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

越来越多的证据表明，长新冠肺炎的患病率正在上升，这是一个最近创造的术语，指的是急性新冠肺炎后临床症状持续六个月以上的未康复患者。虽然免疫系统脱轨被认为是可能的原因，但目前还没有手段来识别急性新冠肺炎后早期长新冠肺炎患者。我们最近展示了使用全血转录组学来构建急性新冠肺炎的疾病分类器，以及通过分子表型分析疾病的异质性。德科(德国新冠肺炎)网络在德国的多个地点建立了患者队列，事实证明，这些患者在分析和了解急性新冠肺炎方面非常有价值。我们将把临床科学家、DFG资助的测序中心和计算专家聚集在一起，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，阐明长新冠肺炎。我们将使用这些队列中的样本来建立全血转录组签名和分类器，以识别长新冠肺炎患者并确定他们的分子表型，以阐明疾病的异质性。此外，我们将通过异常表达分析以及评估血液微生物谱作为潜在的生物标记物来确定长新冠肺炎可能的遗传易感性。总的来说，这些分析将使人们能够识别与新冠肺炎长期相关的生物学的分子机制，以及在临床试验中进一步开发的潜在治疗靶点。

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.