ABSTRACT
Clinical testing has been the cornerstone of public health monitoring and infection control efforts in communities throughout the COVID-19 pandemic. With the extant and anticipated reduction of clinical testing as the disease moves into an endemic state, SARS-CoV-2 wastewater surveillance (WWS) is likely to have greater value as an important diagnostic tool to inform public health. As the widespread adoption of WWS is relatively new at the scale employed for COVID-19, interpretation of data, including the relationship to clinical cases, has yet to be standardized. An in-depth analysis of the metrics derived from WWS is required for public health units/agencies to interpret and utilize WWS-acquired data effectively and efficiently. In this study, the SARS-CoV-2 wastewater signal to clinical cases (WC) ratio was investigated across seven different cities in Canada over periods ranging from 8 to 21 months. Significant increases in the WC ratio occurred when clinical testing eligibility was modified to appointment-only testing, identifying a period of insufficient clinical testing in these communities. The WC ratio decreased significantly during the emergence of the Alpha variant of concern (VOC) in a relatively non-immunized communitys wastewater (40-60% allelic proportion), while a more muted decrease in the WC ratio signaled the emergence of the Delta VOC in a relatively well-immunized communitys wastewater (40-60% allelic proportion). Finally, a rapid and significant decrease in the WC ratio signaled the emergence of the Omicron VOC, likely because of the variants greater effectiveness at evading immunity, leading to a significant number of new reported clinical cases, even when vaccine-induced community immunity was high. The WC ratio, used as an additional monitoring metric, complements clinical case counts and wastewater signals as individual metrics in its ability to identify important epidemiological occurrences, adding value to WWS as a diagnostic technology during the COVID-19 pandemic and likely for future pandemics.
ABSTRACT
1The COVID-19 pandemic has stimulated wastewater-based surveillance, allowing public health to track the epidemic by monitoring the concentration of the genetic fingerprints of SARS-CoV-2 shed in wastewater by infected individuals. Wastewater-based surveillance for COVID-19 is still in its infancy. In particular, the quantitative link between clinical cases observed through traditional surveillance and the signals from viral concentrations in wastewater is still developing and hampers interpretation of the data and actionable public-health decisions. We present a modelling framework that includes both SARS-CoV-2 transmission at the population level and the fate of SARS-CoV-2 RNA particles in the sewage system after faecal shedding by infected persons in the population. Using our mechanistic representation of the combined clinical/wastewater system, we perform exploratory simulations to quantify the effect of surveillance effectiveness, public-health interventions and vaccination on the discordance between clinical and wastewater signals. We also apply our model to surveillance data from three Canadian cities to provide wastewater-informed estimates for the actual prevalence, the effective reproduction number and incidence forecasts. We find that wastewater-based surveillance, paired with this model, can complement clinical surveillance by supporting the estimation of key epidemiological metrics and hence better triangulate the state of an epidemic using this alternative data source.
ABSTRACT
Objective::To explore the effect and mechanisms of Buyang Huanwu Tang (BYHWT) on atherosclerotic plaque based on regulatory T cells (Treg) and inflammation. Method::Totally 50 ApoE knockout(ApoE-/-)mice aged 8 weeks were randomly divided into model group, low, medium, high-dose BYHWT groups, positive control group, and C57/BL mice were taken as control group. The model group and the BYHWT group were given high-fat diet for 12 weeks, while the control group was given normal diet. After successful modeling, BYHWT groups were given drugs (5, 10, 20 g·kg-1) through intragastric administration, the positive control group was given rapamycin (4 mg·kg-1), while the control group and the model group were given equal doses normal saline through intragastric administration for 4 weeks. Four weeks later, the mice were sacrificed. Manufactured paraffin sections were prepared for the aortic sinus of the heart. The plaque area was evaluated by hematoxylin and eosin (HE) staining, and the number of Treg cells in immunohistochemical staining plaque was detected. Blood was collected from eye canthus of mice, the expression of inflammatory factors in peripheral blood was detected by enzyme-linked immunosorbent assay (ELISA), and the forkhead box P3 (Foxp3) gene expression in peripheral blood was detected by Real-time fluorescent quantitative polymerase chain reaction (PCR). Result::Compared with the control group, the area of atherosclerotic plaques in the model group was significantly increased (P<0.01), the contents of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly increased (P<0.05), and transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) were significantly decreased (P<0.05), and the peripheral blood Fxop3 mRNA expression was decreased (P<0.05). Compared with the model group, the plaque areas in middle-dose and high-dose BYHWT groups were significantly reduced(P<0.05), the peripheral blood TNF-α and IL-6 contents were decreased (P<0.01), the TGF-β and IL-10 expressions were increased in the high-dose group (P<0.05, P<0.01), the number of Treg cells in the plaque was increased in the high-dose group (P<0.01), and the peripheral blood Fxop3 mRNA expression was increased in each BYHWT group (P<0.01). Conclusion::BYHWT has an anti-atherosclerosis effect, which may be related to the increase of the number of Treg cells and thereby inhibiting the inflammatory response in vivo.
ABSTRACT
BACKGROUND@#Studies have reported that low bone mineral density (BMD) is prevalent in human immunodeficiency virus (HIV)-infected patients; however, the factors that contribute to HIV-related BMD changes are yet to be fully understood. Due to the application of dual X-ray absorptiometry (DXA) among a select group of hospitals only, the prevalence and risk factors of low BMD in HIV-infected populations have not been intensively investigated in China. Thus, the aim of our study was to investigate the prevalence of and risk factors associated with BMD changes among antiretroviral therapy (ART)-naive HIV-positive patients in China.@*METHODS@#The assessment of the prevalence of and risk factors associated with BMD changes was conducted among 156 ART-naive HIV-infected patients. Demographic and clinical data, as well as results of fasting blood tests were obtained from patients. Further, all patients underwent DXA scans to determine BMD, which was then used to classify patients with osteopenia/osteoporosis. The risk factors of reduced BMD were then evaluated using binary logistic regression.@*RESULTS@#Among the 156 ART-naive HIV-infected participants, osteopenia and osteoporosis were diagnosed in 48.7% (76/156) and 4.5% (7/156) of patients, respectively. The lumbar spine was most likely to have reduced BMD (49.4% [77/156]), and the proportion of osteopenia in the left hip (32.7% [51/156]) was higher than in the right hip (24.4% [38/156]). In the lumbar spine, bone loss rate in the L1 section (60.9% [95/156]) was the most significant (L2, 53.2% [83/156]; L3, 45.5% [71/156]; L4, 52.6% [82/156]). Further analysis showed that, compared with the neck (26.9% [42/156] in the left, 18.6% [29/156] in the right) and the interior (15.4% [24/156] in the left, 13.5% [21/156] in the right), the trochanter had the greatest probability of reduced BMD (46.2% [72/156] in the left, 28.8% [45/156] in the right). In the risk factor analysis, low body mass index (BMI: <18.5 kg/m2) was positively associated with reduced BMD (Exp (B) = 39.743, 95% confidence interval: 3.234-488.399, P = 0.004), and was specifically positively correlated with BMD values at three sites (r = 0.335 at right hip, r = 0.327 at left hip, r = 0.311 at lumbar spine).@*CONCLUSION@#Reduced BMD was found in the majority of ART-naive HIV-infected patients and BMI was identified as an additional risk factor for reduced BMD. Our results show that BMD reduction was simultaneously present in the left hip, right hip, and lumbar spine among nearly one fifth of patients. Our work highlights the importance of closely monitoring BMD in ART-naive patients and provides a foundation for the clinical intervention of bone demineralization in them.
