Severe COVID-19 and non-COVID-19 severe sepsis converge transcriptionally after a week in the intensive care unit, indicating common disease mechanisms

Frontiers in Immunology

Immunology

Peter Zhang¹  Andy Y. An¹  Reza Falsafi¹  Robert E. W. Hancock¹  Arjun Baghela¹  Amy H. Lee²  Andrew J. Baker³  Claudia C. dos Santos³  Uriel Trahtemberg⁴ 

[1] Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada;Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada;The Department of Critical Care, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada;The Department of Critical Care, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada;Department of Critical Care, Galilee Medical Center, Nahariya, Israel;

关键词: COVID-19;    sepsis;    gene expression;    immune dysfunction;    longitudinal analyses;   

DOI  :  10.3389/fimmu.2023.1167917

 received in 2023-02-17, accepted in 2023-03-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionSevere COVID-19 and non-COVID-19 pulmonary sepsis share pathophysiological, immunological, and clinical features. To what extent they share mechanistically-based gene expression trajectories throughout hospitalization was unknown. Our objective was to compare gene expression trajectories between severe COVID-19 patients and contemporaneous non-COVID-19 severe sepsis patients in the intensive care unit (ICU).MethodsIn this prospective single-center observational cohort study, whole blood was drawn from 20 COVID-19 patients and 22 non-COVID-19 adult sepsis patients at two timepoints: ICU admission and approximately a week later. RNA-Seq was performed on whole blood to identify differentially expressed genes and significantly enriched pathways.ResultsAt ICU admission, despite COVID-19 patients being almost clinically indistinguishable from non-COVID-19 sepsis patients, COVID-19 patients had 1,215 differentially expressed genes compared to non-COVID-19 sepsis patients. After one week in the ICU, the number of differentially expressed genes dropped to just 9 genes. This drop coincided with decreased expression of antiviral genes and relatively increased expression of heme metabolism genes over time in COVID-19 patients, eventually reaching expression levels seen in non-COVID-19 sepsis patients. Both groups also had similar underlying immune dysfunction, with upregulation of immune processes such as “Interleukin-1 signaling” and “Interleukin-6/JAK/STAT3 signaling” throughout disease compared to healthy controls.DiscussionEarly on, COVID-19 patients had elevated antiviral responses and suppressed heme metabolism processes compared to non-COVID-19 severe sepsis patients, although both had similar underlying immune dysfunction. However, after one week in the ICU, these diseases became indistinguishable on a gene expression level. These findings highlight the importance of early antiviral treatment for COVID-19, the potential for heme-related therapeutics, and consideration of immunomodulatory therapies for both diseases to treat shared immune dysfunction.

【 授权许可】

Unknown   
Copyright © 2023 An, Baghela, Zhang, Falsafi, Lee, Trahtemberg, Baker, dos Santos and Hancock