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1.
Tunnelling and Underground Space Technology ; : 104528, 2022.
Article in English | ScienceDirect | ID: covidwho-1799682

ABSTRACT

The metro (or underground railways) has become a backbone in the transit systems of many cities. It has numerous externalities, such as ameliorating traffic congestion and enhancing nearby property prices. Previous studies extensively focused on the relationship between metro accessibility and property prices and obtained various interesting findings and enriched practical implications. However, this relationship in the era of the coronavirus disease 2019 (COVID-19) and other epidemic shocks has not been investigated. Based on a unique property transaction dataset (including tens of thousands of transactions stretching from 2018 to 2020) in Chengdu, China, this study develops a battery of hedonic pricing models and difference-in-differences models to decipher the time-varying relationship between metro accessibility and residential property prices. The results show that the implicit price of metro accessibility modestly decreases in COVID-19, which can be explained by the declining role of the metro. Specifically, the price elasticity of distance to the metro is −0.024 before COVID-19, but it turns to −0.018 during the pandemic. The relative price of properties within 500 m from metro stations to those farther away (500 m − 3 km) decreases by 15.4% during the pandemic. Additionally, COVID-19 does not jeopardize property prices in Chengdu. The plausibility and robustness of the core findings have been confirmed through alternative treatment groups, alternative model specifications, and placebo tests.

2.
Front Public Health ; 10: 808988, 2022.
Article in English | MEDLINE | ID: covidwho-1776006

ABSTRACT

Objective: This study aimed to assess the knowledge, attitude, and practice (KAP) of diabetic subjects with diabetic retinopathy (DR) and those without DR (NDR) in an urban community in Northeast China, as well as their risk factors in subjects with DR and NDR. Methods: A community-based survey involving 1,662 subjects was conducted in Fushun, China, between July 2012 and May 2013. The subjects included diabetics with DR (n = 783) and those NDR (n = 879), and questionnaires were completed to collect information about their sociodemographic and healthcare characteristics. A Chi-square test and multiple logistic analyses were performed to analyze the data. Results: Among the DR group, 21.88% had a good knowledge of DR, 94.15% had a positive attitude, and 68.07% followed good practice, whereas 20.98% of the NDR group had a good knowledge of DR, 94.18% had a positive attitude, and 66.92% followed good practice. There was no significant difference in the KAP of the two groups of subjects. In the NDR group, a good level of knowledge was associated with a high-level of education (OR = 0.1, 0.2; p < 0.05), a good attitude was associated with retirement (OR = 0.2; p < 0.05), and good practice was associated with being female, having a high-level of education, and the type of treatment (OR = 0.5, 0.4, 2.3, 3.1; p < 0.05). In the DR group, good practice was associated with older age and retirement (OR = 0.6, 0.4; p < 0.05). Conclusions: There was no significant difference between the DR and NDR subjects in the overall levels of KAP, but both groups showed a poor level of knowledge. Age, gender, education, occupation, and type of treatment were the main factors associated with the KAP scores, more risk factors in the NDR group than in the DR group. There is an urgent need for coordinated educational campaigns with a prioritized focus on the northeast region of China, especially NDR group.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Health Knowledge, Attitudes, Practice , China , Cross-Sectional Studies , Female , Humans , Urban Population
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315270

