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1.
Signal Transduct Target Ther ; 7(1): 114, 2022 Apr 05.
Article in English | MEDLINE | ID: covidwho-1778593

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.


Subject(s)
Antibodies, Monoclonal , Antibodies, Viral , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Antibodies, Monoclonal/chemistry , Antibodies, Viral/chemistry , COVID-19 , Cryoelectron Microscopy , Humans , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology
2.
Front Med (Lausanne) ; 9: 840498, 2022.
Article in English | MEDLINE | ID: covidwho-1775703

ABSTRACT

With the continuous development of computer technology, big data acquisition and imaging methods, the application of artificial intelligence (AI) in medical fields is expanding. The use of machine learning and deep learning in the diagnosis and treatment of ophthalmic diseases is becoming more widespread. As one of the main causes of visual impairment, myopia has a high global prevalence. Early screening or diagnosis of myopia, combined with other effective therapeutic interventions, is very important to maintain a patient's visual function and quality of life. Through the training of fundus photography, optical coherence tomography, and slit lamp images and through platforms provided by telemedicine, AI shows great application potential in the detection, diagnosis, progression prediction and treatment of myopia. In addition, AI models and wearable devices based on other forms of data also perform well in the behavioral intervention of myopia patients. Admittedly, there are still some challenges in the practical application of AI in myopia, such as the standardization of datasets; acceptance attitudes of users; and ethical, legal and regulatory issues. This paper reviews the clinical application status, potential challenges and future directions of AI in myopia and proposes that the establishment of an AI-integrated telemedicine platform will be a new direction for myopia management in the post-COVID-19 period.

3.
Mamm Genome ; 33(1): 143-156, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1767484

ABSTRACT

Mouse models are essential for dissecting disease mechanisms and defining potential drug targets. There are more than 18,500 mouse strains available for research communities in National Resource Center for Mutant Mice (NRCMM) of China, affiliated with Model Animal Research Center of Nanjing University and Gempharmatech Company. In 2019, Gempharmatech launched the Knockout All Project (KOAP) aiming to generate null mutants and gene floxed strains for all protein-coding genes in mouse genome within 5 years. So far, KOAP has generated 8,004 floxed strains and 9,769 KO (knockout) strains (updated to Oct, 2021). NRCMM also created hundreds of Cre transgenic lines, mutant knock-in models, immuno-deficient models, and humanized mouse models. As a member of the international mouse phenotyping consortium (IMPC), NRCMM provides comprehensive phenotyping services for mouse models. In summary, NRCMM will continue to support biomedical community with new mouse models as well as related services.

4.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329978

ABSTRACT

At the beginning of 2022 the global daily count of new cases of COVID-19 exceeded 3.2 million, a tripling of the historical peak value reported between the initial outbreak of the pandemic and the end of 2021. Aerosol transmission through interpersonal contact is the main cause of the disease’s spread, although control measures have been put in place to reduce contact opportunities. Mobility pattern is a basic mechanism for understanding how people gather at a location and how long they stay there. Due to the inherent dependencies in disease transmission, models for associating mobility data with confirmed cases need to be individually designed for different regions and time periods. In this paper, we propose an autoregressive count data model under the framework of a generalized linear model to illustrate a process of model specification and selection. By evaluating a 14-day-ahead prediction from Sweden, the results showed that for a dense population region, mobility data with a lag of 8 days is most reliable way of predicting the number of confirmed cases in relative numbers at a high coverage rate. It is sufficient for both of the autoregressive terms, studied variable and conditional expectation, to take one day back. For sparsely populated regions, a lag of 10 days produced the lowest error in absolute value for the predictions, where weekly periodicity on the studied variable is recommended for use. Interventions were further included to identify the most relevant mobility categories. Statistical features were also presented to verify the model assumptions.

