Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV-2 Infection.

Area of Science:

• Immunology
• Nephrology
• Genomics

Background:

• Acute kidney injury (AKI) is a frequent complication of SARS-CoV-2 infection, often leading to persistent kidney dysfunction.
• The specific transcriptomic alterations and long-term consequences of AKI severity in COVID-19 remain incompletely understood.

Purpose of the Study:

• To investigate the transcriptomic and proteomic signatures associated with AKI severity in hospitalized SARS-CoV-2 patients.
• To explore the relationship between these molecular profiles and long-term kidney function changes post-discharge.

Main Methods:

• Bulk RNA sequencing of peripheral blood mononuclear cells (PBMCs) and proteomic analysis were performed on SARS-CoV-2 patients.
• Functional enrichment analysis was compared with historical sepsis-AKI data.
• Associations between molecular signatures and estimated glomerular filtration rate (eGFR) changes were examined.

Main Results:

• Severe AKI (stage 2/3) in SARS-CoV-2 patients was associated with significant differential gene expression compared to controls and mild AKI.
• Key pathways implicated in severe AKI include unfolded protein response, cellular stress, and inflammation, with specific links to mitochondrial dysfunction and endoplasmic reticulum stress.
• A 30% functional overlap was observed between COVID-19-associated AKI and sepsis-related AKI transcriptomics. Long-term kidney function decline correlated with disruptions in carbohydrate metabolism, mitochondrial function, and inflammatory responses.

Conclusions:

• Severe AKI in SARS-CoV-2 infection is characterized by mitochondrial dysfunction and ER stress.
• The shared pathways with sepsis-AKI suggest potential for broadly applicable therapeutic strategies.
• Long-term kidney dysfunction is significantly influenced by cellular energy metabolism and immune response dysregulation.