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1.
Front Med (Lausanne) ; 9: 844710, 2022.
Article in English | MEDLINE | ID: covidwho-1825489

ABSTRACT

Background: Surgical masks (SMs) protect medical staff and reduce surgical site infections. Extended SM use may reduce oxygen concentrations in circulation, causing hypoxia, headache, and fatigue. However, no research has examined the effects of wearing SMs on oxygenation and physical discomfort of anesthesiologists. Methods: An electronic questionnaire was established and administered through WeChat, and a cross-sectional survey was conducted to determine SM use duration and related discomfort of operating room medical staff. Then, operating room anesthesiologists were enrolled in a single-arm study. Peripheral blood oxygen saturation (SpO2), heart rate, and respiratory rate were determined at different times before and after SM use. Shortness of breath, dizziness, and headache were subjectively assessed based on the visual analog scale (VAS) scores. Results: In total, 485 operating room medical staff completed the electronic questionnaire; 70.5% of them did not change SMs until after work, and 63.9% wore SMs continuously for more than 4 h. The proportion of anesthesiologists was the highest. After wearing masks for 4 h, the shortness of breath, fatigue, and dizziness/headache rates were 42.1, 34.6, and 30.9%, respectively. Compared with other medical staff, the proportion of subjective discomfort of anesthesiologists increased significantly with prolonged SM use from 1 to 4 h. Thirty-five anesthesiologists completed the study. There was no difference in anesthesiologist SpO2, heart rate, or respiratory rate within 2 h of wearing SMs. After more than 2 h, the variation appears to be statistically rather than clinically significant-SpO2 decreased (98.0 [1.0] vs. 97.0 [1.0], p < 0.05), respiratory rate increased (16.0 [3.0] vs. 17.0 [2.0], p < 0.01), and heart rate remained unchanged. As mask use duration increased, the VAS scores of shortness of breath, dizziness, and headache gradually increased. Conclusion: In healthy anesthesiologists, wearing SMs for more than 2 h can significantly decrease SpO2 and increase respiratory rates without affecting heart rates.

2.
Nat Microbiol ; 7(5): 716-725, 2022 May.
Article in English | MEDLINE | ID: covidwho-1852420

ABSTRACT

Emerging SARS-CoV-2 variants continue to cause waves of new infections globally. Developing effective antivirals against SARS-CoV-2 and its variants is an urgent task. The main protease (Mpro) of SARS-CoV-2 is an attractive drug target because of its central role in viral replication and its conservation among variants. We herein report a series of potent α-ketoamide-containing Mpro inhibitors obtained using the Ugi four-component reaction. The prioritized compound, Y180, showed an IC50 of 8.1 nM against SARS-CoV-2 Mpro and had oral bioavailability of 92.9%, 31.9% and 85.7% in mice, rats and dogs, respectively. Y180 protected against wild-type SARS-CoV-2, B.1.1.7 (Alpha), B.1.617.1 (Kappa) and P.3 (Theta), with EC50 of 11.4, 20.3, 34.4 and 23.7 nM, respectively. Oral treatment with Y180 displayed a remarkable antiviral potency and substantially ameliorated the virus-induced tissue damage in both nasal turbinate and lung of B.1.1.7-infected K18-human ACE2 (K18-hACE2) transgenic mice. Therapeutic treatment with Y180 improved the survival of mice from 0 to 44.4% (P = 0.0086) upon B.1.617.1 infection in the lethal infection model. Importantly, Y180 was also highly effective against the B.1.1.529 (Omicron) variant both in vitro and in vivo. Overall, our study provides a promising lead compound for oral drug development against SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Disease Models, Animal , Dogs , Humans , Mice , Rats
3.
Front Public Health ; 10: 855633, 2022.
Article in English | MEDLINE | ID: covidwho-1847239

ABSTRACT

COVID-19, which occurred at the end of December 2019, has evolved into a global public health threat and affects every aspect of human life. COVID-19's high infectivity and mortality prompted governments and the scientific community to respond quickly to the pandemic outbreak. The application of personal protective equipment (PPE) is of great significance in overcoming the epidemic situation. Since the discovery of severe acute respiratory coronavirus 2 (SARS-CoV-2), bibliometric analysis has been widely used in many aspects of the COVID-19 epidemic. Although there are many reported studies about PPE and COVID-19, there is no study on the bibliometric analysis of these studies. The citation can be used as an indicator of the scientific influence of an article in its field. The aim of this study was to track the research trends and latest hotspots of COVID-19 in PPE by means of bibliometrics and visualization maps.


