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1.
ACS Appl Mater Interfaces ; 15(24): 29561-29567, 2023 Jun 21.
Article in English | MEDLINE | ID: covidwho-20239000

ABSTRACT

Imaging nanoscale objects at interfaces is essential for revealing surface-tuned mechanisms in chemistry, physics, and life science. Plasmonic-based imaging, a label-free and surface-sensitive technique, has been widely used for studying the chemical and biological behavior of nanoscale objects at interfaces. However, direct imaging of surface-bonded nanoscale objects remains challenging due to uneven image backgrounds. Here, we present a new surface-bonded nanoscale object detection microscopy that eliminates strong background interference by reconstructing accurate scattering patterns at different positions. Our method effectively functions at low signal-to-background ratios, allowing for optical scattering detection of surface-bonded polystyrene nanoparticles and severe acute respiratory syndrome coronavirus 2 pseudovirus. It is also compatible with other imaging configurations, such as bright-field imaging. This technique complements existing methods for dynamic scattering imaging and broadens the applications of plasmonic imaging techniques for high-throughput sensing of surface-bonded nanoscale objects, enhancing our understanding of the properties, composition, and morphology of nanoparticles and surfaces at the nanoscale.

3.
International Journal of Food Science & Technology ; : 1, 2023.
Article in English | Academic Search Complete | ID: covidwho-2213640

ABSTRACT

Summary The coronavirus disease‐19 (COVID‐19) pandemic caused dietary changes. Humans reduced social activities to prevent the spread of COVID‐19, which led to increasing demand for machines to help cook. This work studies the effect of different stirrer modes on the texture of celery, asparagus, green peppers, and spinach during the cooking process and the functional loss of components in vegetables by measuring the changes in vitamin C, total polyphenols, and total flavonoids. The results showed that colour changes and loss of nutrients in each vegetable varied under different stirrer modes. Stirring was found to be the best mode for cooking all four vegetables. In addition, there was a positive correlation between the a* value and functional components during the cooking process, which means that the colour difference and nutritional loss of vegetables can be modulated together. This study provides theoretical guidance for developing the stirring unit in a cooking machine. [ FROM AUTHOR]

4.
Frontiers in psychology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2208112

ABSTRACT

The prevention and control of the coronavirus disease 2019 (COVID-19) epidemic in China has entered a phase of normalization. The basis for evaluating and improving public health strategies is understanding the emotions and concerns of the public. This study establishes a fine-grained emotion-classification model to annotate the emotions of 32,698 Sina Weibo posts related to COVID-19 prevention and control from July 2022 to August 2022. The Dalian University of Technology (DLUT) emotion-classification system was adjusted to form four pairs (eight categories) of bidirectional emotions: good-disgust, joy-sadness, anger-fear, and surprise-anticipation. A lexicon-based method was proposed to classify the emotions of Weibo posts. Based on the selected Weibo posts, the present study analyzed the Chinese public's sentiments and emotions. The results showed that positive sentiment accounted for 51%, negative sentiment accounted for 24%, and neutral sentiment accounted for 25%. Positive sentiments were dominated by good and joy emotions, and negative sentiments were dominated by fear and disgust emotions. The proportion of positive sentiments on official Weibo (accounts belonging to government departments and official media) is significantly higher than that on personal Weibo. Official Weibo users displayed a weak guiding effect on personal users in terms of positive sentiment and the two groups of users were almost completely synchronized in terms of negative sentiment. The linear discriminant analysis (LDA) was performed on the two negative emotions of fear and disgust in the personal posts. The present study found that the emotion of fear was mainly related to COVID-19 infection and death, control of people with positive nucleic acid tests, and the outbreak of local epidemic, while the emotion of disgust was mainly related to the long-term existence of the epidemic, the cost of nucleic acid tests, non-implementation of prevention and control measures, and the occurrence of foreign epidemics. These findings suggest that Chinese attitudes toward epidemic prevention and control are positive and optimistic;however, there is also a notable proportion of fear and disgust. It is expected that this study will help public health administrators to evaluate the effectiveness of possible countermeasures and work toward precise prevention and control of the COVID-19 epidemic.

