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The coronavirus disease 2019 (COVID-19) pandemic underlines a persistent threat of respiratory tract infectious diseases and warrants preparedness for a rapid response. At present, COVID-19 has had a serious social impact and imposed a heavy global burden on public health. The exact pathogenesis of COVID-19 has not been fully elucidated. Since the outbreak of COVID-19, a renewed attention has been brought to Toll-like receptors (TLRs). Available data and new findings have demonstrated that the interaction of human TLRs and SARS-CoV-2 is a vital mediator of COVID-19 immunopathogenesis. TLRs such as TLR2, 4, 7 and 8 are potentially important in viral combat and activation of immunity in patients with COVID-19. Therapeutics targeting TLRs are currently considered promising options against the pandemic. A number of TLR-targeting immunotherapeutics are now being investigated in preclinical studies and different phases of clinical trials. In addition, innovative vaccines based on TLRs under development could be a promising approach for building a new generation of vaccines to solve the current challenges. In this review, we summarize recent progress in the role of TLRs in COVID-19, focusing the new candidate drugs targeting TLRs, the current technology and potential paths forward for employing TLR agonists as vaccine adjuvants.Copyright © 2023 The Scandinavian Foundation for Immunology.
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Although most of the mutations in the genome of SARS-CoV-2 are ineffective, rapidly eliminated, or relatively neutral, a small number of mutations will affect its functional characteristics and may change its infectivity, pathogenicity, or interaction with host immunity. Since the emergence of SARS-CoV-2 at the end of 2019, there has been a relative evolution stagnation period lasting about 11 months. However, since the end of 2020, a series of spike protein mutations have occurred in SARS-CoV-2, which affect the characteristics of the virus. The variants of concern (VOC) ranged from Alpha to Omicron. These variants will affect the infectivity and antigenicity of the virus. The evidence has shown that the neutralization effect of serum on some SARS-CoV-2 variants is weakened after vaccination, but a deeper understanding of the relevant factors of protection is still required to assess how this may affect the effectiveness of the vaccine. In this review, we described the evolution of SARS-CoV-2, summarized the literatures on the mutations of SARS-CoV-2 spike protein, and discussed the effects of different variants on the protective effects of vaccines and their coping strategies. © 2023 Editorial Board of Medical Journal of Wuhan University. All rights reserved.
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The COVID‑19 pandemic causes an overwhelming number of hospitalization and deaths with a significant socioeconomic impact. Several studies have linked the severity of COVID‑19 to risk factors such as age, male, hypertension, diabetes, obesity, cardiovascular disease, liver and kidney disease, cancer, and pregnancy. The association between chronic obstructive pulmonary disease (COPD) and asthma, the most common chronic airway inflammatory diseases in the population, and SARS‑CoV‑2 infection is not yet clear. This article will review the comorbidity rates of COPD and asthma in COVID‑19 patients, their effects on COVID‑19, and the possible mechanisms, in order to provide scientific data for clinical practice. © 2022 Editorial Board of Medical Journal of Wuhan University. All rights reserved.