Subject(s)
COVID-19 , Bibliometrics , COVID-19/prevention & control , Humans , Pandemics/prevention & control , Personal Protective Equipment , SARS-CoV-2
4.
Eur J Nucl Med Mol Imaging ; 49(8): 2994-3004, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1844354

ABSTRACT

INTRODUCTION: Distinct physiological states arise from complex interactions among the various organs present in the human body. PET is a non-invasive modality with numerous successful applications in oncology, neurology, and cardiology. However, while PET imaging has been applied extensively in detecting focal lesions or diseases, its potential in detecting systemic abnormalities is seldom explored, mostly because total-body imaging was not possible until recently. METHODS: In this context, the present study proposes a framework capable of constructing an individual metabolic abnormality network using a subject's whole-body 18F-FDG SUV image and a normal control database. The developed framework was evaluated in the patients with lung cancer, the one discharged after suffering from Covid-19 disease, and the one that had gastrointestinal bleeding with the underlying cause unknown. RESULTS: The framework could successfully capture the deviation of these patients from healthy subjects at the level of both system and organ. The strength of the altered network edges revealed the abnormal metabolic connection between organs. The overall deviation of the network nodes was observed to be highly correlated to the organ SUV measures. Therefore, the molecular connectivity of glucose metabolism was characterized at a single subject level. CONCLUSION: The proposed framework represents a significant step toward the use of PET imaging for identifying metabolic dysfunction from a systemic perspective. A better understanding of the underlying biological mechanisms and the physiological interpretation of the interregional connections identified in the present study warrant further research.


Subject(s)
COVID-19 , Lung Neoplasms , Fluorodeoxyglucose F18 , Humans , Lung Neoplasms/pathology , Positron-Emission Tomography/methods , Whole Body Imaging
5.
J Oleo Sci ; 71(4): 587-597, 2022.
Article in English | MEDLINE | ID: covidwho-1835530

ABSTRACT

In this study, we investigated the inhibition effects of matairesinol, pregnanolone, hamamelitannin, secoisolariciresinol, and secoisolariciresinol diglicoside compounds on HMG-CoA reductase and urease enzymes. We have obtained results for the HMG-CoA reductase enzyme at the millimolar level, and for the urease enzyme at the micromolar level. Molecular docking calculations were made for their biological activities were compared. In docking calculations, proteins of experimentally used enzymes, activities of SARS-CoV-2 virus against RNA-dependent RNA polymerase (RdRp) protein, and anti-oxidant protein were compared. Then, ADME/T calculations were made to use the molecules as drugs. Cytotoxicity potential of these complexes against human breast and prostate cancers demonstrated that these compounds had good cytotoxic effects. There is growing attention to phenolic molecules and their presumed role in avoiding diverse degenerative diseases, such as cardiovascular and cancer diseases.


Subject(s)
COVID-19 , Prostatic Neoplasms , COVID-19/drug therapy , Cell Line , Humans , Male , Molecular Docking Simulation , Prostatic Neoplasms/drug therapy , SARS-CoV-2
6.
J Bus Ethics ; : 1-28, 2021 Feb 17.
Article in English | MEDLINE | ID: covidwho-1826598

ABSTRACT

We examine corporate philanthropic decisions in response to the local spread of COVID-19. From a strategic perspective, firms may proactively undertake philanthropic efforts to limit the spread of the pandemic and avoid a degraded business environment. From the perspective of non-trivial costs, increased economic uncertainty can raise concerns about business survival and lead to conservative philanthropic strategies. Following the proverb "prosperity makes friends, adversity tries them," at the provincial level, our results support the second perspective. Specifically, when the spread of the pandemic worsens in a province, local firms are less likely to make COVID-19-related donations in terms of likelihood and amount. Investors also react negatively, not only to the local spread of COVID-19 but also to COVID-19-related philanthropic donations. At the organizational level, our evidence indicates that there is at least some level of cost-benefit analysis underlying corporate philanthropic decisions. Specifically, corporate philanthropic donations, especially those made to the local business environment, are significantly affected by organizational-level factors, such as pre-existing resource availability and motives to acquire political and reputational resources. Overall, our multilevel study presents a comprehensive picture of corporate philanthropic decisions amid the COVID-19 crisis.

