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

Yong Xiong, Yuan Liu, Liu Cao, Dehe Wang, Ming Guo, Ao Jiang, Dong Guo, Wenjia Hu, Jiayi Yang, Zhidong Tang, Honglong Wu, Yongquan Lin, Meiyuan Zhang, Qi Zhang, Mang Shi, Yingle Liu, Yu Zhou, Ke Lan, Yu Chen
Author Information
  1. Yong Xiong: State Key Laboratory of Virology, Department of Infectious Disease, Zhongnan Hospital, Wuhan University, Wuhan, People's Republic of China.
  2. Yuan Liu: State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  3. Liu Cao: The Centre for Infection and Immunity Studies, School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
  4. Dehe Wang: State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  5. Ming Guo: State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  6. Ao Jiang: State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  7. Dong Guo: State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  8. Wenjia Hu: State Key Laboratory of Virology, Department of Infectious Disease, Zhongnan Hospital, Wuhan University, Wuhan, People's Republic of China.
  9. Jiayi Yang: State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  10. Zhidong Tang: State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  11. Honglong Wu: BGI PathoGenesis Pharmaceutical Technology, Shenzhen, People's Republic of China.
  12. Yongquan Lin: BGI PathoGenesis Pharmaceutical Technology, Shenzhen, People's Republic of China. ORCID
  13. Meiyuan Zhang: BGI PathoGenesis Pharmaceutical Technology, Shenzhen, People's Republic of China.
  14. Qi Zhang: State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China. ORCID
  15. Mang Shi: The Centre for Infection and Immunity Studies, School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
  16. Yingle Liu: State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  17. Yu Zhou: State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  18. Ke Lan: State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
  19. Yu Chen: State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China. ORCID

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

References

  1. BMC Biol. 2019 Jul 18;17(1):59 [PMID: 31319842]
  2. Genomics Proteomics Bioinformatics. 2017 Feb;15(1):14-18 [PMID: 28387199]
  3. J Med Virol. 2020 Apr;92(4):418-423 [PMID: 31967327]
  4. Cell Rep. 2019 Feb 5;26(6):1627-1640.e7 [PMID: 30726743]
  5. Lancet. 2003 Jun 7;361(9373):1985 [PMID: 12801759]
  6. Nucleic Acids Res. 2020 Jan 8;48(D1):D756-D761 [PMID: 31691824]
  7. Nature. 2020 Mar;579(7798):270-273 [PMID: 32015507]
  8. Immunol Res. 2014 Aug;59(1-3):118-28 [PMID: 24845462]
  9. Viruses. 2019 Oct 18;11(10): [PMID: 31635238]
  10. Am J Respir Crit Care Med. 2005 Apr 15;171(8):850-7 [PMID: 15657466]
  11. Bioinformatics. 2012 Aug 15;28(16):2184-5 [PMID: 22743226]
  12. Annu Rev Med. 2017 Jan 14;68:387-399 [PMID: 27576010]
  13. Bioinformatics. 2014 Apr 1;30(7):923-30 [PMID: 24227677]
  14. Nat Commun. 2019 Dec 13;10(1):5711 [PMID: 31836714]
  15. J Med Virol. 2005 Feb;75(2):185-94 [PMID: 15602737]
  16. Lancet Respir Med. 2020 Apr;8(4):420-422 [PMID: 32085846]
  17. PLoS Pathog. 2008 Dec;4(12):e1000240 [PMID: 19079579]
  18. Cell Host Microbe. 2016 Feb 10;19(2):181-93 [PMID: 26867177]
  19. Bioinformatics. 2009 Jan 15;25(2):288-9 [PMID: 19033274]
  20. Annu Rev Immunol. 2014;32:659-702 [PMID: 24655300]
  21. JAMA. 2020 Mar 17;323(11):1061-1069 [PMID: 32031570]
  22. Nucleic Acids Res. 2019 Jan 8;47(D1):D590-D595 [PMID: 30321428]
  23. J Infect Dis. 2014 May 1;209(9):1331-42 [PMID: 24065148]
  24. N Engl J Med. 2020 Apr 30;382(18):1708-1720 [PMID: 32109013]
  25. PLoS Med. 2006 Sep;3(9):e343 [PMID: 16968120]
  26. OMICS. 2012 May;16(5):284-7 [PMID: 22455463]
  27. Genome Biol. 2014;15(12):550 [PMID: 25516281]
  28. Semin Immunopathol. 2016 Jul;38(4):471-82 [PMID: 26965109]
  29. J Exp Med. 2005 Aug 1;202(3):415-24 [PMID: 16043521]
  30. Pediatrics. 2004 Jan;113(1 Pt 1):e7-14 [PMID: 14702488]
  31. Infect Immun. 2004 Aug;72(8):4410-5 [PMID: 15271897]
  32. Med Hypotheses. 2008 Aug;71(2):298-301 [PMID: 18448259]
  33. Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3799-804 [PMID: 24572573]
  34. J Med Virol. 2006 Apr;78(4):417-24 [PMID: 16482545]
  35. Immunity. 2017 Nov 21;47(5):903-912.e4 [PMID: 29126797]
  36. Emerg Microbes Infect. 2020 Dec;9(1):313-319 [PMID: 32020836]
  37. PLoS Pathog. 2017 Feb 16;13(2):e1006155 [PMID: 28207896]
  38. Nat Rev Microbiol. 2016 Aug;14(8):523-34 [PMID: 27344959]
  39. Bioinformatics. 2013 Jan 1;29(1):15-21 [PMID: 23104886]
  40. Lancet. 2020 Feb 15;395(10223):497-506 [PMID: 31986264]
  41. Int J Infect Dis. 2013 Feb;17(2):e76-83 [PMID: 23069683]
  42. Lancet. 2020 Feb 15;395(10223):473-475 [PMID: 32043983]
  43. BMJ. 2003 Sep 13;327(7415):620 [PMID: 12969939]
  44. Lancet. 2020 Feb 15;395(10223):507-513 [PMID: 32007143]
  45. Nucleic Acids Res. 2020 Jan 8;48(D1):D24-D33 [PMID: 31702008]
  46. J Immunol. 2008 Feb 1;180(3):1903-12 [PMID: 18209088]
  47. Clin Infect Dis. 2003 Sep 15;37(6):857-9 [PMID: 12955652]
  48. Cell Host Microbe. 2016 Feb 10;19(2):139-41 [PMID: 26867172]
  49. Nature. 2020 Mar;579(7798):265-269 [PMID: 32015508]

MeSH Term

Apoptosis
Betacoronavirus
Bronchoalveolar Lavage Fluid
COVID-19
Chemokines
Coronavirus Infections
Cytokines
Humans
Leukocytes, Mononuclear
Lymphopenia
Pandemics
Pneumonia, Viral
RNA-Seq
SARS-CoV-2
Signal Transduction
Transcriptome
Tumor Suppressor Protein p53

Chemicals

Chemokines
Cytokines
TP53 protein, human
Tumor Suppressor Protein p53