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. 2020 Dec;9(1):761-770.
doi: 10.1080/22221751.2020.1747363.

Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients

Yong Xiong  1 , Yuan Liu  2 , Liu Cao  3 , Dehe Wang  2 , Ming Guo  2 , Ao Jiang  2 , Dong Guo  2 , Wenjia Hu  1 , Jiayi Yang  2 , Zhidong Tang  2 , Honglong Wu  4 , Yongquan Lin  4 , Meiyuan Zhang  4 , Qi Zhang  2 , Mang Shi  3 , Yingle Liu  2 , Yu Zhou  2 , Ke Lan  2 , Yu Chen  2
Affiliations

Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients

Yong Xiong et al. Emerg Microbes Infect. 2020 Dec.

Abstract

Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients' lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.

Keywords: COVID-19; cytokine; inflammation; lymphopenia; transcriptome profiling.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Genome-wide profiling of gene expression in BALF and PBMC of COVID-19 patients. (A) Experimental design. PBMC and BALF were prepared from patients or control. Total RNA was extracted and analysed by RNA-seq to identify differentially expressed genes implicated in COVID-19 disease pathogenesis. (B, C) Heat map of genes significantly up-regulated and down-regulated (fold change > 2) in COVID-19 patients BALF (B, WHU01-2 vs. Ctrl1-3) and PBMC (C, P1-3 vs. N1-3) compared to controls, respectively. (D-F) RNA-seq signals in PBMC patients (P1, P2, P3) and healthy controls (N1, N2, N3) for 3 genes: IL6 (D), IL6R (E), and TP53 (F), respectively. The scale on the y axis indicates the read density per million of total normalized reads.
Figure 2.
Figure 2.
GO-term and KEGG pathway enrichment of up-regulated expressed genes in BALF and PBMC of COVID-19 patients. (A) GO-term functional enrichment by 3 categories (BP, MF, CC) and KEGG pathway analysis were performed for up-regulated genes in COVID-19 patients BALF. (B) Same as (A) for up-regulated genes in COVID-19 patients PBMC.
Figure 3.
Figure 3.
GO-term and KEGG pathway enrichment of down-regulated expressed genes in BALF and PBMC of COVID-19 patients. (A) GO-term functional enrichment by 3 categories (BP, MF, CC) and KEGG pathway analysis were performed for down-regulated genes in COVID-19 patients BALF. (B) Same as (A) for down-regulated genes in COVID-19 patients PBMC.
Figure 4.
Figure 4.
Inflammatory cytokines expression in COVID-19 patients. Heat map depicting inflammatory cytokine genes expression in COVID-19 patients BALF (A, WHU01-02 vs. Ctrl1-3) and PBMC (B, P1-3 vs. N1-3) compared with control. Genes significantly up-regulated and down-regulated are labelled with asterisks.
Figure 5.
Figure 5.
Apoptosis-related pathway in PBMC. The heatmaps show the expression levels of differentially expressed genes in different signaling pathways, including (A) autophagy (- animal species) signal pathway, (B) apoptosis signal pathway, (C) p53 signaling pathway. Genes significantly up-regulated and down-regulated are labelled with asterisks.
Figure 6.
Figure 6.
Comparison of differentially expressed genes in BALF and PBMC. (A) Venn diagram showing the number of changed genes with same or different trends between BALF and PBMC samples. (B) Heat map depicting the scaled gene expression changes with same or different trends between BALF and PBMC samples.
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Grants and funding

This study was supported by Special Fund for COVID-19 Research of Wuhan University, National Science and Technology Major Project (#2018ZX10733403), China NSFC grants (#81672008, 31871316), Hubei Natural Science Foundation (#2018CFA035), Basic Scientific Research Foundation of Central Universities (#2042019gf0026), Ministry of Science and Technology of China, the National Mega Project on Major Infectious Disease Prevention (#2017ZX10103005) and National Key Research and Development Program of China (#2018YFE0204500).