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AIMS: This study aims to assess the effectiveness of COVID-19 vaccination against all-cause death in patients with type 2 diabetes mellitus (T2DM). METHODS: Subjects were patients with T2DM who were administered by general practitioner (GP). Use electronic exchange platform to obtain the information on COVID-19 vaccination, all-cause deaths and risk factors. Logistic regression models were used to calculate the odd ratio (OR) and 95% CI for the association between COVID-19 vaccination and mortality. The vaccine effectiveness (VE) was calculated as (1- adjusted OR) × 100%. RESULTS: A total of 26,916 subjects had 53.81%, 17.65%, and 23.43% coverage for the booster, full, and partial COVID-19 vaccination, reported 328 deaths and a mortality of 1.2%. The adjusted OR (95%CI) was 0.85(0.60-1.21) for those received partial vaccination, 0.31(0.22-0.43) for those received full vaccination, and 0.12(0.08-0.18) for those received booster vaccination, compared to the unvaccinated individuals. The VE (95%CI) was 88.00%(82.30-91.80) of booster vaccination, 69.30%(56.60-78.30) of full vaccination, and 17.60%(-17.10-42.00) of partial vaccination. CONCLUSION: COVID-19 vaccination could effectively prevent the all-cause death in patients with T2DM during the omicron variant outbreak period, after the cancellation of the "Dynamic Zero Policy" in mainland China.
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Viruses evade the innate immune response by suppressing the production or activity of cytokines such as type I interferons (IFNs). Here we report the discovery of a mechanism by which the SARS-CoV-2 virus coopts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-ß. We reveal that the SARS-CoV-2 encoded nonstructural protein 2 (NSP2) directly interacts with the cellular GIGYF2 protein. This interaction enhances the binding of GIGYF2 to the mRNA cap-binding protein 4EHP, thereby repressing the translation of the Ifnb1 mRNA. Depletion of GIGYF2 or 4EHP significantly enhances IFN-ß production, which inhibits SARS-CoV-2 replication. Our findings reveal a target for rescuing the antiviral innate immune response to SARS-CoV-2 and other RNA viruses.
Subject(s)
COVID-19 , Carrier Proteins , Interferon Type I , Viral Nonstructural Proteins , COVID-19/genetics , Carrier Proteins/metabolism , Cell Line , Eukaryotic Initiation Factor-4E/metabolism , Humans , Immunity, Innate , Interferon Type I/metabolism , Protein Biosynthesis , RNA, Messenger/genetics , SARS-CoV-2 , Viral Nonstructural Proteins/metabolism , Virus ReplicationABSTRACT
Porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus in the family Coronaviridae, causes acute diarrhea and/or vomiting, dehydration, and high mortality in neonatal piglets. It has caused huge economic losses to animal husbandry worldwide. Current commercial PEDV vaccines do not provide enough protection against variant and evolved virus strains. No specific drugs are available to treat PEDV infection. The development of more effective therapeutic anti-PEDV agents is urgently needed. Our previous study suggested that porcine milk small extracellular vesicles (sEV) facilitate intestinal tract development and prevent lipopolysaccharide-induced intestinal injury. However, the effects of milk sEV during viral infection remain unclear. Our study found that porcine milk sEV, which was isolated and purified by differential ultracentrifugation, could inhibit PEDV replication in IPEC-J2 and Vero cells. Simultaneously, we constructed a PEDV infection model for piglet intestinal organoids and found that milk sEV also inhibited PEDV infection. Subsequently, in vivo experiments showed that milk sEV pre-feeding exerted robust protection of piglets from PEDV-induced diarrhea and mortality. Strikingly, we found that the miRNAs extracted from milk sEV inhibited PEDV infection. miRNA-seq, bioinformatics analysis, and experimental verification demonstrated that miR-let-7e and miR-27b, which were identified in milk sEV targeted PEDV N and host HMGB1, suppressed viral replication. Taken together, we revealed the biological function of milk sEV in resisting PEDV infection and proved its cargo miRNAs, miR-let-7e and miR-27b, possess antiviral functions. This study is the first description of the novel function of porcine milk sEV in regulating PEDV infection. It provides a better understanding of milk sEV resistance to coronavirus infection, warranting further studies to develop sEV as an attractive antiviral.
