Background The earliest coronavirus disease-2019 (COVID-19) cases in Central Asia were announced in March 2020 by Kazakhstan. Despite the implementation of aggressive measures to curb infection spread, gaps remain in the understanding of the clinical and epidemiologic features of the regional pandemic. Methods We did a retrospective, observational cohort study of patients with laboratory-confirmed COVID-19 hospitalized in Kazakhstan between February and April 2020. We compared demographic, clinical, laboratory and radiological data of patients with different COVID-19 severities on admission. Logistic regression was used to assess factors associated with disease severity and in-hospital death. Whole-genome SARS-CoV-2 analysis was performed in 53 patients. Findings Of the 1072 patients with laboratory-confirmed COVID-19 in March-April 2020, the median age was 36 years (IQR 24–50) and 484 (45%) were male. On admission, 683 (64%) participants had asymptomatic/mild, 341 (32%) moderate, and 47 (4%) severe-to-critical COVID-19 manifestation; 20 in-hospital deaths (1•87%) were reported by 5 May 2020. Multivariable regression indicated increasing odds of severe disease associated with older age (odds ratio 1•05, 95% CI 1•03-1•07, per year increase; p<0•001), the presence of comorbidities (2•34, 95% CI 1•18-4•85; p=0•017) and elevated white blood cell count (WBC, 1•13, 95% CI 1•00-1•27; p=0•044) on admission, while older age (1•09, 95% CI 1•06-1•13, per year increase; p<0•001) and male sex (5•63, 95% CI 2•06-17•57; p=0•001) were associated with increased odds of in-hospital death. The SARS-CoV-2 isolates grouped into seven phylogenetic lineages, O/B.4.1, S/A.2, S/B.1.1, G/B.1, GH/B.1.255, GH/B.1.3 and GR/B.1.1.10; 87% of the isolates were O and S sub-types descending from early Asian lineages, while the G, GH and GR isolates were related to lineages from Europe and the Americas. Interpretation Older age, comorbidities, increased WBC count, and male sex were risk factors for COVID-19 disease severity and mortality in Kazakhstan. The broad SARS-CoV-2 diversity suggests multiple importations and community-level amplification predating travel restriction. Funding Ministry of Education and Science of the Republic of Kazakhstan.
We have investigated the diversity and composition of gut microbiotas isolated from AD (Alzheimer's disease) patients (n = 41) and healthy seniors (n = 43) from Nur-Sultan city (Kazakhstan). The composition of the gut microbiota was characterized by 16S ribosomal RNA sequencing. Our results demonstrated significant differences in bacterial abundance at phylum, class, order, and genus levels in AD patients compared to healthy aged individuals. Relative abundance analysis has revealed increased amount of taxa belonging to Acidobacteriota, Verrucomicrobiota, Planctomycetota and Synergistota phyla in AD patients. Among bacterial genera, microbiotas of AD participants were characterized by a decreased amount of Bifidobacterium, Clostridia bacterium, Castellaniella, Erysipelotrichaceae UCG-003, Roseburia, Tuzzerella, Lactobacillaceae and Monoglobus. Differential abundance analysis determined enriched genera of Christensenellaceae R-7 group, Prevotella, Alloprevotella, Eubacterium coprostanoligenes group, Ruminococcus, Flavobacterium, Ohtaekwangia, Akkermansia, Bacteroides sp. Marseille-P3166 in AD patients, whereas Levilactobacillus, Lactiplantibacillus, Tyzzerella, Eubacterium siraeum group, Monoglobus, Bacteroides, Erysipelotrichaceae UCG-003, Veillonella, Faecalibacterium, Roseburia, Haemophilus were depleted. We have also found correlations between some bacteria taxa and blood serum biochemical parameters. Adiponectin was correlated with Acidimicrobiia, Faecalibacterium, Actinobacteria, Oscillospiraceae, Prevotella and Christensenellaceae R-7. The Christensenellaceae R-7 group and Acidobacteriota were correlated with total bilirubin, while Firmicutes, Acidobacteriales bacterium, Castellaniella alcaligenes, Lachnospiraceae, Christensenellaceae and Klebsiella pneumoniae were correlated with the level of CRP in the blood of AD patients. In addition, we report the correlations found between disease severity and certain fecal bacteria. This is the first reported study demonstrating gut microbiota alterations in AD in the Central Asian region.