5.
Int J Environ Res Public Health ; 19(20)2022 Oct 13.
Article in English | MEDLINE | ID: covidwho-2154983

ABSTRACT

(1) Background: The psychological status of employees, especially vulnerable populations, has received considerable research attention. However, as a newly emerging and popular occupation in the gig industry, food delivery drivers have received little attention. The majority of these workers are immigrants who are already in a precarious position due to a lack of available jobs, inadequate medical care, poor diets, and communication and acculturation difficulties even before they take these jobs, which involve long working hours and exposure to the elements. (2) Methods: To examine the anxiety and depression symptoms of these workers and possible influencing factors, a cross-sectional study was conducted with a sample of food delivery drivers working for the Meituan Company (one of the largest e-platform companies in China). Anxiety and depression scales were adapted from the GAD-7, and the PHQ-9 was used to assess participants' related symptoms. Differences were compared in terms of sociodemographic, work situation, and lifestyle variables. Binary logistic regressions were conducted to analyze the effects of various factors on the two psychological dimensions. (3) Results: Among the 657 participants, the proportions of participants reporting anxiety and depression symptoms were 46.0% and 18.4%, respectively. Lack of communication with leaders (ORAN = 2.620, 95% CI: 1.528-4.493, p < 0.001; ORDE = 1.928, 95% CI: 1.039-3.577, p = 0.037) and poor sleep quality (ORAN = 2.152, 95% CI: 1.587-2.917, p < 0.001; ORDE = 2.420, 95% CI: 1.672-3.504, p < 0.001) were significant risk factors for both anxiety and depression symptoms. Women (OR = 2.679, 95% CI: 1.621-4.427, p < 0.001), those who climbed ≥31 floors per day (OR = 2.415, 95% CI: 1.189-4.905, p = 0.015), and those with a high frequency of breakfast consumption (OR = 3.821, 95% CI: 1.284-11.369, p = 0.016) were more likely to have anxiety symptoms. Participants who earned less than 5000 RMB (OR = 0.438, 95% CI: 0.204-0.940, p = 0.034), were unwilling to seek medical help (OR = 3.549, 95% CI: 1.846-6.821, p < 0.001), or had a high frequency of smoking (OR = 5.107, 95% CI: 1.187-21.981, p = 0.029) were more likely to be depressive. (4) Conclusion: The existence of communication channels with leaders and good sleep quality are protective factors for anxiety and depression symptoms. Participants who were female, climbed ≥31floors per day, and had a high frequency of eating breakfast were more likely to have anxiety symptoms, while earning less, unwillingness to seek medical help, and a high frequency of smoking were risk factors for depression symptoms.


Subject(s)
Anxiety , Depression , Female , Humans , Male , Depression/psychology , Cross-Sectional Studies , China/epidemiology , Anxiety/psychology , Anxiety Disorders
6.
Zhongguo Bingdubing Zazhi = Chinese Journal of Viral Diseases ; - (5):353, 2022.
Article in English | ProQuest Central | ID: covidwho-2119063

