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1.
Physics of fluids (Woodbury, N.Y. : 1994) ; 33(12), 2021.
Article in English | EuropePMC | ID: covidwho-1602666

ABSTRACT

The continuance of the COVID-19 pandemic largely depends on the spread of virus-carrying aerosols in ambient air. The mechanism of virus transmission and infection remains under intense investigation. In this study, an evaporation flow model of airborne sputum droplets is proposed which considers the evolution effects of the humidity field under different particle distributions and solid/salt fraction interactions. The incompressible Navier–Stokes equations characterize a stream of airflow jets, and the convection-diffusion-evaporation process is used to account for the inhomogeneous humidity field caused by the respiratory tract. Momentum equations for droplet dynamics which involve the effects of drag, gravity, and Brownian motion on sputum droplets are introduced to quantify the transport of droplets in a humidity field. The Lattice Boltzmann method is used to track the evolution of the aerosol in space and time under different ambient temperature and relative humidity conditions. The results of the simulation demonstrate that airborne humidity accelerates the evaporation rate of droplet, while supersaturated humid air forms a vapor mass in front of the respiratory tract. Despite the short lifespan of this phenomenon, it significantly hinders the evaporation of the droplets. Besides, the droplet vortex dynamics in a humidity field are sensitive to the droplet size.

2.
Preprint | EuropePMC | ID: ppcovidwho-296793

ABSTRACT

Purpose: This study aimed to explore the influences of online support of an Internet plus Shared Care diabetes management model on metabolic indicators and the differences before and after the coronavirus disease 2019 (COVID-19) pandemic. Method: Type 2 diabetes patients who visited the Peking University First Hospital Internet plus Shared Care clinic from May 18, 2020 to June 20, 2020 (after the COVID-19 pandemic subsided) were enrolled in the study. The age, gender, usage of insulin, and duration of diabetes of the patients were collected. The glycosylated hemoglobin (HbA1c), interval between two consecutive visits, communication frequencies with online diabetes educators through an app, online self-monitoring of blood glucose (SMBG) and upload count and SMBG pairing count (before–after meal) were collected before (prior to January 20, 2020) and after (from May 18, 2020 to June 20, 2020) the COVID-19 pandemic for logistic regression analysis. The R-3.4.4 and TWANG programs were used for analysis. The group of patients whose HbA1c did not change during the pandemic was the control group, while the group of patients with improved HbA1c was the dependent variable. Independent variables included age, gender, duration of disease, insulin usage, online communication amount, SMBG count, and SMBG pairing count. Propensity score matching (PSM) was applied with age, duration, gender, body mass index (BMI), HbA1c, low density lipoprotein- cholesterol (LDL-C), and blood pressure (BP) at baseline as the concomitant variable. After the PSM weighting, the average treatment effect (ATE) of post-pandemic BMI, HbA1c, LDL-C, and BP was compared with the baseline. Results: A total of 387 patients were enrolled in the study including 184 female (47.5%). The baseline values were the following: age, 61.7±9.4 year;, duration of diabetes, 11.7±8.2 years;BMI, 25.9±3.8Kg/m 2 ;HbA1c, 7.2±1.3%;LDL-C, 2.49±0.85mmol/L;systolic BP, 130.8±14.9 mmHg;and diastolic BP, 81.1±40.9 mmHg. Among variables, online communication amounted to a statistically significant contribution to the HbA1c improvement after the COVID-19 pandemic (OR=2.178, p=0.003). During the pandemic, each patient received 18 (3, 56) times online communication support per quarter. Patients were divided into four groups by quartiles: Q1 (more than 56 times/quarter, n=95), Q2 (18–56 times/quarter, n=97), Q3 (3–18 times/quarter, n=93), and Q4 (0–3 times/quarter, n=102). After PSM, post-pandemic data showed significant differences. Between-group variance was found in HbA1c (Q1 vs. Q3, -0.42±0.16%, p=0.009;Q1 vs. Q4, -0.53±0.15%, p=0.0009) and BMI (Q1 vs. Q3, -1.2±0.5, p=0.02;Q1 vs. Q4 -1.5±0.7, p=0.01) of patients. Conclusion: During the COVID-19 pandemic, high-quality online support of the Internet plus Shared Care diabetes management model can significantly improve the HbA1c and BMI of type 2 diabetes patients.