Background Psoriasis is a chronic inflammatory condition that predominantly affects the skin and is associated with extracutaneous disorders, such as inflammatory bowel disease and arthritis. Changes in gut immunology and microbiota are important drivers of proinflammatory disorders and could play a role in the pathogenesis of psoriasis. Therefore, we explored whether psoriasis in a Central Asian cohort is associated with alterations in select immunological markers and/or microbiota of the gut. Methods We undertook a case-control study of stool samples collected from outpatients, aged 30–45 years, of a dermatology clinic in Kazakhstan presenting with plaque, guttate, or palmoplantar psoriasis ( n = 20), and age-sex matched subjects without psoriasis ( n = 20). Stool supernatant was subjected to multiplex ELISA to assess the concentration of 47 cytokines and immunoglobulins and to 16S rRNA gene sequencing to characterize microbial diversity in both psoriasis participants and controls. Results The psoriasis group tended to have higher concentrations of most analytes in stool (29/47 = 61.7%) and gut IL-1α was significantly elevated (4.19-fold, p = 0.007) compared to controls. Levels of gut IL-1α in the psoriasis participants remained significantly unaltered up to 3 months after the first sampling ( p = 0.430). Psoriasis was associated with alterations in gut Firmicutes , including elevated Faecalibacterium and decreased Oscillibacter and Roseburia abundance, but no association was observed between gut microbial diversity or Firmicutes/Bacteroidetes ratios and disease status. Conclusions Psoriasis may be associated with gut inflammation and dysbiosis. Studies are warranted to explore the use of gut microbiome-focused therapies in the management of psoriasis in this under-studied population.
Sputnik-V (Gam-COVID-Vac) is a heterologous, recombinant adenoviral (rAdv) vector-based, COVID-19 vaccine now used in > 70 countries. Yet there is a shortage of data on this vaccine's performance in diverse populations. Here, we performed a prospective cohort study to assess the reactogenicity and immunologic outcomes of Sputnik-V vaccination in Kazakhstan. COVID-19-free participants (n = 82 at baseline) were followed at day 21 after Sputnik-V dose 1 (rAd5) and dose 2 (rAd26). Self-reported local and systemic adverse events were captured using questionnaires. Blood and nasopharyngeal swabs were collected to perform SARS-CoV-2 diagnostic and immunologic assays. We observed that most of the reported adverse events were mild-to-moderate injection site or systemic reactions, no severe or potentially life-threatening conditions were reported, and dose 1 appeared to be more reactogenic than dose 2. The seroconversion rate was 97% post-dose 1, remaining the same post-dose 2. The proportion of participants with detectable virus neutralization was 83% post-dose 1, increasing to 98% post-dose 2, with the largest relative increase observed in participants without prior COVID-19 exposure. Dose 1 boosted nasal S-IgG and S-IgA, while the boosting effect of dose 2 on mucosal S-IgG, but not S-IgA, was only observed in subjects without prior COVID-19. Systemically, vaccination reduced serum levels of growth regulated oncogene (GRO), which correlated with an elevation in blood platelet count. Overall, Sputnik-V dose 1 elicited both blood and mucosal SARS-CoV-2 immunity, while the immune boosting effect of dose 2 was minimal. Thus, adjustments to the current vaccine dosing regimen are necessary to optimize immunization efficacy and cost-effectiveness. While Sputnik-V reactogenicity is similar to that of other COVID-19 vaccines, the induced alterations to the GRO/platelet axis warrant investigation of the vaccine’s effects on systemic immunology.
Colorectal cancer is a type of oncopathology widespread in Kazakhstan. The genetic component, as well as the possible etiopathogenetic mechanisms, is widely studied. One of the most promising areas is the study of diagnostic and prognostic possibilities of inflammatory biomarkers in patients with different degrees of tumor differentiation. The following biomarkers were included in the study panel: stem cell factor (SCF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF2), interleukin 6 (IL6), interleukin 8 (IL8), macrophage migration inhibitory factor (MIF), soluble Fas (SFAS), soluble Fas ligand (sFASL), transforming growth factor β (TGF), tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand (TRAIL), and programmed death ligand 1 (PD-L1). The data of our study show that most of the basic proinflammatory cytokines are involved in the systemic process and their levels do not depend on the level of tissue differentiation. Serum PD-L1 has shown itself to be a promising marker for tumor growth, which depends on the degree of differentiation.
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