的早期免疫签名。

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  • 来源
    《Nature》 |2020年第7821期|463-469|共7页
  • 作者

    Lucas Carolina; Wong Patrick; Klein Jon; Castro Tiago B. R.; Silva Julio; Sundaram Maria; Ellingson Mallory K.; Mao Tianyang; Oh Ji Eun; Israelow Benjamin; Takahashi Takehiro; Tokuyama Maria; Lu Peiwen; Venkataraman Arvind; Park Annsea; Mohanty Subhasis; Wang Haowei; Wyllie Anne L.; Vogels Chantal B. F.; Earnest Rebecca; Lapidus Sarah; Ott Isabel M.; Moore Adam J.; Muenker M. Catherine; Fournier John B.; Campbell Melissa; Odio Camila D.; Casanovas-Massana Arnau; Herbst Roy; Shaw Albert C.; Medzhitov Ruslan; Schulz Wade L.; Grubaugh Nathan D.; Dela Cruz Charles; Farhadian Shelli; Ko Albert I.; Omer Saad B.; Iwasaki Akiko; Obaid Abeer; Lu-Culligan Alice; Nelson Allison; Brito Anderson; Nunez Angela; Martin Anjelica; Watkins Annie; Geng Bertie; Kalinich Chaney; Harden Christina; Todeasa Codruta; Jensen Cole; Kim Daniel; McDonald David; Shepard Denise; Courchaine Edward; White Elizabeth B.; Song Eric; Silva Erin; Kudo Eriko; DeIuliis Giuseppe; Rahming Harold; Park Hong-Jai; Matos Irene; Nouws Jessica; Valdez Jordan; Fauver Joseph; Lim Joseph; Rose Kadi-Ann; Anastasio Kelly; Brower Kristina; Glick Laura; Sharma Lokesh; Sewanan Lorenzo; Knaggs Lynda; Minasyan Maksym; Batsu Maria; Petrone Mary; Kuang Maxine; Nakahata Maura; Campbell Melissa; Linehan Melissa; Askenase Michael H.; Simonov Michael; Smolgovsky Mikhail; Sonnert Nicole; Naushad Nida; Vijayakumar Pavithra; Martinello Rick; Datta Rupak; Handoko Ryan; Bermejo Santos; Prophet Sarah; Bickerton Sean; Velazquez Sofia; Alpert Tara; Rice Tyler; Khoury-Hanold William; Peng Xiaohua; Yang Yexin; Cao Yiyun; Strong Yvette;

  • 作者单位

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Rockefeller Univ Lab Mucosal Immunol 1230 York Ave New York NY 10021 USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA|Yale Univ Infect Dis Sect Dept Med Sch Med New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Infect Dis Sect Dept Med Sch Med New Haven CT USA;

    Yale Univ Infect Dis Sect Dept Med Sch Med New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Infect Dis Sect Dept Med Sch Med New Haven CT USA;

    Yale Univ Infect Dis Sect Dept Med Sch Med New Haven CT USA;

    Yale Univ Infect Dis Sect Dept Med Sch Med New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Sch Med Yale Canc Ctr New Haven CT USA|Smilow Canc Hosp New Haven CT USA;

    Yale Univ Infect Dis Sect Dept Med Sch Med New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA|Howard Hughes Med Inst Chevy Chase MD USA;

    Yale Univ Sch Med Dept Lab Med New Haven CT USA|Yale New Haven Med Ctr Ctr Outcomes Res & Evaluat New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Sch Med Sect Pulm & Crit Care Med Dept Med New Haven CT USA;

    Yale Univ Infect Dis Sect Dept Med Sch Med New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA|Yale Univ Infect Dis Sect Dept Med Sch Med New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA|Yale Univ Infect Dis Sect Dept Med Sch Med New Haven CT USA|Yale Univ Yale Inst Global Hlth New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA|Howard Hughes Med Inst Chevy Chase MD USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med Dept Biochem & Mol Biol New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med Sect Pulm & Crit Care Med Dept Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Sch Med Yale Viral Hepatitis Program New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med Yale Ctr Clin Invest New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Sch Publ Hlth Dept Epidemiol Microbial Dis New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Howard Hughes Med Inst Chevy Chase MD USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med Dept Neurol New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Infect Dis Sect Dept Med Sch Med New Haven CT USA;

    Yale Univ Infect Dis Sect Dept Med Sch Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med Dept Mol Cellular & Dev Biol New Haven CT USA;

    Yale Univ Sch Med Dept Biochem & Mol Biol New Haven CT USA;

    Yale Univ Sch Med Dept Neurol New Haven CT USA;

    Yale Univ Infect Dis Sect Dept Med Sch Med New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med Dept Immunobiol New Haven CT USA;

    Yale Univ Sch Med New Haven CT USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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