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1.
Age and ageing ; 52(1):afac308, 2023.
Article in English | EuropePMC | ID: covidwho-2212703

ABSTRACT

BackgroundLong-term care facilities (LTCFs) were high-risk settings for COVID-19 outbreaks.ObjectiveTo assess the impacts of the COVID-19 pandemic on LTCFs, including rates of infection, hospitalisation, case fatality, and mortality, and to determine the association between control measures and SARS-CoV-2 infection rates in residents and staff.MethodWe conducted a systematic search of six databases for articles published between December 2019 and 5 November 2021, and performed meta-analyses and subgroup analyses to identify the impact of COVID-19 on LTCFs and the association between control measures and infection rate.ResultsWe included 108 studies from 19 countries. These studies included 1,902,044 residents and 255,498 staff from 81,572 LTCFs, among whom 296,024 residents and 36,807 staff were confirmed SARS-CoV-2 positive. The pooled infection rate was 32.63% (95%CI: 30.29 ~ 34.96%) for residents, whereas it was 10.33% (95%CI: 9.46 ~ 11.21%) for staff. In LTCFs that cancelled visits, new patient admissions, communal dining and group activities, and vaccinations, infection rates in residents and staff were lower than the global rate. We reported the residents' hospitalisation rate to be 29.09% (95%CI: 25.73 ~ 32.46%), with a case-fatality rate of 22.71% (95%CI: 21.31 ~ 24.11%) and mortality rate of 15.81% (95%CI: 14.32 ~ 17.30%). Significant publication biases were observed in the residents' case-fatality rate and the staff infection rate, but not in the infection, hospitalisation, or mortality rate of residents.ConclusionSARS-CoV-2 infection rates would be very high among LTCF residents and staff without appropriate control measures. Cancelling visits, communal dining and group activities, restricting new admissions, and increasing vaccination would significantly reduce the infection rates.

2.
Engineering ; 2023.
Article in English | ScienceDirect | ID: covidwho-2178443

ABSTRACT

Recombinant adenovirus serotype 5 (Ad5) vector has been widely applied in vaccine development targeting infectious diseases, such as Ebola virus disease and coronavirus disease 2019 (COVID-19). However, the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines. Thus, there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors. Herein, we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions. We show that positively charged human serum albumin nanoparticles ((+)HSAnp), which are capable of forming a complex with Ad5, significantly increase the transgene expression of Ad5 in both coxsackievirus-adenovirus receptor-positive and -negative cells. Furthermore, in charge- and dose-dependent manners, Ad5/(+)HSAnp complexes achieve robust (up to 227-fold higher) and long-term (up to 60 days) transgene expression in the lungs of mice following intranasal instillation. Importantly, in the presence of preexisting anti-Ad5 immunity, complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity. These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.

3.
Computers in Biology and Medicine ; 153:106517, 2023.
Article in English | ScienceDirect | ID: covidwho-2165195

ABSTRACT

The growing and aging of the world population have driven the shortage of medical resources in recent years, especially during the COVID-19 pandemic. Fortunately, the rapid development of robotics and artificial intelligence technologies help to adapt to the challenges in the healthcare field. Among them, intelligent speech technology (IST) has served doctors and patients to improve the efficiency of medical behavior and alleviate the medical burden. However, problems like noise interference in complex medical scenarios and pronunciation differences between patients and healthy people hamper the broad application of IST in hospitals. In recent years, technologies such as machine learning have developed rapidly in intelligent speech recognition, which is expected to solve these problems. This paper first introduces IST's procedure and system architecture and analyzes its application in medical scenarios. Secondly, we review existing IST applications in smart hospitals in detail, including electronic medical documentation, disease diagnosis and evaluation, and human-medical equipment interaction. In addition, we elaborate on an application case of IST in the early recognition, diagnosis, rehabilitation training, evaluation, and daily care of stroke patients. Finally, we discuss IST's limitations, challenges, and future directions in the medical field. Furthermore, we propose a novel medical voice analysis system architecture that employs active hardware, active software, and human-computer interaction to realize intelligent and evolvable speech recognition. This comprehensive review and the proposed architecture offer directions for future studies on IST and its applications in smart hospitals.