ABSTRACT

Objective To understand the epidemiology and etiology of a cluster of cases with gastroenteritis in a nursing home in Anning district of Lanzhou, and to provide a scientific evidence for the prevention and control of norovirus diarrhea in community nursing centers. Methods From January 28 to February 4 2021, an epidemiological investigation was conducted on all diarrhea cases, nursing staff and chefs in a nursing home in Anning district, Lanzhou city.Samples of patients′ anal swabs, feces, vomitus were collected for norovirus detection by real-time fluorescent PCR.ORF1/ORF2 junction region of norovirus in some selected positive samples(Ct value ≤ 25) was sequenced.MEGA-X software was used to construct a phylogenetic tree for genetic evolution analysis using the neighboring method. Results The first case was confirmed on January20,2021,and the number of cases peaked during January 25and 29.A total of 58clinically diagnosed cases were reported,57were older people,with an incidence of(57/360,15.83%).Diarrhea(50/58,86.21%),vomiting(35/58,60.34%),nausea(13/58,22.41%)and abdominal pain(6/58,10.34%)were common symptoms,all cases were mild.Fifty-three asymptomatic cases were detected among chefs,housekeepers and nurses.A total of 163specimens were tested,the positive rate of norovirus GⅡwas 49.08%(80/163).The positive rate of fecal samples collected from nurses,chefs and housekeepers was 48.62%(53/109),and was11.11%(2/18)in environmental surface swabs.The possibility of other pathogenic infections such as SARS-CoV-2was ruled out by further tests.Thirteen positive samples were selected for sequencing,and 9were successfully sequenced,they were all recombinant GⅡ.4Sydney_2012 [P16]genotypes,forming an independent cluster,while in a large evolutionary branch with the 2020GⅡ.10 [P16]and 2019GⅡ.2 [P16]virus strains in Lanzhou city,showing a relative close genetic connection. Conclusions GⅡ.4Sydney_2012[P16]genotype of norovirus is found to be causative pathogen of this outbreak,and close contact is the main reason of the outbreak and persistence of the infection,so asymptomatic infections of norovirus play an important role in the disease spreading.Therefore,public health management in nursing homes and other centralized nursing facilities should be strengthened especially for asymptomatic workers in order to prevent virus transmission.

7.
Nature Machine Intelligence ; 4(11):964-976, 2022.
Article in English | Web of Science | ID: covidwho-2121932

ABSTRACT

The effects of novel antibodies are hard to predict owing to the complex interactions between antibodies and antigens. Zhang and colleagues use a graph-based method to learn a dynamic representation that allows for predictions of neutralization activity and demonstrate the method by recommending probable antibodies for human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, influenza and dengue. Most natural and synthetic antibodies are 'unseen'. That is, the demonstration of their neutralization effects with any antigen requires laborious and costly wet-lab experiments. The existing methods that learn antibody representations from known antibody-antigen interactions are unsuitable for unseen antibodies owing to the absence of interaction instances. The DeepAAI method proposed herein learns unseen antibody representations by constructing two adaptive relation graphs among antibodies and antigens and applying Laplacian smoothing between unseen and seen antibodies' representations. Rather than using static protein descriptors, DeepAAI learns representations and relation graphs 'dynamically', optimized towards the downstream tasks of neutralization prediction and 50% inhibition concentration estimation. The performance of DeepAAI is demonstrated on human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, influenza and dengue. Moreover, the relation graphs have rich interpretability. The antibody relation graph implies similarity in antibody neutralization reactions, and the antigen relation graph indicates the relation among a virus's different variants. We accordingly recommend probable broad-spectrum antibodies against new variants of these viruses.

8.
Pulmonary circulation ; 12(3), 2022.
Article in English | EuropePMC | ID: covidwho-2045191

ABSTRACT

The Coronavirus disease 2019 (COVID‐19) pandemic has severely affected the lives of people around the world, especially some patients with severe chronic diseases. This study aims to evaluate the impact of the COVID‐19 outbreak from December 2019 to April 2020 on treating patients with PH. A questionnaire regarding the medical condition of PH patients during the COVID‐19 pandemic was designed by PH diagnostic experts in The First Affiliated Hospital of Guangzhou Medical University, China Respiratory Center. One hundred and fifty‐six subjects with PH from non‐Hubei regions in China were invited to participate in this survey online. 63.4% (n = 99) of them had difficulty seeing a doctor, and the main reason was fear of contracting severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in the hospital. Medical treatment was affected in 25% (n = 39) of patients, and who lived in rural areas, and discontinued medical therapy for financial reasons were at a higher risk of medical treatment being affected. Patients who reduced nutrition, and had difficulty seeing a doctor were more likely to get deteriorated. During the epidemic, the hospitalization rate of PH patients was 33.33%. Patients with aggravated PH had a high risk of hospitalization (odds ratio [OR] = 2.844), while patients who visited a doctor during the epidemic reduced the risk of hospitalization (OR = 0.33). In conclusion, during the COVID‐19 pandemic, PH patients had difficulty seeing a doctor, and their medical treatment was affected, even worsened, and increased the risk of hospitalization.

