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Immunity ; 2022 Oct 27.
Article in English | MEDLINE | ID: covidwho-2086313

ABSTRACT

Increased immune evasion by SARS-CoV-2 variants of concern highlights the need for new therapeutic neutralizing antibodies. Immunization with nanoparticles co-displaying spike receptor-binding domains (RBDs) from eight sarbecoviruses (mosaic-8 RBD-nanoparticles) efficiently elicits cross-reactive polyclonal antibodies against conserved sarbecovirus RBD epitopes. Here, we identified monoclonal antibodies (mAbs) capable of cross-reactive binding and neutralization of animal sarbecoviruses and SARS-CoV-2 variants by screening single mouse B cells secreting IgGs that bind two or more sarbecovirus RBDs. Single-particle cryo-EM structures of antibody-spike complexes, including a Fab-Omicron complex, mapped neutralizing mAbs to conserved class 1/4 RBD epitopes. Structural analyses revealed neutralization mechanisms, potentials for intra-spike trimer cross-linking by IgGs, and induced changes in trimer upon Fab binding. In addition, we identified a mAb-resembling Bebtelovimab, an EUA-approved human class 3 anti-RBD mAb. These results support using mosaic RBD-nanoparticle vaccination to generate and identify therapeutic pan-sarbecovirus and pan-variant mAbs.

3.
Archives of Design Research ; 35(3):113-127, 2022.
Article in En ko | Scopus | ID: covidwho-2030380

ABSTRACT

Background Due to COVID-19, digital alienation in kiosks is intensifying. While many studies are conducted to address this issue, they mainly focus on improving the user interface design, rarely considering psychological aspects of the elderly. We aim to investigate how to help the elderly better accept kiosk technology by understanding their psychological characteristics. Methods We started with an understanding of the kiosk industry and the psychological problems experienced by the elderly. Then, we identified from the literature several factors affecting technology acceptance and integrate them into the user experience (UX) design process. Through observations and interviews with the elderly, psychological problems experienced by the elderly were identified and analyzed. Additional interviews with educators were conducted to further understand the factors and educational methods that affect the elderly’s acceptance of kiosks, which were followed by an on-site observation of kiosk education. Results Most of the elderly remained in the expected and introduction stages due to unfamiliar kiosk culture, social pressure, and low self-efficacy. These barriers can be overcome by providing supporters, motivating the elderly, improving store environment and line-up experience, and accumulating success experiences. We also found that repetitive use should be induced and socially supported so that the elderly can accept, habituate, and integrate technology. Conclusions We propose a new way to improve the kiosk UX that focuses on the technology acceptance psychology of the elderly against previous studies that focus on improving the user interface. We expect that our study results can serve as a basis for future studies on systemic design solutions for improved Kiosk UX. © This is an Open Access article distributed under the terms of the Creative Commons Attribution NonCommercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted educational and non-commercial use, provided the original work is properly cited.

4.
25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021 ; : 147-148, 2021.
Article in English | Scopus | ID: covidwho-2011699

ABSTRACT

Rapid polymerase chain reaction (PCR) utilizing plasmon-driven photothermal cycling requires real-time quantification of amplicons during PCR and miniaturization of real-time PCR (qPCR) system for point-of-care (POC) diagnostics. In this work, we have demonstrated handheld photothermal qPCR system with disposable aluminum PCR chips for the ultrafast amplification and real-time quantification of plasmids expressing SARSCoV-2 envelope protein within 5 min. This novel system provides stable and useful point-of-care diagnostic platform for prevention of fast-spreading pandemic in airport and harbor. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

5.
Science (New York, N.Y.) ; 2022.
Article in English | EuropePMC | ID: covidwho-1939926

ABSTRACT

To combat future SARS-CoV-2 variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles presenting randomly-arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded, rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD-nanoparticles in mice and macaques, observing stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants including Omicrons and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest mosaic-8 RBD-nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers. Description

6.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.06.28.497989

ABSTRACT

Protection from SARS-related coronaviruses with spillover potential and SARS-CoV-2 variants could prevent and/or end pandemics. We show that mice immunized with nanoparticles co-displaying spike receptor-binding domains (RBDs) from eight sarbecoviruses (mosaic-8 RBD-nanoparticles) efficiently elicit cross-reactive anti-sarbecovirus antibodies against conserved class 1/4 and class 3 RBD epitopes. Monoclonal antibodies (mAbs) identified from initial screening of <10,000 single B-cells secreting IgGs binding two or more sarbecovirus RBDs showed cross-reactive binding and neutralization of SARS-CoV-2 variants and animal sarbecoviruses. Single-particle cryo-EM structures of antibody-spike complexes, including a Fab-Omicron complex, mapped neutralizing mAbs to conserved class 1/4 RBD epitopes and revealed neutralization mechanisms, potentials for intra-spike trimer crosslinking by single IgGs, and induced changes in trimer upon Fab binding. In addition, we identified a mAb resembling Bebtelovimab, an EUA-approved human class 3 anti-RBD mAb. These results support using mosaic RBD-nanoparticles to identify therapeutic pan-sarbecovirus and pan-variant mAbs and to elicit them by vaccination.