4.
IEEE Transactions on Intelligent Transportation Systems ; 23(12):25062-25076, 2022.
Article in English | ProQuest Central | ID: covidwho-2152549

ABSTRACT

As transportation system plays a vastly important role in combatting newly-emerging and severe epidemics like the coronavirus disease 2019 (COVID-19), the vehicle routing problem (VRP) in epidemics has become an emerging topic that has attracted increasing attention worldwide. However, most existing VRP models are not suitable for epidemic situations, because they do not consider the prevention cost caused by issues such as viral tests and quarantine during the traveling. Therefore, this paper proposes a multi-objective VRP model for epidemic situations, named VRP4E, which considers not only the traditional travel cost but also the prevention cost of the VRP in epidemic situations. To efficiently solve the VRP4E, this paper further proposes a novel algorithm named multi-objective ant colony system algorithm for epidemic situations, termed MOACS4E, together with three novel designs. First, by extending the efficient “multiple populations for multiple objectives” framework, the MOACS4E adopts two ant colonies to optimize the travel and prevention costs respectively, so as to improve the search efficiency. Second, a pheromone fusion-based solution generation method is proposed to fuse the pheromones from different colonies to increase solution diversity effectively. Third, a solution quality improvement method is further proposed to improve the solutions for the prevention cost objective. The effectiveness of the MOACS4E is verified in experiments on 25 generated benchmarks by comparison with six state-of-the-art and modern algorithms. Moreover, the VRP4E in different epidemic situations and a real-world case in the Beijing-Tianjin-Hebei region, China, are further studied to provide helpful insights for combatting COVID-19-like epidemics.

5.
Biosensors and Bioelectronics: X ; : 100289, 2022.
Article in English | ScienceDirect | ID: covidwho-2149406

ABSTRACT

The recent emergence of human coronaviruses (CoVs) causing severe acute respiratory syndrome (SARS) is posing a great threat to global public health. Therefore, the rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people's lives and preventing epidemics. Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are natural biopolymers composed of nucleotides that store, transmit, and express genetic information. Applications of nucleic acid detection range from genotyping and genetic prognostics, to expression profiling and detection of infectious disease. The nucleic acid detection for infectious diseases is widely used, as evidenced by the widespread use of COVID-19 tests for the containment of the pandemic. Nanotechnology influences all medical disciplines and has been considered as an essential tool for novel diagnostics, nanotherapeutics, vaccines, medical imaging, and the utilization of biomaterials for regenerative medicine. In this review, the recent advances in the development of nanotechnology-based diagnostic methods for coronavirus, and their applications in nucleic acid detection are discussed in detail. The techniques for the amplification of nucleic acids are summarized, as well as the use of magnetic nanoparticles for nucleic acid extraction. Besides, current challenges and future prospects are proposed, along with the great potential of nanotechnology for the effective diagnosis of coronavirus.

6.
Adv Clin Exp Med ; 2022 Nov 30.
Article in English | MEDLINE | ID: covidwho-2145671

ABSTRACT

BACKGROUND: Influenza is an acute respiratory infectious disease caused by the influenza virus, which poses a certain threat to humans due to its short incubation period, fast transmission and strong infectivity. OBJECTIVES: To evaluate the awareness and prevention behavior against influenza among healthcare workers on the eve of the coronavirus disease 2019 (COVID-19) epidemic in Beijing, China. MATERIAL AND METHODS: Using the cross-sectional research design based on the principle of convenience sampling, an online questionnaire survey on the knowledge of flu, vaccination, medical protection behavior, and flu medication was conducted between January and February 2020. Healthcare workers from different healthcare facilities and different job positions in Beijing participated in this survey. RESULTS: A total of 1910 healthcare workers from different medical institutions and jobs were included in the study. The mean age of the participants was 32.69 ±8.72 years (range: 18-64 years). There were significant differences in knowledge about clinical signs about flu and prevention approaches among different age groups, individuals with different work experience and job titles (χ2 = 8.903-32.839; p < 0.05). Personnel with different job positions and education levels differed only in the knowledge about clinical signs of flu and identification of high-risk populations. A multivariate logistic regression analysis revealed that age (odds ratio (OR) = 0.979, 95% confidence interval (95% CI): 0.966-0.992) and education level (OR = 0.736, 95% CI: 0.588-0.921) were risk factors for hand hygiene practices, whereas job position (OR = 1.757, 95% CI: 1.146-2.695) and awareness of high-risk populations (OR = 1.405, 95% CI: 1.096-1.800) were protective factors influencing hand hygiene practices (p < 0.05). The only factor influencing mask wearing was the education level (OR = 0.610, 95% CI: 0.450-0.828). CONCLUSION: The knowledge level and preventive behavior of healthcare workers before the outbreak of COVID-19 has been insufficient.

