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Svetlana I Kolesnichenko,1,&ast; Irina A Kadyrova,1 Alyona V Lavrinenko,1 Zhibek A Zhumadilova,1 Olga V Avdienko,1 Yelena V Vinogradskaya,2 Yevgeniy A Fominykh,3 Lyudmila G Panibratec,3 Lyudmila L Akhmaltdinova1,4,&ast; 1Shared Resource Laboratory, Research Centre, Karaganda Medical University, Karaganda, Kazakhstan; 2Regional Clinical Hospital of Karaganda, Perinatal Center No. 1, Karaganda, Kazakhstan; 3Regional Clinical Hospital of Karaganda, Perinatal Center No. 2, Karaganda, Kazakhstan; 4National Scientific Cardiac Surgery Center, Nur-Sultan, Kazakhstan&ast;These authors contributed equally to this workCorrespondence: Svetlana I Kolesnichenko, Shared Resource Laboratory, Research Centre, Karaganda Medical University, 40 Gogol St, Karaganda, 100008, Kazakhstan, Tel +7 702 599 0225, Email kolesnichenko@kgmu.kzPurpose: This study aimed to determine predisposing factors for negative outcome in infants with early neonatal sepsis during COVID-19.Patients and Methods: A prospective cohort study of 172 newborns up to 4 days diagnosed with neonatal sepsis was carried out in Karaganda (Kazakhstan). The microbiological examination was used to identify a causative agent of bloodstream infection. ELISA was performed to determine the total anti-SARS-CoV-2 antibodies. Gestational age, mode of delivery, birth weight, C-reactive protein and procalcitonin levels, comorbidities, type of pathogen, duration of hospitalization and mother’s infection diseases were used for statistical analysis.Results: Mortality in infants with neonatal sepsis was 22% (38/172). Anti-SARS-CoV-2 antibodies were detected in 68.3% of the newborns. Culture-negative ELBW infants have a 5.3-fold higher risk of death (p< 0.001). Low gestational age and a shorter period of hospitalization were statistically associated with fatality. CRP is generally higher in deceased children (p=0.002). Necrotizing enterocolitis (p< 0.001), pneumonia (p=0.009) and anemia (p=0.016) were significantly associated with negative outcome. And, 31.4% of the infants with sepsis had positive blood cultures. The leading cause of sepsis in newborns was CoNS – 57%.Conclusion: During COVID-19 pandemic neonatal sepsis mortality was associated with low birth weight, gestational age, and comorbidities as in non-pandemic time. The relationship between COVID-19 in the mother and neonatal mortality was not found. However, anti-SARS-CoV-2 antibodies were detected in more than half of newborns.Keywords: neonatal sepsis, preterm infants, mortality, coagulase-negative staphylococci, COVID-19