7.
Immunity ; 55(6): 998-1012.e8, 2022 06 14.
Article in English | MEDLINE | ID: covidwho-1778212

ABSTRACT

SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor-binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for antibodies. Here, we use NTD-specific probes to capture anti-NTD memory B cells in a longitudinal cohort of infected individuals, some of whom were vaccinated. We found 6 complementation groups of neutralizing antibodies. 58% targeted epitopes outside the NTD supersite, 58% neutralized either Gamma or Omicron, and 14% were broad neutralizers that also neutralized Omicron. Structural characterization revealed that broadly active antibodies targeted three epitopes outside the NTD supersite including a class that recognized both the NTD and SD2 domain. Rapid recruitment of memory B cells producing these antibodies into the plasma cell compartment upon re-infection likely contributes to the relatively benign course of subsequent infections with SARS-CoV-2 variants, including Omicron.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , Epitopes , Humans , Memory B Cells , SARS-CoV-2
8.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.03.25.485875

ABSTRACT

To combat future SARS-CoV-2 variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles presenting randomly-arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against conserved/relatively-occluded, rather than variable/immunodominant/exposed, epitopes. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD-nanoparticles in mice and macaques, observing stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants including Omicron and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest mosaic-8 RBD-nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.

10.
Public Administration and Policy-an Asia-Pacific Journal ; 24(1):76-91, 2021.
Article in English | Web of Science | ID: covidwho-1691678

ABSTRACT

Purpose - This paper attempts to theorise about China's strategy in combating the coronavirus pandemic with an embryonic framework - 3H (Heart-Head-Hand) framework. By adopting a descriptive approach, the paper introduces the case of coronavirus outbreak in China and how the public health administration coped with it The 3H framework has been applied to analyse China's strategy, and the framework's assumptions are initially tested. Design/methodology/approach - The pandemic case is created based on credible reports, press releases from different respected sources, World Health Organization (WHO) statistics, interview transcripts and broadcasting stations' video clippings. Interpretive analysis with pragmatism approach has been conducted in analysing the data and information collected. Triangulation, wherever possible, has been done to validate the data and information. Findings - As an exploratory study, its findings show that 3H framework distinguishes the effectiveness of a country's strategy and practice for combating the pandemic. Countries, which failed to observe the assumed principles of 3H domains tend to have much more infected cases and deaths. Originality/value - The 3H framework conceptualised a holistic management approach and its assumptions have been initially tested with this pandemic case. The framework shows its predictability value for a country's pandemic management effectiveness.

13.
Hong Kong Med J ; 26(3): 176-183, 2020 06.
Article in English | MEDLINE | ID: covidwho-1468777

ABSTRACT

INTRODUCTION: This study evaluated the preparedness of family doctors during the early phase of the coronavirus disease 2019 (COVID-19) outbreak in Hong Kong. METHODS: All members of the Hong Kong College of Family Physicians were invited to participate in a cross-sectional online survey using a 20-item questionnaire to collect information on practice preparedness for the COVID-19 outbreak through an email followed by a reminder SMS message between 31 January 2020 and 3 February 2020. RESULTS: Of 1589 family doctors invited, 491 (31%) participated in the survey, including 242 (49%) from private sector. In all, 98% surveyed doctors continued to provide clinical services during the survey period, but reduced clinic service demands were observed in 45% private practices and 24% public clinics. Almost all wore masks during consultation and washed hands between or before patient contact. Significantly more private than public doctors (80% vs 26%, P<0.001) experienced difficulties in stocking personal protective equipment (PPE); more public doctors used guidelines to manage suspected patients. The main concern of the respondents was PPE shortage. Respondents appealed for effective public health interventions including border control, quarantine measures, designated clinic setup, and public education. CONCLUSION: Family doctors from public and private sectors demonstrated preparedness to serve the community from the early phase of the COVID-19 outbreak with heightened infection control measures and use of guidelines. However, there is a need for support from local health authorities to secure PPE supply and institute public health interventions.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Disease Outbreaks/prevention & control , Family Practice/organization & administration , Health Care Surveys/methods , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Surveys and Questionnaires , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/methods , Clinical Laboratory Techniques/statistics & numerical data , Communicable Disease Control/methods , Coronavirus Infections/diagnosis , Disease Outbreaks/statistics & numerical data , Female , Hong Kong/epidemiology , Humans , Male , Outcome Assessment, Health Care , Physicians, Family/statistics & numerical data
15.
PLoS ONE ; 16(2), 2021.
Article in English | CAB Abstracts | ID: covidwho-1410635

