The Rs17713054 and Rs1800629 Polymorphisms of Genes Lztfl1 and Tnfare Associated with Covid-19 Severity

Both genetic and non-genetic factors are responsible for high interindividual variability in response to SARS-CoV-2. Despite the fact that multiple genetic polymorphisms have been identified as risk factors of severe COVID-19, such polymorphisms are still insufficiently studied in the Russian population. The study was aimed to identify genetic determinants associated with severe COVID-19 in the sample of patients from the Russian Federation. The correlation of the rs17713054 polymorphism in gene LZTFL1 and rs1800629 polymorphism in gene TNF (tumor necrosis factor) with the COVID-19 severity was assessed. DNA samples obtained from 713 patients (324 males and 389 females) aged 18-95 with COVID-19 of varying severity were analyzed. The rs1800629 polymorphism of gene TNF (OR = 1.5;p = 0.02) and rs17713054 polymorphism of gene LZTFL1 (OR = 1.60;p = 0.0043) were identified as risk factors of severe disease. The TNF polymorphism rs1800629 and LZTFL1 polymorphism rs17713054 could be considered as potential predictive biomarkers. The rs17713054 G > A polymorphism was strongly associated with severe disease. In the future the findings may provide the basis for the development of test-systems for prediction of the risk of severe viral respiratory diseases.

Association of HLA Class I Genotype with Mortality in Patients with Diabetes Mellitus and COVID-19.

Numerous studies showed that diabetes mellitus (DM) increases the risk of death from COVID-19 by five times. It is generally accepted that the high lethality of COVID-19 against the background of DM is due to the main complications of this disease: micro- and macroangiopathies, as well as heart and kidney failure. In addition, it was shown that acute respiratory viral infection increases the production of interferon gamma, increases muscle resistance to insulin, and modulates the activity of effector CD8+ T cells. The ability of CD8+ T cells to recognize SARS-CoV-2-infected cells depends not only on humoral factors but also on individual genetic characteristics, including the individual set of major histocompatibility complex class I (MHC-I) molecules. In this study, the relationship of the MHC-I genotype of patients with DM aged less than 60 years with the outcome of COVID-19 was studied using a sample of 222 patients. It was shown that lethal outcomes of COVID-19 in patients with DM are associated with the low affinity of the interaction of an individual set of MHC-I molecules with SARS-CoV-2 peptides.

THE RS17713054 AND RS1800629 POLYMORPHISMS OF GENES LZTFL1 AND TNF ARE ASSOCIATED WITH COVID-19 SEVERITY

Both genetic and non-genetic factors are responsible for high interindividual variability in response to SARS-CoV-2. Despite the fact that multiple genetic polymorphisms have been identified as risk factors of severe COVID-19, such polymorphisms are still insufficiently studied in the Russian population. The study was aimed to identify genetic determinants associated with severe COVID-19 in the sample of patients from the Russian Federation. The correlation of the rs17713054 polymorphism in gene LZTFL1 and rs1800629 polymorphism in gene TNF (tumor necrosis factor) with the COVID-19 severity was assessed. DNA samples obtained from 713 patients (324 males and 389 females) aged 18-95 with COVID-19 of varying severity were analyzed. The rs1800629 polymorphism of gene TNF (OR = 1.5;p = 0.02) and rs17713054 polymorphism of gene LZTFL1 (OR = 1.60;p = 0.0043) were identified as risk factors of severe disease. The TNF polymorphism rs1800629 and LZTFL1 polymorphism rs17713054 could be considered as potential predictive biomarkers. The rs17713054 G > A polymorphism was strongly associated with severe disease. In the future the findings may provide the basis for the development of test-systems for prediction of the risk of severe viral respiratory diseases.

Relationship of Covid-19 Severity with SARS-CoV-2 NS8 Protein Mutations Depending on Virus Strain.

In mid-2021, the Delta strain of SARS-CoV-2 caused the third wave of the COVID-19 pandemic. Huge efforts have been devoted to studying the effect of its mutations on the effectiveness of neutralizing antibodies. Much less attention was paid to the individual features of the presentation of its peptides by molecules of the major histocompatibility complex class I (MCHC-I). In this study, the correlation of the HLA-I genotype of patients under the age of 60 years with the severity of COVID-19 caused by the two most common variants of the SARS-CoV-2 Delta strain in the summer of 2021: AY.122 and B.1.617.2 was studied. Analysis of the severity of the course of COVID-19 revealed a more severe course of the disease caused by the AY.122 variant. Comparison of the mutation profile of the two most common variants of the Delta strain showed that that the G8R mutation in the NS8 protein makes the greatest contribution to the ability of MHC-I to present viral peptides. Given that the NS8 protein is able to suppress the maturation of MHC-I molecules, the appearance of a mutation in one of its immunogenic epitopes could make a significant contribution to the prevalence of the AY.122 variant in the Russian population.

[ORGANIZATION OF GENOMIC SURVEILLANCE FOR SARS-CoV-2 WITHIN THE MOSCOW CITY HEALTH DEPARTMENT].

An important goal of COVID-19 surveillance is to detect outbreaks using modern molecular epidemiology techniques based on methods to decode the full genome of the virus, since rapidly evolving RNA viruses, which include SARS-CoV-2, are constantly accumulating changes in their genomes. In addition to using these changes to identify the different virus lines spreading in the population, the availability of sequence information is very important. It will allow the identification of altered variants that may be more transmissible, cause more severe forms of disease, or be undetectable by existing diagnostic test systems. The global scientific community is particularly interested in changes in the spike protein (S-protein, Spike) because they are responsible for binding and penetration into the host cell, lead to false-negative results in diagnostic tests, and affect transmission rates, health outcomes, therapeutic interventions, and vaccine efficacy.Genomic surveillance uses next-generation sequencing (NGS) applications and makes data on the full genome of the virus available. These methods offer new means to detect variants that differ phenotypically or antigenically. This approach promotes earlier prediction as well as effective strategies to mitigate and contain outbreaks of SARS-CoV-2 and other new viruses long before they spread worldwide.Today, molecular typing of strains is playing an increasingly important role in this process, as it makes it possible to identify samples that share a common molecular «fingerprint¼.