Variation in COVID-19 mortality rate across populations, polymorphism in genes, and gender-associated genetic patterns

Abstract

A severe onset of COVID-19 leads to death due to respiratory failure and ARDS is the common finding of lung histopathology in different people with different comorbidities. It can invade the nervous system leading to the manifestation of neurological symptoms and brain damage including encephalitis and stroke. Genetic polymorphism, comorbidities, and gender differences is playing a pivotal role in conferring resistance and susceptibility to COVID-19. Despite almost the same ACE2 expression profile in males and females, males have shown a high mortality rate due to higher expression of TMPRSS2 (pivotal for S protein binding) as these genes are androgen responsive. While women have shown higher expression of ADAM17, ADAM10 genes are associated with the shedding of ACE2 receptors and are estrogen-responsive, leading to low levels of membrane-bound ACE2 which is indispensable for SARS-Cov2 entry into the cell. People with blood Groups A, and AB are comparatively more susceptible to COVID-19 than people with blood group O, the reason for the O group is attributed to the presence of Anti A antibodies.