Whole transcriptome sequencing of peripheral blood mononuclear cells from patients with COVID-19

Understanding the process of immune remodeling and regulation in SARS-CoV-2 infected patients from hospitalization to rehabilitation is crucial for therapy of patients with COVID-19. Here, we performed a longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell (PBMC) samples of 18 patients with mild, moderate or severe COVID-19 symptoms during the treatment, convalescence and rehabilitation stages. After identifying the differentially expressed mRNAs, miRNAs and lncRNAs between different clinical stages or different clinical types and predicting the target genes of non-coding RNAs, we analyzed the functional and regulatory networks of their interactions. The type I interferon response was found to be significantly down-regulated after the patient rehabilitation, and the humoral immunity declined rapidly from the convalescence stage. Robust T-cell activation and differentiation at the whole transcriptome level constituted the main events during the recovery process of COVID-19. The formation of this T cell immune memory had the characteristics of multi-directional and multi-level regulation, and presented a higher early differentiation in mild patients. These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the formation of immune protection against COVID-19. Overall design: Peripheral blood mononuclear cells (PBMC) from 18 patients with COVID-19 were collected and subjected to total RNA extraction. rRNA-depleted library and small RNA library were constructed for each sample to capture the expression of mRNA, lncRNA, and miRNA. In a total of 18 patients with COVID-19, there were 6, 7, and 5 patients with mild, moderate, and severe symptoms, respectively. PBMC samples were collected at the treatment stage, convalescence stage, and rehabilitation stage for each sample.