ABSTRACT

Background: Coronavirus disease (COVID-19) has resulted in high mortality worldwide. However, information regarding cardiac markers for precise risk-stratification is limited. We aimed to discover a sensitive and reliable early-warning biomarker for optimizing management and improving COVID-19 patients’ prognosis. Methods: : This single-center case series was conducted between February 4 and April 10, 2020. In total, 2,954 consecutive COVID-19 patients who were receiving treatment at Wuhan Huoshenshan Hospital in China were included in the retrospectively selected cohort. All patients were diagnosed with COVID-19 and treated at the study site. Data of serum levels of cardiac markers, coronary artery disease (CAD) diagnosis, and survival were collected after admission. Single-cell RNA-sequencing was performed to analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor expression. Results: : Median patient age was 60 years (range, 50-68 years);1,461 (49.5%) were female, and 1,515 (51.3%) patients were in a severe/critical condition. Compared to mild/moderate patients (1,439, 48.7%), severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. Among severe/critical COVID-19 patients, those with abnormal serum levels of brain natriuretic peptide had a significantly higher mortality rate than patients with normal levels. Severe/critical COVID-19 patients with pre-existing CAD (165/1,155 [10.9%]) had more cases of abnormal brain natriuretic peptide levels than those without CAD. Enhanced SARS-CoV-2 receptor expression was observed in patients with CAD. Regression analysis revealed that patients with elevated brain natriuretic peptide levels were at a higher risk of death (hazards ratio, 1.001 [95% confidence interval, 1.0003-1.002]). Conclusions: : Brain natriuretic peptide is an effective biomarker for early risk assessment in COVID-19 patients with or without pre-existing CAD. Monitoring BNP status will improve the risk-stratification management and prognosis of patients within one week after admission.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315224

ABSTRACT

Background: Public health workers at the Chinese Centre for Disease Control and Prevention (China CDC) and primary health care institutes (PHIs) were among the main workers who implemented prevention, control, and containment measures. However, their efforts and health status have not been well documented. We aimed to investigate the working conditions and health status of front line public health workers in China during the COVID-19 epidemic. Methods: : Between 18 February and 1 March 2020, we conducted an online cross-sectional survey of 2,313 CDC workers and 4,004 PHI workers in five provinces across China experiencing different scales of COVID-19 epidemic. We surveyed all participants about their work conditions, roles, burdens, perceptions, mental health, and self-rated health using a self-constructed questionnaire and standardised measurements (i.e., Patient Health Questionnaire and General Anxiety Disorder scale). To examine the independent associations between working conditions and health outcomes, we used multivariate regression models controlling for potential confounders. Results: : The prevalence of depression, anxiety, and poor self-rated health was 21.3%, 19.0%, and 9.8%, respectively, among public health workers (27.1%, 20.6%, and 15.0% among CDC workers and 17.5%, 17.9%, and 6.8% among PHI workers). The majority (71.6%) made immense efforts in both field and non-field work. Nearly 20.0% have worked all night for more than 3 days, and 45.3% had worked throughout the Chinese New Year holiday. Three risk factors and two protective factors were found to be independently associated with all three health outcomes in our final multivariate models: working all night for >3 days (multivariate odds ratio [ORm]=1.67~1.75, p <0.001), concerns about infection at work (ORm=1.46~1.89, p <0.001), perceived troubles at work (ORm=1.10~1.28, p <0.001), initiating COVID-19 prevention work after January 23 (ORm=0.78~0.82, p =0.002~0.008), and ability to persist for > 1 month at the current work intensity (ORm=0.44~0.55, p <0.001). Conclusions: : Chinese public health workers made immense efforts and personal sacrifices to control the COVID-19 epidemic and faced the risk of mental health problems. Efforts are needed to improve the working conditions and health status of public health workers and thus maintain their morale and effectiveness during the fight against COVID-19.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323715

ABSTRACT

Objective: We aimed to describe the chest CT findings in sixty-seven patients infected by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Method and material: We retrospectively reviewed 67 patients hospitalized in Ruian People's Hospital. All the patients received the positive diagnosis of SARS-CoV-2 infection. The CT and clinical data were collected between January 23 rd , 2020 and February 10 th , 2020. The CT images were analyzed by the senior radiologists. Conclusion: There are 54 patients with positive CT findings and 13 patients with negative CT findings. The typical CT findings in hospitalized patients with SARS-CoV-2 infection were ground glass opacities (42/54), lesions located in the peripheral area (50/54), multiple lesions (46/54), and lesions located in the lower lobes (42/54). There were less typical CT findings, including air bronchogram (18/54), pleural thickening or pleural effusion (14/54), consolidation (12/54), lesions in the upper lobes (12/54), interlobular septal thickening (11/54), reversed halo sign (9/54), single lesion (8/54), air cavities (4/54), bronchial wall thickening (3/54), and intrathoracic lymph node enlargement (2/54).

