Association of inflammatory mediators with mitochondrial DNA mutations in geriatric COVID-19 patients

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 (aged over 65 years) were enrolled. mtDNA was extracted from buffy coat samples and sequenced using a chip-based resequencing system (Affymetrix MitoChip v2.0) which detects both homoplasmic and heteroplasmic mtDNA mutations, and allows the assessment of low-level heteroplasmy. Serum concentration 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 mutation 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 mutation burden and low-level heteroplasmy were associated with increased levels of IL-6, TNF-α, and IFN-α. The study population comprised elderly individuals with COVID-19 (n=30, experimental group) and age-matched controls (n=33). Blood samples were collected from individuals who were admitted to the IRCCS INRCA Hospital, Ancona, Italy, and were enrolled in either the Report-Age COVID (experimental patients) or Report-Age (control subjects) projects, respectively. The aim of the Report-Age COVID project is to provide a deeper understanding of COVID-19 disease in elderly patients (≥ 65 years). The experimental subjects were COVID-19 positive cases as confirmed by the detection of SARS-CoV-2 RNA in nasal/oropharyngeal swabs while controls were COVID-19 negative elderly subjects. Demographic and anamnestic data, biochemical and hematological variables, information on treatments, comorbidities, and survival were collected in a retrospective manner and anonymized before release.