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

Overview

Journal Aging Dis

Specialty Geriatrics

Date 2024 Feb 20

PMID 38377022

Authors

Tiziana Casoli

Anna Rita Bonfigli

Mirko Di Rosa

Belinda Giorgetti

Marta Balietti

Robertina Giacconi

Maurizio Cardelli

Francesco Piacenza

Francesca Marchegiani

Fiorella Marcheselli

Rina Recchioni

Roberta Galeazzi

Salvatore Vaiasicca

Adrianapia Maria Lamedica

Alessia Fumagalli

Letizia Ferrara

Fabrizia Lattanzio

Affiliations

Soon will be listed here.

Abstract

COVID-19 remains a serious concern for elderly individuals with underlying comorbidities. SARS-CoV-2 can target and damage mitochondria, potentially leading to mutations in mitochondrial DNA (mtDNA). This study aimed to evaluate single nucleotide substitutions in mtDNA and analyze their correlation with inflammatory biomarkers in elderly COVID-19 patients. A total of 30 COVID-19 patients and 33 older adult controls without COVID-19 (aged over 65 years) were enrolled. mtDNA was extracted from buffy coat samples and sequenced using a chip-based resequencing system (MitoChip v2.0) which detects both homoplasmic and heteroplasmic mtDNA variants (40-60% heteroplasmy) and allows the assessment of low-level heteroplasmy (<10% heteroplasmy). Serum concentrations of IL-6, IFN-α, TNF-α and IL-10 were determined in patients by a high-sensitivity immunoassay. We found a higher burden of total heteroplasmic variants in COVID-19 patients compared to controls with a selective increment in ND1 and COIII genes. Low-level heteroplasmy was significantly elevated in COVID-19 patients, especially in genes of the respiratory complex I. Both heteroplasmic variant burden and low-level heteroplasmy were associated with increased levels of IL-6, TNF-α, and IFN-α. These findings suggest that SARS-CoV-2 may induce mtDNA mutations that are related to the degree of inflammation.

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