Host genetic factors involved in the susceptibility and severity of COVID-19

Background: SARS-CoV-2 infection ranges from asymptomatic forms to very serious manifestations of COVID-19 that can compromise life. The impact of the COVID-19 pandemic raises the need to identify the risk factors that determine interindividual variability in susceptibility to SARS-CoV-2 infection, pathophysiology and disease progression. Several authors suggest that the genetic component plays a key role in the complex virus-host interaction, where population differences are responsible for such heterogeneity. Method(s): A scoping review of the literature published to date was carried out in order to learn about the biological markers that seem to affect the evolution of the SARS-CoV-2 infection and the genetic polymorphisms of molecules potentially involved in the complex virus-host interaction. Result(s): Numerous evidences indicate that allelic variants of genes encoding molecules working in the early stages of virus-cell interaction or during events that define the immune response of the host, could favor the infection and/or the disease severity by SARS-CoV-2. The ABO blood group seems to play a role in immunopathogenesis, with group O individuals showing a lower risk of being infected with SARS-CoV-2, although other genetic, physiological and metabolic components of the host, such as the differential expression of toll-like receptors, HLA antigens, proinflammatory cytokines, chemokines or other effectors of the innate and acquired immune response would also be participating. Conclusion(s): The success and progression of the viral infection towards the development of clinical manifestations and the severity grade depend largely on the interaction between viral factors and the host's response, as well as seem to be conditioned by epigenetic factors and pre-existing comorbidities. The contribution of the genetic component raises the potential application of targeted preventive strategies, the identification of therapeutic targets and the development of new drugs. Copyright © 2021, Revista Salus. All rights reserved.

Biology and genetic diversity of SARS-CoV-2, the causative agent of COVID-19

The infection generated by SARS-CoV-2 has caused more than 200 million cases and 4.5 million deaths worldwide. SARS-CoV-2 has accumulated mutations that allow it to be classified into different lineages. Some of these lineages have been designated variants by the WHO: under monitoring (VUM), of interest (VOI), or of concern (VOC). Methodology. Different strategies for genomic surveillance of these SARS-CoV-2 variants have been described in each country. In Venezuela, the strategies include the amplification of a fragment of the spike, PCR-RFLP, and sequencing of the complete viral genome, which has allowed us to monitor the introduction of VOCs and VOIs to the country. Results. By October 2021, in Venezuela, the circulation of three VOCs, Alpha, Gamma, and Delta, and the two VOIs (Lambda and Mu) have been described. Globally, the Delta variant predominates in practically all continents except some Latin American countries, although it is estimated that it will soon prevail in the region as well. Discussion. The circulation of variants in the countries is a very dynamic process and Venezuela does not escape from this reality;therefore, it is important to continue genomic surveillance of this virus. Copyright © 2021, Revista Salus. All rights reserved.

Sub-lineages of the Omicron variant of SARS-CoV-2: characteristic mutations and their relation to epidemiological behavior

By the end of 2021, the Omicron variant of SARS-CoV-2, the coronavirus responsible for COVID-19, emerges, causing immediate concern, due to the explosive increase in cases in South Africa and a large number of mutations. This study describes the characteristic mutations of the Omicron variant in the Spike protein, and the behavior of the successive epidemic waves associated to the sub-lineages throughout the world. The mutations in the Spike protein described are related to the virus ability to evade the protec-tion elicited by current vaccines, as well as with possible reduced susceptibility to host proteases for priming of the fusion process, and how this might be related to changes in tropism, a replication enhanced in nasal epithelial cells, and reduced in pulmonary tissue;traits probably associated with the apparent reduced severity of Omicron compared to other variants. © 2022, Instituto de Investigaciones Clinicas. All rights reserved.

Detection of the Omicron variant of SARS-CoV-2 by restriction analysis targeting the mutations K417N and N440K of the spike protein

By the end of 2021, the Omicron variant of concern (VOC) emerges in South Africa. This variant caused immediate concern, due to the explosive increase in cases associated with it and the large number of mutations it exhibits. In this study, the restriction sites that allow detecting the mutations K417N and N440K in the Spike gene are described. This analysis al-lows us to propose a rapid method for the identification of cases infected with the Omicron variant. We show that the proposed methodology can contribute to provide more information on the prevalence and rapid detection of cases of this new VOC. © 2022, Instituto de Investigaciones Clinicas. All rights reserved.

SARS-CoV-2 genetic diversity in Venezuela: predominance of D614G variants and analysis of one outbreak

SARS-CoV-2 is the new coronavirus responsible for COVID-19 disease. The first two cases of COVID-19 were detected in Venezuela on March 13, 2020. The aim of this study was the genetic characterization of Venezuelan SARS-CoV-2 isolates. A total of 7 full SARS-CoV-2 genome sequences were obtained by Sanger sequencing, from patients of different regions of Venezuela, mainly from the beginning of the epidemic. Ten out of 11 isolates (6 complete genomes and 4 partial spike genomic regions) belonged to lineage B, bearing the D614G mutation in the Spike protein. Isolates from the first outbreak that occurred in the Margarita Island harbored an in-frame deletion in its sequence, without amino acids 83-85 of the NSP1 of the ORF1. The search for deletions in 48,635 sequences showed that the NSP1 gene exhibit the highest frequency of deletions along the whole genome. Structural analysis suggests a change in the N-terminal domain with the presence of this deletion. In contrast, isolates circulating later in this island lacked the deletion, suggesting new introductions to the island after this first outbreak. In conclusion, a high diversity of SARS-CoV-2 isolates were found circulating in Venezuela, with predominance of the D614G mutation. The first small outbreak in Margarita Island seemed to be associated with a strain carrying a small deletion in the NSP1 protein, but these isolates do not seem to be responsible for the larger outbreak which started in July.

Biology and evolution of the coronavirus that causes COVID-19

The new coronavirus that causes COVID-19 is called SARS-CoV-2 and belongs to the subgenus Sarbecovirus, like its predecessor SARS-CoV. Bats appear to be the hosts of the ancestral viruses that originated these viruses, through recombination with the virus of an intermediate animal, which might be the pangolin. The virus interacts with the ACE2 receptor (angiotensin converting enzyme 2) and enters the cell by the endocytic pathway, through an early or late endosome. Viral RNA serves as messenger RNA for the translation of the first reading frame and the rest of the messenger RNAs are produced by discontinuous transcription. This peculiarity confers to this viral family a high frequency of recombination, which is associated to the high frequency of species jumping. Viruses belonging to the order Nidovirales are the only known RNA viruses with a polymerase with proof correction capacity;therefore their mutation rate is reduced. However, these genomes appear to be susceptible to be deaminated by cellular enzymes. All these mechanisms of generation of diversity leads to the existence of lineages, including those with the D614G mutation in the spike associated with a higher transmissibility. However, mutations associated with greater severity are not known to date. Just as there are different viral variants, the clinical manifestation of the disease is also highly variable. Some genetic, physiological and metabolic factors are being known that could be determining a more severe clinical presentations, often associated with the immunopathology of this disease.