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Objective:To observe the efficacy and safety of Fuzheng Huayu tabletsFHTfor treating pulmonary inflammation in patients with coronavirus disease 2019COVID-19. Method(s):A total of 704 cases were lost to follow-up, and 66 cases were finally completedCOVID-19 patients were recruited from February 1 to April 15 in 2020. They were assigned to a control group35 patientsand a FHT group31 patients. The patients in the control group received routine treatment alone and those in the FHT group received FHT in addition to routine treatment. The primary outcome was the ratio of patients showing improvement in chest computed tomographic manifestations after 14 days. The secondary outcome measures included remission rate or progression rate of critical illness,clinical remission rate of respiratory symptoms,routine blood examination, C-reactive proteinCPRlevel,procalcitoninPCTlevel,and blood oxygen saturationSPO2 . The safety was assessed based on liver and kidney functions and adverse events. Result(s): After the 14-day treatment,the ratio of patients showing improvement in the FHT group100%was higher than that in the control group 77.1%chi2 =8.063,P<0.01. The ratio of disease stages after treatment showed no significant difference between two groups. In the FHT group,the symptoms including cough,dyspnea,and fatigue were alleviated after treatmentP<0.01. In the control group,the symptoms including fever,cough,and dyspnea were alleviatedP<0.01,while the fatigue was not relieved after treatment. No significant difference was observed in the clinical symptoms between the two groups after treatment. After treatment,the FHT group showed decreased white blood cellWBCcount and neutrophil-to-lymphocyte ratioNLRP<0.01,elevated plateletPLTlevelP<0.05,lowered CRP levelP<0.05,and no significant difference in lymphocyte LYM,hemoglobinHb,SPO2 or PCT level. The control group showed decreased NLRP<0.05and WBC countP<0.01,elevated PCT levelP<0.05,and no significant change in LYM,Hb,PLT,SPO2 or CRP level after treatment. Furthermore,the FHT group had higher PLT level than the control groupP<0.05after treatment,and other indicators had no significant differences between the two groups. The liver and kidney functions had no significant difference between the two groups after treatment. Conclusion(s): FHT can safely promote the absorption of acute pulmonary inflammation in COVID-19 patients.Copyright © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.
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In this paper, we propose and investigate the SIQR epidemic model with a generalized incidence rate function, a general treatment function and vaccination term. We firstly consider the existence and uniqueness of the global nonnegative solution to the deterministic model. Further, we show the locally asymptotic stability of the disease-free equilibrium and endemic equilibrium of the deterministic model, and obtain the basic reproduction number R0. Then we study the existence and uniqueness of the global positive solution to the stochastic model with any positive initial value. Meanwhile, we obtain sufficient conditions for the extinction of the disease in the stochastic epidemic model, and find that the large noise can make the disease die out exponentially. Finally, we make an empirical analysis by the COVID-19 data of Russia and Serbia. By the performance comparison of different models, it shows that the model with vaccination and treatment we proposed is better for the real situation, which is also verified by different estimation methods. Especially, that shows the recovery rate of the infected increases by 0.042 and the death rate of the recovered is 1.525 times that of normal human in Russia. Through statistical analysis, the short-term trend of epidemic transmission is predicted: under the condition of unchanged prevention and control policies, it may reach a stable endemic equilibrium state in Russia and the epidemic will eventually extinct in Serbia. © 2023 Elsevier Inc.