An Orthomyxoviridae Alphainfluenza virus Influenza A virus strain, A/Kazakhstan/Flu-H11-6/2022(H1N1 ), was isolated in Karaganda, Central Kazakhstan during a study of acute respiratory infections among hospital inpatients in 2022. Here, we present the complete genome sequence of this strain.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) could aid the diagnosis of acute respiratory infections (ARIs) owing to its affordability and high-throughput capacity. MALDI-TOF MS has been proposed for use on commonly available respiratory samples, without specialized sample preparation, making this technology especially attractive for implementation in low-resource regions. Here, we assessed the utility of MALDI-TOF MS in differentiating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vs non-COVID acute respiratory infections (NCARIs) in a clinical lab setting in Kazakhstan. Nasopharyngeal swabs were collected from inpatients and outpatients with respiratory symptoms and from asymptomatic controls (ACs) in 2020-2022. PCR was used to differentiate SARS-CoV-2+ and NCARI cases. MALDI-TOF MS spectra were obtained for a total of 252 samples (115 SARS-CoV-2+, 98 NCARIs, and 39 ACs) without specialized sample preparation. In our first sub-analysis, we followed a published protocol for peak preprocessing and machine learning (ML), trained on publicly available spectra from South American SARS-CoV-2+ and NCARI samples. In our second sub-analysis, we trained ML models on a peak intensity matrix representative of both South American (SA) and Kazakhstan (Kaz) samples. Applying the established MALDI-TOF MS pipeline "as is" resulted in a high detection rate for SARS-CoV-2+ samples (91.0%), but low accuracy for NCARIs (48.0%) and ACs (67.0%) by the top-performing random forest model. After re-training of the ML algorithms on the SA-Kaz peak intensity matrix, the accuracy of detection by the top-performing support vector machine with radial basis function kernel model was at 88.0%, 95.0%, and 78% for the Kazakhstan SARS-CoV-2+, NCARI, and AC subjects, respectively, with a SARS-CoV-2 vs rest receiver operating characteristic area under the curve of 0.983 [0.958, 0.987]; a high differentiation accuracy was maintained for the South American SARS-CoV-2 and NCARIs. MALDI-TOF MS/ML is a feasible approach for the differentiation of ARI without specialized sample preparation. The implementation of MALDI-TOF MS/ML in a real clinical lab setting will necessitate continuous optimization to keep up with the rapidly evolving landscape of ARI.IMPORTANCEIn this proof-of-concept study, the authors used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and machine learning (ML) to identify and distinguish acute respiratory infections (ARI) caused by SARS-CoV-2 versus other pathogens in low-resource clinical settings, without the need for specialized sample preparation. The ML models were trained on a varied collection of MALDI-TOF MS spectra from studies conducted in Kazakhstan and South America. Initially, the MALDI-TOF MS/ML pipeline, trained exclusively on South American samples, exhibited diminished effectiveness in recognizing non-SARS-CoV-2 infections from Kazakhstan. Incorporation of spectral signatures from Kazakhstan substantially increased the accuracy of detection. These results underscore the potential of employing MALDI-TOF MS/ML in resource-constrained settings to augment current approaches for detecting and differentiating ARI., Competing Interests: The authors declare no conflict of interest.

