ObjectiveA critical role in coronavirus disease 2019 (COVID-19) pathogenesis is played by immune dysregulation that leads to a generalized uncontrolled multisystem inflammatory response, caused by overproduction of proinflammatory cytokines, known as “a cytokine storm” (CS), strongly associated with a severe course of disease. The aim of this study is to identify prognostic biomarkers for CS development in COVID-19 patients and integrate them into a prognostic score for CS-associated risk applicable to routine clinical practice.Materials and MethodsThe authors performed a review of 458 medical records from COVID-19 patients (241 men and 217 women aged 60.0 ± 10.0) who received treatment in the St. Petersburg State Budgetary Institution of Healthcare City Hospital 40 (City Hospital 40, St. Petersburg), from Apr. 18, 2020 to Nov. 21, 2020. The patients were split in two groups: one group included 100 patients with moderate disease symptoms; the other group included 358 patients with progressive moderately severe, severe, and extremely severe disease. The National Early Warning Score (NEWS) score was used alongside with clinical assessment, chest computed tomographic (CT) scans, electrocardiography (ECG), and lab tests, like ferritin, C-reactive protein (CRP), interleukin (IL)-6, lactate dehydrogenase (LDH), and D-dimer.ResultsThe basic risk factors for cytokine storms in COVID-19 patients are male gender, age over 40 years, positive test result for replicative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, absolute lymphocyte count, dynamics in the NEWS score, as well as LDH, D-dimer, ferritin, and IL-6 levels. These clinical and instrumental findings can be also used as laboratory biomarkers for diagnosis and dynamic monitoring of cytokine storms. The suggested prognostic scale (including the NEWS score dynamics; serum IL-6 greater than 23 pg/ml; serum CRP 50 mg/L or greater; absolute lymphocyte count less than 0.72 × 109/L; positive test result for replicative coronavirus (SARS-CoV-2) RNA; age 40 years and over) is a useful tool to identify patients at a high risk for cytokine storm, requiring an early onset of anti-inflammatory therapy.

Here we report a pilot-sized study to compare the taxonomic composition of sputum microbiome in 17 newly-diagnosed lung cancer (LC) patients and 17 controls. Another object was to compare the representation of individual bacterial genera and species in sputum with the frequency of chromosomal aberrations in the blood lymphocytes of LC patients and in controls. Both groups were male; average age 56.1 ± 11.5 in patients and 55.7 ± 4.1 in controls. Differences in the species composition of bacterial communities in LC patients and controls were significant (pseudo-F = 1.94; p = 0.005). Increased prevalence in LC patients was detected for the genera Haemophilus and Bergeyella; whereas a decrease was observed for the genera Atopobium, Stomatobaculum, Treponema and Porphyromonas. Donors with high frequencies of chromosomal aberrations had a significant reduction in the microbiome of representatives of the genus Atopobium in the microbiome and a simultaneous increase in representatives of the species Alloprevotella compared to donors with a low level of chromosomal aberrations in lymphocytes. Thus, a comparison of the bacterial composition in the sputum of donors with cytogenetic damages in theirs lymphocytes, warrants further investigations on the potential role of microorganisms in the process of mutagenesis in somatic cells of the host body.

Although high altitude training has been increasingly popular among endurance athletes, the molecular and cellular bases of this adaptation remain poorly understood. We aimed to define the underlying physiological changes and screen for potential biomarkers of adaptation using transcriptional profiling of whole blood. Seven elite female speed skaters were profiled on the 18th day of high-altitude adaptation. Whole blood RNA-seq before and after an intense 1 h skating bout was used to measure gene expression changes associated with exercise. In order to identify the genes specifically regulated at high altitudes, we have leveraged the data from eight previously published microarray datasets studying blood expression changes after exercise at sea level. Using cell type-specific signatures, we were able to deconvolute changes of cell type abundance from individual gene expression changes. Among these were PHOSPHO1, with a known role in erythropoiesis, and MARC1 with a role in endogenic NO metabolism. We find that platelet and erythrocyte counts uniquely respond to altitude exercise, while changes in neutrophils represent a more generic marker of intense exercise. Publicly available data from both single cell atlases and exercise-related blood profiling dramatically increases the value of whole blood RNA-seq for the dynamic evaluation of physiological changes in an athlete’s body.