7.
Microb Pathog ; 165: 105498, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1814972

ABSTRACT

OBJECTIVE: To estimate the accuracy of clustered regularly interspaced short palindromic repeats (CRISPR) in determining coronavirus disease-19 (COVID-19). METHODS: As of January 31, 2022, PubMed, Web of Science, Embase, Science Direct, Wiley and Springer Link were searched. Sensitivity, specificity, likelihood ratio (LR), diagnostic odds ratio (DOR) and area under the summary receiver-operating characteristic (AUC) curve were used to assess the accuracy of CRISPR. RESULTS: According to the inclusion criteria, 5857 patients from 54 studies were included in this meta-analysis. The pooled sensitivity, specificity and AUC were 0.98, 1.00 and 1.00, respectively. For CRISPR-associated (Cas) proteins-12, the sensitivity, specificity was 0.96, 1.00, respectively. For Cas-13, the sensitivity and specificity were 0.99 and 0.99. CONCLUSION: This meta-analysis showed that the diagnostic performance of CRISPR is close to the gold standard, and it is expected to meet the Point of care requirements in resource poor areas.


Subject(s)
COVID-19 , COVID-19/diagnosis , CRISPR-Cas Systems , Humans
8.
Frontiers in public health ; 10, 2022.
Article in English | EuropePMC | ID: covidwho-1787236

ABSTRACT

Reducing neonatal mortality is an important goal in the Sustainable Development Goals (SDGs), and with the outbreak of the new crown epidemic and severe global inflation, it is extremely important to explore the relationship between inflation and infant mortality. This paper investigates the causal relationship between inflation and infant mortality using a mixed frequency vector autoregressive model (MF-VAR) without any filtering procedure, along with impulse response analysis and forecast misspecification variance decomposition, and compares it with a low frequency vector autoregressive model (LF-VAR). We find that there is a causal relationship between inflation and infant mortality, specifically, that is inflation increases infant mortality. Moreover, the contribution of CPI to IMR is greater in the forecast error variance decomposition in the MF-VAR model compared to the LF-VAR model, indicating that CPI has stronger explanatory power for IMR in mixed-frequency data. The results of the study have important implications for China and other developing countries in reducing infant mortality and achieving the Sustainable Development Goals (SDGs). Policymakers should focus on inflation as a macroeconomic variable that reduces the potential negative impact of inflation on infant mortality. The results of the analysis further emphasize the importance of price stability in the context of global inflation caused by the outbreak of the coronavirus pandemic outbreak.

9.
Adv Sci (Weinh) ; 9(17): e2105904, 2022 06.
Article in English | MEDLINE | ID: covidwho-1782563

ABSTRACT

Infectious virus outbreaks pose a significant challenge to public healthcare systems. Early and accurate virus diagnosis is critical to prevent the spread of the virus, especially when no specific vaccine or effective medicine is available. In clinics, the most commonly used viral detection methods are molecular techniques that involve the measurement of nucleic acids or proteins biomarkers. However, most clinic-based methods require complex infrastructure and expensive equipment, which are not suitable for low-resource settings. Over the past years, smartphone-based point-of-care testing (POCT) has rapidly emerged as a potential alternative to laboratory-based clinical diagnosis. This review summarizes the latest development of virus detection. First, laboratory-based and POCT-based viral diagnostic techniques are compared, both of which rely on immunosensing and nucleic acid detection. Then, various smartphone-based POCT diagnostic techniques, including optical biosensors, electrochemical biosensors, and other types of biosensors are discussed. Moreover, this review covers the development of smartphone-based POCT diagnostics for various viruses including COVID-19, Ebola, influenza, Zika, HIV, et al. Finally, the prospects and challenges of smartphone-based POCT diagnostics are discussed. It is believed that this review will aid researchers better understand the current challenges and prospects for achieving the ultimate goal of containing disease-causing viruses worldwide.