3.
Sensors (Basel) ; 21(23)2021 Nov 23.
Article in English | MEDLINE | ID: covidwho-1560624

ABSTRACT

Non-contact physiological measurements based on image sensors have developed rapidly in recent years. Among them, thermal cameras have the advantage of measuring temperature in the environment without light and have potential to develop physiological measurement applications. Various studies have used thermal camera to measure the physiological signals such as respiratory rate, heart rate, and body temperature. In this paper, we provided a general overview of the existing studies by examining the physiological signals of measurement, the used platforms, the thermal camera models and specifications, the use of camera fusion, the image and signal processing step (including the algorithms and tools used), and the performance evaluation. The advantages and challenges of thermal camera-based physiological measurement were also discussed. Several suggestions and prospects such as healthcare applications, machine learning, multi-parameter, and image fusion, have been proposed to improve the physiological measurement of thermal camera in the future.

4.
Cell Biosci ; 11(1): 199, 2021 Dec 05.
Article in English | MEDLINE | ID: covidwho-1556288

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible and has caused a pandemic named coronavirus disease 2019 (COVID-19), which has quickly spread worldwide. Although several therapeutic agents have been evaluated or approved for the treatment of COVID-19 patients, efficacious antiviral agents are still lacking. An attractive therapeutic target for SARS-CoV-2 is the main protease (Mpro), as this highly conserved enzyme plays a key role in viral polyprotein processing and genomic RNA replication. Therefore, the identification of efficacious antiviral agents against SARS-CoV-2 Mpro using a rapid, miniaturized and economical high-throughput screening (HTS) assay is of the highest importance at the present. RESULTS: In this study, we first combined the fluorescence polarization (FP) technique with biotin-avidin system (BAS) to develop a novel and step-by-step sandwich-like FP screening assay to quickly identify SARS-CoV-2 Mpro inhibitors from a natural product library. Using this screening assay, dieckol, a natural phlorotannin component extracted from a Chinese traditional medicine Ecklonia cava, was identified as a novel competitive inhibitor against SARS-CoV-2 Mpro in vitro with an IC50 value of 4.5 ± 0.4 µM. Additionally, dieckol exhibited a high affinity with SARS-CoV-2 Mpro using surface plasmon resonance (SPR) analysis and could bind to the catalytic sites of Mpro through hydrogen-bond interactions in the predicted docking model. CONCLUSIONS: This innovative sandwich-like FP screening assay enables the rapid discovery of antiviral agents targeting viral proteases, and dieckol will be an excellent lead compound for generating more potent and selective antiviral agents targeting SARS-CoV-2 Mpro.

5.
Methods ; 2021 Sep 23.
Article in English | MEDLINE | ID: covidwho-1433917

ABSTRACT

The coronavirus disease 2019 (COVID-19) has outbreak since early December 2019, and COVID-19 has caused over 100 million cases and 2 million deaths around the world. After one year of the COVID-19 outbreak, there is no certain and approve medicine against it. Drug repositioning has become one line of scientific research that is being pursued to develop an effective drug. However, due to the lack of COVID-19 data, there is still no specific drug repositioning targeting the COVID-19. In this paper, we propose a framework for COVID-19 drug repositioning. This framework has several advantages that can be exploited: one is that a local graph aggregating representation is used across a heterogeneous network to address the data sparsity problem; another is the multi-hop neighbors of the heterogeneous graph are aggregated to recall as many COVID-19 potential drugs as possible. Our experimental results show that our COVDR framework performs significantly better than baseline methods, and the docking simulation verifies that our three potential drugs have the ability to against COVID-19 disease.

6.
Front Cell Neurosci ; 15: 682272, 2021.
Article in English | MEDLINE | ID: covidwho-1295666

ABSTRACT

Human cerebral organoid (CO) is a three-dimensional (3D) cell culture system that recapitulates the developing human brain. While CO has proved an invaluable tool for studying neurological disorders in a more clinically relevant matter, there have still been several shortcomings including CO variability and reproducibility as well as lack of or underrepresentation of certain cell types typically found in the brain. As the technology to generate COs has continued to improve, more efficient and streamlined protocols have addressed some of these issues. Here we present a novel scalable and simplified system to generate microglia-containing CO (MCO). We characterize the cell types and dynamic development of MCOs and validate that these MCOs harbor microglia, astrocytes, neurons, and neural stem/progenitor cells, maturing in a manner that reflects human brain development. We introduce a novel technique for the generation of embryoid bodies (EBs) directly from induced pluripotent stem cells (iPSCs) that involves simplified steps of transitioning directly from 3D cultures as well as orbital shaking culture in a standard 6-well culture plate. This allows for the generation of MCOs with an easy-to-use system that is affordable and accessible by any general lab.

