Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease.
Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease.
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DOI：
10.1016/j.immuni.2021.05.010
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发表时间：
2021-06-08
期刊：
影响因子：
32.4
通讯作者：
Smith KGC
中科院分区：
文献类型：
--
作者：
Bergamaschi L;Mescia F;Turner L;Hanson AL;Kotagiri P;Dunmore BJ;Ruffieux H;De Sa A;Huhn O;Morgan MD;Gerber PP;Wills MR;Baker S;Calero-Nieto FJ;Doffinger R;Dougan G;Elmer A;Goodfellow IG;Gupta RK;Hosmillo M;Hunter K;Kingston N;Lehner PJ;Matheson NJ;Nicholson JK;Petrunkina AM;Richardson S;Saunders C;Thaventhiran JED;Toonen EJM;Weekes MP;Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration;Göttgens B;Toshner M;Hess C;Bradley JR;Lyons PA;Smith KGC
尚未严格评估COVID-19各严重程度组的免疫变化动力学。使用免疫表型分析、RNA测序和血清细胞因子分析，我们分析了207例SARS-CoV 2感染者的系列样本，这些患者从症状发作起12周内具有一系列疾病严重程度。早期强的旁观者CD 8 + T细胞免疫应答，无全身炎症，特征为无症状或轻度疾病。住院的个体具有延迟的旁观者反应和在症状发作附近已经明显的全身性炎症，表明免疫病理学在一些个体中可能是不可避免的。病毒载量与这种早期病理反应无关，但与随后的疾病严重程度相关。免疫恢复是复杂的，在严重疾病中具有与改变的炎症反应相关的深刻的持续细胞异常，与增加的氧化磷酸化相关的特征取代了由细胞因子肿瘤坏死因子（TNF）和白细胞介素（IL）-6驱动的特征。这些晚期免疫代谢和免疫缺陷可能具有临床意义。不同疾病严重程度的COVID-19患者的纵向分析早期旁观者CD 8 + T细胞和浆母细胞反应表征轻度疾病在较严重的COVID-19中首次出现明显的全身炎症免疫/炎症异常在严重疾病中持续到症状后60天COVID-19严重程度的免疫变化尚未完全确定。通过分析COVID-19患者的纵向队列并整合炎症因子，免疫表型和转录组数据，Bergamaschi et al.识别早期和持续免疫变化，以区分轻度和/或无症状疾病与更严重的疾病。
The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8+ T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications. Longitudinal analysis of COVID-19 patients with a range of disease severity Early bystander CD8+ T cell and plasmablast responses characterize mild disease Pronounced systemic inflammation evident at first presentation in more severe COVID-19 Immune/inflammatory abnormalities persist in severe disease to 60 days post symptoms The immune changes that underlie COVID-19 severity have not been fully defined. By analyzing a longitudinal cohort of COVID-19 patients and integrating inflammatory factors, immunophenotyping, and transcriptome data, Bergamaschi et al. identify both early and persistent immune changes that distinguish mild and/or asymptomatic from more severe disease.
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DOI：
10.1126/science.abd3072
发表时间：
2020-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Daly JL;Simonetti B;Klein K;Chen KE;Williamson MK;Antón-Plágaro C;Shoemark DK;Simón-Gracia L;Bauer M;Hollandi R;Greber UF;Horvath P;Sessions RB;Helenius A;Hiscox JA;Teesalu T;Matthews DA;Davidson AD;Collins BM;Cullen PJ;Yamauchi Y
通讯作者：
Yamauchi Y
影响因子：
20.3
作者：
Kamphuis, Elisabeth;Junt, Tobias;Kalinke, Ulrich
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Kalinke, Ulrich
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
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Schlesner, Matthias
DOI：
10.1084/jem.20031051
发表时间：
2003-11-17
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Berg RE;Crossley E;Murray S;Forman J
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Forman J
影响因子：
30.5
作者：
Kaech, SM;Tan, JT;Ahmed, R
通讯作者：
Ahmed, R