Subject(s)
COVID-19 , Zika Virus Infection , Zika Virus , COVID-19/diagnosis , Clinical Laboratory Techniques , Humans , Laboratories , Point-of-Care Testing , Smartphone , Zika Virus Infection/diagnosis
10.
Front Psychiatry ; 13: 806149, 2022.
Article in English | MEDLINE | ID: covidwho-1785423

ABSTRACT

Objective: During the COVID-19 pandemic, face-to-face intervention services for families of children with autism spectrum disorder (ASD) were limited. This study aimed to evaluate the effectiveness of an 8-week, online-delivered Project ImPACT program for children with ASD and their parents in China during the COVID-19 pandemic. Methods: A pilot non-randomized study with a waitlist control group was conducted in 68 children with ASD and their parents in the Department of Developmental and Behavioral Pediatrics between April 15, 2020 and March 19, 2021. Participants were allocated to either the intervention (IG) or the waitlist group (WLG) according to their order of recruitment. Parents in the IG immediately received 8 weeks of the online-delivered Project ImPACT program, and the WLG received the same program with a delay when the IG had completed all sessions. Participants in both groups received treatment as usual during the research period. Results: The online-delivered Project ImPACT program significantly improved the parent-reported social communication skills of children with ASD. Furthermore, parent's involvement in the training program produced a collateral reduction in parenting stress and an increase in perceived competence in the parental role. Parents rated the program acceptable in terms of curriculum schedule, session content, homework assignments, and therapist feedback. Conclusions: The 8-week, online-delivered Project ImPACT program is a feasible and effective social skill training program for families of children with ASD in China during the COVID-19 pandemic. Due to the methodological limitations, randomized controlled studies with larger sample sizes are suggested to provide more solid evidence.

11.
Front Public Health ; 9: 666135, 2021.
Article in English | MEDLINE | ID: covidwho-1771101

ABSTRACT

BACKGROUND: The implementation of evidence-based approaches by general practitioners (GPs) is new in the primary care setting, and few quantitative studies have evaluated the impact of contextual factors on the attendance of these approaches. METHODS: In total, 892 GPs from 75 community healthcare centers (CHCs) in Shanghai completed our survey. We used logistic regression to analyze factors affecting the number of evidence-based chronic disease programs attended by GPs and whether they had held the lead position in such a program. RESULTS: A total of 346 (38.8%) of the practitioners had never participated in any evidence-based chronic disease prevention (EBCDP) program. The EBCDP interventions in which the GPs had participated were predominantly related to hypertension, diabetes, and cardiovascular disease. However, the proportion of GPs in the lead role was relatively low, between 0.8% (programs involving prevention and control of asthma) and 5.0% (diabetes). Organizational factors and areas were significantly associated with evidence-based practices (EBPs) of the GP, while monthly income and department were the most significantly related to GPs who have the lead role in a program. The results indicated that GPs who had taken the lead position had higher scores for policy and economic impeding factors. GPs who were men, had a higher income, and worked in prevention and healthcare departments and urban areas were more likely to take the lead position. CONCLUSION: Evidence-based programs for chronic diseases should be extended to different types of diseases. Personal, organizational, political, and economic factors and the factors of female sex, lower income, department type, and suburban area environment should be considered to facilitate the translation of evidence to practice.


Subject(s)
General Practitioners , China , Chronic Disease , Female , Humans , Male , Primary Health Care
12.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1743503

ABSTRACT

Infection with SARS-CoV-2, the causative agent of the Coronavirus disease 2019 (COVID-19) pandemic, causes respiratory problems and multifaceted organ dysfunction. A crucial mechanism of COVID-19 immunopathy is the recruitment and activation of neutrophils at the infection site, which also predicts disease severity and poor outcomes. The release of neutrophil extracellular traps (NETs), occurring during a regulated form of neutrophil cell death known as NETosis, is a key effector function that mediates harmful effects caused by neutrophils. Abundant NETosis and NET generation have been observed in the neutrophils of many COVID-19 patients, leading to unfavorable coagulopathy and immunothrombosis. Moreover, excessive NETosis and NET generation are now more widely recognized as mediators of additional pathophysiological abnormalities following SARS-CoV-2 infection. In this minireview, we introduce subtypes of NET-producing neutrophils (e.g., low-density granulocytes) and explain the biological importance of NETs and the protein cargos of NETs in COVID-19. In addition, we discuss the mechanisms by which SARS-CoV-2 causes NETosis by upregulating viral processes (e.g., viral entry and replication) as well as host pro-NET mechanisms (e.g., proinflammatory mediator release, platelet activation, and autoantibody production). Furthermore, we provide an update of the main findings of NETosis and NETs in immunothrombosis and other COVID-19-related disorders, such as aberrant immunity, neurological disorders, and post COVID-19 syndromes including lung fibrosis, neurological disorder, tumor progression, and deteriorated chronic illness. Finally, we address potential prospective COVID-19 treatment strategies that target dysregulated NETosis and NET formation via inhibition of NETosis and promotion of NET degradation, respectively.