7.
Sci Adv ; 7(27)2021 Jul.
Article in English | MEDLINE | ID: covidwho-1295156

ABSTRACT

Transmission-blocking vaccines are urgently needed to reduce transmission of SARS-CoV 2, the cause of the COVID-19 pandemic. The upper respiratory tract is an initial site of SARS-CoV-2 infection and, for many individuals, remains the primary site of virus replication. An ideal COVID-19 vaccine should reduce upper respiratory tract virus replication and block transmission as well as protect against severe disease. Here, we optimized a vaccine candidate, parainfluenza virus 5 (PIV5) expressing the SARS-CoV-2 S protein (CVXGA1), and then demonstrated that a single-dose intranasal immunization with CVXGA1 protects against lethal infection of K18-hACE2 mice, a severe disease model. CVXGA1 immunization also prevented virus infection of ferrets and blocked contact transmission. This mucosal vaccine strategy inhibited SARS-CoV-2 replication in the upper respiratory tract, thus preventing disease progression to the lower respiratory tract. A PIV5-based mucosal vaccine provides a strategy to induce protective innate and cellular immune responses and reduce SARS-CoV-2 infection and transmission in populations.

8.
Sheng Wu Gong Cheng Xue Bao ; 37(4): 1334-1345, 2021 Apr 25.
Article in Chinese | MEDLINE | ID: covidwho-1209675

ABSTRACT

The main protease (Mpro) of SARS-CoV-2 is a highly conserved and mutation-resistant coronaviral enzyme, which plays a pivotal role in viral replication, making it an ideal target for the development of novel broad-spectrum anti-coronaviral drugs. In this study, a codon-optimized Mpro gene was cloned into pET-21a and pET-28a expression vectors. The recombinant plasmids were transformed into E. coli Rosetta(DE3) competent cells and the expression conditions were optimized. The highly expressed recombinant proteins, Mpro and Mpro-28, were purified by HisTrapTM chelating column and its proteolytic activity was determined by a fluorescence resonance energy transfer (FRET) assay. The FRET assay showed that Mpro exhibits a desirable proteolytic activity (25 000 U/mg), with Km and kcat values of 11.68 µmol/L and 0.037/s, respectively. The specific activity of Mpro is 25 times that of Mpro-28, a fusion protein carrying a polyhistidine tag at the N and C termini, indicating additional residues at the N terminus of Mpro, but not at the C terminus, are detrimental to its proteolytic activity. The preparation of active SARS-CoV-2 Mpro through codon-optimization strategy might facilitate the development of the rapid screening assays for the discovery of broad-spectrum anti-coronaviral drugs targeting Mpro.


Subject(s)
COVID-19 , SARS-CoV-2 , Codon/genetics , Cysteine Endopeptidases/genetics , Escherichia coli/genetics , Humans , Peptide Hydrolases , Viral Nonstructural Proteins/genetics
9.
Preprint in English | medRxiv | ID: ppmedrxiv-21253375

ABSTRACT

The ongoing COVID-19 pandemic has created an urgent need for antiviral treatments that can be deployed rapidly. Drug repurposing represents a promising means of achieving this objective, but repurposing efforts are often unsuccessful. A common hurdle to effective drug repurposing is a failure to achieve a sufficient therapeutic window in the new indication. A clear example is the use of ivermectin in COVID-19, where the approved dose (administered orally) fails to achieve therapeutic concentrations in the lungs. Our proposed solution to the problem of ineffective drug repurposing for COVID-19 antivirals is two-fold: to broaden the therapeutic window by reformulating therapeutics for the pulmonary route, and to select drug repurposing candidates based on their model-predicted therapeutic index for inhalation. In this article, we propose a two-stage model-driven screening and validation process for selecting inhaled antiviral drug repurposing candidates. While we have applied this approach in the specific context of COVID-19, this in vitro-in vivo translational methodology is also broadly applicable to repurposing drugs for diseases of the lower respiratory tract.

10.
Preprint in English | bioRxiv | ID: ppbiorxiv-432379

ABSTRACT

The duration of natural immunity in response to SARS-CoV-2 is a matter of some debate in the literature at present. For example, in a recent publication characterizing SARS-CoV-2 immunity over time, the authors fit pooled longitudinal data, using fitted slopes to infer the duration of SARS-CoV-2 immunity. In fact, such approaches can lead to misleading conclusions as a result of statistical model-fitting artifacts. To exemplify this phenomenon, we reanalyzed one of the markers (pseudovirus neutralizing titer) in the publication, using mixed-effects modeling, a methodology better suited to longitudinal datasets like these. Our findings showed that the half-life was both longer and more variable than reported by the authors. The example selected by us here illustrates the utility of mixed-effects modeling in provide more accurate estimates of the duration and heterogeneity of half-lives of molecular and cellular biomarkers of SARS-CoV-2 immunity.