7.
Digital health ; 8, 2022.
Article in English | EuropePMC | ID: covidwho-2102805

ABSTRACT

Background Persistence of long-term COVID-19 pandemic is putting high pressure on healthcare services worldwide for several years. This article aims to establish models to predict infection levels and mortality of COVID-19 patients in China. Methods Machine learning models and deep learning models have been built based on the clinical features of COVID-19 patients. The best models are selected by area under the receiver operating characteristic curve (AUC) scores to construct two homogeneous ensemble models for predicting infection levels and mortality, respectively. The first-hand clinical data of 760 patients are collected from Zhongnan Hospital of Wuhan University between 3 January and 8 March 2020. We preprocess data with cleaning, imputation, and normalization. Results Our models obtain AUC = 0.7059 and Recall (Weighted avg) = 0.7248 in predicting infection level, while AUC=0.8436 and Recall (Weighted avg) = 0.8486 in predicting mortality ratio. This study also identifies two sets of essential clinical features. One is C-reactive protein (CRP) or high sensitivity C-reactive protein (hs-CRP) and the other is chest tightness, age, and pleural effusion. Conclusions Two homogeneous ensemble models are proposed to predict infection levels and mortality of COVID-19 patients in China. New findings of clinical features for benefiting the machine learning models are reported. The evaluation of an actual dataset collected from January 3 to March 8, 2020 demonstrates the effectiveness of the models by comparing them with state-of-the-art models in prediction.

8.
Sustainability ; 14(21):14297, 2022.
Article in English | MDPI | ID: covidwho-2099793

ABSTRACT

The impact of COVID-19 on traffic volume makes it essential to study the spatial heterogeneity and impact mechanisms of the recovery of road traffic volume to promote the sustainability of related industries. As the research method, this study used a principal component analysis to evaluate the recovery of road traffic volume in China quantitatively, and further conducted an empirical study using a spatial autocorrelation index and a dynamic spatial panel model. The results show that income has a negative impact on the recovery of road traffic volume, while climate suitability has a positive impact. Economic development and COVID-19 can play moderating and mediating effects, respectively. From the aspect of spatial heterogeneity, the recovery of road traffic volume has a positive spatial spillover effect on the surrounding provinces, while the spread of COVID-19 has a negative short-term indirect spatial spillover effect. Corresponding practical insights are provided for the stakeholders based on the above findings. The results of this study will contribute to the development of effective policies to facilitate the recovery of road traffic volume from the impact of COVID-19 and the revitalization of the transportation industry.

9.
Journal of Affective Disorders ; 2022.
Article in English | ScienceDirect | ID: covidwho-2082562

ABSTRACT

Background Evidence on the relationship between burnout and post-traumatic stress disorder (PTSD) is limited. We aimed to evaluate the association between burnout and PTSD symptoms among medical staff two years after the coronavirus disease 2019 (COVID-19) pandemic in Wuhan, China, and explore the mediating roles of social support and psychological resilience. Methods A multicenter survey was conducted online from January to March 2022 among healthcare professionals from six general hospitals. Hierarchical linear regression was used to detect the predictors of PTSD symptoms. Structural equation modeling (SEM) was used to analyze the pathways from burnout to PTSD symptoms. Results Hierarchical linear regression showed that burnout, social support, and psychological resilience were significant predictors of PTSD symptoms among medical staff. In the SEM, the standardized total effect of burnout on PTSD symptoms was 0.336(bias-corrected 95 % confidence interval [0.303, 0.367], P < 0.001). Social support and psychological resilience partially mediated the relationship between burnout and PTSD symptoms (indirect effects accounted for 22.3 % of the total effect). Limitations Owing to the cross-sectional design, only clues to causal explanations can be provided. Conclusions Burnout has significant direct and indirect effects on PTSD symptoms. Furthermore, social support and psychological resilience might be effective ways to reduce the impact of burnout on PTSD symptoms in medical staff after a major public health outbreak.