ABSTRACT

Importance: Intensity and duration of the COVID-19 pandemic, and planning required to balance concerns of saving lives and avoiding economic collapse, could depend significantly on whether SARS-CoV-2 transmission is sensitive to seasonal changes.

16.
Curr Med Sci ; 41(6): 1096-1104, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1404664

ABSTRACT

OBJECTIVE: To study data about SARS-CoV-2 virus shedding and clarify the risk factors for prolonged virus shedding. METHODS: Data were retrospectively collected from adults hospitalized with laboratory-confirmed coronavirus disease-19 (COVID-19) in Wuhan Union Hospital. We compared clinical features among patients with prolonged (a positive SARS-CoV-2 RNA on day 23 after illness onset) and short virus shedding and evaluated risk factors associated with prolonged virus shedding by multivariate regression analysis. RESULTS: Among 238 patients, the median age was 55.5 years, 57.1% were female, 92.9% (221/238) were administered with arbidol, 58.4% (139/238) were given arbidol in combination with interferon. The median duration of SARS-CoV-2 virus shedding was 23 days (IQR, 17.8-30 days) with a longest one of 51 days. The patients with prolonged virus shedding had higher value of D-dimer (P=0.002), IL-6 (P<0.001), CRP (P=0.005) and more lobes lung lesion (P=0.014) on admission, as well as older age (P=0.017) and more patients with hypertension (P=0.044) than in those the virus shedding less than 23 days. Multivariate regression analysis revealed that prolonged viral shedding was significantly associated with initiation arbidol >8 days after symptom onset [OR: 2.447, 95% CI (1.351-4.431)], ≥3 days from onset of symptoms to first medical visitation [OR: 1.880, 95% CI (1.035-3.416)], illness onset before Jan. 31, 2020 [OR: 3.289, 95% CI (1.474-7.337)]. Arbidol in combination with interferon was also significantly associated with shorter virus shedding [OR: 0.363, 95% CI (0.191-0.690)]. CONCLUSION: Duration of SARS-CoV-2 virus shedding was long. Early initiation of arbidol and arbidol in combination with interferon as well as consulting doctor timely after illness onset were helpful for SARS-CoV-2 clearance.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , COVID-19/virology , Indoles/administration & dosage , SARS-CoV-2 , Virus Shedding , Adult , Aged , COVID-19/epidemiology , China/epidemiology , Cohort Studies , Female , Hospitalization , Humans , Interferons/administration & dosage , Logistic Models , Male , Middle Aged , Multivariate Analysis , Pandemics , RNA, Viral/analysis , Retrospective Studies , Risk Factors , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Time Factors , Virus Shedding/drug effects
17.
Cell Rep ; 36(13): 109760, 2021 09 28.
Article in English | MEDLINE | ID: covidwho-1401299

ABSTRACT

Many anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) neutralizing antibodies target the angiotensin-converting enzyme 2 (ACE2) binding site on viral spike receptor-binding domains (RBDs). Potent antibodies recognize exposed variable epitopes, often rendering them ineffective against other sarbecoviruses and SARS-CoV-2 variants. Class 4 anti-RBD antibodies against a less-exposed, but more-conserved, cryptic epitope could recognize newly emergent zoonotic sarbecoviruses and variants, but they usually show only weak neutralization potencies. Here, we characterize two class 4 anti-RBD antibodies derived from coronavirus disease 2019 (COVID-19) donors that exhibit breadth and potent neutralization of zoonotic coronaviruses and SARS-CoV-2 variants. C118-RBD and C022-RBD structures reveal orientations that extend from the cryptic epitope to occlude ACE2 binding and CDRH3-RBD main-chain H-bond interactions that extend an RBD ß sheet, thus reducing sensitivity to RBD side-chain changes. A C118-spike trimer structure reveals rotated RBDs that allow access to the cryptic epitope and the potential for intra-spike crosslinking to increase avidity. These studies facilitate vaccine design and illustrate potential advantages of class 4 RBD-binding antibody therapeutics.


