Understanding the dynamic relation between wastewater SARS-CoV-2 signal and clinical metrics throughout the pandemic

Wastewater surveillance (WWS) of SARS-CoV-2 was proven to be a reliable and complementary tool for population-wide monitoring of COVID-19 disease incidence but was not as rigorously explored as an indicator for disease burden throughout the pandemic. Prior to global mass immunization campaigns and during the spread of the wildtype COVID-19 and the Alpha variant of concern (VOC), viral measurement of SARS-CoV-2 in wastewater was a leading indicator for both COVID-19 incidence and disease burden in communities. As the two-dose vaccination rates escalated during the spread of the Delta VOC in Jul. 2021 through Dec. 2021, relations weakened between wastewater signal and community COVID-19 disease incidence and maintained a strong relationship with clinical metrics indicative of disease burden (new hospital admissions, ICU admissions, and deaths). Further, with the onset of the vaccine-resistant Omicron BA.1 VOC in Dec. 2021 through Mar. 2022, wastewater again became a strong indicator of both disease incidence and burden during a period of limited natural immunization (no recent infection), vaccine escape, and waned vaccine effectiveness. Lastly, with the populations regaining enhanced natural and vaccination immunization shortly prior to the onset of the Omicron BA.2 VOC in mid-Mar 2022, wastewater is shown to be a strong indicator for both disease incidence and burden. Hospitalization-to-wastewater ratio is further shown to be a good indicator of VOC virulence when widespread clinical testing is limited. In the future, WWS is expected to show moderate indication of incidence and strong indication of disease burden in the community during future potential seasonal vaccination campaigns. HighlightsO_LINeed to elucidate interpretation of CoV-2 WWS for seasonal vaccination campaigns. C_LIO_LIWWS to incidence relation weakens with peak natural and vaccination immunization. C_LIO_LIWWS to hospitalization remains strong with natural and vaccination immunization. C_LIO_LIWWS as indicator of hospitalization during future seasonal vaccination campaigns. C_LIO_LIWWS/hospitalization as indicator of VOC virulence with limited clinical testing. C_LI

Wastewater to clinical case (WC) ratio of COVID-19 identifies insufficient clinical testing, onset of new variants of concern and population immunity in urban communities

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.

Quantitative analysis of SARS-CoV-2 RNA from wastewater solids in communities with low COVID-19 incidence and prevalence

In the absence of an effective vaccine to prevent COVID-19 it is important to be able to track community infections to inform public health interventions aimed at reducing the spread and therefore reduce pressures on health-care units, improve health outcomes and reduce economic uncertainty. Wastewater surveillance has rapidly emerged as a potential tool to effectively monitor community infections for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through measuring trends of viral RNA signal in wastewater systems. In this study SARS-CoV-2 viral RNA N1 and N2 genes are quantified in solids collected from influent post grit solids (PGS) and primary clarified sludge (PCS) in two water resource recovery facilities (WRRF) serving Canadas national capital region, i.e., the City of Ottawa, ON (pop. {approx} 1.1M) and the City of Gatineau, QC (pop. {approx} 280K). PCS samples show signal inhibition using RT-ddPCR compared to RT-qPCR, with PGS samples showing similar quantifiable concentrations of RNA using both assays. RT-qPCR shows higher frequency of detection of N1 and N2 genes in PCS (92.7, 90.6%) as compared to PGS samples (79.2, 82.3%). Sampling of PCS may therefore be an effective approach for SARS-CoV-2 viral quantification, especially during periods of declining and low COVID-19 incidence in the community. The pepper mild mottle virus (PMMV) is determined to have a less variable RNA signal in PCS over a three month period for two WRRFs, regardless of environmental conditions, compared to Bacteroides 16S rRNA or human eukaryotic 18S rRNA, making PMMV a potentially useful biomarker for normalization of SARS-CoV-2 signal. PMMV-normalized PCS RNA signal from WRRFs of two cities correlated with the regional public health epidemiological metrics, identifying PCS normalized to a fecal indicator (PMMV) as a potentially effective tool for monitoring trends during decreasing and low-incidence of infection of SARS-Cov-2 in communities.

