Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19.
Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19.
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DOI：
10.1016/j.xcrm.2022.100652
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发表时间：
2022-06-21
影响因子：
14.3
通讯作者：
Kox, Matthijs
中科院分区：
文献类型：
--
作者：
Frishberg, Amit;Kooistra, Emma;Nuesch-Germano, Melanie;Pecht, Tal;Milman, Neta;Reusch, Nico;Warnat-Herresthal, Stefanie;Bruse, Niklas;Haendler, Kristian;Theis, Heidi;Kraut, Michael;van Rijssen, Esther;van Cranenbroek, Bram;Koenen, Hans JPM.;Heesakkers, Hidde;van den Boogaard, Mark;Zegers, Marieke;Pickkers, Peter;Becker, Matthias;Aschenbrenner, Anna C.;Ulas, Thomas;Theis, Fabian J.;Shen-Orr, Shai S.;Schultze, Joachim L.;Kox, Matthijs
疾病恢复动态通常难以评估，因为患者表现出不同的恢复过程。为了模拟以严重COVID-19为例的恢复动力学，我们对纵向采样的血液转录组应用了一种计算方案，生成恢复状态，然后将其与细胞和分子机制联系起来，提出了一个框架，用于研究随时间推移与非恢复的恢复动力学以及疾病的长期影响。具体来说，成熟中性粒细胞的减少是恢复过程中最强的细胞效应，对疾病结果有直接影响。此外，我们提出了与细胞组成变化分离的基因程序的全球调控变化的强有力迹象，包括T细胞激活和分化的早期上升，导致干扰素和NF-κB活性之间的免疫再平衡和细胞稳态的恢复。总的来说，我们提出了一个临床相关的疾病恢复建模计算框架，为未来研究其他疾病和组织的恢复动力学铺平了道路。成熟中性粒细胞的逐渐减少是COVID-19恢复的细胞标志，T细胞激活的早期上升是COVID-19恢复的功能标志。Frishberg等人在COVID-19恢复期间干扰素和NF-κB反应之间的过渡引入了一个通用框架，用于确定异质患者队列中共享的疾病恢复动态。该研究说明了该框架在确定COVID-19严重恢复期潜在细胞和分子变化方面的实用性，这些变化是基于时间顺序的标准分析框架无法检测到的。
Disease recovery dynamics are often difficult to assess, as patients display heterogeneous recovery courses. To model recovery dynamics, exemplified by severe COVID-19, we apply a computational scheme on longitudinally sampled blood transcriptomes, generating recovery states, which we then link to cellular and molecular mechanisms, presenting a framework for studying the kinetics of recovery compared with non-recovery over time and long-term effects of the disease. Specifically, a decrease in mature neutrophils is the strongest cellular effect during recovery, with direct implications on disease outcome. Furthermore, we present strong indications for global regulatory changes in gene programs, decoupled from cell compositional changes, including an early rise in T cell activation and differentiation, resulting in immune rebalancing between interferon and NF-κB activity and restoration of cell homeostasis. Overall, we present a clinically relevant computational framework for modeling disease recovery, paving the way for future studies of the recovery dynamics in other diseases and tissues. A quantitative assessment of severe COVID-19 patients’ recovery dynamics Gradual reduction in mature neutrophils is a cellular hallmark of COVID-19 recovery Early rise in T cell activation is a functional hallmark of COVID-19 recovery Transition between interferon and NF-κB responses during COVID-19 recovery Frishberg et al. introduce a generalizable framework for determining shared disease recovery dynamics in heterogeneous patient cohorts. The study illustrates the utility of this framework in determining underlying cellular and molecular changes during severe COVID-19 recovery, which cannot be detected by standard analysis frameworks, based on chronological time.
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影响因子：
30.5
作者：
Choi S;Warzecha C;Zvezdova E;Lee J;Argenty J;Lesourne R;Aravind L;Love PE
通讯作者：
Love PE
影响因子：
7.3
作者：
Hazeldine J;Lord JM
通讯作者：
Lord JM
影响因子：
12.3
作者：
Aschenbrenner AC;Mouktaroudi M;Krämer B;Oestreich M;Antonakos N;Nuesch-Germano M;Gkizeli K;Bonaguro L;Reusch N;Baßler K;Saridaki M;Knoll R;Pecht T;Kapellos TS;Doulou S;Kröger C;Herbert M;Holsten L;Horne A;Gemünd ID;Rovina N;Agrawal S;Dahm K;van Uelft M;Drews A;Lenkeit L;Bruse N;Gerretsen J;Gierlich J;Becker M;Händler K;Kraut M;Theis H;Mengiste S;De Domenico E;Schulte-Schrepping J;Seep L;Raabe J;Hoffmeister C;ToVinh M;Keitel V;Rieke G;Talevi V;Skowasch D;Aziz NA;Pickkers P;van de Veerdonk FL;Netea MG;Schultze JL;Kox M;Breteler MMB;Nattermann J;Koutsoukou A;Giamarellos-Bourboulis EJ;Ulas T;German COVID-19 Omics Initiative (DeCOI)
通讯作者：
German COVID-19 Omics Initiative (DeCOI)
影响因子：
16.6
作者：
Lu N;Li Y;Zhang Z;Xing J;Sun Y;Yao S;Chen L
通讯作者：
Chen L
影响因子：
6
作者：
Martonik D;Parfieniuk-Kowerda A;Rogalska M;Flisiak R
通讯作者：
Flisiak R