Subject(s)
Coronavirus Infections , MicroRNAs , Porcine epidemic diarrhea virus , Swine Diseases , Chlorocebus aethiops , Animals , Swine , Vero Cells , Porcine epidemic diarrhea virus/genetics , Milk , MicroRNAs/genetics , MicroRNAs/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Diarrhea/drug therapy , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Coronavirus Infections/drug therapy , Swine Diseases/prevention & controlABSTRACT
Wearing masks reduces the spread of COVID-19, but compliance with mask mandates varies across individuals, time, and space. Accurate and continuous measures of mask wearing, as well as other health-related behaviors, are important for public health policies. This article presents a novel approach to estimate mask wearing using geotagged Twitter image data from March through September, 2020 in the United States. We validate our measure using public opinion survey data and extend the analysis to investigate county-level differences in mask wearing. We find a strong association between mask mandates and mask wearing-an average increase of 20%. Moreover, this association is greatest in Republican-leaning counties. The findings have important implications for understanding how governmental policies shape and monitor citizen responses to public health crises.
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COVID-19 , Humans , United States/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , Government , Public Health , Public Opinion , Public PolicyABSTRACT
China has basically controlled the COVID-19 epidemic as a result of widespread vaccination and other containment strategies, despite localized outbreaks, as of September 2021. This study investigates the knowledge, attitudes, and practices (KAP) of COVID-19 and COVID-19 vaccines among Chinese small-town residents to provide suggestions for public health policy. Residents who were vaccinated against COVID-19 were asked to complete a paper questionnaire on KAP in Xidian, Zhejiang. The knowledge questionnaire consisted of 12 questions regarding COVID-19 and 12 questions regarding COVID-19 vaccines. Attitude and practice evaluation included agreement on the eventual control of COVID-19 and having recently worn a mask outside. Of 405 survey responders, 52.3% were male, 71.4% had middle school education or less, and 59.0% engaged in physical labor as an occupation. The correct answer rates of the COVID-19 section and the vaccine section were 79.2% and 71.7%, respectively. Age groups of 18 to 29 years and > 50 years, occupations of physical labor and unemployment, and primary school education and less were associated with lower knowledge scores. The majority of participants (91.6%) believed that COVID-19 will eventually be controlled, whereas women, students, and patients with chronic held relatively negative attitudes toward epidemic control. Most participants (87.4%) wore masks outside recently. In conclusion, Chinese small-town residents have a medium level of knowledge regarding COVID-19 and vaccines, hold positive attitudes, and have appropriate practices. Health education should be provided to the target populations to enrich their knowledge of COVID-19 and vaccines, and to improve their attitudes toward epidemic control.
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Objective: The long-term impact of COVID-19 on patient health has been a recent focus. This study aims to determine the persistent symptoms and psychological conditions of patients hospitalized with COVID-19 15 months after onset, that patients first developed symptoms. The potential risk factors were also explored. Methods: A cohort of COVID-19 patients discharged from February 20, 2020 to March 31, 2020 was recruited. Follow-ups were conducted using validated questionnaires and psychological screening scales at 15 months after onset to evaluate the patients' health status. The risk factors for long-term health impacts and their associations with disease severity was analyzed. Findings: 534 COVID-19 patients were enrolled. The median age of the patients was 62.0 years old (IQR 52.0-70.0) and 295 were female (55.2%). The median time from onset to follow-up was 460.0 (451.0-467.0) days. Sleep disturbance (18.5%, 99/534) and fatigue (17.2%, 92/534) were the most common persistent symptoms. 6.4% (34/534) of the patients had depression, 9.2% (49/534) were anxious, 13.0% (70/534) had insomnia and 4.7% (25/534) suffered from post-traumatic stress disorder (PTSD). Multivariate adjusted logistic regression analysis showed that glucocorticoid use during hospitalization (OR 3.58, 95% CI 1.12-11.44) was significantly associated with an increased risk of fatigue. The OR values for anxiety and sleep disorders were 2.36 (95% CI 1.07-5.20) and 2.16 (95% CI 1.13-4.14) in females to males. The OR value of PTSD was 25.6 (95% CI 3.3-198.4) in patients with persistent symptoms to those without persistent symptoms. No significant associations were observed between fatigue syndrome or adverse mental outcomes and disease severity. Conclusions: 15-month follow-up in this study demonstrated the need of extended rehabilitation intervention for complete recovery in COVID-19 patients.