13.
Huan Jing Ke Xue ; 43(3): 1268-1276, 2022 Mar 08.
Article in Chinese | MEDLINE | ID: covidwho-1732501

ABSTRACT

Many restrictive measures were implemented in China from January-February 2020 to control the rapid spread of COVID-19. Many studies reported that the COVID-19 lockdown impacted PM2.5, SO2, volatile organic compounds (VOCs), etc. VOCs play important roles in the production of ozone and PM2.5. Ambient VOCs in Xiong'an were measured from December 25, 2019 to January 24, 2020 (prior to epidemic prevention, P1) and from January 25, 2020 to February 24, 2020 (during epidemic prevention, P2) through a VOCs online instrument. In the study, VOCs characteristics and ozone generation potential (OFP) of ambient VOCs were analyzed, and source apportionment of VOCs were analyzed by using Positive Matrix Factorization (PMF). The results showed that φ(TVOCs) during epidemic prevention and control was 45.1×10-9, which was approximately half of that before epidemic prevention and control (90.5×10-9). The chemical composition of VOCs showed significant changes after epidemic prevention and control, the contribution rate of alkanes increased from 37.6% to 53.8%, and the contribution rate of aromatic hydrocarbons and halogenated hydrocarbons decreased from 13.3% and 12.0% to 7.5% and 7.8%, respectively. Aromatic hydrocarbons, halogenated hydrocarbons, and OVOCs decreased by more than 60%. Seven types of the top ten species were the same before and during the epidemic prevention and control, mainly low-carbon alkanes, olefins, aldehydes, and ketones. Dichloromethane, trichloromethane, and BTEXs decreased significantly. The OPP was 566 µg·m-3 and 231 µg·m-3 in P1 and P2, respectively. The OPP of VOCs decreased by more than 30%. The proportion of OFP contribution of aromatic hydrocarbons decreased significantly after the epidemic prevention and control, and the proportion of OFP contribution of alkanes and alkynes increased significantly. Positive matrix factorization (PMF) was then applied for VOCs sources apportionment. Six sources were identified, including background sources, oil-gas volatile sources, combustion sources, industrial sources, solvent use sources, and vehicle exhaust sources. The results showed that after the epidemic prevention and control, the contribution rate of solvent use sources to TVOCs decreased from 24% to 9%. The contribution rates of background sources, oil-gas volatile sources, and combustion sources increased from 13%, 34%, and 24% to 6%, 14%, and 13%, respectively. The relative contributions of vehicle exhaust sources before and after epidemic prevention and control were 21% and 18%, respectively. The observation points were affected by the emission of VOCs from paroxysmal industrial sources before the epidemic prevention and control. The emission was stopped after the epidemic prevention and control, and its contribution rate was reduced from 22% before the epidemic prevention and control to 1%. The concentrations of industrial sources, solvent sources, motor vehicle tail gas sources, and combustion sources decreased by 97%, 82%, 61%, and 15%, respectively, after the epidemic prevention and control. The concentration of background sources remained stable, and the concentration of oil and gas volatile sources increased by 7%. The control of production and traffic activities cannot reduce the emission of VOCs from oil and gas volatile sources, which is the focus of VOCs control in Xiong'an.