9.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.09.05.22279621

ABSTRACT

Objectives To assess the association of habitual glucosamine use with coronavirus 2 (SARS-CoV-2) infection, hospital admission, or mortality with Corona Virus Disease-19 (COVID-19) in a large population based cohort. Design Population based, prospective cohort study. Setting UK Biobank. Participants Participants with complete information on habitual glucosamine use and SARS-CoV-2 infection or COVID-19-related outcomes were included. These participants were registered from 2006 to 2010, followed up until 2022 and participated in SARS-CoV-2 tests between 2020 and 2022. Main outcome measures SARS-CoV-2 infection, COVID-19 hospital admission, and COVID-19 mortality. Results At baseline, 20,118 (15.9%) of the 126,518 participants reported as habitual glucosamine users. During the median follow-up 12.16 years, there were 53,682 cases of SARS-CoV-2 infection, 2,120 cases of COVID-19 hospital admission and 548 cases of COVID-19 mortality. The multivariate adjusted hazard ratios of habitual glucosamine users to non-users were 1.02 (95% confidence interval [CI] 0.99 to 1.05) for SARS-CoV-2 infection, 0.73 (95% CI 0.63 to 0.85) for COVID-19 hospital admission, and 0.74 (95% CI 0.56 to 0.98) for COVID-19 mortality. The Cox proportional hazard analysis after propensity-score matching yielded consistent results. Conclusions Habitual glucosamine use seems to be associated with a lower risk of hospital admission and mortality with COVID-19, but not the risk of SARS-CoV-2 infection.

10.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.08.21.22279047

ABSTRACT

Objective Concerns have been raised about the widespread use of proton pump inhibitors (PPIs), and current findings linking the regular use of PPIs to respiratory infections remain inconsistent. Our study aims to evaluate whether PPI use increases the risk of pneumonia, influenza, and COVID-19. Method The presented study included 160,923 eligible participants from the UK Biobank (mean age 56.5 years, 53% women). Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Effect modifications by stratifications, including indications and CYP2C19 phenotypes were tested. Results The regular use of PPIs was associated with increased risks of developing pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26-1.59) and influenza (HR 1.31, 95% CI 1.11-1.55). However, the risk of COVID-19 infection among regular PPI users was not significantly increased (HR 1.05, 95% CI 0.95-1.16). The burden was more notably observed in patients without indications of PPI use (HR 1.52, 95% CI 1.33-1.73 for pneumonia; HR 1.36, 95% CI 1.12-1.64 for influenza). The risk for pneumonia was higher among the CYP2C19 rapid and ultrarapid metabolizers (HR 1.45, 95% CI 1.22-1.73, P for interaction < 0.001). The propensity score-matching analyses yielded similar trends. Conclusions The regular use of PPIs is associated with increased susceptibility to pneumonia and influenza, but not COVID-19 infection. The risks are even higher among recipients without main indications. Our study highlights the appropriate use and de-prescribing of PPIs according to indications and CYP2C19 phenotypes for patients and clinical practitioners.

11.
Int J Environ Res Public Health ; 19(10)2022 05 18.
Article in English | MEDLINE | ID: covidwho-1862783

ABSTRACT

Drawing on the work-home resources model, our aim in this study was to explore the negative effects of employee stewardship behavior on work-family conflict (WFC) through work-to-family border permeation (WFBP) for employees. A conditional process model linking employee stewardship behavior (ESB), family-supportive supervisor behavior (FBBS), work-to-family border permeation (WFBP), family support, and work-family conflict (WFC) was developed. Longitudinal data collected at two different time points from 323 employees of three internet companies in south China were examined. The results revealed that WFBP mediates the impact of ESB on WFC. Family-supportive supervisor behavior substantially weakens the relationship between ESB and WFBP and the indirect effect of WFBP. Similarly, family support undermines the relationship between WFBP and WFC and the indirect effect of WFBP. Employee-level stewardship and blurred work-family boundaries have been common phenomena in contemporary China, especially during the COVID-19 pandemic. This study is among the first to focus on the negative impacts of employee stewardship behaviors on the employee, especially on their family, from a Chinese context. These findings also increase our understanding of the effects of ESB and provide some new insights into how to mitigate WFC.