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321219

ABSTRACT

Background: Infection with SARS-CoV-2 has been associated with liver dysfunction, aggravation of liver burden, and liver injury. This study aimed to assess the effects of liver injuries on the clinical outcomes of patients with COVID-19. Methods: A total of 1,564 patients with severe or critical COVID-19 from Huoshenshan Hospital, Wuhan, were enrolled. Chronic liver disease (CLD) was confirmed by consensus diagnostic criteria. Laboratory test results were compared between different groups. scRNA-seq data and bulk gene expression profiles were used to identify cell types associated with liver injury. Results: A total of 10.98% of patients with severe or critical COVID-19 developed liver injury after admission that was associated with significantly higher rates of mortality (21.74%, p <0.001) and intensive care unit admission (26.71%, p <0.001). A pre-existing CLD was not associated with a higher risk. However, fatty liver disease and cirrhosis were associated with higher risks, supported by evidences from single cell and bulk transcriptome analysis that showed more TMPRSS2 + cells in these tissues. By generating a model, we were able to predict the risk and severity of liver injury during hospitalization. Conclusion: We demonstrate that liver injury occurring during therapy in patients with COVID-19 is significantly associated with the severity of disease and mortality, but the presence of CLD is not associated. We provide a risk-score model that can predict whether patients with COVID-19 will develop liver injury or proceed to higher risk stages during subsequent hospitalizations. These findings may prove beneficial for the clinical management of patients infected with SARS-CoV-2.

7.
Sci Adv ; 7(48): eabl6096, 2021 Nov 26.
Article in English | MEDLINE | ID: covidwho-1537883

ABSTRACT

The SARS-CoV-2 pandemic, and the likelihood of future coronavirus pandemics, emphasized the urgent need for development of novel antivirals. Small-molecule chemical probes offer both to reveal aspects of virus replication and to serve as leads for antiviral therapeutic development. Here, we report on the identification of amiloride-based small molecules that potently inhibit OC43 and SARS-CoV-2 replication through targeting of conserved structured elements within the viral 5'-end. Nuclear magnetic resonance­based structural studies revealed specific amiloride interactions with stem loops containing bulge like structures and were predicted to be strongly bound by the lead amilorides in retrospective docking studies. Amilorides represent the first antiviral small molecules that target RNA structures within the 5' untranslated regions and proximal region of the CoV genomes. These molecules will serve as chemical probes to further understand CoV RNA biology and can pave the way for the development of specific CoV RNA­targeted antivirals.

8.
Endocrine ; 75(1): 1-9, 2022 01.
Article in English | MEDLINE | ID: covidwho-1491380

ABSTRACT

Type 2 diabetes (T2D) increases the risk of coronavirus disease (COVID-19). This study investigates the association between glucose control of COVID-19 patients with T2D in first 7 days after hospital admission and prognosis. A total of 252 infected inpatients with T2D in China were included. Well-controlled blood glucose was defined as stable fasting blood glucose (FBG) levels in the range of 3.9-7.8 mmol/L during first 7 days using indicators of average (FBGA), maximum (FBGM) or first-time (FBG1) FBG levels. The primary endpoint was admission to intensive care unit or death. Hazard ratio (HR) of poorly controlled glucose level group compared with well-controlled group were 4.96 (P = 0.021) for FBGM and 5.55 (P = 0.014) for FBGA. Well-controlled blood glucose levels in first 7 days could improve the prognosis of COVID-19 inpatients with diabetes.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Blood Glucose , Diabetes Mellitus, Type 2/complications , Humans , Inpatients , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2
10.
Front Immunol ; 12: 700449, 2021.
Article in English | MEDLINE | ID: covidwho-1325531