Subject(s)
Air Pollutants , COVID-19 , Ozone , Volatile Organic Compounds , Air Pollutants/analysis , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Communicable Disease Control , Environmental Monitoring/methods , Humans , Ozone/analysis , SARS-CoV-2 , Vehicle Emissions/analysis , Volatile Organic Compounds/analysis
14.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315675

ABSTRACT

The fluctuation of water supply is affected by the living habits and population mobility, so the daily water supply is significantly non-stationarity, which presents a great challenge to the water demand prediction based on data-driven model. To solve this problem, the Hodrick-Prescott (HP) and wavelet transform (WT) time series decomposition methods, and ensemble learning (EL) were introduced, coupling model bidirectional long short term memory (BLSTM), seasonal autoregressive integrated moving average (SARIMA) and Gaussian radial basis function neural network (GRBFNN) were developed, and interval prediction was carried out based on student's t-test (T-test). This research method was applied to the daily water demand prediction in Shenzhen and cross-validation was performed. It is found that the decomposed subseries has obvious law, and WT is superior to HP decomposition method. However, the maximum decomposition level (MDL) of WT should not be set too high, otherwise the trend characteristics of subseries will be weakened. The results show that the potential characteristics and quantitative relationships of historical data can be learned accurately based on WT and coupling model. Although the corona virus disease 2019 (COVID-19) outbreak in 2020 caused a variation in water supply law, this variation is still within the interval prediction. The WT and coupling model satisfactorily predicted water demand and provided the lowest mean square error (0.17%), mean relative error (0.1) and mean absolute error (3.32%) and the highest Nash-Sutcliffe efficiency (97.21%) and correlation coefficient (0.99) in testing set.

15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315671

ABSTRACT

Background: The outbreak and the rampant spread of SARS-CoV-2-infected pneumonia (COVID-19) first identified in Wuhan, China, has infected thousands of patients and killed more than two thousand. We aimed to find indicators that could predict the progression of SARS-CoV-2 pneumonia. Methods Medical history, clinical features, laboratory and radiological results were retrospectively reviewed from 112 patients with clinically diagnosed SARS-CoV-2 pneumonia in Renmin Hospital of Wuhan University from Jan 1 to Jan 31, 2020. Clinical outcomes were followed up to Feb 9, 2020. Results Based on their outcomes, we divided these patients into groups of remission, deterioration and death respectively, and analyzed the counts of lymphocyte and its subsets. A decreased combination of CD3+, CD4+ and CD8+ T lymphocyte counts was observed as the SARS-CoV-2 pneumonia progressed. Among them, the CD4+ T lymphocyte counts were reduced at the early stage, while CD8+ counts were decreased at advanced stage or end stage. Conclusions We identified in our study of 112 hospitalized patients that CD3+, CD4+ and CD8+ T lymphocyte counts were useful markers to predict the clinical progression of SARS-CoV-2 pneumonia at different stages. Considering the large number of patients with severe pneumonia, and the urgency of this ongoing global public health emergency, the counts of lymphocyte and its subsets from laboratory examinations could be easy and useful indicators for physicians to determine a timely and proper therapeutic strategy for patients and an early warning sign for predicting or reducing mortality in SARS-CoV-2-infected pneumonia.

16.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315670

ABSTRACT

Telehealth and remote health monitoring have become increasingly important during the SARS-CoV-2 pandemic and it is widely expected that this will have a lasting impact on healthcare practices. These tools can help reduce the risk of exposing patients and medical staff to infection, make healthcare services more accessible, and allow providers to see more patients. However, objective measurement of vital signs is challenging without direct contact with a patient. We present a video-based and on-device optical cardiopulmonary vital sign measurement approach. It leverages a novel multi-task temporal shift convolutional attention network (MTTS-CAN) and enables real-time cardiovascular and respiratory measurements on mobile platforms. We evaluate our system on an Advanced RISC Machine (ARM) CPU and achieve state-of-the-art accuracy while running at over 150 frames per second which enables real-time applications. Systematic experimentation on large benchmark datasets reveals that our approach leads to substantial (20%-50%) reductions in error and generalizes well across datasets.

17.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315360

ABSTRACT

The main protease (Mpro) is one of the best-characterized drug targets among coronaviruses. In the current study, we adopted a multiple cross-docking strategy against different crystal structures of SARS-CoV-2 Mpro to perform computer-based high-throughput virtual screening of possible inhibitors from a drug database using Autodock Vina and SeeSAR software, combined with our in-house automatic processing scripts. The KDs between screened candidates and Mpro were determined using Biacore. Seven drugs were found to fit the substrate-binding pocket of Mpro with a stable conformation, showing high KDs that ranged from 6.79E-7 M to 5.20E-5 M. Finally, mutagenesis studies confirmed that these drugs interact with Mpro specifically, suggesting that our method was reliable and convincing. Given the safety of these old drugs, they may serve as promising candidates to treat the infection of SARS-CoV-2. Our results also provide rational explanations for the behaviour of five drugs evaluated in clinical trials.

