COVID-19 and demographic factors
Mitochondrial quality is relevant to COVID-19 pathology, which could also be influenced by age and gender. Aging is proven to lead to poor mitochondrial function, which may contribute to the suppression of immunity and altered inflammation (Miller & Allman, 2003; Miller & Allman, 2005; Min, Montecino-Rodriguez & Dorshkind, 2004). Mitochondrial dysfunction induces senescence, which accumulates during aging and contributes to inflammation that also impairs macrophages (Franceschi et al., 2000; Wiley et al., 2016). This could contribute to susceptibility to COVID-19 in older patients. Another relevant principle is that mitochondrial inheritance is maternal. The mitochondria in the egg’s cytoplasm may contain mutations harmful for females, which could be eliminated by quality control mechanisms [114] but may not be eliminated for males. This phenomenon may also impact mitochondrial function and contribute to additional factors where more severe infections could affect males. Additionally, it is claimed that the secondary sex characteristics that men develop come at the cost of immunity, as androgens are anti-inflammatory (Newsome, Flores, Ayala, Gregory & Reichner, 2011; Rettew, Huet-Hudson & Marriott, 2008). Also, in females, the X chromosome mosaicism where X chromosomes are randomly inactivated can also influence the gender difference in viral progression. The ACE-2 receptor encoded by the ACE-2 gene from the X chromosome is responsible for the entry of the SARS-CoV-2 virus. Since the gene is on the X chromosome, it may have a random distribution in cells leading to a heterogeneous expression in females. However, males are capable of expressing only one ACE-2 allele as every cell has the same X chromosome. This may limit infectibility and give females a relative resistance to the infection in comparison to males (Kloc, Ghobrial & Kubiak, 2020). The ties between gender and immune defenses to the mitochondria reveal a potential area of research that could lead to the identification of effective treatment options.