ABSTRACT

The identification of asymptomatic, non-severe presymptomatic, and severe presymptomatic coronavirus disease 2019 (COVID-19) in patients may help optimize risk-stratified clinical management and improve prognosis. This single-center case series from Wuhan Huoshenshan Hospital, China, included 2,980 patients with COVID-19 who were hospitalized between February 4, 2020 and April 10, 2020. Patients were diagnosed as asymptomatic (n = 39), presymptomatic (n = 34), and symptomatic (n = 2,907) upon admission. This study provided an overview of asymptomatic, presymptomatic, and symptomatic COVID-19 patients, including detection, demographics, clinical characteristics, and outcomes. Upon admission, there was no significant difference in clinical symptoms and CT image between asymptomatic and presymptomatic patients for diagnosis reference. The mean area under the receiver operating characteristic curve (AUC) of the differential diagnosis model to discriminate presymptomatic patients from asymptomatic patients was 0.89 (95% CI, 0.81-0.98). Importantly, the severe and non-severe presymptomatic patients can be further stratified (AUC = 0.82). In conclusion, the two-step risk-stratification model based on 10 laboratory indicators can distinguish among asymptomatic, severe presymptomatic, and non-severe presymptomatic COVID-19 patients on admission. Moreover, single-cell data analyses revealed that the CD8+T cell exhaustion correlated to the progression of COVID-19.


Subject(s)
Asymptomatic Infections , COVID-19/diagnosis , Aged , CD8-Positive T-Lymphocytes/pathology , China/epidemiology , Diagnosis, Differential , Disease Progression , Female , Humans , Male , Middle Aged , Models, Statistical , Prognosis , Risk Assessment , SARS-CoV-2
11.
Front Public Health ; 9: 622677, 2021.
Article in English | MEDLINE | ID: covidwho-1247938

ABSTRACT

Background: The COVID-19 outbreak in China has created multiple stressors that threaten individuals' mental health, especially among public health workers (PHW) who are devoted to COVID-19 control and prevention work. This study aimed to investigate the prevalence of mental help-seeking and associated factors among PHW using Andersen's Behavioral Model of Health Services Use (BMHSU). Methods: A cross-sectional survey was conducted among 9,475 PHW in five provinces across China between February 18 and March 1, 2020. The subsample data of those who reported probable mental health problems were analyzed for this report (n = 3,417). Logistic and hierarchical regression analyses were conducted to examine the associations of predisposing, enabling, need, and COVID-19 contextual factors with mental health help-seeking. Results: Only 12.7% of PHW reported professional mental help-seeking during the COVID-19 outbreak. PHW who were older, had more days of overnight work, received psychological training, perceived a higher level of support from the society, had depression and anxiety were more likely to report mental help-seeking (ORm range: 1.02-1.73, all p < 0.05) while those worked in Centers for Disease Control and Prevention were less likely to seek help (ORm = 0.57, p < 0.01). The belief that mental health issues were not the priority (64.4%), lack of time (56.4%), and shortage of psychologists (32.7%) were the most frequently endorsed reasons for not seeking help. Conclusions: The application of BMHSU confirmed associations between some factors and PHW's mental health help-seeking. Effective interventions are warranted to promote mental health help-seeking of PHW to ameliorate the negative impact of mental illness and facilitate personal recovery and routine work.


Subject(s)
COVID-19 , Mental Health , China/epidemiology , Cross-Sectional Studies , Depression , Disease Outbreaks , Humans , Public Health , SARS-CoV-2 , United States
12.
Crit Care ; 25(1): 158, 2021 04 26.
Article in English | MEDLINE | ID: covidwho-1204102

