Long-term changes in the phenotype and cytokine production of monocytes in COVID-19 recovered and vaccinated individuals.

Monocytes play a crucial role in the immune response against pathogens. Here, we sought to determine COVID-19 and the vaccine Gam-COVID-Vac induce long-term changes in the phenotype and cytokine production of circulating monocytes. Monocytes were purified from peripheral blood mononuclear cells of healthy donors who had not had COVID-19 or vaccination, who had received two doses of Gam-COVID-Vac, and who had mild/moderate COVID-19 in the last 6 months and evaluated by flow cytometry. To investigate the effect of SARS-CoV-2 proteins, monocytes were cultured for 2 days with or without stimulation with recombinant SARS-CoV-2 S1 and N peptides. Monocytes obtained from vaccinated and recovered individuals showed increased basal expression of HLA-DR, CD63, CXCR2, and TLR7. We also observed an increased frequency of CD63+ classical monocytes in both groups, as well as an increased frequency of HLA-DR+ non-classical monocytes in the COVID-19-recovered group compared to the control group. Monocytes from vaccinated and recovered donors produced higher basal levels of IL-6, IL-1ß, and TNF-α cytokines. Ex vivo stimulation with SARS-CoV-2 antigens induced increased expression of HLA-DR and TLR7 on monocytes obtained from the control group. The challenge with SARS-CoV-2 antigens had no effect on the production of IL-6, IL-1ß, and TNF-α cytokines by monocytes. The acquired data offer compelling evidence of enduring alterations in both the phenotype and functional status of circulating monocytes subsequent to vaccination with Gam-COVID-Vac and mild/moderate COVID-19 infection. At least some of these changes appear to be a consequence of exposure to SARS-CoV-2 S1 and N antigens.

Lethal pulmonary embolism in a pregnant woman with severe acute respiratory syndrome coronavirus-2 receiving prophylactic anticoagulation: a case report.

BACKGROUND: A limited number of studies have described thrombotic complications in pregnant women with COVID-19. Here we report on fatal pulmonary embolism in a pregnant woman with laboratory confirmed SARS-CoV-2 infection. CASE PRESENTATION: A 28-year-old Kazakh woman was hospitalized with muscle pain, dry cough and a temperature of 37.5 °C at the 29th week of gestation. Upon admission, a blood test demonstrated elevated neutrophil-to-lymphocyte ratio, decreased levels of erythrocytes and hemoglobin, as well as prolonged prothrombin and activated partial thromboplastin time. Within 14 days of admission, she experienced respiratory distress and underwent transfer to the intensive care unit, intubation and a cesarean section. The patient received intravenous antibiotics, antiviral medications, systemic corticosteroids and dual anticoagulation with aspirin and enoxaparin. Death outcome was reported on day 18 of illness despite aggressive supportive care. Histological analysis demonstrated that obstruction of the main pulmonary arthery and disseminated intravascular coagulation were the causes of death. CONCLUSIONS: This case demonstrates that in the management of pregnancy and childbirth in patients with suspected or confirmed COVID-19 infection, special attention should be paid to coagulation system parameters and timely appropriate prophylaxis of thromboembolic complications, which has yet to be determined.

Molecular and seroepidemiological investigation of Сoxiella burnetii and spotted fever group rickettsiae in the southern region of Kazakhstan.

Ticks are involved in the circulation of a number of human pathogens, including spotted fever group (SFG) Rickettsia spp. and Coxiella burnetii. Little is known about the occurrence of these microorganisms in the southern region of Kazakhstan. In 2018-2022, a total of 726 ticks were collected from bitten humans, livestock, and vegetation in four oblasts of the southern region of Kazakhstan and subjected to DNA extraction. The overall infection rate of Coxiella spp. and Rickettsia spp. in the ticks was 3.3% (24/726) and 69.9% (300/429), respectively. Phylogenetic analysis of ompA and gltA genes revealed the presence of three pathogenic SFG rickettsiae: Candidatus R. tarasevichiae, R. aeschlimannii and R. raoultii in ticks collected from bitten humans. In addition, Candidatus R. barbariae was detected in six Rhipicephalus turanicus ticks for the first time in Kazakhstan. To determine the seroprevalence of C. burnetii infection, we performed a serological analysis of samples collected from 656 domestic ruminants (cattle, sheep, and goats) in the region. Overall, 23.5% (154/656) of the animals tested were positive for IgG against C. burnetii. Seroprevalence at the herd level was 54% (28/52). Goats (43%; 12/28; odds ratio (OD) = 28.9, p < 0.05) and sheep (31.9%; 137/430; OD = 18.1, p < 0.05) had higher seroprevalence than cattle (2.5%; 5/198). Among the risk factors considered in this study, age (p = 0.003) and the oblast in which the animals were sampled (p = 0.049) were statistically associated with seropostivity for Q fever in sheep, according to the results of multivariate logistic regression analysis. Seroprevalence ranged from 0% to 55.5% in animals in different districts of the southern region of Kazakhstan. Active C. burnetii bacteremia was detected in four of 154 (2.6%) seropositive animals. The data obtained provide strong evidence of the presence of pathogenic rickettsiae and C. burnetii in the southern region of Kazakhstan and emphasize the need to improve epidemiological surveillance in the region.