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Background: Public health education is essential for epidemic prevention and control in the post-COVID-19 era. This randomized controlled trial (RCT) aims to evaluate the effect of reading leaflets during the observation period after vaccination on knowledge of COVID-19 disease and vaccines in Chinese small town residents and to provide suggestions for public health education. Methods: Residents were recruited during the observation period after getting vaccinated against COVID-19 in Xidian and were randomly divided into an education group and a control group. The education group was asked to complete the questionnaire after reading a leaflet, whereas the control group directly completed the questionnaire. The questionnaire comprised two sections on COVID-19 knowledge and vaccine knowledge, and the scores were used to assess the resident's knowledge. Results: A total of 142 participants in the education group and 154 participants in the control group were enrolled. The rates of correct knowledge in the education group and the control group were 90.7 and 83.1%, respectively. The scores of the two sections and the aggregate knowledge score of the education group were significantly higher than those of the control group (P < 0.001). The rates of correct responses to questions on clinical manifestations and transmission routes of COVID-19 and indications and contraindications of vaccines significantly increased after reading the leaflets (P < 0.05). Knowledge of different groups of genders, ages, marital statuses, education levels and occupations all improved (P < 0.05), and the 18-29-year-old and never-married group revealed a higher growth rate of correct responses. Conclusion: Chinese small town residents have a median level of knowledge regarding COVID-19 disease and vaccines. Reading leaflets during the observation period after vaccination effectively improved their knowledge. This low-cost and efficient health education approach can be widely applied.
Subject(s)
COVID-19 , Vaccines , Adolescent , Adult , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Humans , SARS-CoV-2 , Vaccination , Young AdultABSTRACT
Contributed to by the prevalence of digital technology, various cases of new ventures achieve resilience quickly despite experiencing hardship. Growing attention has been devoted to mindfulness-being alert and acting swiftly-to explain recovery. Scholars have primarily focused on mindful resource preparation pre-crisis. Nevertheless, how to mindfully organize resources as a crisis occurs remains under-explored. Based on an inductive study of a ride-sharing vehicle venture, which rapidly became an open service platform during the COVID-19 pandemic in China, we develop a framework termed "swift resilience" to understand how new ventures mindfully organize resources, driven by digital innovation. In particular, we critically trace three mechanisms-"data-driven stretching," "collective sharing," and "rapid pivoting"-and develop a process model to understand how new ventures build swift resilience. Our emerging findings shed light on the scholarship of organizational resilience, mindfulness, and digital entrepreneurship, and provide guidance to managers on achieving resilience quickly.
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The concept of "new luxury" has challenged the conventional marketing of luxury goods as prestigious, leading to greater expansion of mass luxury meaning. This has become more evident since the outbreak of COVID-19, which has been a catalyst for consumption in the luxury market. This paper investigates the mass marketing of luxury goods and explores the essence of masstige luxury consumption since the outbreak of COVID-19. An interpretive approach was conducted based on semi-structured, in-depth interviews with 31 participants. It analyzes four themes of mass luxury: self as content, self as process, self as context, and self-other. We further argue that the mass consumption of luxury reduces cognitive dissonance, with the pandemic resolving the dark side of conventional luxury consumption. Our findings provide important insights for both scholars and practitioners in the development of a more holistic understanding of masstige in the post-COVID era.
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Over the past 20 years, the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and SARS-CoV-2 emerged, causing severe human respiratory diseases throughout the globe. Developing broad-spectrum drugs would be invaluable in responding to new, emerging coronaviruses and to address unmet urgent clinical needs. Main protease (Mpro; also known as 3CLpro) has a major role in the coronavirus life cycle and is one of the most important targets for anti-coronavirus agents. We show that a natural product, noncovalent inhibitor, shikonin, is a pan-main protease inhibitor of SARS-CoV-2, SARS-CoV, MERS-CoV, human coronavirus (HCoV)-HKU1, HCoV-NL63, and HCoV-229E with micromolar half maximal inhibitory concentration (IC50) values. Structures of the main protease of different coronavirus genus, SARS-CoV from the betacoronavirus genus and HCoV-NL63 from the alphacoronavirus genus, were determined by X-ray crystallography and revealed that the inhibitor interacts with key active site residues in a unique mode. The structure of the main protease inhibitor complex presents an opportunity to discover a novel series of broad-spectrum inhibitors. These data provide substantial evidence that shikonin and its derivatives may be effective against most coronaviruses as well as emerging coronaviruses of the future. Given the importance of the main protease for coronavirus therapeutic indication, insights from these studies should accelerate the development and design of safer and more effective antiviral agents. IMPORTANCE The current pandemic has created an urgent need for broad-spectrum inhibitors of SARS-CoV-2. The main protease is relatively conservative compared to the spike protein and, thus, is one of the most promising targets in developing anti-coronavirus agents. We solved the crystal structures of the main protease of SARS-CoV and HCoV-NL63 that bound to shikonin. The structures provide important insights, have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational design of broad-spectrum anti-coronavirus ligands as new therapeutic agents.
Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Protease Inhibitors/chemistry , Catalytic Domain , Coronavirus/classification , Coronavirus/enzymology , Coronavirus 3C Proteases/chemistry , Crystallography, X-Ray , Molecular Docking Simulation , Naphthoquinones/chemistry , Protein BindingABSTRACT
Human coronavirus NL63 (HCoV-NL63), which belongs to the genus Alphacoronavirus, mainly infects children and the immunocompromized and is responsible for a series of clinical manifestations, including cough, fever, rhinorrhoea, bronchiolitis and croup. HCoV-NL63, which was first isolated from a seven-month-old child in 2004, has led to infections worldwide and accounts for 10% of all respiratory illnesses caused by etiological agents. However, effective antivirals against HCoV-NL63 infection are currently unavailable. The HCoV-NL63 main protease (Mpro), also called 3C-like protease (3CLpro), plays a vital role in mediating viral replication and transcription by catalyzing the cleavage of replicase polyproteins (pp1a and pp1ab) into functional subunits. Moreover, Mpro is highly conserved among all coronaviruses, thus making it a prominent drug target for antiviral therapy. Here, four crystal structures of HCoV-NL63 Mpro in the apo form at different pH values are reported at resolutions of up to 1.78â Å. Comparison with Mpro from other human betacoronaviruses such as SARS-CoV-2 and SARS-CoV reveals common and distinct structural features in different genera and extends knowledge of the diversity, function and evolution of coronaviruses.
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Coronavirus NL63, Human/chemistry , Crystallization/methods , Crystallography, X-Ray/methods , Humans , Hydrogen-Ion Concentration , Protein ConformationABSTRACT
OBJECTIVE: To investigate the dynamic characteristics of serological antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is of much current significance. METHODS: The dynamic changes and prevalence of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against SARS-CoV-2 were assessed from the time of symptom onset up to 210 days. Antibodies were detected using a chemiluminescence immunoassay. RESULTS: The average titers and IgG/IgM positivity rates reached a peak within 30 days of symptom onset and then began to decline continuously. Between 180 and 210 days following symptom onset, the titers of IgG and IgM were 43.1 ± 27.0 AU/mL and 4.4 ± 5.2 AU/mL, respectively, while the respective positivity rates were 84.3% and 12.0%. Further statistical analyses revealed that the dynamic changes and prevalence of the SARS-CoV-2 IgG/IgM antibodies were related to age and disease severity, but not to sex. The dynamic changes and the prevalence were similar for both the IgM and the IgG antibodies. Even so, there was a more rapid rate of decline for the IgM antibodies. It was found that an IgG level of 16.33 ± 3.15 AU/mL may represent a threshold value that should act as an alert, as it may indicate that the IgG level will become undetectable within the next 30-60 days. CONCLUSION: The results provide important information concerning COVID-19 and may be of relevance for diagnosis, treatment, and vaccine development.
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COVID-19 , SARS-CoV-2 , Antibodies, Viral , Humans , Immunoglobulin G , Immunoglobulin M , PrevalenceABSTRACT
In recent years, the CRISPR/Cas9-based gene-editing techniques have been well developed and applied widely in several aspects of research in the biological sciences, in many species, including humans, animals, plants, and even in viruses. Modification of the viral genome is crucial for revealing gene function, virus pathogenesis, gene therapy, genetic engineering, and vaccine development. Herein, we have provided a brief review of the different technologies for the modification of the viral genomes. Particularly, we have focused on the recently developed CRISPR/Cas9-based gene-editing system, detailing its origin, functional principles, and touching on its latest achievements in virology research and applications in vaccine development, especially in large DNA viruses of humans and animals. Future prospects of CRISPR/Cas9-based gene-editing technology in virology research, including the potential shortcomings, are also discussed.