ABSTRACT

BACKGROUND: COVID-19 has resulted in high mortality worldwide. Information regarding cardiac markers for precise risk-stratification is limited. We aim to discover sensitive and reliable early-warning biomarkers for optimizing management and improving the prognosis of COVID-19 patients. METHODS: A total of 2954 consecutive COVID-19 patients who were receiving treatment from the Wuhan Huoshenshan Hospital in China from February 4 to April 10 were included in this retrospective cohort. Serum levels of cardiac markers were collected after admission. Coronary artery disease diagnosis and survival status were recorded. Single-cell RNA-sequencing and bulk RNA-sequencing from different cohorts of non-COVID-19 were performed to analyze SARS-CoV-2 receptor expression. RESULTS: Among 2954 COVID-19 patients in the analysis, the median age was 60 years (50-68 years), 1461 (49.5%) were female, and 1515 (51.3%) were severe/critical. Compared to mild/moderate (1439, 48.7%) patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. In severe/critical COVID-19 patients, those with abnormal serum levels of BNP (42 [24.6%] vs 7 [1.1%]), hs-TNI (38 [48.1%] vs 6 [1.0%]), α- HBDH (55 [10.4%] vs 2 [0.2%]), CK-MB (45 [36.3%] vs 12 [0.9%]), and LDH (56 [12.5%] vs 1 [0.1%]) had a significantly higher mortality rate compared to patients with normal levels. The same trend was observed in the ICU admission rate. Severe/critical COVID-19 patients with pre-existing coronary artery disease (165/1,155 [10.9%]) had more cases of BNP (52 [46.5%] vs 119 [16.5%]), hs-TNI (24 [26.7%] vs 9.6 [%], α- HBDH (86 [55.5%] vs 443 [34.4%]), CK-MB (27 [17.4%] vs 97 [7.5%]), and LDH (65 [41.9%] vs 382 [29.7%]), when compared with those without coronary artery disease. There was enhanced SARS-CoV-2 receptor expression in coronary artery disease compared with healthy controls. From regression analysis, patients with five elevated cardiac markers were at a higher risk of death (hazards ratio 3.4 [95% CI 2.4-4.8]). CONCLUSIONS: COVID-19 patients with pre-existing coronary artery disease represented a higher abnormal percentage of cardiac markers, accompanied by high mortality and ICU admission rate. BNP together with hs-TNI, α- HBDH, CK-MB and LDH act as a prognostic biomarker in COVID-19 patients with or without pre-existing coronary artery disease.


Subject(s)
Biomarkers/blood , COVID-19/blood , COVID-19/therapy , Coronary Artery Disease/blood , Aged , COVID-19/epidemiology , China/epidemiology , Coronary Artery Disease/epidemiology , Female , Hospitalization , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment/methods
13.
BMC Psychol ; 9(1): 55, 2021 Apr 12.
Article in English | MEDLINE | ID: covidwho-1181128

ABSTRACT

BACKGROUND: Poor mental health status and associated risk factors of public health workers have been overlooked during the COVID-19 pandemic. This study used the effort-reward imbalance model to investigate the association between work-stress characteristics (effort, over-commitment, reward) and mental health problems (anxiety and depression) among front-line public health workers during the COVID-19 pandemic in China. METHODS: A total of 4850 valid online questionnaires were collected through a self- constructed sociodemographic questionnaire, the adapted ERI questionnaire, the 9-item Patient Health Questionnaire (PHQ-9) and the 7-item General Anxiety Disorder Scale (GAD-7). Hierarchical logistic regression analysis was conducted to investigate the association between ERI factors and mental health problems (i.e., depression and anxiety), with reward treated as a potential moderator in such associations. RESULTS: The data showed that effort and over-commitment were positively associated with depression and anxiety, while reward was negatively associated with depression and anxiety. Development and job acceptance were the two dimensions of reward buffered the harmful effect of effort/over-commitment on depression and anxiety, whereas esteem was non-significant. CONCLUSIONS: This study confirmed the harmful effects of effort and over-commitment on mental health among public health workers during the COVID-19 pandemic in China. Such effects could be alleviated through an appropriate reward system, especially the development and job acceptance dimensions of such a system. These findings highlight the importance of establishing an emergency reward system, comprising reasonable work-allocation mechanism, bonuses and honorary titles, a continuous education system and better career-development opportunities.


Subject(s)
COVID-19 , Pandemics , China/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Humans , Mental Health , Prevalence , Public Health , Reward , SARS-CoV-2 , Stress, Psychological/epidemiology , Surveys and Questionnaires
14.
Hepatol Int ; 15(1): 202-212, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1064606