10.
Brain Behav ; 12(11): e2785, 2022 11.
Article in English | MEDLINE | ID: covidwho-2074926

ABSTRACT

BACKGROUND: In December 2019, coronavirus disease (COVID-19) was first reported in Wuhan, China, and has had a negative psychological impact on the medical staff. However, the long-term psychological effects of COVID-19 were still unclear. We aimed to assess the posttraumatic stress disorder (PTSD) and depression among medical staff 2 years after COVID-19 pandemic in Wuhan, China. METHODS: We conducted a multicenter study in five general hospitals in Wuhan, China. PTSD was assessed using the PTSD Checklist-5. Depression was measured by the Center for Epidemiologic Studies Depression Scale. Multivariate adjusted logistic regression models were used to evaluate the association among demographic variables, depressive indicators, and PTSD. RESULTS: In a sample of 1795 medical staff, 295 (16.40%) participants reported PTSD and 329 (18.30%) reported depression. After multivariate adjusted logistic regression analyses, participants involved in COVID-19 clinical work, unsafe working environment, poor doctor-patient relationship, unhealth status, work dissatisfaction, and low family support were at a high risk for PTSD and depression 2 years after the outbreak of COVID-19 pandemic. CONCLUSIONS: Although it has been more than 2 years after the COVID-19 pandemic outbreak, the mental health of medical staff remains a concern. In particular, medical staff involved in the clinical care of COVID-19 patients showed a higher risk of PTSD and depression 2 years after the COVID-19 pandemic. This study may provide some useful suggestions for psychological interventions for medical staff.


Subject(s)
COVID-19 , Stress Disorders, Post-Traumatic , Humans , Pandemics , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/psychology , COVID-19/epidemiology , Physician-Patient Relations , Anxiety/psychology , Medical Staff , China/epidemiology
11.
Cell Host Microbe ; 2022 Oct 18.
Article in English | MEDLINE | ID: covidwho-2068781

ABSTRACT

SARS-CoV-2 spread in humans results in continuous emergence of new variants, highlighting the need for vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation-patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x) that contains key regions and residues across multiple SAR-CoV-2 variants. STFK1628x demonstrated high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine composed of STFK and STFK1628x elicited high titers of broad-spectrum neutralizing antibodies to 19 circulating SARS-CoV-2 variants, including Omicron sublineages BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5. Furthermore, this vaccine conferred robust protection against intranasal challenges by either SARS-CoV-2 ancestral strain or immune-evasive Beta and Omicron BA.1. Strikingly, vaccination with the bivalent vaccine in hamsters effectively blocked within-cage virus transmission of ancestral SARS-CoV-2, Beta variant, and Omicron BA.1 to unvaccinated sentinels. Thus, our study provided insight and antigen candidates for the development of next-generation COVID-19 vaccines.

12.
Vaccine ; 40(47): 6839-6848, 2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2042193

ABSTRACT

The ongoing coronavirus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has drastically changed our way of life and continues to have an unmitigated socioeconomic impact across the globe. Research into potential vaccine design and production is focused on the spike (S) protein of the virus, which is critical for virus entry into host cells. Yet, whether the degree of glycosylation in the S protein is associated with vaccine efficacy remains unclear. Here, we first optimized the expression of the S protein in mammalian cells. While we found no significant discrepancy in purity, homogeneity, or receptor binding ability among S proteins derived from 293F cells (referred to as 293F S-2P), 293S GnTI- cells (defective in N-acetylglucosaminyl transferase I enzyme; 293S S-2P), or TN-5B1-4 insect cells (Bac S-2P), there was significant variation in the glycosylation patterns and thermal stability of the proteins. Compared with the partially glycosylated 293S S-2P or Bac S-2P, the fully glycosylated 293F S-2P exhibited higher binding reactivity to convalescent sera. In addition, 293F S-2P induced higher IgG and neutralizing antibody titres than 293S or Bac S-2P in mice. Furthermore, a prime-boost-boost regimen, using a combined immunization of S-2P proteins with various degrees of glycosylation, elicited a more robust neutralizing antibody response than a single S-2P alone. Collectively, this study provides insight into ways to design a more effective SARS-CoV-2 immunogen.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Humans , Mice , Animals , SARS-CoV-2 , Glycosylation , COVID-19/prevention & control , Antibodies, Neutralizing , Antibodies, Viral , Mammals/metabolism
13.
Jiangsu Journal of Agricultural Sciences ; 38(4):1099-1105, 2022.
Article in Chinese | CAB Abstracts | ID: covidwho-2040042

ABSTRACT

In this paper, fuzzy-set qualitative comparative analysis (fsQCA) was used to analyze the relationship between export growth of edible fungi and trade environment under the background of COVID-19 prevalence from a configurational perspective. The results showed that, single environmental factor did not constitute a necessary condition for high export growth. There were three trade environment configurations that generated high export growth, and there was a complementary relationship between epidemic risk of COVID-19 and economic growth, technical barrier. Both epidemic risk of COVID-19 and technical barrier showed a bidirectional effect on export growth. Economic cardinality and economic growth jointly affected the sensitivity of export growth to transportation cost.

