The COVID-19 pandemic has drawn the attention of many researchers to the interaction between pathogen and host genomes. Over the last two years, numerous studies have been conducted to identify the genetic risk factors that predict COVID-19 severity and outcome. However, such an analysis might be complicated in cohorts of limited size and/or in case of limited breadth of genome coverage. In this work, we tried to circumvent these challenges by searching for candidate genes and genetic variants associated with a variety of quantitative and binary traits in a cohort of 840 COVID-19 patients from Russia. While we found no gene- or pathway-level associations with the disease severity and outcome, we discovered eleven independent candidate loci associated with quantitative traits in COVID-19 patients. Out of these, the most significant associations correspond to rs1651553 in MYH14p = 1.4 × 10⁻⁷), rs11243705 in SETX (p = 8.2 × 10⁻⁶), and rs16885 in ATXN1 (p = 1.3 × 10⁻⁵). One of the identified variants, rs33985936 in SCN11A, was successfully replicated in an independent study, and three of the variants were found to be associated with blood-related quantitative traits according to the UK Biobank data (rs33985936 in SCN11A, rs16885 in ATXN1, and rs4747194 in CDH23). Moreover, we show that a risk score based on these variants can predict the severity and outcome of hospitalization in our cohort of patients. Given these findings, we believe that our work may serve as proof-of-concept study demonstrating the utility of quantitative traits and extensive phenotyping for identification of genetic risk factors of severe COVID-19.

The formation of biobanks in the structure of scientific and treatment and diagnostic institutions with prospects for interregional integration is a fundamental link in monitoring and predicting diseases of various origins, creating and testing highly effective diagnostics, and developing novel therapeutic agents. Aim . To describe standard operating procedures and principles for the formation of bioresource collections (BRC) in medical institutions with biobanking. Material and methods . The data of scientific and practical biomedical projects using BRC obtained from patients with genetic, multifactorial and infectious diseases in St. Petersburg and Surgut are presented. As of September 2022, the BRC collected on the basis of the Pediatric Research and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency includes biosamples from 1619 patients, and the BRC collected in the Medical Institute of Surgut State University includes biosamples from 450 patients and healthy individuals of different sex and age. The selection of biosamples from apparently healthy individuals and patients with various diseases can serve as a strategically important resource for future research in terms of etiology, epidemiology, the development of regulatory environment and scales, innovations in the development of diagnostic approaches and treatment of the Russian population.

Cardiovascular diseases (CVD) are a leading cause of mortality in many countries worldwide. Genetic testing is an integral part of CVD prevention. The most common hereditary diseases in the practice of a cardiologist are cardiomyopathy and channelopathy (arrhythmogenic syndromes), as well as familial hypercholesterolemia, which causes a high risk of atherosclerosis and coronary heart disease (CHD). The total carrier frequency of pathogenic variants is 1:100. Timely genetic diagnosis is necessary for conditions that can lead to sudden cardiac death (for example, long QT syndrome, Brugada syndrome, arrhythmogenic cardiomyopathies). Pharmacogenetic testing is also important in cardiology, since it allows taking into account the role of genetic factors in the formation of a response to therapy. Incorporating individual patient characteristics can increase efficiency and minimize the likelihood of complications. The design of modern targeted cardiopanels must necessarily take into account monogenic and oligogenic forms of dyslipidemia and cardiovascular pathologies, polymorphic markers associated with a violation of the lipid spectrum of blood plasma and the early development of CVD in a particular population, as well as a minimum set of pharmacogenetic markers according to modern recommendations for clinical pharmacologists. In this review we provide a justification for the optimal design of such a panel for use in medical practice and scientific research.

