Whole-Transcriptome RNA Sequencing Reveals Significant Differentially Expressed mRNAs, miRNAs, and lncRNAs and Related Regulating Biological Pathways in the Peripheral Blood of COVID-19 Patients.

Cai-Xia Li,Jin-Hui Li,Xiao Hu,Lei-Lei Li,Jian Chen,Shu-Kai Lv,Yaoyao Xia

doi:10.1155/2021/6635925

Cai-Xia Li, Jin-Hui Li + Show 5 more

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https://doi.org/10.1155/2021/6635925

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially identified in China and currently worldwide dispersed, resulting in the coronavirus disease 2019 (COVID-19) pandemic. Notably, COVID-19 is characterized by systemic inflammation. However, the potential mechanisms of the “cytokine storm” of COVID-19 are still limited. In this study, fourteen peripheral blood samples from COVID-19 patients (n = 10) and healthy donors (n = 4) were collected to perform the whole-transcriptome sequencing. Lung tissues of COVID-19 patients (70%) presenting with ground-glass opacity. Also, the leukocytes and lymphocytes were significantly decreased in COVID-19 compared with the control group (p < 0.05). In total, 25,482 differentially expressed messenger RNAs (DE mRNA), 23 differentially expressed microRNAs (DE miRNA), and 410 differentially expressed long noncoding RNAs (DE lncRNAs) were identified in the COVID-19 samples compared to the healthy controls. Gene Ontology (GO) analysis showed that the upregulated DE mRNAs were mainly involved in antigen processing and presentation of endogenous antigen, positive regulation of T cell mediated cytotoxicity, and positive regulation of gamma-delta T cell activation. The downregulated DE mRNAs were mainly concentrated in the glycogen biosynthetic process. We also established the protein-protein interaction (PPI) networks of up/downregulated DE mRNAs and identified 4 modules. Functional enrichment analyses indicated that these module targets were associated with positive regulation of cytokine production, cytokine-mediated signaling pathway, leukocyte differentiation, and migration. A total of 6 hub genes were selected in the PPI module networks including AKT1, TNFRSF1B, FCGR2A, CXCL8, STAT3, and TLR2. Moreover, a competing endogenous RNA network showed the interactions between lncRNAs, mRNAs, and miRNAs. Our results highlight the potential pathogenesis of excessive cytokine production such as MSTRG.119845.30/hsa-miR-20a-5p/TNFRSF1B, MSTRG.119845.30/hsa-miR-29b-2-5p/FCGR2A, and MSTRG.106112.2/hsa-miR-6501-5p/STAT3 axis, which may also play an important role in the development of ground-glass opacity in COVID-19 patients. This study gives new insights into inflammation regulatory mechanisms of coding and noncoding RNAs in COVID-19, which may provide novel diagnostic biomarkers and therapeutic avenues for COVID-19 patients.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is a novel lineage B betacoronavirus that causes zoonotic diseases and was first reported in Wuhan, China, in December 2019 [1, 2]
We found that 25,482 differentially expressed messenger RNAs (DE mRNA), 23 DE miRNA, and 410 DE long ncRNAs (lncRNAs) when peripheral blood samples of COVID-19 patients were compared to control, respectively
We identified 95 module targets involved in the positive regulation of cytokine production, including AKT1, TNFRSF1B, FCGR2A, CXCL8, Signal transducer and activator of transcription 3 (STAT3), and toll-like receptor 2 (TLR2)

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is a novel lineage B betacoronavirus that causes zoonotic diseases and was first reported in Wuhan, China, in December 2019 [1, 2]. The pandemic caused by SARSCoV-2 was named as coronavirus disease 2019 Previous studies have reported that the COVID-19 patients suffered from asymptomatic or mild respiratory. Mediators of Inflammation infection to acute respiratory distress syndrome (ARDS) or multiorgan failure, and this disease was more likely to occur in elderly people with a weak immune function [1, 5, 6]. The majority of patients with COVID-19 have a pleasing prognosis, but there were still ARDS and multiorgan dysfunction that occurred rapidly, resulting in death within a short time [7, 8]. Understanding the genomic landscape of serum of COVID-19 patients will help in improving the treatment avenues and diagnosis strategies

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