Subject(s)
Broadly Neutralizing Antibodies/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Binding Sites/immunology , Broadly Neutralizing Antibodies/pharmacology , Cross Reactions , Epitopes/metabolism , Humans , Protein Binding , Protein Interaction Domains and Motifs , Receptors, Virus/metabolism , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology
19.
Jurnal Infektologii ; 13(2):44-52, 2021.
Article in Russian | EMBASE | ID: covidwho-1344647

ABSTRACT

Introduction. The issue of protection against vaccine-preventable diseases has acquired new urgency in connection with the decrease in the vaccination rate established by WHO against the background of the COVID-19 pandemic. This creates the conditions for outbreaks and puts patients with immunopathological diseases at particular risk, who are most often not vaccinated from the moment of diagnosis Purpose of the study – to assess the safety of specific antibodies to measles, mumps, rubella and diphtheria in children with JIA, depending on the duration of vaccination, the duration of the disease and the therapy received. Materials and methods. The vaccination rate of 171 children with juvenile idiopathic arthritis (JIA) aged (11,31±0,31 years) with the duration of the disease at the time of examination was 4,69±0,29 years, who had previously received 1-2 vaccinations against measles, mumps, rubella and 3-6 vaccinations against diphtheria. Antibodies to these infections were determined by ELISA. Results. 42.1% of children had no protective titers of antibodies to measles, 19,9% – to mumps, 9,4% – to rubella and 16,4% – to diphtheria. Among 93 vaccinated and revaccinated patients, there were no protective titers of antibodies to measles – 40,9% (38 children), mumps – 13,9% (13 people), rubella – 5,4% (5 children), and among 78 vaccinated once, respectively: measles – 43.6% (34 children), mumps – 25.6% (20 children), rubella – 14,1% (11). The level of protection against diphtheria was comparable for those who received 3-5 vaccinations. Depending on the therapy, 3 groups were identified: group 1-71 children received metatrexate and glucocorticosteroids, 2-82 children received modifying anti-rheumatic drugs (DMARD) and 18 children without this therapy (Group 3). Children of the 2nd group were on average older (12,48±0,42 years) than in the 1st and 3rd groups (10,04±0,48 and 10,96±0,96 years, respectively), they had significantly more frequent systemic variant and polyarthritis (64,6% compared to 36,6% and 16,7%, px2<0,001). The number of vaccine doses received by children in all groups before the onset of the disease did not significantly differ. The average level of antibodies to measles in children of group 2 (0,32±0,07 IU/ml) was 2,8 times less than in group 3 and significantly less than in group 1 (0,78±0,16, Pt=0.009), the average value of antibodies to rubella was also significantly less in group 2 (84,48±7,34 IU/ml) than in group 1 (109,73±8,09, Pt=0,022) and in group 3 (120,01±15,42, Pt=0,042). The analysis showed that the safety of antibodies to antigens of live vaccines, especially against measles, is negatively affected by the duration of the disease and the nature of therapy. Children who received combined therapy with anti-TNF, anti-IL-6 and anti-CD-80 drugs had a longer duration of the disease (7,5±0,97 years)=0,00082 compared to those who received only anti-IL-6 (2,9±0,7 years) and anti-TNF therapy (6,1±0,5 years) and with a comparable number of vaccine doses received, significantly lower average values of antibodies and a larger number of unprotected ones. Conclusions. The duration of the disease, the lack of timely age-related revaccinations, as well as the presence of combination therapy aimed at suppressing various mechanisms of the immune response in children with JIA are factors that lead to an increase in the number of unprotected from controlled infections. Immunity to measles suffers the most – 40.9% of revaccinated people are unprotected.

20.
Journal of Asian Economics ; 76, 2021.
Article in English | Scopus | ID: covidwho-1316384

ABSTRACT

By considering the term-of-trade and volume-of-trade effects, Jones (2012) examines the distributive effect in a competitive economy with non-traded goods. This paper reexamines the effect in an imperfectively competitive economy with firm dynamics. A rise in foreign demand can generate revenue and also mitigate market distortion, whereas skilled-unskilled wage inequality can be magnified or mitigated via the effect on firm entry or exit. Thus, how to achieve the trade-off among growth, inequality and the environment becomes an important task for government decision-makers, especially so during the pandemic of Covid-19. © 2021 Elsevier Inc.

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