Subject(s)
COVID-19 , COVID-19/epidemiology , Conflict, Psychological , Family Conflict , Humans , Pandemics , Workplace
12.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.05.07.491043

ABSTRACT

Tissues are highly complicated with spatial heterogeneity in gene expression. However, the cutting-edge single-cell RNA-seq technology eliminates the spatial information of individual cells, which contributes to the characterization of cell identities. Herein, we propose s ingle- c ell s patial p osition a ssociated c o- e mbeddings (scSpace), an integrative algorithm to distinguish spatially variable cell subclusters by reconstructing cells onto a pseudo-space with spatial transcriptome references (Visium, STARmap, Slide-seq, etc.). We demonstrated that scSpace can define biologically meaningful cell subpopulations neglected by single-cell RNA-seq or spatially resolved transcriptomics. The use of scSpace to uncover the spatial association within single-cell data, reproduced, the hierarchical distribution of cells in the brain cortex and liver lobules, and the regional variation of cells in heart ventricles and the intestinal villus. scSpace identified cell subclusters in intratelencephalic neurons, which were confirmed by their biomarkers. The application of scSpace in melanoma and Covid-19 exhibited a broad prospect in the discovery of spatial therapeutic markers.

13.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1527855.v1

ABSTRACT

Transdermal drug delivery has been regarded as an alternative to oral delivery and subcutaneous injection for its non-invasiveness, improved patient compliance and avoidance of the first-pass effect. However, needleless transdermal delivery of biomacromolecules remains a challenge. Herein, a transdermal delivery platform is developed to achieve highly efficient non-invasive transdermal delivery of biomacromolecules. In this system, fluorocarbon modified chitosan (FCS) is optimized as an effective yet biocompatible transdermal carrier to assemble with different proteins including immune checkpoint blockade (ICB) antibodies, and antigens such as the spike (S) protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The formed FCS-containing nanocomplexes exhibited rather effective transdermal penetration ability via both intercellular and transappendageal routes. Interestingly, non-invasive transdermal delivery of ICB antibodies by FCS induced stronger immune responses to treat mouse melanoma compared to intravenous injection of free antibodies, while presenting reduced systemic toxicity. Moreover, transdermal delivery of SARS-CoV-2 vaccine using FCS-containing nanocomplexes resulted in comparable humoral immunity as well as improved cell immunity and immune memory compared to that achieved with subcutaneous vaccine injection. Thus, FCS-based transdermal delivery systems may provide a compelling opportunity to overcome the skin barrier for efficient transdermal delivery of biomacromolecules, widening the range of therapeutics that can be topically administered.

