Sex Differences in Energy Sensing, Inflammatory State, and Mitochondrial Biogenesis in Geriatric Post-COVID-19 Patients

Viral infections including, respiratory viruses such as the SARS-CoV-2, cause mitochondrial dysfunction and exacerbate systemic inflammation. In the present study, sex differences were investigated in patients who have recovered from the acute phase of infection regardless of whether they have ongoing symptoms (post-COVID-19 condition). Peripheral blood mononuclear cells (PBMCs) and plasma samples were collected from hospitalized geriatric patients following their PCR-confirmed negative result for SARS-CoV-2infection. The inflammatory state was assessed by measuring the expression of inflammatory markers using real-time PCR and ELISA. Furthermore, the expression of oxidative, and mitochondrial markers along with metabolic sensors, i.e., AMPK and Sirt1, was examined. The metabolic sensor AMPK was activated (pAMPK/AMPK ratio) only in post-COVID-19 women and was accompanied by women-specific elevation of circulating TNF-α levels in plasma and upregulation of pro-inflammatory mediators IL-1β and IL-18 in their PBMCs. The expression of the antioxidant SOD2 and its acetylation were reduced in PBMCs obtained from male post-COVID-19 patients, whereas SOD2 was hyperacetylated in women. The NRF1 expression was notably upregulated in post-COVID-19 female PBMCs. In addition, the mitochondrial genes cox1 and nd4 were upregulated in post-COVID-19 female patients, whereas, the expression of Sirt1, Sirt3, and TFAM remained unchanged in all studied groups. In summary, the present study revealed a women-specific elevation of inflammatory markers associated with increased AMPK activity and acetylation of mitochondrial SOD2.