Findings collected over two and a half years of the COVID-19 pandemic demonstrated that the level immunity resulting from vaccination and infection is insufficient to stop the circulation of new genetic variants. The short-term decline in morbidity was followed by a steady increase. The early identification of new genetic lineages that will require vaccine adaptation in the future is an important research target. In this study, we summarised data on the variability of genetic line composition throughout the COVID-19 pandemic in Moscow, Russia, and evaluated the virological and epidemiological features of dominant variants in the context of selected vaccine prophylaxes. The prevalence of the Omicron variant highlighted the low effectiveness of the existing immune layer in preventing infection, which points to the necessity of optimising the antigens used in vaccines in Moscow. Logistic growth curves showing the rate at which the new variant displaces the previously dominant variants may serve as early indicators for selecting candidates for updated vaccines, along with estimates of efficacy, reduced viral neutralising activity against the new strains, and viral load in previously vaccinated patients.
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.
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.
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