5.
Clin Infect Dis ; 74(4): 630-638, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1699192

ABSTRACT

BACKGROUND: Knowledge of COVID-19 epidemiology remains incomplete and crucial questions persist. We aimed to examine risk factors for COVID-19 death. METHODS: A total of 80 543 COVID-19 cases reported in China, nationwide, through 8 April 2020 were included. Risk factors for death were investigated by Cox proportional hazards regression and stratified analyses. RESULTS: Overall national case-fatality ratio (CFR) was 5.64%. Risk factors for death were older age (≥80: adjusted hazard ratio, 12.58; 95% confidence interval, 6.78-23.33), presence of underlying disease (1.33; 1.19-1.49), worse case severity (severe: 3.86; 3.15-4.73; critical: 11.34; 9.22-13.95), and near-epicenter region (Hubei: 2.64; 2.11-3.30; Wuhan: 6.35; 5.04-8.00). CFR increased from 0.35% (30-39 years) to 18.21% (≥70 years) without underlying disease. Regardless of age, CFR increased from 2.50% for no underlying disease to 7.72% for 1, 13.99% for 2, and 21.99% for ≥3 underlying diseases. CFR increased with worse case severity from 2.80% (mild) to 12.51% (severe) and 48.60% (critical), regardless of region. Compared with other regions, CFR was much higher in Wuhan regardless of case severity (mild: 3.83% vs 0.14% in Hubei and 0.03% elsewhere; moderate: 4.60% vs 0.21% and 0.06%; severe: 15.92% vs 5.84% and 1.86%; and critical: 58.57% vs 49.80% and 18.39%). CONCLUSIONS: Older patients regardless of underlying disease and patients with underlying disease regardless of age were at elevated risk of death. Higher death rates near the outbreak epicenter and during the surge of cases reflect the deleterious effects of allowing health systems to become overwhelmed.


Subject(s)
COVID-19 , China/epidemiology , Disease Outbreaks , Humans , Proportional Hazards Models , Risk Factors , SARS-CoV-2
6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325310

ABSTRACT

Background: COVID-19 is a global pandemic and an anxiety-provoking event. Therefore, a study was conducted to identify potential risk and protective factors related to anxiety during COVID-19 pandemic. Methods: : We collected information on demographic data and lifestyles by conducting a web-based survey of 19,802 participants from 34 provinces in China during COVID-19 pandemic. Level of anxiety was evaluated using the Self-Rating Anxiety Scale. We used ordinal multivariable logistic regression to estimate the associations of anxiety level with potential risk and protective factors, and further developed a new score to simplify the assessment of anxiety disorder during COVID-19 crisis. Results: : Among 19,802 participants (mean [SD] age, 25.3 [8.1], years;10,121 [51.1%] men), we found that those who were front-line medical personnel, suffered from chronic diseases, with present symptom of SARS-CoV-2 infection or contact history had 112%, 93%, 40% and 15% increase risk of higher anxiety level;while those with knowledge about personal protective measures or wore masks had 75% and 29% lower risk of higher anxiety level respectively. We developed a risk score by calculating the sum of single score of 17 factors. Each one increase of the risk score was associated with a 297% increase in anxiety index score. In categorical analysis, low risk (the risk score between 1 to 2), the moderate risk group (the risk score of 3) and high risk group (the risk score ≥4) had a -0.40 (95% CI: -1.55, 0.76), 1.44 (95% CI: 0.27, 2.61) and 9.18 (95% CI: 8.04, 10.33) increase in anxiety index score, and a 26% (95% CI: -7%, 72%), 172% (95% CI: 100%, 270%), and 733% (95% CI: 516%, 1026%) higher risk of anxiety disorder respectively, when compared with the very low risk group (the risk score of 0). The AUC was 0.73 (95% CI: 0.72, 0.74) for the model fitted the developed risk score, with the cut-off point of 3.5. Conclusions: : These findings revealed protective and risk factors associated with anxiety disorder, and propose a practical and simple method of identifying people who are at an increased risk of anxiety disorder during COVID-19 pandemic.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323604

ABSTRACT

Background: : Dental departments generally employ cone-beam computed tomography (CBCT) instead of conventional computed tomography (CT), due to its lower price, smaller dosage, and high spatial resolution. During the corona virus disease 2019 (COVID-19) outbreak, CBCT is highly recommended to replace intraoral radiography because it greatly reduces the risk of exposure to salivary droplets. However, CBCT's inability to quantitatively measure tissue attenuation limits its application in differential diagnosis. Methods: : We employed a U-Net based network to generate synthetic CT from dental CBCT. The deep neural network can be trained end-to-end to learn the complex mapping between CBCT and CT values. By the U-Net architecture, low-level and high-level features are both utilized to get fine detailed synthetic CT. We applied our method on the collected dataset contains 62 patients. Results: : Experimental results on four metrics -- mean absolute error (MAE), root-mean-square error (RMSE), structural similarity index (SSIM), and peak-signal-to-noise ratio (PSNR) -- showed significant improvement of the synthetic CT compared to the original CBCT data. The MAE and RMSE improvement percentages are 64.44% and 66.44%.The MAE level of synthetic CT for most of the tissues are small enough to separate most important tissues,including dentin and cancellous bone, dentin and root canal,implants and cortical bone. Conclusions: : CBCT and synthetic CT values can be used to distinguish different high-attenuation structures that are of interest to dentists. The application of CBCT assisted by this U-net based network in medical imaging of other parts of the body is promising.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309643