According to modern classification, there are two forms of inherited ichthyoses: syndromic and non-syndromic, each of them consists of more than ten different nosologies. The commonest types of the ichthyosis are X-linked recessive (prevalence 1/2000–6000 in men) and autosomal dominant, or ichthyosis vulgaris with incomplete penetrance (1/250–1000). The X-linked form is associated with mutations in steroid sulfatase STS gene, it is noteworthy that there is a full deletion of the gene in 90% of cases. Ichthyosis vulgaris is caused by heterozygous mutations in the FLG gene encoding filaggrin. It is important to note that the clinical forms of these diseases are indistinguishable. The aim of this study was to search for pathogenic or likely pathogenic mutations which are associated with various forms of the inherited ichthyosis such as other inherited diseases with similar phenotypic signs. The sequencing was done on a HiSeq 4000 sequencer (Illumina) by paired-end reading (2 × 150 bp). The identified mutation p.Arg2037Ter in the heterozygous condition has been described before in databases as being pathogenic. Also, our patient has a full deletion of the STS gene and it was found that our patient carries two pathogenic mutations which are related to different forms of the inherited ichthyosis.

Цель исследования -оценка эффективности и безопасности фавипиравира для лечения новой коронавирусной инфекции (COVID-19) легкого и среднетяжелого течения.Материал и методы. Проведено открытое рандомизированное многоцентровое клиническое исследование с активным контролем у амбулаторных и госпитализированных пациентов с COVID-19 легкого и сред-

Aim. Using a collection of samples from the biobank ofCityHospital № 40 ofSt. Petersburg, to study the cytokine profile in patients with coronavirus disease 2019 (COVID-19) and sepsis, in comparison with patients with abdominal inflammation and septicemia.Material and methods. The study included serum samples from 181 patients with sepsis and COVID-19 (127 patients with a diagnosis confirmed by polymerase chain reaction (PCR); 54 patients with a negative PCR test, but with a characteristic computed tomographic lung performance) and 47 patients with abdominal sepsis. The content of cytokines was determined using a multiplex immunofluorescence analysis based on the Luminex xMAP technology using the HCYTOMAG60K panel — a soluble CD40 ligand (sCD40L), interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNFα), vascular endothelial growth factor (VEGF). Other laboratory parameters (C-reactive protein (CRP), ferritin, procalcitonin) were taken from patient records. Normality of distribution was assessed by the Shapiro-Wilk test. To compare groups, the Mann-Whitney test for independent samples, Wilcoxon test for dependent samples, and the Kruskal-Wallis test with Bonferroni correction for multiple comparisons were used.Results. In patients with sepsis and COVID-19 infection, no differences in the concentrations of cytokines, ferritin and CRP were found between the groups with detected and not detected virus by PCR test. Based on this, this group was considered homogeneous when studying the cytokine profile. It was shown that in patients with sepsis and COVID-19, significantly higher levels of sCD40L (p<0,0001) and VEGF (p=0,037) and relatively low levels of CRP (p<0,0001), IL-6 (p<0,0001), IL-8 (p<0,0001), TNFα (p<0,00058).Conclusion. These results indicate that sepsis in patients with COVID-19 courses with less elevation in inflammatory cytokine than in abdominal sepsis. At the same time, a critically high level of sCD40L indicates the significant endothelial damage.

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.

We studied the differences in the characteristics of T-cell immunity in clinically healthy volunteers of three groups: “no previous COVID-19, not vaccinated”, “recovered”, and “vaccinated” as well as the relationship between the presence of IFNγ-releasing T cells in response to stimulation with peptide pools overlapping the main S, N, M, ORF3, and ORF7 protein sequences and the presence of IgG to the SARS-CoV-2 S protein. In the “no previous COVID-19, non-vaccinated” group, T cells specific to both S protein and other virus proteins were absent in 95% subjects. In the “recovered from COVID-19” group, T cells specific to the spike protein were present in samples from 39% subjects. In the same group, T-cell immunity to other viral proteins was present in 58% subjects. In vaccinated subjects, specific T cells responding to stimulation with S protein peptides were found in 47% cases and Т cells specific to N, M, ORF3, ORF7 proteins were detected in only 22% subjects.