ABSTRACT

BACKGROUND: Infection with SARS-CoV-2 has been associated with liver dysfunction, aggravation of liver burden, and liver injury. This study aimed to assess the effects of liver injuries on the clinical outcomes of patients with COVID-19. METHODS: A total of 1520 patients with severe or critical COVID-19 from Huoshenshan Hospital, Wuhan, were enrolled. Chronic liver disease (CLD) was confirmed by consensus diagnostic criteria. Laboratory test results were compared between different groups. scRNA-seq data and bulk gene expression profiles were used to identify cell types associated with liver injury. RESULTS: A total of 10.98% of patients with severe or critical COVID-19 developed liver injury after admission that was associated with significantly higher rates of mortality (21.74%, p < 0.001) and intensive care unit admission (26.71%, p < 0.001). Pre-existing CLDs were not associated with a higher risk. However, fatty liver disease and cirrhosis were associated with higher risks, supported by evidences from single cell and bulk transcriptome analysis that showed more TMPRSS2+ cells in these tissues. By generating a model, we were able to predict the risk and severity of liver injury during hospitalization. CONCLUSION: We demonstrate that liver injury occurring during therapy as well as pre-existing CLDs like fatty liver disease and cirrhosis in patients with COVID-19 is significantly associated with the severity of disease and mortality, but the presence of other CLD is not associated. We provide a risk-score model that can predict whether patients with COVID-19 will develop liver injury or proceed to higher-risk stages during subsequent hospitalizations.


Subject(s)
COVID-19/complications , COVID-19/therapy , Liver Diseases/diagnosis , Liver Diseases/virology , Adult , Aged , COVID-19/mortality , China , Critical Care , Extracorporeal Membrane Oxygenation , Female , Hospitalization , Humans , Liver Diseases/mortality , Male , Middle Aged , Oxygen Inhalation Therapy , Respiration, Artificial , Risk Factors , Severity of Illness Index , Survival Rate
15.
BMC Public Health ; 21(1): 106, 2021 01 09.
Article in English | MEDLINE | ID: covidwho-1015855

ABSTRACT

BACKGROUND: Public health workers at the Chinese Centre for Disease Control and Prevention (China CDC) and primary health care institutes (PHIs) were among the main workers who implemented prevention, control, and containment measures. However, their efforts and health status have not been well documented. We aimed to investigate the working conditions and health status of front line public health workers in China during the COVID-19 epidemic. METHODS: Between 18 February and 1 March 2020, we conducted an online cross-sectional survey of 2,313 CDC workers and 4,004 PHI workers in five provinces across China experiencing different scales of COVID-19 epidemic. We surveyed all participants about their work conditions, roles, burdens, perceptions, mental health, and self-rated health using a self-constructed questionnaire and standardised measurements (i.e., Patient Health Questionnaire and General Anxiety Disorder scale). To examine the independent associations between working conditions and health outcomes, we used multivariate regression models controlling for potential confounders. RESULTS: The prevalence of depression, anxiety, and poor self-rated health was 21.3, 19.0, and 9.8%, respectively, among public health workers (27.1, 20.6, and 15.0% among CDC workers and 17.5, 17.9, and 6.8% among PHI workers). The majority (71.6%) made immense efforts in both field and non-field work. Nearly 20.0% have worked all night for more than 3 days, and 45.3% had worked throughout the Chinese New Year holiday. Three risk factors and two protective factors were found to be independently associated with all three health outcomes in our final multivariate models: working all night for >3 days (multivariate odds ratio [ORm]=1.67~1.75, p<0.001), concerns about infection at work (ORm=1.46~1.89, p<0.001), perceived troubles at work (ORm=1.10~1.28, p<0.001), initiating COVID-19 prevention work after January 23 (ORm=0.78~0.82, p=0.002~0.008), and ability to persist for > 1 month at the current work intensity (ORm=0.44~0.55, p<0.001). CONCLUSIONS: Chinese public health workers made immense efforts and personal sacrifices to control the COVID-19 epidemic and faced the risk of mental health problems. Efforts are needed to improve the working conditions and health status of public health workers and thus maintain their morale and effectiveness during the fight against COVID-19.