14.
Front Immunol ; 12: 789905, 2021.
Article in English | MEDLINE | ID: covidwho-1581321

ABSTRACT

Facing the imminent need for vaccine candidates with cross-protection against globally circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants, we present a conserved antigenic peptide RBD9.1 with both T-cell and B-cell epitopes. RBD9.1 can be recognized by coronavirus disease 2019 (COVID-19) convalescent serum, particularly for those with high neutralizing potency. Immunization with RBD9.1 can successfully induce the production of the receptor-binding domain (RBD)-specific antibodies in Balb/c mice. Importantly, the immunized sera exhibit sustained neutralizing efficacy against multiple dominant SARS-CoV-2 variant strains, including B.1.617.2 that carries a point mutation (SL452R) within the sequence of RBD9.1. Specifically, SY451 and SY454 are identified as the key amino acids for the binding of the induced RBD-specific antibodies to RBD9.1. Furthermore, we have confirmed that the RBD9.1 antigenic peptide can induce a S448-456 (NYNYLYRLF)-specific CD8+ T-cell response. Both RBD9.1-specific B cells and the S448-456-specific T cells can still be activated more than 3 months post the last immunization. This study provides a potential vaccine candidate that can generate long-term protective efficacy over SARS-CoV-2 variants, with the unique functional mechanism of activating both humoral and cellular immunity.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Animals , Antibodies, Neutralizing/immunology , COVID-19 Vaccines/pharmacology , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/immunology , Humans , Mice , Mice, Inbred BALB C , SARS-CoV-2/immunology , Vaccines, Subunit/immunology
15.
Discrete Dynamics in Nature and Society ; 2021, 2021.
Article in English | ProQuest Central | ID: covidwho-1556854

ABSTRACT

Corporate social responsibility (CSR) is the concrete practice of sustainable development at the enterprise level, emphasizing the human value in the production process. The proposal of Industry 5.0 begins to take the coordinated development between human and various production factors as one of the key points of corporate sustainable management. Therefore, this paper studies the optimization of medical enterprise’s operations management considering enterprise CSR under Industry 5.0. A mixed-integer programming (MIP) model is developed to maximize the CSR with the consideration of the impact of precision medical technologies such as surgical robots (SRs) and 3D bone printing on employee social welfare, corporate profits, social environment, and customer surplus value. An improved variable neighborhood tabu search (IVNTS) algorithm which combines the variable neighborhood tabu search (VNTS) algorithm and simulated annealing (SA) algorithm is designed to solve the model, and numerical experiments are analyzed to verify the effectiveness of the proposed IVNTS. The research aids medical enterprise to make reasonable operations management decisions, while providing a reference for the government to draft and implement related policies, thereby achieving sustainable social development.

16.
researchsquare; 2021.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-1054453.v1

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) evolves in some pediatric patients following acute infection with SARS-CoV-2 by hitherto unknown mechanisms. Whereas acute-COVID-19 severity and outcome were previously correlated with Notch4 expression on regulatory T (Treg) cells, here we show that the Treg cells in MIS-C are destabilized in association with increased Notch1 expression. Genetic analysis revealed that MIS-C patients were enriched in rare deleterious variant impacting inflammation and autoimmunity pathways, including dominant negative mutations in the Notch1 regulators NUMB and NUMBL. Notch1 signaling in Treg cells induced CD22, leading to their destabilization in an mTORC1 dependent manner and to the promotion of systemic inflammation. These results establish a Notch1-CD22 signaling axis that disrupts Treg cell function in MIS-C and point to distinct immune checkpoints controlled by individual Treg cell Notch receptors that shape the inflammatory outcome in SARS-CoV-2 infection.

17.
biorxiv; 2021.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2021.10.20.464686

ABSTRACT

S100A8 and S100A9 are members of the Alarmin family; these proteins are abundantly expressed in neutrophils and form a heterodimer complex. Recently, both proteins were identified as novel biomarkers of SARS-CoV-2 infection and were shown to play key roles in inducing an aggressive inflammatory response by mediating the release of large amounts of pro-inflammatory cytokines, called the cytokine storm. Although co-infection with SARS-CoV-2 in people living with HIV-1 may result in an immunocompromised status, the role of the S100A8/A9 complex in HIV-1 replication in primary T cells and macrophages is still unclear. Here, we evaluated the roles of the proteins in HIV replication to elucidate their functions. We found that the complex had no impact on virus replication in both cell types; however, the subunits of S100A8 and S100A9 inhibits HIV in macrophages. These findings provide important insights into the regulation of HIV viral loads during SARS-CoV-2 co-infection.

