Molecular epidemiology of SARS-CoV-2 in Mongolia, first experience with nanopore sequencing in lower- and middle-income countries setting.

BACKGROUND: Coronavirus disease (COVID-19) has had a significant impact globally, and extensive genomic research has been conducted on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage patterns and its variants. Mongolia's effective response resulted in low prevalence until vaccinations became available. However, due to the lack of systematically collected data and absence of whole genome sequencing capabilities, we conducted a two-stepped, nationally representative molecular epidemiologic study of SARS-CoV-2 in Mongolia for 2020 and 2021. METHODS: We used retrospective analysis of stored biological samples from November 2020 to October 2021 and a variant-specific real-time reverse transcription polymerase chain reaction (RT-PCR) test to detect SARS-CoV-2 variants, followed by whole genome sequencing by Nanopore technology. Samples were retrieved from different sites and stored at -70°C deep freezer, and tests were performed on samples with cycle threshold <30. RESULTS: Out of 4879 nucleic acid tests, 799 whole genome sequencing had been carried out. Among the stored samples of earlier local transmission, we found the 20B (B.1.1.46) variant predominated in the earlier local transmission period. A slower introduction and circulation of alpha and delta variants were observed compared to global dynamics in 2020 and 2021. Beta or Gamma variants were not detected between November 2020 and September 2021 in Mongolia. CONCLUSIONS: SARS-CoV-2 variants of concerns including alpha and delta were delayed in circulation potentially due to public health stringencies in Mongolia. We are sharing our initial experience with whole genome sequencing of SARS-CoV-2 from Mongolia, where sequencing data is sparse.

Mongolia health situation: based on the Global Burden of Disease Study 2019.

BACKGROUND: Over the past few decades, economic, political, and social changes have directly and indirectly affected the health of the Mongolian population. To date, no comprehensive analysis has been conducted on the burden of diseases in this country. Thus, we aimed to describe the leading causes of death and disabling conditions and their trends between 1990 and 2019 in the Mongolian population. METHODS: We used the data from the Global Burden of Disease (GBD) 2019 study. In the current study, we examined life expectancy at birth, healthy life expectancy, the 20 leading causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted-life-years (DALYs), and the contribution of major risk factors to DALYs in Mongolia. FINDINGS: The life expectancy at birth in Mongolia has gradually increased since 1995 and reached 63.8 years for men and 72.7 for women in 2019. The highest increase in the age-standardised death rate between 1990 and 2019 occurred in alcohol use disorders (628.6%; 95% UI 10.0-1109.6) among men, and in liver cancer (129.1%; UI 65.3-222.4) among women. Ischaemic heart disease and stroke showed the highest rates of death, YLLs, and DALYs among both men and women. In 2019, the highest age-standardised rates of DALYs were attributable to high systolic blood pressure and dietary risks. INTERPRETATION: Although Mongolia saw substantial improvements across many communicable diseases, maternal and neonatal disorders, and under-5 mortality between 1990 and 2019, non-communicable diseases remained leading causes of mortality. The mortality from the most preventable causes such as injury, alcohol use, and dietary risks remain substantially high, suggesting that individual and social efforts are needed to tackle these diseases. Our analyses will support the development of policy priorities and action plans in multiple sectors to improve the overall health of the Mongolian population. FUNDING: Bill & Melinda Gates Foundation.

Bestatin, an inhibitor for aminopeptidases, modulates the production of cytokines and chemokines by activated monocytes and macrophages.

The aim of this study was to clarify the effect of bestatin, an aminopeptidase inhibitor, on the production of cytokines from peripheral blood monocytes and alveolar macrophages (AM). Human monocytes isolated from peripheral blood of healthy volunteers were incubated with or without lipopolysaccharide (LPS) in the presence or absence of bestatin. AM obtained from patients with sarcoidosis were incubated in the presence or absence of bestatin. The concentration of cytokines in the culture supernatant was determined by enzyme-linked immunosorbent assay. The expression of mRNA was determined by reverse transcription polymerase chain reaction. Bestatin suppressed the production and expression of proinflammatory cytokines and chemokines, interleukin (IL)-6, CXCL8/IL-8, CCL3/macrophage inflammatory protein (MIP)-1alpha by LPS-stimulated monocytes. The mean percentage of the inhibition of IL-6, CXCL8/IL-8, CCL3/MIP-1alpha by bestatin at a concentration of 50 microg/mL was 71.2%, 29.7% and 61.0%, respectively. On the other hand, bestatin increased the production and mRNA expression of IL-10 by LPS-stimulated monocytes. The treatment with bestatin significantly inhibited the production of IL-6 and CXCL8/IL-8 by AM from patients with sarcoidosis. The data presented here indicate that bestatin suppresses the production of the pro-inflammatory cytokines and stimulates the anti-inflammatory cytokine by activated human monocytes. This study suggests that bestatin may be useful as an anti-inflammatory agent in various inflammatory diseases.

Cathepsin G: the significance in rheumatoid arthritis as a monocyte chemoattractant.

Human cathepsin G (EC 3.4.21.20) has been reported to have the in vitro chemotactic activity for human monocytes. In this study, we examined the role of cathepsin G in monocyte involvement in joint inflammation of rheumatoid arthritis (RA) as a monocyte chemoattractant. Eighteen patients with RA and four patients with osteoarthritis (OA) were used in this study. Thiobenzylester substrate, Succ-Phe-Leu-Phe-S-Bzl, was used to measure the activity of cathepsin G in synovial fluids. Monocyte migration induced by cathepsin G and synovial fluids was assessed by a 48-well microchemotaxis chamber technique. Immunohistochemical staining was performed to determine the cellular origin of cathepsin G in RA synovial tissue. A very low activity of cathepsin G was detected in synovial fluids from patients with OA. On the other hand, significantly increased activity of cathepsin G was detected in patients with RA when compared with the value of OA patients. A considerable monocyte chemotactic activity was detected in the synovial fluid of RA patients, and the activity was partially decreased by the treatment with inhibitors for cathepsin G, alpha1-antichymotrypsin and phenylmethylsulfonyl fluoride. The activity of cathepsin G was significantly correlated with the neutrophil counts in synovial fluids and the concentration of interleukin-6. Immunohistochemical studies showed that cathepsin G was strongly expressed by synovial lining cells, and weakly expressed by macrophages and neutrophils in synovial tissues. This study indicates that the monocyte chemotactic activity of cathepsin G may have a role in the pathogenesis of RA synovial inflammation.

Defensins- and cathepsin G-ANCA in systemic lupus erythematosus.

In this study, we examined the content of antineutrophil cytoplasmic antibodies (ANCA) against defensins and cathepsin G in sera from systemic lupus erythematosus (SLE) patients and their significance in estimating the activity of SLE. Defensins- and cathepsin G-ANCA in sera from 28 patients with SLE, eight patients with rheumatoid arthritis (RA) and eight patients with microscopic polyangitis (mPA) were measured by ELISA. Significantly increased defensins- and cathepsin G-ANCA were found in sera of patients with SLE and mPA when compared with the value of normal controls. Though significantly higher defensins- and cathepsin G-ANCA were detected in both active and inactive SLE patients, the value in active SLE patients was significantly higher than inactive SLE patients. After the therapy with high dose of prednisolone, the serum level of defensins- and cathepsin G-ANCA was decreased, and this decrease was sustained for at least 16 weeks. This study suggests that defensins- and cathepsin G-ANCA may serve as useful markers of the disease activity of SLE.