Mitochondrial haplogroups and variants defines differential severity of COVID-19 in the Pakistani population

Mitochondria play a crucial role in cellular functions, including immune responses and their dysfunction is observed in SARS-CoV-2-infected cells. Here we investigated mitochondrial DNA (mtDNA) variations and COVID-19 severity, focusing on potential impact of mitochondrial variants and/or haplogroups. COVID-19 PCR cases (n = 147) and healthy controls (HC; n = 40) were recruited, mt-DNA was amplified, sequenced and analyzed for haplogroups and genetic variations. COVID-19 cases were categorized as Critical severe (CS; n = 40), Moderate (MOD; n = 43) and Asymptomatic/mild (AMD; n = 64) disease. Haplogroup analysis showed major haplogroup M negatively associated with COVID-19 and CS disease. Whereas haplogroup U showed a positive association with CS disease. Haplogroup W was associated with an increased AMD COVID-19. Furthermore, 46 mitochondrial variants significantly associated with the COVID-19 were identified. More importantly mt.5186A > T in ND2 gene with high mutpred score was significantly associated with COVID-19. Overall, mitochondrial DNA variants and haplogroups are associated with COVID-19 and its severity in Pakistani population.