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Biomedical Research , CRISPR-Cas Systems , Gene Editing , Vaccinology/methods , Viral Vaccines/genetics , Viruses/genetics , Animals , Biomedical Research/methods , Genetic Therapy/methods , Humans , Viral Vaccines/immunology , Viruses/immunologyABSTRACT
BACKGROUND: Following the outbreak of the COVID-19 pandemic, a change in the incidence and transmission of respiratory pathogens was observed. Here, we retrospectively analyzed the impact of COVID-19 on the epidemiologic characteristics of Mycoplasma pneumoniae infection among children in Chengdu, one of the largest cities of western China. METHOD: M. pneumoniae infection was diagnosed in 33,345 pediatric patients with respiratory symptoms at the Chengdu Women's & Children's Central Hospital between January 2017 and December 2020, based on a serum antibody titer of ≥1:160 measured by the passive agglutination assay. Differences in infection rates were examined by sex, age, and temporal distribution. RESULTS: Two epidemic outbreaks occurred between October-December 2017 and April-December 2019, and two infection peaks were detected in the second and fourth quarters of 2017, 2018, and 2019. Due to the public health response to COVID-19, the number of positive M. pneumoniae cases significantly decreased in the second quarter of 2020. The number of M. pneumoniae infection among children aged 3-6 years was higher than that in other age groups. CONCLUSIONS: Preschool children are more susceptible to M. pneumoniae infection and close contact appears to be the predominant factor favoring pathogen transmission. The public health response to COVID-19 can effectively control the transmission of M. pneumoniae.
Subject(s)
COVID-19 , Pneumonia, Mycoplasma , Child , Child, Preschool , China/epidemiology , Female , Humans , Infant , Mycoplasma pneumoniae , Pandemics , Pneumonia, Mycoplasma/diagnosis , Pneumonia, Mycoplasma/epidemiology , Retrospective Studies , SARS-CoV-2ABSTRACT
Background. Following the outbreak of the COVID-19 pandemic, a change in the incidence and transmission of respiratory pathogens was observed. Here, we retrospectively analyzed the impact of COVID-19 on the epidemiologic characteristics of Mycoplasma pneumoniae infection among children in Chengdu, one of the largest cities of western China.Method. M. pneumoniae infection was diagnosed in 33,345 pediatric patients with respiratory symptoms at the Chengdu Women’s & Children’s Central Hospital between January 2017 and September 2020, based on a titer of ³1:160 measured by the passive agglutination assay. Differences in infection rates were examined by sex, age, and temporal distribution.Results. Two epidemic outbreaks occurred between October–December 2017 and April–December 2019, and two infection peaks were detected in the second and fourth quarters of 2017, 2018, and 2019. Due to the public health response to COVID-19, the number of positive M. pneumoniae cases significantly decreased in the second quarter of 2020. The rate of M. pneumoniae infection among children aged 3–6 years was higher than that in other age groups.Conclusion. Preschool children are more susceptible to M. pneumoniae infection and close contact appears to be the predominant factor favoring pathogen transmission. The public health response to COVID-19 can effectively control the transmission of M. pneumoniae.
Subject(s)
Pneumonia, Mycoplasma , Pneumonia , COVID-19ABSTRACT
OBJECTIVE: Low viral load from patients infected with SARS-CoV-2 during infection late stage easily lead to false negative nucleic acid testing results, thus having great challenges to the prevention and control of the current pandemic. In present study, we mainly aimed to evaluate specimen types and specimen collection timepoint on the positive detection of 2019 novel coronavirus from patients at infection late stage based on RT-PCR testing. METHODS: Paired nasopharyngeal swabs, nasal swabs, oropharyngeal swabs and anal swabs were collected from patients infected with SARS-CoV-2 during infection late stage before washing in the morning and afternoon on the same day. Then virus RNA was extracted and tested for 2019-nCoV identification by RT-PCR within 24 h. RESULTS: Viral load was low at late infection stage. Specimens collected before washing in the morning would increase the detection ratio of 2019-nCoV. Detection ratio of nasopharyngeal swab [65 (95 % CI: 49.51-77.87) vs 42.5(95 % CI: 28.51-57.8)] or nasal swab [57.5 (95 % CI: 42.2-71.49) vs 35 (95 % CI: 22.13-50.49)] is higher not only than oropharyngeal swab[22.5 (95 % CI: 12.32-37.5) vs 7.5 (95 % CI: 2.58-19.86)], but also anal swab[2.5 (95 % CI: 0.44-12.88) vs 5 (95 % CI: 1.38-16.5)]. CONCLUSIONS: In summary, our research discovers that nasopharyngeal or nasal swab collected before washing in the morning might be more suitable for detecting of large-scale specimens from patients infected with low SARS-CoV-2 load during infection late stage. Those results could facilitate other laboratories in collecting appropriate specimens for improving detection of SARS-CoV-2 from patients during infection late stage as well as initially screening.