COVID-19 vaccines have played a critical role in controlling the COVID-19 pandemic. Although overall considered safe, COVID-19 vaccination has been associated with rare but severe thrombotic events, occurring mainly in the context of adenoviral vectored vaccines. A better understanding of mechanisms underlying vaccine-induced hypercoagulability and prothrombotic state is needed to improve vaccine safety profile. We assessed changes to the biomarkers of endothelial function (endothelin, ET-1), coagulation (thrombomodulin, THBD and plasminogen activator inhibitor, PAI) and platelet activation (platelet activating factor, PAF, and platelet factor 4 IgG antibody, PF4 IgG) within a three-week period after the first (prime) and second (boost) doses of Gam-Covid-Vac, an AdV5/AdV26-vectored COVID-19 vaccine. Blood plasma collected from vaccinees (n = 58) was assayed using ELISA assays. Participants were stratified by prior COVID-19 exposure based on their baseline SARS-CoV-2-specific serology results. We observed a significant post-prime increase in circulating ET-1, with levels sustained after the boost dose compared to baseline. ET-1 elevation following dose 2 was most pronounced in vaccinees without prior COVID-19 exposure. Prior COVID-19 was also associated with a mild increase in post-dose 1 PAI. Vaccination was associated with elevated ET-1 up to day 21 after the second vaccine dose, while no marked alterations to other biomarkers, including PF4 IgG, were seen. A role of persistent endothelial activation following COVID-19 vaccination warrants further investigation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Turmukhambetova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To study the role of biological markers of immunothrombosis and polymorphisms of cytokine genes IL2, IL6, IL10 and their influence on the severity of COVID-19 in a Kazakh population., Methods: A total of 301 patients of Kazakh nationality with a confirmed diagnosis of COVID-19 participated in the retrospective study, including 142 patients with severe and 159 with a mild course. Single nucleotide polymorphisms IL2R rs1801274, IL6 rs2069840, and IL10 rs1800872 were genotyped by real-time PCR. Activated partial thromboplastin time, normalized ratio, prothrombin index, prothrombin time, fibrinogen prothrombin time, fibrinogen, D-dimer, and C-reactive protein analysis were also conducted., Results: The average age of patients with severe COVID-19 is higher than of patients with mild COVID-19 (p = 0.03). The findings showed that fibrinogen, D-dimer, and C-reactive protein were significantly greater in the group of patients with severe COVID-19 (p = 0.0001). A very strong correlation between the severity of COVID-19 with the D-dimer and C-reactive protein (p = 0.9) (p = 0.02) was found., Conclusion: The results of our study confirm that D-dimer, fibrinogen, and CRP are biomarkers of inflammation and hypercoagulation that serve as predictors of immunothrombosis affecting the severity of COVID-19. D-dimer is also associated with IL10 rs1800872 gene polymorphism in the Kazakh population with severe COVID-19., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yessenbayeva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Our study was carried out to characterize respiratory tract microbiota in patients with "COVID-like pneumonia" in Kazakhstan and analyze differences between COVID-19 positive and negative groups. Sputum samples were collected from hospitalized patients, ≥18 years old, in the three cities in Kazakhstan with the highest COVID-19 burden in July 2020. Isolates were identified by MALDI-TOF MS. Susceptibility testing was performed by disk diffusion. We used SPSS 26 and MedCalc 19 for statistical analysis. Among 209 patients with pneumonia, the median age was 62 years and 55% were male. RT-PCR-confirmed SARS-CoV-2 cases were found in 40% of patients, and 46% had a bacterial co-infection. Co-infection was not associated with SARS-CoV-2 RT-PCR test results, but antibiotic use was. The most frequent bacteria were Klebsiella pneumoniae (23%), Escherichia coli (12%), and Acinetobacter baumannii (11%). Notably, 68% of Klebsiella pneumoniae had phenotypic evidence of extended-spectrum beta-lactamases in disk diffusion assays, 87% of Acinetobacter baumannii exhibited resistance to beta-lactams, and >50% of E. coli strains had evidence of ESBL production and 64% were resistant to fluoroquinolones. Patients with a bacterial co-infection had a higher proportion of severe disease than those without a co-infection. The results reinforce the importance of using appropriate targeted antibiotics and effective infection control practices to prevent the spread of resistant nosocomial infections.

Background: Monoclonal antibody (mAb) therapy is a promising antiviral intervention for Coronovirus disease (COVID-19) with a potential for both treatment and prophylaxis. However, a major barrier to implementing mAb therapies in clinical practice is the intricate nature of mAb preparation and delivery. Therefore, here, in a pre-clinical model, we explored the possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mAb delivery using a mAb-expressing encapsulated cell system., Methods: Murine G-8 myoblasts were transfected with plasmids coding for the heavy and light chains of CR3022, a well-characterized SARS-CoV-2 mAb that targets the Spike receptor binding domain (RBD), and then encapsulated into alginate microcapsules. The microcapsules were then intraperitoneally implanted into immunocompetent (C57/BL6J) mice and changes in circulating CR3022 titres were assessed. The in vitro and ex vivo characterization of the mAb was performed using western blotting, RBD ELISA, and microscopy., Results: Transfected G-8 myoblasts expressed intact CR3022 IgG at levels comparable to transfected HEK-293 cells. Cell encapsulation yielded microcapsules harbouring approximately 1000 cells/capsule and sustainably secreting CR3022 mAb. Subsequent peritoneal G-8 microcapsule implantation into mice resulted in a gradual increase of CR3022 concentration in blood, which by day 7 peaked at 1923 [1656-2190] ng/mL and then gradually decreased ~4-fold by day 40 post-implantation. Concurrently, we detected an increase in mouse anti-CR3022 IgG titers, while microcapsules recovered by day 40 post-implantation showed a reduced per-microcapsule mAb production., Summary: We demonstrate here that cell microencapsulation is a viable approach to systemic delivery of intact SARS-CoV-2 mAb, with potential therapeutic applications that warrant further exploration.