18.
Nat Metab ; 3(11): 1466-1475, 2021 11.
Article in English | MEDLINE | ID: covidwho-1440484

ABSTRACT

Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 is a virus-induced inflammatory disease of the airways and lungs that leads to severe multi-organ damage and death. Here we show that cellular lipid synthesis is required for SARS-CoV-2 replication and offers an opportunity for pharmacological intervention. Screening a short-hairpin RNA sublibrary that targets metabolic genes, we identified genes that either inhibit or promote SARS-CoV-2 viral infection, including two key candidate genes, ACACA and FASN, which operate in the same lipid synthesis pathway. We further screened and identified several potent inhibitors of fatty acid synthase (encoded by FASN), including the US Food and Drug Administration-approved anti-obesity drug orlistat, and found that it inhibits in vitro replication of SARS-CoV-2 variants, including more contagious new variants, such as Delta. In a mouse model of SARS-CoV-2 infection (K18-hACE2 transgenic mice), injections of orlistat resulted in lower SARS-CoV-2 viral levels in the lung, reduced lung pathology and increased mouse survival. Our findings identify fatty acid synthase inhibitors as drug candidates for the prevention and treatment of COVID-19 by inhibiting SARS-CoV-2 replication. Clinical trials are needed to evaluate the efficacy of repurposing fatty acid synthase inhibitors for severe COVID-19 in humans.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/metabolism , COVID-19/virology , Fatty Acids/biosynthesis , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Virus Replication/drug effects , Animals , Antiviral Agents/therapeutic use , COVID-19/mortality , Cell Line , Disease Models, Animal , Disease Susceptibility , Dose-Response Relationship, Drug , Drug Development , Gene Knockdown Techniques , Host-Pathogen Interactions/genetics , Humans , Lipid Metabolism/drug effects , Mice , fas Receptor/antagonists & inhibitors , fas Receptor/deficiency , fas Receptor/metabolism , COVID-19 Drug Treatment
19.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.04.29.21256317

ABSTRACT

Background: To investigate the differences in vaccine hesitancy and preference of the currently available COVID-19 vaccines between two countries, viz. China and the United States (US). Method: A cross-national survey was conducted in both China and the US, and discrete choice experiments as well as Likert scales were utilized to assess vaccine preference and the underlying factors contributing to the vaccination acceptance. A propensity score matching (PSM) was performed to enable a direct comparison between the two countries. Results: A total of 9,077 (5,375 and 3,702, respectively, from China and the US) respondents have completed the survey. After propensity score matching, over 82.0% respondents from China positively accept the COVID-19 vaccination, while 72.2% respondents form the US positively accept it. Specifically, only 31.9% of Chinese respondents were recommended by a doctor to have COVID-19 vaccination, while more than half of the US respondents were recommended by a doctor (50.2%), local health board (59.4%), or friends and families (64.8%). The discrete choice experiments revealed that respondents from the US attached the greatest importance to the efficacy of COVID-19 vaccines (44.41%), followed by the cost of vaccination (29.57%), whereas those from China held a different viewpoint that the cost of vaccination covers the largest proportion in their trade-off (30.66%), and efficacy ranked as the second most important attribute (26.34%). Also, respondents from China tend to concern much more about the adverse effect of vaccination (19.68% vs 6.12%) and have lower perceived severity of being infected with COVID-19. Conclusion: While the overall acceptance and hesitancy of COVID-19 vaccination in both countries are high, underpinned distinctions between countries are observed. Owing to the differences in COVID-19 incidence rates, cultural backgrounds, and the availability of specific COVID-19 vaccines in two countries, the vaccine rollout strategies should be nation-dependent.

20.
biorxiv; 2021.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2021.04.19.440481

ABSTRACT

Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus displayed remarkable efficacy against authentic B.1.351 virus. Each of these 3 mAbs in combination with one neutralizing Ab recognizing non-competing epitope exhibited synergistic effect against authentic SARS-CoV-2 virus. Surprisingly, structural analysis revealed that 58G6 and 13G9, encoded by the IGHV1-58 and the IGKV3-20 germline genes, both recognized the steric region S470-495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly bound to another region S450-458 in the RBD. Significantly, 58G6 and 510A5 both demonstrated prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. These 2 ultrapotent neutralizing Abs can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.

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