Genetic Risk Factors for the Development of COVID-19 Coronavirus Infection

Abstract

The COVID-19 coronavirus pandemic has spread to 215 countries around the world and caused tens of millions of infections and more than a million deaths worldwide. In the midst of COVID-19 infection, it is extremely important to identify new protein and gene targets that may be highly sensitive diagnostic and prognostic markers of the severity and outcome of the disease for combating this pandemic. Identification of individual genetic predisposition allows personalizing programs of medical rehabilitation and therapy. It has now been shown that the transmissibility and severity of COVID-19 infection can be affected by gene variants in both the human body ( ACE2 , HLA-B*4601 , Fc γ RIIA , MBL , TMPRSS2 , TNFA, IL6, blood group A antigen, etc.) and the virus itself ( ORF8 in RNA polymerase, ORF6 in RNA primase, S, N, E proteins). The presence of mutations in the proteins of the virus can change the affinity and specificity for the binding of targeted drugs to them, being the molecular basis of individual differences in the response of the human body to antiviral drugs and/or vaccines. The review summarizes the data on the variants of the genomes of the coronavirus and humans associated with an individual predisposition to an increased or decreased risk of transmission, severity, and outcome of COVID-19 infection. Targeted drugs and vaccines being developed for the therapy of COVID-19 infection are briefly reviewed.

Genetic Association between ACE2 (rs2285666 and rs2074192) and TMPRSS2 (rs12329760 and rs2070788) Polymorphisms with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors

“…The genotype distributions deviated from that expected based on the Hardy–Weinberg equilibrium ( p < 0.01) which has been also extensively found in previous studies [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Overall, no significant differences in long-COVID symptoms were observed depending on the genotypes of any SNP: ACE2 rs2285666 ( Table 2 ), ACE2 rs2074192 ( Table 3 ), TMPRSS2 rs12329760 ( Table 4 ), TMPRSS2 rs2070788 ( Table 5 ).…”

“…Among different genes potentially involved in COVID-19, the association between the polymorphisms of renin-angiotensin-aldosterone system-related genes, i.e., ACE2 and TMPRSS2 and the severity of COVID-19 disease have been the most investigated [ 3 ]. In fact, ACE2 rs2285666 and TMPRSS2 rs12329760 single nucleotide polymorphisms (SNPs) have been investigated in several studies, although their results are controversial.…”

“…Most studies investigating the role of these ACE2 or TMPRSS2 SNPs have focused on the risk of being infected or the severity of COVID-19 disease in the acute phase [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. No study has investigated the potential association between polymorphisms of ACE2 (rs2285666 and rs2074192) and TMPRSS2 (rs12329760 and rs2070788) genes and the presence of long-term post-COVID symptoms.…”

The association of COVID-19 severity and susceptibility and genetic risk factors: A systematic review of the literature

“…Recently, it caused a global pandemic with deleterious effects on a large scale leading to unprecedented damage and high number of deaths worldwide ( Ferreira Caceres, M.M., Sosa, J.P., Lawrence, J.A., Sestacovschi, C., Tidd-Johnson, A., Rasool, M.H.U., Gadamidi, V.K., Ozair, S., Pandav, K., Cuevas-Lou, C., Parrish, M., Rodriguez, I., Fernandez, J.P., Division of Research & Academic Affairs, Larkin Community Hospital, South Miami, Florida, USA, Department of Medicine, American University of Antigua, Coolidge, Antigua, Family Medicine, Larkin Community Hospital Palm Springs Campus, Hialeah, Florida, USA, Family Medicine, Larkin Community Hospital South Campus, Miami, Florida, USA, Pulmonary Disease and Critical Care Medicine, Larkin Community Hospital Palm Springs Campus, Hilaeah, Florida, USA, 2022 , Go et al, 2020 , Hathaway et al, 2020 , Sarfraz et al, 2021 , Sosa et al, 2021 ). The severity of COVID-19 seems to be affected by various risk factors ( Glotov et al, 2021 ). Heightened risk of COVID-19 associated mortality is seen in about 27-30% of the population suffering from arterial hypertension, 16.2% of the diabetic population, and 5.8% patients with cardiovascular issues ( Glotov et al, 2021 ).…”

“…The severity of COVID-19 seems to be affected by various risk factors ( Glotov et al, 2021 ). Heightened risk of COVID-19 associated mortality is seen in about 27-30% of the population suffering from arterial hypertension, 16.2% of the diabetic population, and 5.8% patients with cardiovascular issues ( Glotov et al, 2021 ). In addition, approximately 60% of the deceased patients are reportedly males ( D’Amico et al, 2021 ).…”