Long-term longitudinal analysis of peripheral blood transcriptome in COVID-19 patients

We performed the longitudinal peripheral blood transcriptome profiling after diagnosis in five patients, and found that patients' blood transcriptomes undergo dramatic and consistent changes in early recovery stage (ERS). Meanwhile, the blood transcriptome did not fully return to the healthy state even after more than one month of recovery. We also realized that differential expressed genes (DEGs) are enriched in biological processes of antigen processing and related processes, and promoter regions of these genes enrich key transcription factors (TFs) involved in T cell differentiation and activation. We further provided potential mechanisms underlying these orchestrated processes, by revealing these specific TFs mediated gene co-expression network. Examination between recovery stage and healthy control. Differential gene expression analysis was performed using DESeq2 (Love et al., 2014). Genes that displayed ±1 log2FC (FDR <0.01) between ERS or LRS and healthy control samples were considered as significantly differentially expressed.本研究对5名患者确诊后的外周血转录组进行了纵向表达谱分析，发现患者的血液转录组在早期恢复阶段（Early Recovery Stage, ERS）发生了显著且一致的变化。与此同时，即便在康复满1个月后，患者的血液转录组仍未完全恢复至健康状态。本研究同时发现，差异表达基因（Differentially Expressed Genes, DEGs）显著富集于抗原加工及相关生物学过程，且这些基因的启动子区域富集了参与T细胞分化与活化的关键转录因子（Transcription Factors, TFs）。本研究进一步通过解析这些特异性转录因子介导的基因共表达网络，阐明了上述协同调控过程的潜在分子机制。本研究对各恢复阶段样本与健康对照样本开展了比较分析，差异基因表达分析采用DESeq2工具（Love等人，2014）完成。在早期恢复阶段（ERS）或晚期恢复阶段（Late Recovery Stage, LRS）样本与健康对照样本之间，表现出±1 log₂倍变化且错误发现率（False Discovery Rate, FDR）<0.01的基因，被认定为显著差异表达基因。