Impact of Peripheral Mitochondrial DNA Level on Immune Response after COVID-19 Vaccination

Background: The efficacy of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is reported to be low in the elderly, partially owing to immunosenescence induced by a decrease in mitochondrial DNA (mtDNA). We aimed to evaluate the association between mtDNA levels in peripheral leukocytes and immune response against the SRAS-CoV-2 vaccine.Methods: A total of 210 participants (median age 79.5 years, 147 women) consisted of 83 nursing home residents or inpatients of long-term care units older than 60 years (Frail group), 70 outpatients more aged than 60 years (Robust group), and 57 younger than 60 years (Young group), was analyzed. Anti-spike IgG antibody (IgG(S)) titers were serially evaluated from before the first vaccination to six months after the third vaccination. We measured mtDNA levels in 45 elderly and cell-mediated immunity against SARS-CoV-2 in 22 elderly two months after the third vaccination.Findings: IgG(S) titers were consistently higher in the Robust group than in the Frail group. Significant but weak positive correlations were found between mtDNA levels and IgG(S) titers one and two months after the second vaccination (r=0.41 and 0.34, P<0.01 and P=0.02, respectively). In addition, a significant positive correlation was found between mtDNA levels and cell-mediated immunity (r=0.50 and P=0.02).Interpretation: Our data indicate that mtDNA levels in peripheral leukocytes are positively associated with vaccine-induced immunity. Further studies for therapeutic approaches to maintaining mtDNA levels can provide critical insights into immunosenescence in the elderly. Funding: There was no funding source for this study.Declaration of Interests: None.Ethics Approval: This study was carried out in accordance with the principles of the Declaration of Helsinki, as revised in 2008. This study was approved by the Haradoi Hospital institutional ethics review committee prior to data collection (Approval No. 2020-08), and all participants provided written informed consent prior to enrollment.