Role of genetic variants and host polymorphisms on COVID-19: From viral entrance mechanisms to immunological reactions

Abstract

Coronavirus disease 2019 (COVID-19), caused by a highly pathogenic emerging virus, is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Knowledge regarding the pathogenesis of this virus is in infancy; however, investigation on the pathogenic mechanisms of the SARS-CoV-2 is underway. In COVID-19, one of the most remarkable characteristics is the wide range of disease manifestation and severity seen across individuals of different ethnic backgrounds and geographical locations. To effectively manage COVID-19 in the populations, beyond SARS-CoV-2 detection, serological response assessment, and analytic techniques, it is critical to obtain knowledge about at-risk individuals and comprehend the identified variations in the disease's severity in general and also in the populations' levels. Several factors can contribute to variation in disease presentation, including population density, gender and age differences, and comorbid circumstances including diabetes mellitus, hypertension, and obesity. Genetic factors presumably influence SARS-CoV-2 infection susceptibility. Besides this, COVID-19 has also been linked with a higher risk of mortality in men and certain ethnic groups, revealing that host genetic characteristics may affect the individual risk of death. Also, genetic variants involved in pathologic processes, including virus entrance into cells, antiviral immunity, and inflammatory response, are not entirely understood. Regarding SARS-CoV-2 infection characteristics, the present review suggests that various genetic polymorphisms influence virus pathogenicity and host immunity, which might have significant implications for understanding and interpreting the matter of genetics in SARS-CoV-2 pathogenicity and customized integrative medical care based on population investigation.

Keywords: ACE2; COVID-19; SARS-CoV-2; TMPRSS2; genetic diversity; polymorphism.

Figure 1

Diversity of type I IFN production and life‐threatening COVID‐19 pneumonia. It has been demonstrated that variants at the TLR3‐ and IRF7‐dependent type I IFN immunity are related to life‐threatening COVID‐19 pneumonia and asymptomatic infection. COVID‐19, coronavirus disease 2019; IRF7, interferon regulatory factor 7; IFN, interferon; TLR3, toll‐like receptor 3 (TLR3)

Figure 2

ACE2 polymorphism and effects on SARS‐CoV‐2 entrance and outcomes. It has been found that the AA genotype of the rs2285666 is mediated to higher ACE2 expression that causes more virus attachment and can affect the infection course. Besides this, the GG genotype of this polymorphism is medicated to higher expression of CCL2, a chemokine that regulates the formation of chemotaxis and inflammatory mediators from macrophages and monocytes. ACE2, angiotensin‐converting enzyme 2; CCL2, C‐C Motif Chemokine Ligand 2