Human herpes virus 6A (HHV-6A) is able to integrate into the telomeric and subtelomeric regions of human chromosomes representing chromosomally integrated HHV-6A (ciHHV-6A). The integration starts from the right direct repeat (DR_R) region. It has been shown experimentally that perfect telomeric repeats (pTMR) in the DR_R region are required for the integration, while the absence of the imperfect telomeric repeats (impTMR) only slightly reduces the frequency of HHV-6 integration cases. The aim of this study was to determine whether telomeric repeats within DR_R may define the chromosome into which the HHV-6A integrates. We analysed 66 HHV-6A genomes obtained from public databases. Insertion and deletion patterns of DR_R regions were examined. We also compared TMR within the herpes virus DR_R and human chromosome sequences retrieved from the Telomere-to-Telomere consortium. Our results show that telomeric repeats in DR_R in circulating and ciHHV-6A have an affinity for all human chromosomes studied and thus do not define a chromosome for integration.

Purpose: To characterize clinical and laboratory features of infectious mononucleosis (IM) of EBV and HHV-6 etiology among children. Material and methods. A single-center prospective study was performed at Pediatric Research and Clinical Center for Infectious Diseases in 2021 — 2022, which included 84 patients with IM EBV (n = 40), HHV-6 (n = 11), EBV + HHV-6 (n = 33). Methods of laboratory diagnostics were clinical, biochemical blood tests, qualitative and quantitative PCR of blood (whole blood, plasma) to herpesvirus 4—6 types. Results. Patients with EBV IM were significantly older than children with HHV-6 IM and EBV + + HHV-6 IM (р ≤ 0,004). The main complaint of patients was fever (median 39,0°С, Q1—Q3 38,5—39,3°С). Nasal stuffiness (93%), tonsillitis (86%), peripheral cervical lymphadenopathy (100%) dominated among clinical manifestations in all groups. Splenomegaly was noted more rarely than hepatomegaly in children. There were no significant differences in the level of leukocytes among patients (р > 0,05). Increased values of lymphocytes, atypical mononuclear cells, hepatic cytolysis syndrome were characteristic of EBV-monoinfection (р ≤ 0,007). On the contrary, level of neutrophils was significantly higher in the HHV-6 IM group. Genotype HHV-6B was detected in 100% of cases. Assay of EBV viral load showed following: this indicator in plasma (р = 0,0008) and whole blood (р = 0,028) in EBV patients was significantly higher than among EBV + HHV-6 IM. A direct moderate correlation was found between viral loads in different human fluids (r = 0,413, р < 0,05). Conclusions. The results emphasize the importance of clinical and etiological diagnosis, including HHV-6 determination, for the well-timed registration of children with IM and their coverage with regular medical check-up.

Inflammatory bowel diseases (IBD) and acute graft-versus-host disease (GVHD) are associated with persistent intestinal dysfunction preceded by gut bacterial dysbiosis. There are limited data on intestinal bacteriophages in these conditions. The aim of the present work was to detect associations between dominant intestinal bacteria by means of 16S rRNA gene sequencing, and some clinically significant viruses detected with a customized primer panel for NGS-based study. The clinical group included patients with Crohn’s disease (IBD, n = 9), or GVHD (n = 6) subjected to fecal microbiota transplantation (FMT) from healthy donors. The stool specimens were taken initially, and 5 times post-FMT until day 120. Using NGS approach, we have found a higher abundance of Proteobacterota phylum in GVHD, especially, at later terms post-FMT. Moreover, we found an early increase of Klebsiella and E. coli/Shigella abundance in GVHD, along with decreased relative content of Faecalibacterium. Upon evaluation of intestinal phageome, the relative amount of Caudoviricetes class was higher in GVHD. A significant correlation was found between Proteobacteria and Caudoviricetes, thus suggesting their association during the post-FMT period. Moreover, the relative amounts of five Caudoviricetes phage species showed distinct correlations with Klebsiella and Enterococcus ratios at different terms of FMT. In conclusion, parallel use of 16S rRNA gene sequencing and targeted NGS viral panel is a feasible and useful option for tracing specific viral strains in fecal microbiota. The developed array of viral primers may be extended to detect other phages infecting the clinically relevant bacteria.