ABSTRACT

Background: To share our experiences of resumption of the treatment for gynecologic patients after lifting lockdown in a hotspot area of the Corona Virus Disease 2019 (COVID-19)pandemic. Methods: The triage process used to resume the medical activities for gynecologic patients at the Wuhan Union Hospital after a 76-day lockdown of the city is described and its effectiveness to avoid COVID-19 nosocomial transmission is shown. Results: The non-emergency patients are pre-triaged by contact history and body temperature at outpatient clinic and negative COVID-19 screening tests are required for an admissionin the buffering rooms at the gynecologic department. The buffering lastsfor at least three days for symptom monitoring and a second round of COVID-19 tests before they can be transferred to the regular gynecologic wards. For patients who need emergency surgery, the first screening should be completed at the quarantine wards after the surgery, followed by buffering at the gynecologic department. We received 19298 outpatient visits, admitted 326 patients, and performed 223 operations in the first two months after the lockdown was lifted, andno single COVID-19 case occurredin the hospitalized patients while the proportion of potentially high-risk patients with cancer and severe anemia were increased in comparison with the same period in 2019 and the latest two months before the lockdown. Conclusions: We provide an effective triage system with buffering at two levels to guarantee safe and timely treatment for non-COVID-19 gynecologic patients in a post-lockdown phase.

9.
Sustainability ; 14(3):1487, 2022.
Article in English | ProQuest Central | ID: covidwho-1686999

ABSTRACT

The sustainability of market performance of mobile applications (apps) updates is a vital goal for e-commerce firms to continuously innovate for products and functions. E-commerce firms must formulate effective app update strategies and tackle the temporal uncertainties associated with different types of app updates. However, the existing literature on app updates mainly focuses on the effects of update frequency. At the same time, scant attention has been paid to clarifying the temporal effects of different types of app updates. Accordingly, based on the framework of exploration vs. exploitation, we investigate the temporal effects of different kinds of app updates on market performance in the hypercompetitive context of online travel mobile applications. We collected data on release notes and downloads of seven Chinese online travel apps available from the Android Market from April 2013 to January 2015;conducted structured content analysis to identify different types of app updates;and adopted the feasible generalized least-squares (FGLS) estimation to test our model. We found that exploitative app updates have an instant and continuous positive impact on market performance, while explorative app updates have no significant effect in the short term but will have a positive effect on market performance in the long term. Moreover, competition intensity shortens the duration of the positive effect of exploitative app updates and delays the time that explorative app updates have to take effect. By studying the different impacts that two types of app updates have on market performance from a time dimension, this study helps resolve the mixed findings on the effects of app updates and guides e-commerce firms on how to effectively formulate app update strategies in a hypercompetitive context.

10.
Healthcare (Basel) ; 10(2)2022 Jan 29.
Article in English | MEDLINE | ID: covidwho-1667118

ABSTRACT

During the first year of the coronavirus disease 2019 (COVID-19) pandemic, prevention measures included quarantining and facility closures. Because cancer screening is dependent on interventions in facilities, the extent of the COVID-19 impact on screening was questioned. A claims registry from a large health system was queried for colorectal and prostate cancer screening. A screening gap and screening loss ratio were calculated by comparing 2020 screening to historical reference years. All cancer screenings decreased in the first four months of the pandemic. Colorectal cancer screening returned to baseline in the latter six months of 2020. Prostate cancer screening exceeded baseline in the latter six months, but with a lesser gain than previous years. Populations disproportionately affected by decreased cancer screening included men and black people. To catch-up after the initial deficit in screening, it is estimated that the rate of colorectal cancer screening needs to increase by 50%.

