NDLI: Bacterial sepsis causes more dramatic pathogenetic changes in the Th1 pathway than does viral (COVID-19) sepsis: a prospective observational study of whole blood transcriptomes

Content Provider	Springer Nature : BioMed Central
Author	Muratsu, Arisa Oda, Sayaka Onishi, Shinya Yoshimura, Jumpei Matsumoto, Hisatake Togami, Yuki Mitsuyama, Yumi Ito, Hiroshi Okuzaki, Daisuke Ogura, Hiroshi Oda, Jun
Abstract	Objectives This study aimed to comprehensively compare host responses of patients with bacterial sepsis and those with viral (COVID-19) sepsis by analyzing messenger RNA (mRNA) and microRNA (miRNA) profiles to shed light on their distinct pathophysiological mechanisms. Design Prospective observational study. Setting Whole blood RNA sequencing was used to analyze mRNA and miRNA profiles of patients diagnosed as having bacterial sepsis or viral (COVID-19) sepsis at the Department of Trauma and Emergency Medicine, Osaka University Graduate School of Medicine. Patients Twenty-two bacterial sepsis patients, 35 viral (COVID-19) sepsis patients, and 15 healthy subjects admitted to the department were included. We diagnosed bacterial sepsis patients according to the sepsis-3 criterion that the Sequential Organ Failure Assessment score must increase to 2 points or more among patients with suspected infections. Viral (COVID-19) sepsis patients were diagnosed using SARS-CoV-2 RT-PCR testing, and presence of pneumonia was assessed through chest computed tomography scans. Interventions None. Measurements and main results For RNA sequencing, 14,500 mRNAs, 1121 miRNAs, and 2556 miRNA-targeted mRNAs were available for analysis in the bacterial sepsis patients. Numbers of genes showing upregulated: downregulated gene expression (false discovery rate < 0.05, \|log2 fold change\| > 1.5) were 256:2887 for mRNA, 53:5 for miRNA, and 49:2507 for miRNA-targeted mRNA. Similarly, in viral (COVID-19) sepsis patients, 14,500 mRNAs, 1121 miRNAs, and 327 miRNA-targeted mRNAs were analyzed, with numbers of genes exhibiting upregulated: downregulated gene expression of 672:1147 for mRNA, 3:4 for miRNA, and 165:162 for miRNA-targeted mRNA. This analysis revealed significant differences in the numbers of upregulated and downregulated genes expressed and pathways between the bacterial sepsis and viral (COVID-19) sepsis patients. Bacterial sepsis patients showed activation of the PD-1 and PD-L1 cancer immunotherapy signaling pathway and concurrent suppression of Th1 signaling. Conclusion Our study illuminated distinct molecular variances between bacterial sepsis and viral (COVID-19) sepsis. Bacterial sepsis patients had a greater number of upregulated and downregulated genes and pathways compared to viral (COVID-19) sepsis patients. Especially, bacterial sepsis caused more dramatic pathogenetic changes in the Th1 pathway than did viral (COVID-19) sepsis.
Related Links	https://virologyj.biomedcentral.com/counter/pdf/10.1186/s12985-024-02451-6.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12985-024-02451-6
Journal	Virology Journal
Issue Number	1
Volume Number	21
Language	English
Publisher	BioMed Central
Publisher Date	2024-08-19
Access Restriction	Open
Subject Keyword	Virology COVID-19 PD-1 and PD-L1 cancer immunotherapy signaling pathways Bacterial sepsis Th1 signaling Whole blood transcriptome
Content Type	Text
Resource Type	Article
Subject	Virology Infectious Diseases
Journal Impact Factor	4/2023
5-Year Journal Impact Factor	3.8/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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