Abstract
Circulating in China and 75 other countries and territories, 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 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 signaling 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. 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). Declaration of Interest: The authors declare no competing interests. Ethical Approval: This study was approved by the Ethics Committee of the Zhongnan Hospital of Wuhan University. The RNA-seq analyses of BALF samples and PBMC were performed on existing samples collected during standard diagnostic tests, posing no extra burden to patients.
Highlights
The recent ongoing outbreak of viral pneumonia (COVID-19) has sparked worldwide concern
Through transcriptomic analyses of these datasets, we identified several immune pathways and pro-inflammatory cytokines induced by SARS-CoV-2 infection, notably CCL2, CXCL2, CCL8, CXCL1, IL33, CCL3L1 in bronchoalveolar lavage fluid (BALF) and CXCL10, TNFSF10, TIMP1, C5, IL18, AREG, NRG1, IL10 in peripheral blood mononuclear cells (PBMC), evidencing a sustained inflammation and cytokine storm in the patients
We performed quality control analysis on the RNAseq data, and summarized the statistics of reads mapped to the human genome and the SARS-CoV-2 genome (GenBank MN988668) in the Supplementary Tables 1 and 2 for BALF and PBMC samples, respectively
Summary
The recent ongoing outbreak of viral pneumonia (COVID-19) has sparked worldwide concern. First reported in December 2019 in Wuhan, COVID-19 spread rapidly across other areas and caused a major epidemic with 80,894 confirmed cases including 3237 deaths in China by 17 March 17 2020. A novel highly infectious coronavirus, officially called the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), was subsequently identified as the causative pathogen of this outbreak by deep sequencing and etiological investigations [1,2,3]. Some COVID-19 patients rapidly develop severe pneumonia symptoms and complications including acute respiratory distress syndrome (ARDS), pulmonary oedema, acute kidney injury, or multiple organ failure [4,5,6]. The case fatality rate of COVID-19 is around 3.7% according to the national official statistics in China
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