The SARS-CoV-2 pandemic has claimed approximately 18.2 million lives globally. Historical infectious agents have influenced human genotype evolution, affecting mitochondrial DNA (mtDNA) and its encoded components.
Mitochondrial haplogroups (HG) serve as genetic markers reflecting accumulated variations in mtDNA through generations due to maternal inheritance. These markers allow for ancestry tracking and classification into different haplogroups. Variations in HG can lead to amino acid changes in oxidative phosphorylation (OxPhos) subunits, which are crucial for cellular metabolism regulation.
Most genetic studies on infectious disease susceptibility have focused on the immune system. However, evidence suggests that mitochondrial haplogroups influence survival during sepsis, particularly regarding individuals' ability to tolerate increased body temperatures.
A recent study published in Communications Biology identified specific genetic variants in the mtDNA of the European population that may offer protection against severe COVID-19 forms. It reveals that the mitochondrial HV branch (HGs H, V, and HV) acts as a protective factor against SARS-CoV-2 severity, independent of general genetic background, comorbidities, age, or sex.
The study analyzed data from over 14,300 patients in the SCOURGE cohort, finding that individuals with certain genetic variants, especially those associated with haplogroup HV, exhibited a lower likelihood of developing severe symptoms. These variants are found in mtDNA, which is inherited exclusively from the mother and plays a crucial role in energy production and inflammatory response.
Research on mitochondrial haplogroups has indicated that haplogroup H provides advantages during pandemics and epidemics. For example, studies have documented higher survival rates in patients with HG H compared to those with other HGs in intensive care unit sepsis situations.
Patients with HG H can tolerate higher body temperatures, suggesting that fever might be a factor in the observed survival differences. This recent study confirms that haplogroups significantly influence SARS-CoV-2 severity, with the HV branch playing a particularly protective role.
Despite medical advancements reducing the relationship between susceptibility, severity, and survival in infectious diseases, these effects remain relevant today. The studied HG markers are prevalent in human populations, not diminishing oxidative phosphorylation system efficiency under normal physiological conditions. However, in extreme situations like hyperthermia, minor differences in respiratory complex stability could critically affect disease outcomes.
Previous studies have indicated that HG markers linked to HG H, such as 7028C, offer protection against severe forms of COVID-19. The findings from this multivariate model, based on extensive patient cohort data, provide robust evidence of mitochondrial HGs as modulatory factors in the risk of developing severe disease, irrespective of patients' genetic background, comorbidities, age, or sex.
From an evolutionary perspective, these results underscore the significance of genotype H and its influence on the oxidative phosphorylation system's function, highlighting its role in defending against infectious pathogens.