Myeloid-derived suppressor cells in COVID-19: A review.

Coronavirus disease 2019 (COVID-19) is a potentially life-threatening infection characterized by excessive inflammation, coagulation disorders and organ damage. A dysregulated myeloid cell compartment is one of the most striking immunopathologic signatures of this newly emerged infection. A growing number of studies are reporting on the expansion of myeloid cells with immunoregulatory activities in the periphery and airways of COVID-19 patients. These cells share phenotypic and functional similarities with myeloid-derived suppressor cells (MDSCs), which were first described in cancer patients. MDSCs are a heterogeneous population of pathologically activated myeloid cells that exert immunosuppressive activities against mainly effector T cells. The increased frequency of these cells in COVID-19 patients suggests that they are involved in immune regulation during this infection. In this article, we review the current findings on MDSCs in COVID-19 and discuss the complex role of these cells in the immunopathology of COVID-19.

No Association between the rs1799836 Polymorphism of the Monoamine Oxidase B Gene and the Risk of Autism Spectrum Disorders in the Kazakhstani Population.

Autism spectrum disorders (ASDs) are heterogeneous diseases that are triggered by a number of environmental and genetic factors. The aim of the current study was to investigate an association of the rs1799836 genetic variant of the neurotransmitter-related gene MAOB with ASDs. In total, 262 patients diagnosed with ASDs and their 126 healthy siblings were included in the present study. All individuals represented a Kazakhstani population. The distributions of the rs1799836 genotype were in accordance with the Hardy-Weinberg equilibrium among both cases and controls. No statistically significant differences were found in the allelic distributions of this polymorphism between ASD and control subjects (A/G: for males OR = 1.11, 95% 0.59-2.06, p = 0.75; for females OR = 1.14, 95% 0.70-1.86, p = 0.76). However, the increased score in the overall CARS was significantly associated with the A allele of rs1799836 MAOB for females (OR = 2.31, 95% 1.06-5.04, p = 0.03). The obtained results suggest that the rs1799836 polymorphism of the MAOB gene may have little contribution to the development of ASDs but may be involved in pathways contributing to ASD symptom severity in females. Further large-scale investigations are required to uncover possible relationships between rs1799836 MAOB and ASD progression in a gender-specific manner and their possible application as a therapeutic target.

Chronic Inflammation Contributes to Tumor Growth: Possible Role of L-Selectin-Expressing Myeloid-Derived Suppressor Cells (MDSCs).

Recent data have demonstrated that chronic inflammation is a crucial component of tumor initiation and progression. We previously reported that immature myeloid-derived suppressor cells (MDSCs) with immunosuppressive activity toward effector T cells were expanded in experimental chronic inflammation. We hypothesized that elevated levels of MDSCs, induced by chronic inflammation, may contribute to the progression of tumor growth. Using the Ehrlich carcinoma animal model, we found increased tumor growth in mice with chronic adjuvant arthritis, which was accompanied by a persistent increase in the proportion of splenic monocytic and granulocytic MDSCs expressing CD62L (L-selectin), when compared to tumor mice without adjuvant arthritis. Depletion of inflammation-induced MDSCs resulted in decreased tumor growth. In vitro studies demonstrated that increased expression of CD62L by MDSCs was mediated by TNFα, elevated concentrations of which were found in tumor mice subjected to chronic inflammation. Moreover, the addition of exogenous TNFα markedly enhanced the suppressive activity of bone marrow-derived MDSCs, as revealed by the ability to impair the proliferation of CD8+ T cells in vitro. This study provides evidence that chronic inflammation may promote tumor growth via induction of CD62L expression by MDSCs that can facilitate their migration to tumor and lymph nodes and modulation of their suppressor activity.

The determination of genetic markers of age-related cancer pathologies in populations from Kazakhstan.

Aging associates with a variety of pathological conditions such as cancer, cardiovascular, neurodegenerative, autoimmune diseases, and metabolic disorders. The oncogenic alterations overlap frequently with the genes linked to aging. Here, we show that several aging related genes may serve as the genetic risk factors for cervical and esophagus cancers. In our study, we analyzed samples obtained from 115 patients with esophageal and 207 patients with cervical cancer. The control groups were selected to match the ethnicity and age of cancer patients. We examined the genes involved in the processes of xenobiotics detoxification (GSTM1 and GSTT1), DNA repair (XRCC1 and XRCC3), and cell cycle regulation and apoptosis (CCND1 and TP53). Our study revealed that deletions of GSTT1 and GSTM1 genes or the distinct point mutations of XRCC1 gene are associated with cervical and esophageal cancers. These results will lead to development of screening for detection of individuals susceptible to esophageal and cervical cancers. Introduction of the screening programs will allow the early and effective preventive measures that will reduce cancer incidence and mortality in Kazakhstan.