11.
Sci Rep ; 10(1): 20021, 2020 11 18.
Article in English | MEDLINE | ID: covidwho-933724

ABSTRACT

An ongoing novel coronavirus outbreak (COVID-19) started in Wuhan, China, in December 2019. Currently, the spatiotemporal epidemic transmission, prediction, and risk are insufficient for COVID-19 but we urgently need relevant information globally. We have developed a novel two-stage simulation model to simulate the spatiotemporal changes in the number of cases and estimate the future worldwide risk. Simulation results show that if there is no specific medicine for it, it will form a global pandemic. Taiwan, South Korea, Hong Kong, Japan, Thailand, and the United States are the most vulnerable. The relationship between each country's vulnerability and days before the first imported case occurred shows an exponential decrease. We successfully predicted the outbreak of South Korea, Japan, and Italy in the early stages of the global pandemic based on the information before February 12, 2020. The development of the epidemic is now earlier than we expected. However, the trend of spread is similar to our estimation.


Subject(s)
COVID-19/epidemiology , Models, Statistical , Pandemics/statistics & numerical data , COVID-19/transmission , Humans , Spatio-Temporal Analysis
13.
Preprint in English | medRxiv | ID: ppmedrxiv-20034876

ABSTRACT

BackgroundSince late December 2019, the outbreak of the novel coronavirus disease, COVID-19, that began in Wuhan, has become endemic in China and more than 100 countries and regions in the world. So far, there is rare data on the prevalence of COVID-19 in patients with chronic myelogenous leukemia (CML). We aimed to describe the clinical course, outcomes of CML patients with COVID-19 and prevalence of COVID-19 in CML patients. MethodsIn this multicentre, cross-sectional survey, the clinical data of CML patients with COVID-19 in each center were collected. Simultaneously, an online survey was conducted for information about the CML patients under the management at each center by asking the CML patients to complete a questionnaire,from February 15, 2020 to February 21, 2020. The questionnaire includes demographic data, place of residence, smoking status, CML diagnosis and treatment, comorbidities, combined medications, epidemiological history, symptoms(fever, cough, shortness of breath, etc) during the epidemic. Additional clinical data was collected on respondents suspected or confirmed to have COVID-19. We described and analyzed the prevalence of COVID-19 in CML patients, and focus on the clinical characteristics and outcomes of COVID-19 patients. Data were compared between the CML patients with optimal response and those with non-optimal response. The primary outcome was prevalence of COVID-19 in CML patients, as of Feb 21, 2020. Secondary outcomes included the history of epidemiology of CML patients, the clinical characteristics and outcomes of CML patients with COVID-19. FindingsOf 392 respondents, 223(56.9%) were males, and 240(61.2%) were 50 years or younger. Only 10 patients took drugs irregularly due to the influence of the epidemic because of traffic control, pharmacies unable to operate normally, etc. In the history of epidemiology, there were 4 patients with definite contact with COVID-19, of which 3 were remote contact and 1 was close contact. 12 respondents had fever, cough or shortness of breath during the epidemic, 1 case (common type) was confirmed with COVID-19 and cured after treatment. 1 patient was clinically diagnosed and succumbed. 1 of 299 (0.3%) patients with an optimal response was diagnosed with COVID-19. Of the 50 patients who failed to respond to CML treatment or had a poor response, 1 patient (2%) had a clinical diagnosis of COVID-19. InterpretationWhile the 392 CML respondents required regular referrals to hospitals, they did not have much contact with COVID-19 patients during the outbreak. Patients who failed to achieved an optimal response to CML therapy appear more likely to have a symptomatic infection with SARS-CoV-2. Older patients with comorbidities are at increased risk of death. FundingThis work was supported by grants from the National Natural Science Foundation of China(NSFC)(81873440&81700142).

14.
Sci China Life Sci ; 63(5): 706-711, 2020 05.
Article in English | MEDLINE | ID: covidwho-5706

ABSTRACT

Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P=0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Overall, the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.


Subject(s)
Asymptomatic Infections , Betacoronavirus , Clinical Laboratory Techniques , Coronavirus Infections , Pandemics , Pneumonia, Viral , COVID-19 , COVID-19 Testing , China , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/transmission , Humans , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Pneumonia, Viral/transmission , SARS-CoV-2 , Tomography, X-Ray Computed
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