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Background Taletrectinib is a potent, next-generation, CNS-active, ROS1 tyrosine kinase inhibitor (TKI) with selectivity over TRKB. In previous reports from TRUST-I, taletrectinib showed meaningful clinical efficacy and was well tolerated in pts with ROS1+ NSCLC (n = 109) regardless of crizotinib (CRZ) pretreatment status. We report updated efficacy and safety data with ~1.5 yr follow-up. Methods TRUST-I is a multicenter, open-label, single-arm study with two cohorts: ROS1 TKI-naive and CRZ-pretreated. Pts in both cohorts received taletrectinib 600 mg QD. Key study endpoints included IRC-confirmed ORR (cORR), DoR, disease control rate (DCR), PFS, and safety. A pooled analysis of ORR, PFS, and safety including pts from additional clinical trials was also conducted. Results In the 109 pts from TRUST-I (enrolled prior to Feb 2022) the median follow-up was 18.0 mo in TKI-naive (n = 67) and 16.9 mo in CRZ-pretreated pts (n = 42). cORR was 92.5% in TKI-naive and 52.6% in CRZ-pretreated pts (table). Median DoR (mDoR) and mPFS were not reached. Intracranial-ORR was 91.6%;ORR in pts with G2032R was 80.0%. In a pooled analysis with phase I studies, ORR was 89.5% and 50.0% for TKI-naive and CRZ-pretreated pts, respectively;mPFS was 33.2 mo and 9.8 mo. In 178 pts treated at 600 mg QD, treatment-emergent adverse events (TEAEs) were 92.7%;most (64.0%) were grade 1-2. The most common TEAEs were increased AST (60.7%), increased ALT (55.6%), and diarrhea (55.6%). Neurological TEAEs (dizziness, 18.5%;dysgeusia, 12.4%) and discontinuations due to TEAEs (3.4%) were low. Further updated results will be presented. [Formula presented] Conclusions With additional follow-up, taletrectinib continued to demonstrate meaningful efficacy outcomes including high response rates, prolonged PFS, robust intracranial activity, activity against G2032R, and tolerable safety with low incidence of neurological AEs. Clinical trial identification NCT04395677. Editorial acknowledgement Medical writing and editorial assistance were provided by Arpita Kulshrestha of Peloton Advantage, LLC, an OPEN Health company, and funded by AnHeart Therapeutics, Inc Legal entity responsible for the study AnHeart Therapeutics, Inc. Funding AnHeart Therapeutics, Inc. Disclosure S. He: Financial Interests, Personal, Other, Employment: AnHeart Therapeutics. T. Seto: Financial Interests, Institutional, Research Grant: AbbVie, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, MSD, Novartis Pharma, Pfizer Japan, Takeda Pharmaceutical;Financial Interests, Personal, Other, Employment: Precision Medicine Asia;Financial Interests, Personal, Speaker's Bureau, Honoraria for lectures: AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Covidien Japan, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, MSD, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical, Towa Pharmaceutical. C. Zhou: Financial Interests, Personal, Other, Consulting fees: Innovent Biologics Qilu, Hengrui, TopAlliance Biosciences Inc;Financial Interests, Personal, Speaker's Bureau, Payment or honoraria: Eli Lilly China, Sanofi, BI, Roche, MSD, Qilu, Hengrui, Innovent Biologics, C-Stone LUYE Pharma, TopAlliance Biosciences Inc, Amoy Diagnositics, AnHeart. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
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Many transit providers changed their schedules and route configurations during the COVID-19 pandemic, providing more frequent bus service on major routes and curtailing other routes, to reduce the risk of COVID-19 exposure. This research first assessed the changes in Metropolitan Atlanta Rapid Transit Authority (MARTA) service configurations by reviewing the prepandemic versus during-pandemic General Transit Feed Specification (GTFS) files. Energy use per route for a typical week was calculated for pre-pandemic, during-closure, and post-closure periods by integrating GTFS data with MOVES-Matrix transit energy and emission rates (MOVES signifying MOtor Vehicle Emission Simulator). MARTA automated passenger counter data were appended to the routes, and energy use per passenger-mile was compared across routes for the three periods. The results showed that the coupled effect of transit frequency shift and ridership decrease from 2019 to 2020 increased route-level energy use for over 87% of the routes and per-passenger-mile energy use for over 98% of the routes. In 2021, although MARTA service had largely returned to pre-pandemic conditions, ridership remained in an early stage of recovery. Total energy use decreased to about pre-pandemic levels, but per-passenger energy use remained higher for more than 91% of routes. The results confirm that while total energy use is more closely associated with trip schedules and routes, perpassenger energy use depends on both trip service and ridership. The results also indicate a need for data-based transit planning, to help avoid inefficiency associated with over-provision of service or inadequate social distancing protection caused by under-provision of service. © National Academy of Sciences: Transportation Research Board 2022.