Subject(s)
COVID-19/epidemiology , Epidemics , Health Personnel/psychology , Health Personnel/statistics & numerical data , Health Status , Public Health , Work/statistics & numerical data , Adult , China/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Surveys and Questionnaires
16.
Preprint in English | bioRxiv | ID: ppbiorxiv-409821

ABSTRACT

The SARS-CoV-2 pandemic, and the likelihood of future coronavirus pandemics, has rendered our understanding of coronavirus biology more essential than ever. Small molecule chemical probes offer to both reveal novel aspects of virus replication and to serve as leads for antiviral therapeutic development. The RNA-biased amiloride scaffold was recently tuned to target a viral RNA structure critical for translation in enterovirus 71, ultimately uncovering a novel mechanism to modulate positive-sense RNA viral translation and replication. Analysis of CoV RNA genomes reveal many conserved RNA structures in the 5-UTR and proximal region critical for viral translation and replication, including several containing bulge-like secondary structures suitable for small molecule targeting. Following phylogenetic conservation analysis of this region, we screened an amiloride-based small molecule library against a less virulent human coronavirus, OC43, to identify lead ligands. Amilorides inhibited OC43 replication as seen in viral plaque assays. Select amilorides also potently inhibited replication competent SARS-CoV-2 as evident in the decreased levels of cell free virions in cell culture supernatants of treated cells. Reporter screens confirmed the importance of RNA structures in the 5-end of the viral genome for small molecule activity. Finally, NMR chemical shift perturbation studies of the first six stem loops of the 5-end revealed specific amiloride interactions with stem loops 4, 5a, and 6, all of which contain bulge like structures and were predicted to be strongly bound by the lead amilorides in retrospective docking studies. Taken together, the use of multiple orthogonal approaches allowed us to identify the first small molecules aimed at targeting RNA structures within the 5-UTR and proximal region of the CoV genome. These molecules will serve as chemical probes to further understand CoV RNA biology and can pave the way for the development of specific CoV RNA-targeted antivirals.

17.
Nucleic Acids Res ; 48(22): 12415-12435, 2020 12 16.
Article in English | MEDLINE | ID: covidwho-917705

ABSTRACT

The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5' end, the ribosomal frameshift segment and the 3'-untranslated region (3'-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention.


Subject(s)
COVID-19/prevention & control , Magnetic Resonance Spectroscopy/methods , Nucleic Acid Conformation , RNA, Viral/chemistry , SARS-CoV-2/genetics , 3' Untranslated Regions/genetics , Base Sequence , COVID-19/epidemiology , COVID-19/virology , Frameshifting, Ribosomal/genetics , Genome, Viral/genetics , Humans , Models, Molecular , Pandemics , SARS-CoV-2/physiology
19.
Zhongguo Jishui Paishui = China Water & Wastewater ; - (6):22, 2020.
Article in Chinese | WHO COVID | ID: covidwho-833165

ABSTRACT

Based on the problem that the novel coronavirus (SARS-CoV-2) can enter the urban drainage system through the excretion of patients' faces into the sewer, the fate of infective viruses in the urban water cycle was analyzed. Then, it was concluded that attention should be paid to the risk of virus spreading through sludge after the virus enters the urban drainage system. In the case of COVID-19 epidemic, it is impartant to summarize and reflect on the pathogen control during sludge treatment and disposal process in China. Therefore, the relevant standards and policies of sludge sterilization and disinfection in China have been systematically combed, and the relevant research results of the United States and the European Union have been studied. It has been considered that the sludge is a good carrier of pathogens;the standard restrictions on pathogens in sludge in our country are relatively loose currently. So it is necessary to strengthen the experiments and research on inactivation of pathogens in sludge, and to formulate the index and limit value of pathogens. The SARS-CoV-2 is an enveloped virus that can be relatively easily killed by antivirus agent. Therefore, adding disinfectant to the sludge pretreatment section is an effective measure to control pathogens during the epidemic. Aerobic fermentation, anaerobic digestion, lime stabilization, thermal drying, and radiation treatment can effectively reduce pathogens. During the epidemic period, sludge disposal methods are recommended to adopt incineration or co-incineration. For areas where the harmless disposal capacity of sludge is insufficient, the implementation of compliance sludge disposal outlet should be promoted. In addition, in order to reduce the exposure risk, in the sludge treatment and disposal process, the better sealing device should be preferred.

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