Urine-based multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS

Molecular Medicine

Short Report

Karsten Suhre¹  Jan Krumsiek²  Elisa Benedetti²  Richa Batra²  Kelsey Chetnik²  Mustafa Buyukozkan²  Will Simmons³  Katherine L. Hoffman³  Rie Uni⁴  Edwin Patino⁴  Mary E. Choi⁴  Oleh M. Akchurin⁵  Sergio Alvarez-Mulett⁶  Luis G. Gómez-Escobar⁶  Augustine M. K. Choi⁶  Edward Schenck⁶  Soo Jung Cho⁶  William Whalen⁶  Frank Schmidt⁷ 

[1] Bioinformatics Core, Weill Cornell Medicine –Qatar, Qatar Foundation, Doha, Qatar;Department of Physiology and Biophysics, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, Weill Cornell Medicine, 10021, New York, NY, USA;Division of Biostatistics, Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA;Division of Nephrology and Hypertension, Joan and Sanford I. Weill Department of Medicine, New York, NY, USA;Division of Pediatric Nephrology, Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA;New York-Presbyterian Hospital, New York, NY, USA;Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY, USA;Proteomics Core, Weill Cornell Medicine –Qatar, Qatar Foundation, Doha, Qatar;

关键词: COVID-19;    Acute respiratory distress syndrome (ARDS);    Multi-omic;    Mortality signature;    Network-based;    Computational analysis;    Metabolomics;    Proteomics;    Mitochondrial dysfunction;   

DOI  :  10.1186/s10020-023-00609-6

 received in 2022-09-29, accepted in 2023-01-11,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAcute respiratory distress syndrome (ARDS), a life-threatening condition during critical illness, is a common complication of COVID-19. It can originate from various disease etiologies, including severe infections, major injury, or inhalation of irritants. ARDS poses substantial clinical challenges due to a lack of etiology-specific therapies, multisystem involvement, and heterogeneous, poor patient outcomes. A molecular comparison of ARDS groups holds the potential to reveal common and distinct mechanisms underlying ARDS pathogenesis.MethodsWe performed a comparative analysis of urine-based metabolomics and proteomics profiles from COVID-19 ARDS patients (n = 42) and bacterial sepsis-induced ARDS patients (n = 17). To this end, we used two different approaches, first we compared the molecular omics profiles between ARDS groups, and second, we correlated clinical manifestations within each group with the omics profiles.ResultsThe comparison of the two ARDS etiologies identified 150 metabolites and 70 proteins that were differentially abundant between the two groups. Based on these findings, we interrogated the interplay of cell adhesion/extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis through a multi-omic network approach. Moreover, we identified a proteomic signature associated with mortality in COVID-19 ARDS patients, which contained several proteins that had previously been implicated in clinical manifestations frequently linked with ARDS pathogenesis.ConclusionIn summary, our results provide evidence for significant molecular differences in ARDS patients from different etiologies and a potential synergy of extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis. The proteomic mortality signature should be further investigated in future studies to develop prediction models for COVID-19 patient outcomes.

【 授权许可】

CC BY   
© The Author(s) 2023

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