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With the impact of the novel coronavirus on the global economy, the role of live e-commerce as an engine to drive economic and social development has become more and more prominent. In order to further promote the positive development of Taobao Live platform, this article uses SOR theory, multi-dimensional factors such as "people, goods and venues"as stimulus variables, introduces perceived value and perceived risk as mediating variables, and demographic characteristics as moderating variables to construct a model of consumers' purchase intention on Taobao Live e-commerce platform and put forward corresponding hypotheses, and uses SPSS 26.0 and AMOS 24.0 to analyse 223 questionnaires collected to study the influencing factors of consumers' purchase intention and provide corresponding suggestions. The study shows that: consumer perceived value and perceived risk have significant effects on consumer purchase intention;anchor professionalism, consumer herd mentality and situational factors have significant effects on consumer perceived value;anchor professionalism, consumer impulsive traits and herd mentality have significant effects on consumer perceived risk;some demographic characteristics play a moderating role in the process of perceived value and perceived risk on consumer purchase intention. © 2022 ACM.
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After the outbreak of COVID-19, Taiwan has implemented rigorous border control and taken specific measures such as virus detection, contact tracing, and quarantine since 2020. Its epidemic prevention performance has been quite outstanding. Even in May 2021, when the epidemic situation worsens, the people in Taiwan fully cooperate with the government's control measures so as to successfully alleviate and control the epidemic in less than three months. Among them, the detection policy has played a pivotal role. We analyze and discuss the false positive and false negative problems from rapid antigen and PCR detection in the screening policy as well as the timing of using these two instruments. This paper provides theoretical verification of the appropriateness of screening policy in Taiwan, offering a few feasible suggestions for related policies in other countries or regions at different stages of this and other potential epidemics. (c) 2022 by the authors;licensee Growing Science, Canada.
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Objective: To evaluate the household secondary attack rates of the SARS-CoV-2 Delta variant and the associated factors. Methods: A COVID-19 outbreak caused by the Delta variant occurred in Nanjing in July 2021. A total of 235 cases with current addresses in Nanjing were reported from 171 households. The subjects in this study were selected from household close contact(s) of infected cases. The information on household index cases and their contacts were collected, and the household secondary attack rate (HSAR) and the risk factors were analyzed by the multi-factor logistic regression model. Results: A total of 234 cases of household close contacts and 64 household secondary cases were reported from 103 households, and the HSAR was 27.4% (64/234, 95%CI:22.0% to 33.4%). The proportions of household size for 2 to 3, 4 to 5, and 6 to 9 were 64.1% (66), 26.2% (27) and 9.7% (10), respectively. A total of 35 cases of household cluster outbreaks were reported (35/103, 34.0%). The number of the first case in the household (FCH) was 103 and males accounted for 27.2% (28 cases), with the median age (Q1, Q3) of 49 (9, 56). The number of household close contacts was 234 and males accounted for 59.0% (138 cases), with the median age (Q1, Q3) of 42 (20, 55) and the median exposure period (Q1, Q3) of 3 (1, 3) days. The multi-factor logistic regression model showed that the higher HSAR was observed in the FCH with the features of airport staff (OR=2.913, 95%CI:1.469-5.774), detection from home quarantine screening (OR=6.795, 95%CI:1.761-26.219) and detection from mass screening (OR=4.239, 95%CI:1.098-16.368). Meanwhile, higher HSAR was observed in cases with longer household exposure (OR=1.221, 95%CI:1.040-1.432), non-vaccination (OR=2.963, 95%CI:1.288-6.813) and incomplete vaccinations (OR=2.842, 95%CI:0.925-8.731). Conclusion: The generation interval of the Delta variant is shortened, and the ability of transmission within the household is enhanced. In the outbreak in Nanjing, the associated factors of HSAR are occupation, detection route, vaccination and exposure period.
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COVID-19 , SARS-CoV-2 , Male , Humans , COVID-19/epidemiology , Incidence , Family CharacteristicsABSTRACT
As a member of the dibenzyl isoquinoline alkaloid family, cepharathine is an alkaloid from the traditional Chinese medicine cepharathine, which is mainly used for treatment of leukopenia and other diseases. Recent studies of the inhibitory effect of cepharathine against SARS-CoV-2 have attracted widespread attention and aroused heated discussion. As the original discoverer of the anti-SARS-CoV-2 activity of cepharanthine, here we briefly summarize the discovery of cepharanthine and review important progress in relevant studies concerning the discovery and validation of anti-SARS-CoV-2 activity of cepharathine, its antiviral mechanisms and clinical trials of its applications in COVID-19 therapy.