11.
BMC Infect Dis ; 21(1): 1282, 2021 Dec 27.
Article in English | MEDLINE | ID: covidwho-1634834

ABSTRACT

BACKGROUND: The temporal relationship between SARS-CoV-2 and antibody production and clinical progression remained obscure. The aim of this study was to describe the viral kinetics of symptomatic patients with SARS-CoV-2 infection and identify factors that might contribute to prolonged viral shedding. METHODS: Symptomatic COVID-19 patients were enrolled in two hospitals in Wuhan, China, from whom the respiratory samples were collected and measured for viral loads consecutively by reverse transcriptase quantitative PCR (RT-qPCR) assay. The viral shedding pattern was delineated in relate to the epidemiologic and clinical information. RESULTS: Totally 2726 respiratory samples collected from 703 patients were quantified. The SARS-CoV-2 viral loads were at the highest level during the initial stage after symptom onset, which subsequently declined with time. The median time to SARS-CoV-2 negativity of nasopharyngeal test was 28 days, significantly longer in patients with older age (> 60 years old), female gender and those having longer interval from symptom onset to hospital admission (> 10 days). The multivariate Cox regression model revealed significant effect from older age (HR 0.73, 95% CI 0.55-0.96), female gender (HR 0.72, 95% CI 0.55-0.96) and longer interval from symptom onset to admission (HR 0.44, 95% CI 0.33-0.59) on longer time to SARS-CoV-2 negativity. The IgM antibody titer was significantly higher in the low viral loads group at 41-60 days after symptom onset. At the population level, the average viral loads were higher in early than in late outbreak periods. CONCLUSIONS: The prolonged viral shedding of SARS-CoV-2 was observed in COVID-19 patients, particularly in older, female and those with longer interval from symptom onset to admission.


Subject(s)
COVID-19 , Aged , Female , Humans , Middle Aged , Prospective Studies , RNA, Viral , SARS-CoV-2 , Viral Load , Virus Shedding
12.
PLoS One ; 16(12): e0261707, 2021.
Article in English | MEDLINE | ID: covidwho-1623660

ABSTRACT

The objective of this retrospective cohort study was to describe pre-treatment characteristics, treatment patterns, health resource use, and clinical outcomes among adults hospitalized with COVID-19 in the United States (US) who initiated common treatments for COVID-19. The Optum® COVID-19 electronic health records database was used to identify patients >18 years, diagnosed with COVID-19, who were admitted to an inpatient setting and received treatments of interest for COVID-19 between September 2020 and January 2021. Patients were stratified into cohorts based on index treatment use. Patient demographics, medical history, care setting, medical procedures, subsequent treatment use, patient disposition, clinical improvement, and outcomes were summarized descriptively. Among a total of 26,192 patients identified, the most prevalent treatments initiated were dexamethasone (35.4%) and dexamethasone + remdesivir (14.9%), and dexamethasone was the most common subsequent treatment. At day 14 post-index, <10% of patients received any treatments of interest. Mean (standard deviation [SD]) patient age was 65.6 (15.6) years, and the most prevalent comorbidities included hypertension (44.8%), obesity (35.4%), and diabetes (25.7%). At the end of follow-up, patients had a mean (SD) 8.1 (6.6) inpatient days and 1.4 (4.1) days with ICU care. Oxygen supplementation, non-invasive, or invasive ventilation was required by 4.5%, 3.0%, and 3.1% of patients, respectively. At the end of follow-up, 84.2% of patients had evidence of clinical improvement, 3.1% remained hospitalized, 83.8% were discharged, 4% died in hospital, and 9.1% died after discharge. Although the majority of patients were discharged alive, no treatments appeared to alleviate the inpatient morbidity and mortality associated with COVID-19. This highlights an unmet need for effective treatment options for patients hospitalized with COVID-19.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Dexamethasone/therapeutic use , Hypertension/epidemiology , Obesity/epidemiology , Patient Discharge , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Adenosine Monophosphate/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Alanine/therapeutic use , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Comorbidity , Drug Therapy, Combination/methods , Female , Follow-Up Studies , Humans , Male , Middle Aged , RNA, Viral/genetics , Retrospective Studies , Treatment Outcome , United States/epidemiology , Young Adult
13.
Journal of Pest Science ; 95(1):159-168, 2022.
Article in English | Academic Search Complete | ID: covidwho-1616171