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., (© 2022. The Author(s).)

COVID-19 exposure in Central Asia appears underestimated and SARS-CoV-2 seroprevalence data are urgently needed to inform ongoing vaccination efforts and other strategies to mitigate the regional pandemic. Here, in a pilot serologic study we assessed the prevalence of SARS-CoV-2 antibody-mediated immunity in a multi-ethnic cohort of public university employees in Karaganda, Kazakhstan. Asymptomatic subjects (n = 100) were recruited prior to their first COVID-19 vaccination. Questionnaires were administered to capture a range of demographic and clinical characteristics. Nasopharyngeal swabs were collected for SARS-CoV-2 RT-qPCR testing. Serological assays were performed to detect spike (S)-reactive IgG and IgA and to assess virus neutralization. Pre-pandemic samples were used to validate the assay positivity thresholds. S-IgG and -IgA seropositivity rates among SARS-CoV-2 PCR-negative participants (n = 100) were 42% (95% CI [32.2-52.3]) and 59% (95% CI [48.8-69.0]), respectively, and 64% (95% CI [53.4-73.1]) of the cohort tested positive for at least one of the antibodies. S-IgG titres correlated with virus neutralization activity, detectable in 49% of the tested subset with prior COVID-19 history. Serologically confirmed history of COVID-19 was associated with Kazakh ethnicity, but not with other ethnic minorities present in the cohort, and self-reported history of respiratory illness since March 2020. Overall, SARS-CoV-2 exposure in this cohort was ~15-fold higher compared to the reported all-time national and regional COVID-19 prevalence, consistent with recent studies of excess infection and death in Kazakhstan. Continuous serological surveillance provides important insights into COVID-19 transmission dynamics and may be used to better inform the regional public health response., Competing Interests: The authors have declared that no competing interests exist.

Understanding immunoregulation in newborns can help to determine the pathophysiology of neonatal sepsis and will contribute to improve the diagnosis, prognosis, and treatment and remains an urgent and unmet medical need to understand hyperinflammation or hypoinflammation associated with sepsis in newborns. This study included infants (up to 4 days old). The "sepsis" criteria was a positive blood culture. C-reactive protein demonstrates a strong dependence on the pathogen etiology. Therefore, its diagnostic odds ratio in Gram-positive bacteremia was 2.7 and the sensitivity was 45%, while Gram-negative was 15.0 and 81.8%, respectively. A neutrophil-lymphocyte ratio above 1 and thrombocytopenia below 50 ∗ 10 9 cells/L generally do not depend on the type of pathogen and have a specificity of 95%; however, the sensitivity of these markers is low. nCD64 demonstrated good analytical performance and was equally discriminated in both Gram (+) and Gram (-) cultures. The sensitivity was 87.5-89%, and the specificity was 65%. The HLA-DR and programmed cell death protein study found that activation-deactivation processes in systemic infection is different at points of application depending on the type of pathogen: Gram-positive infections showed various ways of activation of monocytes (by reducing suppressive signals) and lymphocytes (an increase in activation signals), and Gram-negative pathogens were most commonly involved in suppressing monocytic activation. Thus, the difference in the bacteremia model can partially explain the problems with the high variability of immunologic markers in neonatal sepsis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Lyudmila Akhmaltdinova et al.)

