**Abstract**

The DNA sequences are different between the distinct individuals and these variations produce the species genetic diversity. SARS-CoV-2 virus is a zoonotic SARS-like coronavirus that spreads globally, causing the COVID-19 pandemic disease. The immune response genes are the most various and different in the human genome, correlating with infectious diseases. Genetic variants in the angiotensinconverting enzyme 2 (ACE2) receptor, TMPRSS2, HO-1, BCL11A, and CYP2D6 are predicted to either encourage or inhibit the interaction with the viral proteins and subsequently contribute to coronavirus genetic risk factors. The genetic susceptibility to SARS-CoV-2 was investigated by analyzing different genes' polymorphisms such as ACE2 and TMPRSS2, HO-1, and BCL11A. A specific genetic susceptibility to COVID-19 was found through different populations in TMPRSS2, ACE2, HO-1, and BCL11A genes. Particularly, ACE2 gene polymorphisms were shown to be correlated with pulmonary and cardiovascular conditions by modifying the angiotensinogen-ACE2 system, which recommends the possible explanations of COVID-19 susceptibility based on genetic diversity. Moreover, the COVID-19 treatment could be complicated by such genetic polymorphisms. In conclusion, a good characterization of functional polymorphisms and the host genetics can assist in identifying the pathophysiology of the disease pathway to stratify the risk evaluation and to personalize the treatment procedures.

**Keywords:** gene polymorphisms, infectious diseases, host genetics, SARS-CoV-2, TMPRSS2, HO-1, ACE-2, BCL11A, coronavirus, COVID-19