ABSTRACT

Spodoptera frugiperda has been reported in China since the beginning of 2019, threatening maize production and raising questions about interactions with indigenous pests on maize. Spodoptera frugiperda is in the same feeding guild as the indigenous species Ostrinia furnacalis, with both pests attacking maize plant tissues such as whorls and tassels. In this study, the interaction of these species was assessed under laboratory and field conditions by examining the survival and predation rate of larvae in maize whorls and tassels. Intraspecific and interspecific interactions of larvae were assessed to characterize movements in arenas in the presence and absence of food. When S. frugiperda and O. furnacalis were present at an equal ratio, S. frugiperda prevailed over O. furnacalis with a high survival rate (over 90%) and predation rate of O. furnacalis (over 40%) under most scenarios in both laboratory and field conditions. When both species occurred at different ratios in the field, S. frugiperda had on average almost 16 times the number of survivors as O. furnacalis on whorls, and 8.3 times the number on tassels, highlighting a substantial advantage in these environments. Spodoptera frugiperda larvae undertook a low frequency of lethal attacks (strikes) and showed a higher incidence of defensive movements compared to O. furnacalis. A field survey showed that S. frugiperda larvae can colonize vegetative plant stages in maize, but it remains to be seen if competitive interactions can be linked to population dynamics of both species though they are expected to favor S. frugiperda. [ FROM AUTHOR] Copyright of Journal of Pest Science is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

14.
Phytomedicine ; 97: 153922, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1586870

ABSTRACT

BACKGROUND: Although Qing-Fei-Pai-Du decoction (QFPDD) is extensively used clinically to treat COVID-19 patients, the mechanism by which it modulates the immunological and metabolic functions of liver tissue remains unknown. PURPOSE: The purpose of this study is to investigate the mechanism of action of QFPDD in the treatment of mice with coronavirus-induced pneumonia by combining integrated hepatic single-cell RNA sequencing and untargeted metabolomics. METHODS: We developed a human coronavirus pneumonia model in BALB/c mice by infecting them with human coronavirus HCoV-229E with stimulating them with cold-damp environment. We initially assessed the status of inflammation and immunity in model mice treated with or without QFPDD by detecting peripheral blood lymphocytes and inflammatory cytokines. Then, single-cell RNA sequencing and untargeted metabolomics were performed on mouse liver tissue. RESULTS: HCoV-229E infection in combination with exposure to a cold-damp environment significantly decreased the percentage of peripheral blood lymphocytes (CD4+ and CD8+ T cells, B cells) in mice, which was enhanced by QFPDD therapy. Meanwhile, the levels of inflammatory cytokines such as IL-6, TNF-α, and IFN-γ were significantly increased in mouse models but significantly decreased by QFPDD treatment. Single-cell RNA sequencing analysis showed that QFPDD could attenuate disease-associated alterations in gene expression, core transcriptional regulatory networks, and cell-type composition. Computational predictions indicated that QFPDD rectified the observed aberrant patterns of cell-cell communication. Additionally, the metabolic profiles of liver tissue in the Model group were distinct from mice in the Control group, and QFPDD significantly regulated hepatic purine metabolism. CONCLUSION: To the best of our knowledge, this study is the first to integrate hepatic single-cell RNA sequencing and untargeted metabolomics into a TCM formula and these valuable findings indicate that QFPDD can improve immune function and reduce liver injury and inflammation.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Metabolomics , Animals , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , COVID-19/drug therapy , Drugs, Chinese Herbal/therapeutic use , Humans , Liver , Mice , Mice, Inbred BALB C , Sequence Analysis, RNA , Single-Cell Analysis
15.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293463

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo . Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.