Apoptosis and expression of Fas/FasL in tumor infiltrating dendritic cells in human endometrioid adenocarcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate apoptosis of tumor infiltrating dendritic cells (TIDC) and their expression of Fas/FasL (CD95/CD95L) in human endometrioid adenocarcinoma.</p><p><b>METHODS</b>The apoptotic rate of TIDC was measured in 45 cases of endometrioid adenocarcinoma and 20 cases of normal endometrium tissues (control) by double-label immunohistochemistry using the monoclonal antibody S-100 protein and TUNEL technique. The expressions of Fas and FasL in TIDCs were detected using double-label immunohistochemistry and imaging analysis.</p><p><b>RESULTS</b>The apoptotic rate of TIDCs in endometrioid adenocarcinoma were significantly higher than that in normal endormetrium [(13.02∓0.64)% vs (6.82∓0.53)%, P<0.05]. The expression levels of Fas in the TIDCs were significantly lower, whereas FasL expression significantly higher in endometrioid adenocarcinoma than in normal endormetrium (7.88∓1.05 vs 19.25∓3.03, P<0.05; 12.95∓2.25 vs 7.51∓1.14, P<0.05).</p><p><b>CONCLUSION</b>Increased apoptosis of the TIDCs and abnormal expression of Fas/FasL in TIDCs in endometrioid adenocarcinoma may lead to tumor immune escape.</p>

Expression of vascular endothelial growth factor in human placental trophoblasts and angiogenesis in the chorionic villi / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of vascular endothelial growth factor (VEGF) in human placental trophoblasts and the role of VEGF in regulating placental villous angiogenesis.</p><p><b>METHODS</b>Placental samples were obtained from 10 pregnant women receiving induced abortion in the first trimester, 10 receiving induced labor in the second trimester and 10 having cesarean section at term delivery, with gestational duration of 6-9, 18-22 and 37-38 weeks, respectively. All the samples were fixed in formalin solution and prepared for the morphological study. The expression of VEGF and vascular distribution in the placental villi were examined and evaluated by immunohistochemistry and stereomorphometry, respectively.</p><p><b>RESULTS</b>In the course of pregnancy, there was a significant decrease in the level of VEGF expression in chorionic villi (28.19+/-3.01, 18.65+/-2.43, 4.95+/-0.86, respectively, P<0.01). The radial parameters of the blood vessels showed no significant changes (26.67+/-7.74, 25.08+/-4.67, 23.36+/-5.30, respectively, P>0.05), but the length density of the blood vessels increased significantly (1.46+/-0.64, 5.58+/-1.31, 19.56+/-1.40, respectively, P<0.01).</p><p><b>CONCLUSION</b>During gestation, VEGF expression in chorionic villi gradually weakens but the length density of the blood vessels increases, indicating that VEGF is not the only regulatory factor of angiogenesis in the chorionic villi.</p>

Effect of comprehensive therapy on depression post stroke / 中国康复理论与实践

@#ObjectiveTo observe the effect of rehabilitation on post stroke depression with different treatment methods.Methods68 post stroke depression patients were randomly divided into treatment group, who accepted Bobath approach combined with Chinese herbs and acupuncture, and control group, who accepted Bobath approach only. Evaluation was conducted before treatment and 3 and 6 weeks after treatment with Hamilton Assess Depression Scale (HAMD), and activity of daily living (ADL).ResultsThere was no significant difference before the treatment between these two groups. 3 weeks after treatment, the score improved, but no significant enough in the both groups. 6 weeks after treatment, the scores of MBI and HAMD in treatment group significantly improved compared with that before treatment(P<0.05). ConclusionBobath approach combined with Chinese medicine is effective on improving depressive symptoms and ADL in post stroke depression patients.