14.
Science ; 369(6511): 1586-1592, 2020 09 25.
Article in English | MEDLINE | ID: covidwho-2038226

ABSTRACT

Intervention strategies are urgently needed to control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The trimeric viral spike (S) protein catalyzes fusion between viral and target cell membranes to initiate infection. Here, we report two cryo-electron microscopy structures derived from a preparation of the full-length S protein, representing its prefusion (2.9-angstrom resolution) and postfusion (3.0-angstrom resolution) conformations, respectively. The spontaneous transition to the postfusion state is independent of target cells. The prefusion trimer has three receptor-binding domains clamped down by a segment adjacent to the fusion peptide. The postfusion structure is strategically decorated by N-linked glycans, suggesting possible protective roles against host immune responses and harsh external conditions. These findings advance our understanding of SARS-CoV-2 entry and may guide the development of vaccines and therapeutics.


Subject(s)
Host-Pathogen Interactions/immunology , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2 , Cryoelectron Microscopy , HEK293 Cells , Humans , Peptidyl-Dipeptidase A/chemistry , Protein Domains , Protein Multimerization , Protein Structure, Secondary , Receptors, Virus/chemistry , Virus Internalization
15.
Sci Total Environ ; 850: 157851, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2036502

ABSTRACT

The rapid spread of coronavirus disease 2019 has increased the consumption of some antiviral drugs, wherein these are discharged into wastewater, posing risks to the ecosystem and human health. Therefore, efforts are being made for the development of advanced oxidation processes (AOPs) to remediate water containing these pharmaceuticals. Here, the toxicity evolution of the antiviral drug ribavirin (RBV) was systematically investigated during its degradation via the UV/TiO2/H2O2 advanced oxidation process. Under optimal conditions, RBV was almost completely eliminated within 20 min, although the mineralization rate was inadequate. Zebrafish embryo testing revealed that the ecotoxicity of the treated RBV solutions increased at some stages and decreased as the reaction time increased, which may be attributed to the formation and decomposition of various transformation products (TPs). Liquid chromatography-mass spectrometry analysis along with density functional theory calculations helped identify possible toxicity increase-causing TPs, and quantitative structure activity relationship prediction revealed that most TPs exhibit higher toxicity than the parent compound. The findings of this study suggest that, in addition to the removal rate of organics, the potential ecotoxicity of treated effluents should also be considered when AOPs are applied in wastewater treatment.


Subject(s)
COVID-19 , Water Pollutants, Chemical , Water Purification , Animals , Antiviral Agents/analysis , Antiviral Agents/toxicity , Ecosystem , Humans , Hydrogen Peroxide/chemistry , Oxidation-Reduction , Pharmaceutical Preparations , Ribavirin/toxicity , Ultraviolet Rays , Waste Water/chemistry , Water/analysis , Water Pollutants, Chemical/analysis , Water Purification/methods , Zebrafish
16.
Sci Immunol ; 7(76): eadd5446, 2022 10 28.
Article in English | MEDLINE | ID: covidwho-1992933

ABSTRACT

SARS-CoV-2 Omicron subvariants have generated a worldwide health crisis due to resistance to most approved SARS-CoV-2 neutralizing antibodies and evasion of vaccination-induced antibodies. To manage Omicron subvariants and prepare for new ones, additional means of isolating broad and potent humanized SARS-CoV-2 neutralizing antibodies are desirable. Here, we describe a mouse model in which the primary B cell receptor (BCR) repertoire is generated solely through V(D)J recombination of a human VH1-2 heavy chain (HC) and, substantially, a human Vκ1-33 light chain (LC). Thus, primary humanized BCR repertoire diversity in these mice derives from immensely diverse HC and LC antigen-contact CDR3 sequences generated by nontemplated junctional modifications during V(D)J recombination. Immunizing this mouse model with SARS-CoV-2 (Wuhan-Hu-1) spike protein immunogens elicited several VH1-2/Vκ1-33-based neutralizing antibodies that bound RBD in a different mode from each other and from those of many prior patient-derived VH1-2-based neutralizing antibodies. Of these, SP1-77 potently and broadly neutralized all SARS-CoV-2 variants through BA.5. Cryo-EM studies revealed that SP1-77 bound RBD away from the receptor-binding motif via a CDR3-dominated recognition mode. Lattice light-sheet microscopy-based studies showed that SP1-77 did not block ACE2-mediated viral attachment or endocytosis but rather blocked viral-host membrane fusion. The broad and potent SP1-77 neutralization activity and nontraditional mechanism of action suggest that it might have therapeutic potential. Likewise, the SP1-77 binding epitope may inform vaccine strategies. Last, the type of humanized mouse models that we have described may contribute to identifying therapeutic antibodies against future SARS-CoV-2 variants and other pathogens.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Mice , Animals , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2 , Membrane Fusion , Antibodies, Viral , Antibodies, Neutralizing , Epitopes , Receptors, Antigen, B-Cell
17.
Proc Natl Acad Sci U S A ; 119(34): e2204256119, 2022 08 23.
Article in English | MEDLINE | ID: covidwho-1991767