16.
Microbiol Spectr ; 9(2): e0131221, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1443363

ABSTRACT

The large (L) polymerase proteins of most nonsegmented, negative-stranded (NNS) RNA viruses have conserved methyltransferase motifs, (G)-G-G-D and K-D-K-E, which are important for the stabilization and translation of mRNA. However, the function of the (G)-G-G-D and K-D-K-E motifs in the NNS RNA virus Newcastle disease virus (NDV) remains unclear. We observed G-G-D and K-D-K-E motifs in all NDV genotypes. By using the infection cloning system of NDV rSG10 strain, recombinant NDVs with a single amino acid mutated to alanine in one motif (G-G-D or K-D-K-E) were rescued. The intracerebral pathogenicity index and mean death time assay results revealed that the G-G-D motif and K-D-K-E motif attenuate the virulence of NDV to various degrees. The replication, transcription, and translation levels of the K-D-K-E motif-mutant strains were significantly higher than those of wild-type virus owing to their altered regulation of the affinity between nucleocapsid protein and eukaryotic translation initiation factor 4E. When the infection dose was changed from a multiplicity of infection (MOI) of 10 to an MOI of 0.01, the cell-to-cell spread abilities of G-G-D- and K-D-K-E-mutant strains were reduced, according to plaque assay and dynamic indirect immunofluorescence assay results. Finally, we found that NDV strains with G-G-D or K-D-K-E motif mutations had less pathogenicity in 3-week-old specific-pathogen-free chickens than wild-type NDV. Therefore, these methyltransferase motifs can affect virulence by regulating the translation and cell-to-cell spread abilities of NDV. This work provides a feasible approach for generating vaccine candidates for viruses with methyltransferase motifs. IMPORTANCE Newcastle disease virus (NDV) is an important pathogen that is widespread globally. Research on its pathogenic mechanism is an important means of improving prevention and control efforts. Our study found that a deficiency in its methyltransferase motifs (G-G-D and K-D-K-E motifs) can attenuate NDV and revealed the molecular mechanism by which these motifs affect pathogenicity, which provides a new direction for the development of NDV vaccines. In addition to the (G)-G-G-D and K-D-K-E motifs of many nonsegmented, negative-stranded RNA viruses, similar motifs have been found in dengue virus, Zika virus, Japanese encephalitis virus (JEV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This suggests that such motifs may be present in more viruses. Our finding also provides a molecular basis for the discovery and functional study of (G)-G-G-D and K-D-K-E motifs of other viruses.


Subject(s)
Amino Acid Motifs/genetics , Methyltransferases/genetics , Newcastle Disease/transmission , Newcastle disease virus/growth & development , Newcastle disease virus/genetics , Viral Proteins/genetics , Animals , Cell Line , Chickens , Chlorocebus aethiops , Cricetinae , Genome, Viral/genetics , Newcastle disease virus/pathogenicity , Poultry Diseases/transmission , Poultry Diseases/virology , RNA, Viral/biosynthesis , RNA, Viral/genetics , Vero Cells , Virulence/genetics , Virus Replication/genetics
17.
Saf Sci ; 145: 105498, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1428491

ABSTRACT

Colleges and universities are considered as one of the "main battlefields" of epidemic prevention and control, wherein, they have difficulty in clarifying and identifying the critical points for emergency management due to the complexity and multiplicity of influencing factors. Therefore, this study aims to identify the most effective Critical Success Factors (CSFs) for COVID-19 prevention and control in China. This study uses the Decision-Making Trial and Evaluation Laboratory (DEMATEL) method. This study has finally identified five Critical Success Factors (CSFs), which are 1) the training of emergency management professionals, 2) the cultivation of coordinating abilities, 3) the establishment of an epidemic prevention and control leadership team, 4) the development of corresponding responsibility awareness, and 5) the regulation of online public opinions. By focusing on these five CSFs, it can effectively facilitate colleges and universities to optimize their entire emergency management system in the process of normalization and professionalization of campus emergency management.

18.
Front Med (Lausanne) ; 8: 657006, 2021.
Article in English | MEDLINE | ID: covidwho-1403481

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are two major infectious diseases posing significant public health threats, and their coinfection (aptly abbreviated COVID-TB) makes the situation worse. This study aimed to investigate the clinical features and prognosis of COVID-TB cases. Methods: The PubMed, Embase, Cochrane, CNKI, and Wanfang databases were searched for relevant studies published through December 18, 2020. An overview of COVID-TB case reports/case series was prepared that described their clinical characteristics and differences between survivors and deceased patients. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for death or severe COVID-19 were calculated. The quality of outcomes was assessed using GRADEpro. Results: Thirty-six studies were included. Of 89 COVID-TB patients, 19 (23.46%) died, and 72 (80.90%) were male. The median age of non-survivors (53.95 ± 19.78 years) was greater than that of survivors (37.76 ± 15.54 years) (p < 0.001). Non-survivors were more likely to have hypertension (47.06 vs. 17.95%) or symptoms of dyspnea (72.73% vs. 30%) or bilateral lesions (73.68 vs. 47.14%), infiltrates (57.89 vs. 24.29%), tree in bud (10.53% vs. 0%), or a higher leucocyte count (12.9 [10.5-16.73] vs. 8.015 [4.8-8.97] × 109/L) than survivors (p < 0.05). In terms of treatment, 88.52% received anti-TB therapy, 50.82% received antibiotics, 22.95% received antiviral therapy, 26.23% received hydroxychloroquine, and 11.48% received corticosteroids. The pooled ORs of death or severe disease in the COVID-TB group and the non-TB group were 2.21 (95% CI: 1.80, 2.70) and 2.77 (95% CI: 1.33, 5.74) (P < 0.01), respectively. Conclusion: In summary, there appear to be some predictors of worse prognosis among COVID-TB cases. A moderate level of evidence suggests that COVID-TB patients are more likely to suffer severe disease or death than COVID-19 patients. Finally, routine screening for TB may be recommended among suspected or confirmed cases of COVID-19 in countries with high TB burden.

