Identification and characterization of Long COVID-19 patients by whole blood transcriptomics

越来越多的证据表明，长期COVID-19的患病率正在上升。长期COVID-19是最近创造的一个术语，指的是急性COVID-19后临床症状持续超过6个月而未康复的患者。尽管免疫系统失调被认为是可能的原因，但目前还没有办法在COVID-19急性后早期识别长期COVID-19患者。我们最近展示了使用全血转录组学来构建急性COVID-19的疾病分类器，并通过分子表型解剖疾病异质性。DeCOI（德国COVID-19组学）网络已在德国多个地点建立了患者队列，这在分析和了解急性COVID-19方面已被证明具有巨大价值。我们将汇集临床科学家、dfg资助的测序中心和计算专家，结合临床感染学、基因组学和机器学习方面的知识和专业知识，阐明COVID-19。我们将使用来自这些队列的样本建立全血转录组特征和分类器，以识别Long - COVID-19患者，并确定其分子表型，以阐明疾病异质性。此外，我们将通过异常表达分析以及评估血液来源微生物谱作为潜在生物标志物来确定Long - COVID-19可能的遗传易感性。总的来说，这些分析将有助于确定covid -19相关生物学的分子机制和潜在的治疗靶点，以便在临床试验中进一步开发。

Increasing evidence indicates a rising prevalence for Long COVID-19, a recently coined term for non-recovering patients with persisting clinical symptoms for more than six months after acute COVID-19. Although a derailed immune system has been postulated as a possible cause, there are currently no means of identifying Long COVID-19 patients early post acute COVID-19. We have recently demonstrated the use of whole blood transcriptomics to build disease classifiers for acute COVID-19 as well as dissect disease heterogeneity by molecular phenotypes. The DeCOI (German COVID-19 Omics) network has established patient cohorts at multiple sites in Germany, which have already proven tremendously valuable in the analysis and understanding of acute COVID-19. Bringing together clinical scientists, DFG-funded sequencing centers, and computational experts, we will combine the knowledge and expertise in clinical infectiology, genomics and machine learning to shed light on Long COVID-19. We will use the samples from these cohorts to establish whole blood transcriptome signatures and classifiers to identify Long COVID-19 patients and determine their molecular phenotypes to elucidate disease heterogeneity. Further, we will identify possible genetic susceptibility for Long COVID-19 by aberrant expression analysis as well as assessing blood-derived microbial profiles as potential biomarker. Collectively, these analyses will enable the identification of molecular mechanisms of Long-COVID-19-related biology and potential therapeutic targets for further exploitation in clinical trials.