Subject(s)
Benzylisoquinolines , COVID-19 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Benzylisoquinolines/pharmacology , Benzylisoquinolines/therapeutic use , Humans , SARS-CoV-2ABSTRACT
In addition to damaging the respiratory system, coronavirus disease 2019 (COVID-19) can also affect the nervous system, and even cause serious clinical consequences. This paper expounds the research status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on nervous system injury from 3 aspects: pathogenesis, clinical symptoms and treatment prognosis, and systematically summarizes the pathological mechanism of nervous system lesions caused by COVID-19, hoping to provide new ideas for the diagnosis and treatment of COVID-19.
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Objective：To observe the efficacy and safety of Fuzheng Huayu tablets（FHT）for treating pulmonary inflammation in patients with coronavirus disease 2019（COVID-19）. Method：A total of 70（4 cases were lost to follow-up, and 66 cases were finally completed）COVID-19 patients were recruited from February 1 to April 15 in 2020. They were assigned to a control group（35 patients）and a FHT group（31 patients）. The patients in the control group received routine treatment alone and those in the FHT group received FHT in addition to routine treatment. The primary outcome was the ratio of patients showing improvement in chest computed tomographic manifestations after 14 days. The secondary outcome measures included remission rate or progression rate of critical illness，clinical remission rate of respiratory symptoms，routine blood examination， C-reactive protein（CPR）level，procalcitonin（PCT）level，and blood oxygen saturation（SPO2 ）. The safety was assessed based on liver and kidney functions and adverse events. Result： After the 14-day treatment，the ratio of patients showing improvement in the FHT group（100%）was higher than that in the control group （77.1%）（χ2 =8.063，P<0.01）. The ratio of disease stages after treatment showed no significant difference between two groups. In the FHT group，the symptoms including cough，dyspnea，and fatigue were alleviated after treatment（P<0.01）. In the control group，the symptoms including fever，cough，and dyspnea were alleviated（P<0.01），while the fatigue was not relieved after treatment. No significant difference was observed in the clinical symptoms between the two groups after treatment. After treatment，the FHT group showed decreased white blood cell（WBC）count and neutrophil-to-lymphocyte ratio（NLR）（P<0.01），elevated platelet（PLT）level（P<0.05），lowered CRP level（P<0.05），and no significant difference in lymphocyte （LYM），hemoglobin（Hb），SPO2 or PCT level. The control group showed decreased NLR（P<0.05）and WBC count（P<0.01），elevated PCT level（P<0.05），and no significant change in LYM，Hb，PLT，SPO2 or CRP level after treatment. Furthermore，the FHT group had higher PLT level than the control group（P<0.05）after treatment，and other indicators had no significant differences between the two groups. The liver and kidney functions had no significant difference between the two groups after treatment. Conclusion： FHT can safely promote the absorption of acute pulmonary inflammation in COVID-19 patients. © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.
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After the outbreak of COVID-19, Taiwan has implemented rigorous border control and taken specific measures such as virus detection, contact tracing, and quarantine since 2020. Its epidemic prevention performance has been quite outstanding. Even in May 2021, when the epidemic situation worsens, the people in Taiwan fully cooperate with the government’s control measures so as to successfully alleviate and control the epidemic in less than three months. Among them, the detection policy has played a pivotal role. We analyze and discuss the false positive and false negative problems from rapid antigen and PCR detection in the screening policy as well as the timing of using these two instruments. This paper provides theoretical verification of the appropriateness of screening policy in Taiwan, offering a few feasible suggestions for related policies in other countries or regions at different stages of this and other potential epidemics. © 2022 by the authors;licensee Growing Science, Canada.