The study was conducted to search for polymorphisms located in the 10th chromosome associated with colorectal adenocarcinoma in representatives of the Kazakhstan population. Study was performed with 282 colorectal cancer (CRC) patients and 159 controls. Genotyping of SNPs was performed by QuantStudio 12K Flex PCR. For four significant SNPs inheritance model analysis was performed. Increasing risk of CRC was noted for rs10795668 in log-additive model (OR = 1.45, 95% CI: 1.05-1.99, p = 0.023); for rs1035209 in log-additive model (OR = 1.79, 95% CI: 1.18-2.72, p = 0.003); for rs11190164 in log-additive model (OR = 1.67, 95% CI: 1.17-2.38, p = 0.004). Decreasing risk of CRC was noted for rs10506868 in log-additive model (OR = 0.56, 95% CI: 0.37-0.85, p = 0.006). We detected SNPs that are associated with CRC risk in the Kazakhstan population., Competing Interests: CONFLICTS OF INTEREST The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflicts of interest., (Copyright: © 2021 Kolesnikova et al.)

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., (Copyright © 2020 Yegorov, Babenko, Kozhakhmetov, Akhmaltdinova, Kadyrova, Nurgozhina, Nurgaziyev, Good, Hortelano, Yermekbayeva and Kushugulova.)

Colorectal cancer is one of the most often diagnosed malignant tumors. In Kazakhstan, high incidence of CC is registered along with other oncology diseases. Despite a significant progress in the disease treatment achieved lately, CC is still one of the major reasons of mortality due to oncologic pathologies. To study the samples MilliplexMap HumanCirculationBiomarker panel in blood serum was used. XMap-based Fluorescence immunoassay was implemented, which comprised magnetic-bead-based simultaneous fluorescence detection of IL-6, IL-8, MIF, FGF-2, SCF, TGF, TNF, TRAIL analytes. Proinflammatory biomarker concentration detection at different CC stages allows to reveal the dynamics of inflammatory response of the organism to tumor and to use them (biomarkers) in further diagnostic and forecast in particular in CC. As a result of our study, it was found that IL-6, which showed the brightest reaction, due to its range of change and considerable shift already in the I stage can be recommended as a component of a complex diagnostic panel. Such markers as FGF2 and MIF also have a role in CC early stage detection., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Termedia.)

Following publication of the original article [1], the authors notified us of a typing error in spelling Dr. Yeleuov's name. The original publication has been corrected.

Background: To date, surgeons and physicians have found positive results treating metabolic syndrome with surgical and non-surgical weight loss therapies. The purpose of this study was to evaluate changes in telomere length in patients with metabolic syndrome after weight loss., Methods/design: This study is a three-arm randomized controlled trial. The first group is composed of patients who have undergone stapleless bypass surgery (one anastomosis gastric bypass with an obstructive stapleless pouch and anastomosis (LOAGB-OSPAN)). The second group of patients underwent standard gastric bypass surgery (laparoscopic mini-gastric bypass-one anastomosis gastric bypass (LMGB-OAGB). The patients in the third group received non-surgical weight loss therapy, including a hypocaloric diet with energy restriction (- 500 kcal/day). The aim is to compare changes-telomere length, body mass index, comorbidities, and quality of life-in patients with metabolic syndrome after weight loss., Discussion: To the best of our knowledge, this is the first randomized study to simultaneously compare the effects of surgical and non-surgical weight loss on changes in telomere length. It could provide a solution to the growing problem of metabolic syndrome. Normalization of the body mass index results in improvements in the health of patients with metabolic syndrome., Trial Registration: ClinicalTrials.gov, NCT03667469 . Registered on 11 September 2018.

Objectives. To develop a mathematical model of stroke probability in the individual patient and social groups. Material and methods. A large amount of laboratory research was performed in a hospital of Karaganda city. Correlations between the event "stroke"and 35 risk factors were determined. A regression model "stroke-risk factors"was developed using logistic regression method. Results and сonclusions. The equations obtained in the study allow to predict the probability of stroke. Since the regression equation is inherently close to the determined one, it can be differentiated. First derivative of the probability of each of the risk factors allowed us to determine the rate of increase of probability. This provision is new.