Implications of the Immune Polymorphisms of the Host and the Genetic Variability of SARS-CoV-2 in the Development of COVID-19

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current pandemic affecting almost all countries in the world. SARS-CoV-2 is the agent responsible for coronavirus disease 19 (COVID-19), which has claimed millions of lives around the world. In most patients, SARS-CoV-2 infection does not cause clinical signs. However, some infected people develop symptoms, which include loss of smell or taste, fever, dry cough, headache, severe pneumonia, as well as coagulation disorders. The aim of this work is to report genetic factors of SARS-CoV-2 and host-associated to severe COVID-19, placing special emphasis on the viral entry and molecules of the immune system involved with viral infection. Besides this, we analyze SARS-CoV-2 variants and their structural characteristics related to the binding to polymorphic angiotensin-converting enzyme type 2 (ACE2). Additionally, we also review other polymorphisms as well as some epigenetic factors involved in the immunopathogenesis of COVID-19. These factors and viral variability could explain the increment of infection rate and/or in the development of severe COVID-19.

Rapid SARS-CoV-2 Intra-Host and Within-Household Emergence of Novel Haplotypes

“…At the gene level, G26144T mutation leads to an NS3:G251V amino acid change, which was reported to increase disease severity by 4.4 times [26]. G11083T (NSP6:L37F), on the other hand, has been hypothesized to prevent the fusion of the autophagosomes to the cell lysosomes, affecting viral replication and evasion from cellular immunity [27,28]. Although the short time window of observation hampered the detection of a natural or purifying selection, most of the non-synonymous mutations found in Vo' emerged independently later during the pandemic in different countries (Table S1).…”

“…At the gene level, G26144T mutation leads to an NS3:G251V amino acid change, which was reported to increase disease severity by 4.4 times [26]. G11083T (NSP6:L37F), on the other hand, has been hypothesized to prevent the fusion of the autophagosomes to the cell lysosomes, affecting viral replication and evasion from cellular immunity [27,28]. Studies on Spike:L5F highlighted the increase in the protein folding and assembly of virions [29], as well as the increase in CD8 T cell recognition and killing [30].…”

The Role of Genetic Factors in the Development of Acute Respiratory Viral Infection COVID-19: Predicting Severe Course and Outcomes

“…In this study, polymorphic markers in genes, the activity of which was associated with the COVID-19 pathogenesis, were analyzed. When creating the research protocol, modern data obtained by scientists from different countries in the process of studying image-recognizing receptors and signaling pathways for immune response development were used [8][9][10]. When forming the list of markers, preference was given to genetic variants in the non-coding regions of genes (5 and 3 untranslated regions, as well as introns).…”

Analysis of Gene Single Nucleotide Polymorphisms in COVID-19 Disease Highlighting the Susceptibility and the Severity towards the Infection

“…The overall damages caused by the hyper-expression of proinflammatory cytokines and interleukins, such as IL-6, may facilitate a factual decrease in the level of vitamin D due to the presence of SNPs at the level of the VDR gene. The reduced presence of vitamin D due to SNPs’ main expression sequences was often found together with a reduced functionality immune responses and decreased renal activity, low eGFR, and an increased mortality risk in patients with preexisting lung disorders and heart failure [ 52 , 53 , 54 , 55 ].…”