Early IFN-a signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19

Supplemental tables of the publication "Early IFN-a signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19" Benjamin Krämer et al., 2021.

Sup. Table S1: Cohort details [related to all Figures]
Sup. Table S2: marker for NK selection and NK subtype marker gene list from the scRNA-seq analyses cohort 1 [related to Figure 2A+D+C and S2A]
Sup. Table S3: Module marker gene list and function analysis from the scRNA-seq analyses cohort 1 [related to Figure 2B]
Sup. Table S4: Module marker gene list, function analysis, TF and ligand prediction from the scRNA-seq analyses cohort 1 [related to Figure 3C]
Sup. Table S5: List of antibodies used for multi-color flow cytometry [related to Figures 1, S1, 2, S2, 3, S3, S4 S6, 7, S7]
Sup. Table S6: Number of donors, samples and cells by experiment [related to all figures]
Sup. Table S7: Oligo-Primer sequences [related to STAR methods]

Benjamin Krämer, Rainer Knoll, Lorenzo Bonaguro, Michael ToVinh, Jan Raabe, Rosario Astaburuaga-García, Jonas Schulte-Schrepping, Kim Melanie Kaiser, Gereon J. Rieke, Jenny Bischoff, Malte B. Monin, Christoph Hoffmeister, Stefan Schlabe, Elena De Domenico, Nico Reusch, Kristian Händler, Gary Reynolds, Nils Blüthgen, Gudrun Hack, Claudia Finnemann, Hans D. Nischalke, Christian P. Strassburg, Emily Stephenson, Yapeng Su, Louis Gardner, Dan Yuan, Daniel Chen, Jason Goldman, Philipp Rosenstiel, Susanne V. Schmidt, Eicke Latz, Kevin Hrusovsky, Andrew J. Ball, Joe M. Johnson, Paul-Albert Koenig, Florian I. Schmidt, Muzlifah Haniffa, James R. Heath, Beate M. Kümmerer, Verena Keitel, Björn Jensen, Paula Stubbemann, Florian Kurth, Leif E. Sander, Birgit Sawitzki, Deutsche COVID-19 OMICS Initiative (DeCOI), Anna C. Aschenbrenner, Joachim L. Schultze, Jacob Nattermann
Summary
Longitudinal analyses of the innate immune system including earliest time points are essential to understand the immunopathogenesis and clinical course of COVID-19. Here, we performed a detailed characterization of natural killer cells in 205 patients (403 samples, day 2-41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated IFN-α plasma levels in early severe COVD-19 alongside increased NK cell expression of ISGs and genes involved in IFN-α signaling, while upregulation of TNF-induced genes was observed in moderate disease. NK cells exert anti-SARS-CoV-2 activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates prolonged IFN-α-induced NK cell response with poorer disease outcome.

本数据集为论文《早期干扰素-α特征与持续性功能障碍是重症新型冠状病毒肺炎（COVID-19）患者自然杀伤细胞（NK）的标志性特征》（Benjamin Krämer等，2021年）的补充表格集：
补充表S1：队列详情[关联所有插图]
补充表S2：来自队列1单细胞RNA测序（scRNA-seq）分析的NK细胞分选标记物及NK细胞亚型标记基因列表[关联图2A、D、C及补充图S2A]
补充表S3：来自队列1scRNA-seq分析的模块标记基因列表及功能分析结果[关联图2B]
补充表S4：来自队列1scRNA-seq分析的模块标记基因列表、功能分析结果、转录因子（TF）及配体预测信息[关联图3C]
补充表S5：多色流式细胞术所用抗体列表[关联图1、S1、2、S2、3、S3、4、S6、7、S7]
补充表S6：按实验分类的供体、样本及细胞数量统计[关联所有插图]
补充表S7：寡核苷酸引物序列[关联STAR方法部分]

作者列表：
Benjamin Krämer, Rainer Knoll, Lorenzo Bonaguro, Michael ToVinh, Jan Raabe, Rosario Astaburuaga-García, Jonas Schulte-Schrepping, Kim Melanie Kaiser, Gereon J. Rieke, Jenny Bischoff, Malte B. Monin, Christoph Hoffmeister, Stefan Schlabe, Elena De Domenico, Nico Reusch, Kristian Händler, Gary Reynolds, Nils Blüthgen, Gudrun Hack, Claudia Finnemann, Hans D. Nischalke, Christian P. Strassburg, Emily Stephenson, Yapeng Su, Louis Gardner, Dan Yuan, Daniel Chen, Jason Goldman, Philipp Rosenstiel, Susanne V. Schmidt, Eicke Latz, Kevin Hrusovsky, Andrew J. Ball, Joe M. Johnson, Paul-Albert Koenig, Florian I. Schmidt, Muzlifah Haniffa, James R. Heath, Beate M. Kümmerer, Verena Keitel, Björn Jensen, Paula Stubbemann, Florian Kurth, Leif E. Sander, Birgit Sawitzki, 德国COVID-19组学倡议（DeCOI）, Anna C. Aschenbrenner, Joachim L. Schultze, Jacob Nattermann

研究摘要：
包含最早时间节点的先天免疫系统纵向分析，对于阐明新型冠状病毒肺炎（COVID-19）的免疫发病机制与临床病程至关重要。本研究针对来自4个独立队列的205例患者（共403份样本，采集时间为症状发作后2~41天），结合单细胞转录组学、蛋白质组学及功能实验，对其自然杀伤细胞（NK）进行了全面表征。我们发现，早期重症COVID-19患者血浆干扰素-α（IFN-α）水平升高，同时NK细胞的干扰素刺激基因（ISGs）及参与IFN-α信号通路的基因表达上调；而中度COVID-19患者则观察到肿瘤坏死因子（TNF）诱导基因的上调。NK细胞具备抗严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）活性，但在重症COVID-19中其功能受损。进一步研究显示，NK细胞功能障碍或与重症COVID-19患者肺纤维化疾病的发生相关，因为此时NK细胞的抗纤维化活性受损。本研究表明，重症与中度COVID-19分别优先诱导IFN-α与TNF应答，并将IFN-α诱导的持续性NK细胞应答与更差的疾病预后相关联。