18.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315267

ABSTRACT

Background: The current worldwide pandemic of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, and the mortality rate of critical ill patients remains high. The purpose of this study was to identify factors that early predict the progression of COVID-19 from severe to critical illness. Methods: : This retrospective cohort study included adult patients with severe or critical ill COVID-19 who were consecutively admitted to the Zhongfaxincheng campus of Tongji Hospital (Wuhan, China) from February 8 to 18, 2020. Baseline variables, data at hospital admission and during hospital stay, as well as clinical outcomes were collected from electronic medical records system. The primary endpoint was the development of critical illness. A multivariable logistic regression model was used to identify independent factors that were associated with the progression from severe to critical illness. Results: : A total of 138 patients were included in the analysis;of them 119 were diagnosed as severe cases and 16 as critical ill cases at hospital admission. During hospital stay, 19 more severe cases progressed to critical illness. For all enrolled patients, longer duration from diagnosis to admission (odds ratio [OR] 1.108, 95% CI 1.022-1.202;P=0.013), pulse oxygen saturation at admission <93% (OR 5.775, 95% CI 1.257-26.535;P=0.024), higher neutrophil count (OR 1.495, 95% CI 1.177-1.899;P=0.001) and higher creatine kinase-MB level at admission (OR 2.449, 95% CI 1.089-5.511;P=0.030) were associated with a higher risk, whereas higher lymphocyte count at admission (OR 0.149, 95% CI 0.026-0.852;P=0.032) was associated with a lower risk of critical illness development. For the subgroup of severe cases at hospital admission, the above factors except creatine kinase-MB level were also found to have similar correlation with critical illness development. Conclusions: : Higher neutrophil count and lower lymphocyte count at admission were early independent predictors of progression to critical illness in severe COVID-19 patients.

19.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312747

ABSTRACT

Objective: This study investigated the influence of Coronavirus Disease 2019 (COVID-19) on lung function in early convalescence phase. Methods: A prospective retrospective study of COVID-19 patients at the Fifth Affiliated Hospital of Sun Yat-sen University were conducted, with serial assessments including lung volumes (TLC), spirometry (FVC, FEV1), lung diffusing capacity for carbon monoxide (DLCO),respiratory muscle strength, 6-minute walking distance (6MWD) and high resolution CT being collected at 30 days after discharged. Results: 57 patients completed the serial assessments. There were 40 non-severe cases and 17 severe cases. Thirty-one patients (54.3%) had abnormal CT findings. Abnormalities were detected in the pulmonary function tests in 43 (75.4%) of the patients. Six (10.5%), 5(8.7%), 25(43.8%) 7(12.3%), and 30 (52.6%) patients had FVC, FEV1, FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. 28 (49.1%) and 13 (22.8%) patients had PImax and PEmax values less than 80% of the corresponding predicted values. Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6%vs42.5%, p=0.019), higher lung total severity score(TSS)and R20, and significantly lower percentage of predicted TLC and 6MWD. No significant correlation between TSS and pulmonary function parameters was found during follow-up visit. Conclusion: Impaired diffusing-capacityDeclining DLCO, lower respiratory muscle strength, and lung imaging abnormalities were detected in more than half of the COVID-19 patients in early convalescence phase. Compared with non-severe cases, severe patients had a higher incidence of DLCO impairment and encountered more TLC decrease and 6MWD decline.

20.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312729

ABSTRACT

Bond mutual funds holding illiquid assets (e.g., corporate bonds) actively manage their positions in Treasuries to buffer redemption shocks. We argue and show supporting evidence that this liquidity management practice can induce fragility in Treasury prices. We find that Treasury pairs commonly held by bond funds exhibit higher return comovement than pairs with little fund common ownership. This effect is more pronounced during downside markets or when funds experience large outflows, but is weak for corporate bond pairs. We address endogeneity concerns by exploiting two plausibly exogenous events: the outbreak of COVID-19 and the 2003 mutual fund scandal.

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