Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.
Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.
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DOI：
10.1016/j.immuni.2020.11.017
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发表时间：
2020-12-15
期刊：
影响因子：
32.4
通讯作者：
Deutsche COVID-19 Omics Initiative (DeCOI)
中科院分区：
文献类型：
--
作者：
Bernardes JP;Mishra N;Tran F;Bahmer T;Best L;Blase JI;Bordoni D;Franzenburg J;Geisen U;Josephs-Spaulding J;Köhler P;Künstner A;Rosati E;Aschenbrenner AC;Bacher P;Baran N;Boysen T;Brandt B;Bruse N;Dörr J;Dräger A;Elke G;Ellinghaus D;Fischer J;Forster M;Franke A;Franzenburg S;Frey N;Friedrichs A;Fuß J;Glück A;Hamm J;Hinrichsen F;Hoeppner MP;Imm S;Junker R;Kaiser S;Kan YH;Knoll R;Lange C;Laue G;Lier C;Lindner M;Marinos G;Markewitz R;Nattermann J;Noth R;Pickkers P;Rabe KF;Renz A;Röcken C;Rupp J;Schaffarzyk A;Scheffold A;Schulte-Schrepping J;Schunk D;Skowasch D;Ulas T;Wandinger KP;Wittig M;Zimmermann J;Busch H;Hoyer BF;Kaleta C;Heyckendorf J;Kox M;Rybniker J;Schreiber S;Schultze JL;Rosenstiel P;HCA Lung Biological Network;Deutsche COVID-19 Omics Initiative (DeCOI)
需要对与COVID-19严重疾病轨迹相关的细胞特征进行时间分辨率分析，以了解偏斜的免疫反应并确定结果的预测因素。在这里，我们使用双中心队列对14名患者进行了纵向多组学研究。我们分析了5个时间点采集的外周血样本的大量转录组、大量DNA甲基化组和单细胞转录组（bbb358,000个细胞，包括BCR谱）。在两个独立的COVID-19患者队列中进行验证。重症COVID-19的特征是增殖、代谢过度活跃的质母细胞增加。与危重疾病相一致，我们也发现了干扰素激活的循环巨核细胞的扩增和红细胞生成的增加，并伴有缺氧信号的特征。巨核细胞和红细胞衍生的共表达模块可预测致命疾病的预后。该研究证明了SARS-CoV-2感染在适应性免疫细胞之外的广泛细胞效应，并为开发生物标志物和针对COVID-19患者的靶向治疗提供了切入点。SARS-CoV2感染引起血液中循环细胞的动态变化严重的COVID-19以代谢活性的质母细胞增加为特征ifn活化的巨核细胞和红细胞在严重的COVID-19中升高细胞类型特异性表达特征与致命的COVID-19结局相关Bernardes等人通过对住院患者外周血样本进行纵向多组学分析来探索COVID-19疾病轨迹。分析发现，浆质母细胞、干扰素激活的巨核细胞和红细胞数量增加是严重疾病的标志，并确定了与致命的COVID-19疾病结局相关的分子特征。
Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. Megakaryocyte- and erythroid-cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond adaptive immune cells and provides an entry point toward developing biomarkers and targeted treatments of patients with COVID-19. SARS-CoV2 infection elicits dynamic changes of circulating cells in the blood Severe COVID-19 is characterized by increased metabolically active plasmablasts Elevation of IFN-activated megakaryocytes and erythroid cells in severe COVID-19 Cell-type-specific expression signatures are associated with a fatal COVID-19 outcome Bernardes et al. explore COVID-19 disease trajectories by performing longitudinal multi-omics analyses in peripheral blood samples from hospitalized patients. The analyses identify increased numbers of plasmablasts, interferon-activated megakaryocytes, and erythroid cells as hallmarks of severe disease and define molecular signatures linked to a fatal COVID-19 disease outcome.
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