The trans-omics landscape of COVID-19

Area of Science:

• Molecular Biology
• Immunology
• Systems Biology

Background:

• Coronavirus disease 2019 (COVID-19) is a global health crisis.
• The molecular basis of COVID-19, particularly in patients without comorbidities, remains incompletely understood.
• Previous omics studies have provided partial insights into COVID-19's molecular landscape.

Purpose of the Study:

• To investigate the molecular hallmarks of COVID-19 in patients without comorbidities.
• To characterize the trans-omics landscape of peripheral blood from COVID-19 patients with varying disease severity.
• To identify potential therapeutic targets and understand pathophysiology through multi-omics analysis.

Main Methods:

• Collected blood samples from 231 COVID-19 patients, excluding those with selected comorbidities.
• Performed integrative analysis of genomic, transcriptomic, proteomic, metabolomic, and lipidomic profiles.
• Analyzed neutrophil heterogeneity and its correlation with disease severity and immune cell function.

Main Results:

• Identified significant neutrophil heterogeneity between asymptomatic and critically ill COVID-19 patients.
• Observed neutrophil over-activation, arginine depletion, and accumulation of tryptophan metabolites in critical patients.
• Found correlations between these molecular changes and T cell dysfunction in severe COVID-19 cases.

Conclusions:

• The study presents a comprehensive trans-omics landscape of COVID-19 in patients without comorbidities.
• Neutrophil alterations and specific metabolic changes are associated with T cell dysfunction in severe COVID-19.
• These findings may guide the development of novel therapeutic strategies for COVID-19.