Association of Inflammatory Mediators with Mitochondrial DNA Variants in Geriatric COVID-19 Patients

Area of Science:

• Mitochondrial biology
• Virology
• Immunology

Background:

• COVID-19 poses significant risks to elderly individuals, especially those with comorbidities.
• SARS-CoV-2 infection can impact cellular mitochondria, potentially causing mutations in mitochondrial DNA (mtDNA).

Purpose of the Study:

• To investigate single nucleotide substitutions in mtDNA within elderly COVID-19 patients.
• To analyze the correlation between mtDNA variants and inflammatory biomarkers in this demographic.

Main Methods:

• Sequencing of mtDNA from buffy coat samples in 30 COVID-19 patients and 33 controls using a chip-based resequencing system (MitoChip v2.0).
• Assessment of both homoplasmic and heteroplasmic mtDNA variants, including low-level heteroplasmy (<10%).
• Measurement of serum inflammatory markers (IL-6, IFN-α, TNF-α, IL-10) via high-sensitivity immunoassay.

Main Results:

• COVID-19 patients exhibited a higher burden of total heteroplasmic variants compared to controls, with notable increases in ND1 and COIII genes.
• Significantly elevated low-level heteroplasmy was observed in COVID-19 patients, particularly in genes of respiratory complex I.
• Both heteroplasmic variant burden and low-level heteroplasmy were associated with elevated IL-6, TNF-α, and IFN-α levels.

Conclusions:

• SARS-CoV-2 infection may induce mtDNA mutations in elderly individuals.
• The observed mtDNA mutations, especially low-level heteroplasmy, are linked to the severity of the inflammatory response in COVID-19 patients.