ABSTRACT

Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Epitopes , SARS Virus , SARS-CoV-2 , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , Conserved Sequence , Cricetinae , Cryoelectron Microscopy , Epitopes/immunology , Humans , Mice , Neutralization Tests , SARS Virus/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics
18.
Journal of Shandong University ; 58(10):105-111, 2020.
Article in Chinese | GIM | ID: covidwho-1975295

ABSTRACT

Objective To explore the distributions of hospital service areas under epidemic situation and the methods of setting centralized isolation points based on service areas from the perspective of space facility layout optimization. Methods A Huff model was applied to analyze the distributions of service areas of tertiary hospitals in Shanghai. Candidate locations were set to achieve maximizing coverage, and a location-allocation model was applied to predict the optimal hospital location. Results Among the tertiary hospitals that can admit COVID-19 cases in Shanghai, the central area had a high density of hospitals. The distributions of service areas in urban and rural hospitals were obviously different, and the service areas of rural hospitals were large. It was recommended to optimize the allocation of a new hospital in the center region of Songjiang District and an appropriate number of hospitals in the central area of Pudong New District. Conclusion Considering the distribution of hospital service areas, isolation points can be set in the communities close to the affiliated hospitals, and the hospitals corresponding to each isolation point should be clearly identified when a case occurs. It is recommended to optimize the configuration to add tertiary hospitals in Songjiang District and Pudong New District.

19.
N Engl J Med ; 387(2): 120-131, 2022 07 14.
Article in English | MEDLINE | ID: covidwho-1967704

ABSTRACT

BACKGROUND: Adagrasib, a KRASG12C inhibitor, irreversibly and selectively binds KRASG12C, locking it in its inactive state. Adagrasib showed clinical activity and had an acceptable adverse-event profile in the phase 1-1b part of the KRYSTAL-1 phase 1-2 study. METHODS: In a registrational phase 2 cohort, we evaluated adagrasib (600 mg orally twice daily) in patients with KRASG12C -mutated non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy and anti-programmed death 1 or programmed death ligand 1 therapy. The primary end point was objective response assessed by blinded independent central review. Secondary end points included the duration of response, progression-free survival, overall survival, and safety. RESULTS: As of October 15, 2021, a total of 116 patients with KRASG12C -mutated NSCLC had been treated (median follow-up, 12.9 months); 98.3% had previously received both chemotherapy and immunotherapy. Of 112 patients with measurable disease at baseline, 48 (42.9%) had a confirmed objective response. The median duration of response was 8.5 months (95% confidence interval [CI], 6.2 to 13.8), and the median progression-free survival was 6.5 months (95% CI, 4.7 to 8.4). As of January 15, 2022 (median follow-up, 15.6 months), the median overall survival was 12.6 months (95% CI, 9.2 to 19.2). Among 33 patients with previously treated, stable central nervous system metastases, the intracranial confirmed objective response rate was 33.3% (95% CI, 18.0 to 51.8). Treatment-related adverse events occurred in 97.4% of the patients - grade 1 or 2 in 52.6% and grade 3 or higher in 44.8% (including two grade 5 events) - and resulted in drug discontinuation in 6.9% of patients. CONCLUSIONS: In patients with previously treated KRASG12C -mutated NSCLC, adagrasib showed clinical efficacy without new safety signals. (Funded by Mirati Therapeutics; ClinicalTrials.gov number, NCT03785249.).


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Proto-Oncogene Proteins p21(ras) , Acetonitriles/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Piperazines/therapeutic use , Proto-Oncogene Proteins p21(ras)/antagonists & inhibitors , Proto-Oncogene Proteins p21(ras)/genetics , Pyrimidines/therapeutic use
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