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Taiwan is known for its effective responses to COVID-19, with only 799 confirmed cases by the end of 2020. Based on the previous research, this article identifies three major technical approaches used in Taiwan to prevent the community spread of COVID-19: (1) Digital fence and entry quarantine system to track close contacts and force 14 days of in-home quarantine;(2) Evolving face mask distribution policy and system to ensure fair allocation of the limited face mask resources;and (3) Open-source software co-developed by the government and tech community to share real-time COVID-19 related information and conduct location history based contact tracing. The combat against COVID-19 in Taiwan is a success in digital governance, with great synergy between the government and every citizen.
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The ongoing coronavirus disease 2019 (COVID-19) pandemic and other major viral infectious diseases have become a significant threat to people's life and economic/social development. In recent years, with the development of nanotechnology, nanomaterial-based antiviral agents have been extensively studied. However, the clinical applications of antiviral nanomaterials are still limited. Herein, the recent advances in nanomaterial-based antiviral strategies, mainly including antiviral nanodrugs, drug nanocarriers, and nanovaccines, are summarized. The clinical challenges and prospects of nanomaterial-based antiviral strategies are also discussed.
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At present, the new type of coronavirus pneumonia is still being broadcast on a large scale worldwide. Based on this research background, the paper uses the new coronary pneumonia as the research foundation. It builds a biomedical infectious disease transmission control model with an intervention mechanism on a complex transmission network based on a numerical simulation method. The thesis dynamically describes the entire process of disease outbreak, spread, and control. Through research, it is found that biomedical, medical intervention and isolation measures can play a certain role in spreading the new coronary pneumonia infectious disease, which provides a reference and basis for the world's disease control and prevention and biomedical intervention. © 2021 ACM.
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The concept of ‘human as sensors’defines a new sensing model, in which humans act as sensors by contributing their observations, perceptions, and sensations. This is crucial for the development of social Internet of Things, which is an integral part of Cyber-Physical-Social systems. Online social media platforms, as the most active places where users act as social sensors, are responsive to real-world events and are useful for gathering situational information in real-time. Unfortunately, posts rarely contain structured geographic information, thus hindering their usage for contributing to various challenges, such as emergency response. We address this limitation by introducing a general approach for extracting place names from tweets, named GazPNE2. It combines global gazetteers (i.e., OpenStreetMap and GeoNames), deep learning, and pretrained transformer models (i.e., BERT and BERTweet), which requires no manually annotated data. It can extract place names at both coarse (e.g., city) and fine-grained (e.g., street and POI) levels and place names with abbreviations. To fully evaluate GazPNE2 and compare it with 11 competing approaches, we use 19 public tweet datasets, containing 38,802 tweets and 22,197 places across the world. The results show GazPNE2 achieves much higher F1 (0.8) than the other approaches. Furthermore, we apply GazPNE2 to three large unannotated tweet datasets related to over 20 crisis events (e.g., COVID-19), containing 560,040 tweets. An F1 of 0.84 is achieved on 3,000 tweets, which are randomly selected from the three datasets and then manually annotated. Code and data are available on GitHub page: https://github.com/uhuohuy/GazPNE2. IEEE
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Cross-border e-commerce, as a new business model, has gradually replaced the traditional trade model. However, during the COVID-19 pandemic, many companies encountered bottlenecks, mainly because products could not adapt to the rapid changes in consumption and products were out of stock due to weak logistics system. Through our observation of the current marketing situation and problems, we analyze that sellers need to enhance their adaptability and risk resistance in the pandemic environment, especially in the face of the new trends in cross-border e-commerce. Based on this, we propose a strategic optimization plan, including product optimization, sales channel optimization, brand optimization and logistics optimization. To ensure the implementation of the strategy, we designed a guaranteed roadmap, including user-demand oriented product development management, improvement of human resource management structure, optimization of operation structure and logistics supply chain enhancement. Finally, we hope this solution to be effective in a pandemic situation. © 2022, ICST Institute for Computer Sciences, Social Informatics and Telecommunications Engineering.