19.
J Microbiol Immunol Infect ; 2021 Aug 25.
Article in English | MEDLINE | ID: covidwho-1370605

ABSTRACT

BACKGROUND: To explore the development of central nervous system (CNS) symptoms and clinical application in predicting the clinical outcomes of SARS-COV-2 patients. METHODS: A retrospective cohort study was performed on the hospitalized patients with SARS-COV-2 recruited from four hospitals in Hubei Province, China from 18 January to 10 March 2020. The patients with CNS symptoms were determined. Data regarding clinical symptoms and laboratory tests were collected from medical records. RESULTS: Of 1268 patients studied, 162 (12.8%) had CNS symptoms, manifested as unconsciousness (71, 5.6%), coma (69, 5.4%), dysphoria (50, 3.9%), somnolence (34, 2.7%) and convulsion (3, 0.2%), which were observed at median of 14 (interquartile range 9-18) days after symptom onset and significantly associated with older age (OR = 5.71, 95% confidence interval [CI] 2.78-11.73), male (OR = 1.73, 95% CI 1.22-2.47) and preexisting hypertension (OR = 1.78, 95% CI 1.23-2.57). The presence of CNS symptoms could be predicted by abnormal laboratory tests across various clinical stages, including by lymphocyte counts of <0.93 × 109/L, LDH≥435 U/L and IL-6≥28.83 pg/L at 0-10 days post disease; by lymphocyte count<0.86 × 109/L, IL-2R ≥ 949 U/L, LDH≥382 U/L and WBC≥8.06 × 109/L at 11-20 days post disease. More patients with CNS symptoms developed fatal outcome compared with patients without CNS symptoms (HR = 33.96, 95% CI 20.87-55.16). CONCLUSION: Neurological symptoms of COVID-19 were related to increased odds of developing poor prognosis and even fatal infection.

20.
J Med Virol ; 93(9): 5544-5554, 2021 09.
Article in English | MEDLINE | ID: covidwho-1363695

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a global epidemic disease caused by a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing serious adverse effects on human health. In this study, we obtained a blood leukocytes sequencing data set of COVID-19 patients from the GEO database and obtained differentially expressed genes (DEGs). We further analyzed these DEGs by protein-protein interaction analysis and Gene Ontology enrichment analysis and identified the DEGs closely related to SARS-CoV-2 infection. Then, we constructed a six-gene model (comprising IFIT3, OASL, USP18, XAF1, IFI27, and EPSTI1) by logistic regression analysis and calculated the area under the ROC curve (AUC) for the diagnosis of COVID-19. The AUC values of the training group, testing group, and entire group were 0.930, 0.914, and 0.921, respectively. The six genes were highly expressed in patients with COVID-19 and positively correlated with the expression of SARS-CoV-2 invasion-related genes (ACE2, TMPRSS2, CTSB, and CTSL). The risk score calculated by this model was also positively correlated with the expression of TMPRSS2, CTSB, and CTSL, indicating that the six genes were closely related to SARS-CoV-2 infection. In conclusion, we comprehensively analyzed the functions of DEGs in the blood leukocytes of patients with COVID-19 and constructed a six-gene model that may contribute to the development of new diagnostic and therapeutic ideas for COVID-19. Moreover, these six genes may be therapeutic targets for COVID-19.


Subject(s)
COVID-19/metabolism , Gene Expression Regulation, Viral , Leukocytes/metabolism , Leukocytes/virology , SARS-CoV-2/metabolism , 2',5'-Oligoadenylate Synthetase , Adaptor Proteins, Signal Transducing , Apoptosis Regulatory Proteins , COVID-19/genetics , Female , Genome-Wide Association Study , Humans , Intracellular Signaling Peptides and Proteins , Logistic Models , Male , Membrane Proteins , Middle Aged , Neoplasm Proteins , SARS-CoV-2/genetics , Ubiquitin Thiolesterase
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