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Background: From August to September 2022, Urumqi, the capital of the Xinjiang Uygur Autonomous Region in China, faced its largest COVID-19 outbreak caused by the emergence of the SARS-CoV-2 Omicron BA.5.2 variants. Although the superspreading of COVID-19 played an important role in triggering large-scale outbreaks, little was known about the superspreading potential and heterogeneity in the transmission of Omicron BA.5 variants. Methods: In this retrospective observational, contact tracing study, we identified 1139 laboratory-confirmed COVID-19 cases of Omicron BA.5.2 variants, and 51 323 test-negative close contacts in Urumqi from 7 August to 7 September 2022. By using detailed contact tracing information and exposure history of linked case-contact pairs, we described stratification in contact and heterogeneity in transmission across different demographic strata, vaccine statuses, and contact settings. We adopted beta-binomial models to characterise the secondary attack rate (SAR) distribution among close contacts and modelled COVID-19 transmission as a branching process with heterogeneity in transmission governed by negative binomial models. Results: After the city lockdown, the mean case cluster size decreased from 2.0 (before lockdown) to 1.6, with decreased proportions of contacts in workplace and community settings compared with household settings. We estimated that 14% of the most infectious index cases generated 80% transmission, whereas transmission in the community setting presented the highest heterogeneity, with 5% index cases seeding 80% transmission. Compared with zero, one, and two doses of inactivated vaccine (Sinopharm), index cases with three doses of vaccine had a lower risk of generating secondary cases in terms of the reproduction number. Contacts of female cases, cases with ages 0-17 years, and household settings had relatively higher SAR. Conclusions: In the context of intensive control measures, active case detection, and relatively high vaccine coverage, but with an infection-naive population, our findings suggested high heterogeneity in the contact and transmission risks of Omicron BA.5 variants across different demographic strata, vaccine statuses, and contact settings. Given the rapid evolution of SARS-CoV-2, investigating the distribution of transmission not only helped promote public awareness and preparedness among high-risk groups, but also highlighted the importance of continuously monitoring the transmission characteristics of genetic variants of SARS-CoV-2.
Subject(s)
COVID-19 , Humans , Female , COVID-19/epidemiology , SARS-CoV-2/genetics , Retrospective Studies , Communicable Disease Control , China/epidemiologyABSTRACT
BACKGROUND AND OBJECTIVES: The progression of pulmonary diseases is a complex progress. Timely predicting whether the patients will progress to the severe stage or not in its early stage is critical to take appropriate hospital treatment. However, this task suffers from the "insufficient and incomplete" data issue since it is clinically impossible to have adequate training samples for one patient at each day. Besides, the training samples are extremely imbalanced since the patients who will progress to the severe stage is far less than those who will not progress to the non-severe stage. METHOD: We consider the severity prediction of pulmonary diseases as a time estimation problem based on CT scans. To handle the issue of "insufficient and incomplete" training samples, we introduced label distribution learning (LDL). Specifically, we generate a label distribution for each patient, making a CT image contribute to not only the learning of its chronological day, but also the learning of its neighboring days. In addition, a cost-sensitive mechanism is introduced to explore the imbalance data issue. To identify the importance of pulmonary segments in pulmonary disease severity prediction, multi-kernel learning in composite kernel space is further incorporated and particle swarm optimization (PSO) is used to find the optimal kernel weights. RESULTS: We compare the performance of the proposed CS-LD-MKSVR algorithm with several classical machine learning algorithms and deep learning (DL) algorithms. The proposed method has obtained the best classification results on the in-house data, fully indicating its effectiveness in pulmonary disease severity prediction. CONTRIBUTIONS: The severity prediction of pulmonary diseases is considered as a time estimation problem, and label distribution is introduced to describe the conversion time from non-severe stage to severe stage. The cost-sensitive mechanism is also introduced to handle the data imbalance issue to further improve the classification performance.
Subject(s)
Algorithms , Lung Diseases , Humans , Lung Diseases/diagnostic imaging , Machine Learning , Tomography, X-Ray ComputedABSTRACT
Background: A sharp rise in household consumption of disinfectants triggered by COVID-19 pandemic has generated tremendous environmental burden and risks of disinfectant emissions in the post-pandemic period. To address this emerging challenge, replacing highly hazardous disinfectants with more environmental friendly alternatives has been accepted as an inherently effective solution to environment issues posed by disinfectant emerging contaminants. However, no study has yet been done to explore the potential customers' attitudes and the market prospect of environmental friendly disinfectants until now. Methods: This cross-sectional questionnaire-based survey was conducted from January to March, 2022, among resident volunteers in China, to explore the practices, knowledge and attitudes of the public regarding environmental friendly disinfectants for household use. Results: Among a total of 1,861 Chinese residents finally included in the analyses, 18% agreed or strongly agreed that they paid special attention to the environmental certification label on the product, and only bought the environmental certified disinfectant products; 16% and 10% were using environmental friendly disinfectants for hand sanitization and environmental disinfection, respectively. The mean self-assessed and actual knowledge scores were 2.42 ± 1.74 and 2.12 ± 1.97, respectively, out of a total of 5. Participants having good practices of consuming environmental friendly disinfectants achieved higher knowledge scores. Residents' overall attitudes toward the development, consumption and application of environmental friendly disinfectants were very positive. "Possible conflict between disinfection effectiveness and environmental factor of disinfectants in a context of severe COVID-19 pandemic" was considered as the most important barrier jeopardizing the participants' usage intention for environmental friendly disinfectants. Conclusions: These data suggested most residents of China had a positive attitude, poor knowledge and practices toward environmental friendly disinfectants. More should be done to enhance the residents' environmental knowledge levels about disinfectants, and to further develop and promote disinfectant products with both excellent disinfection activity and environmentally friendly attributes.
Subject(s)
COVID-19 , Disinfectants , Humans , COVID-19/prevention & control , Pandemics , Health Knowledge, Attitudes, Practice , Cross-Sectional Studies , ChinaABSTRACT
Wastewater-based epidemiology (WBE) has exhibited great utility in the early and rapid identification of SARS-CoV-2. However, the efficacy of wastewater surveillance under China's previous strict epidemic prevention policy remains to be described. We collected the WBE data of wastewater treatment plants (WWTPs) in the Third People's Hospital of Shenzhen and several communities to determine the significant effectiveness of routine wastewater surveillance in monitoring the local spread of SARS-CoV-2 under tight containment of the epidemic. The results of 1 month of continuous wastewater surveillance showed that positive signals for SARS-CoV-2 RNA were detected in the wastewater samples, and a significant positive correlation was observed between the virus concentration and the number of daily cases. In addition, the community's domestic wastewater surveillance results were confirmed even 3 days before, or simultaneously with, the infected patient being confirmed as having the virus. Meanwhile, an automated sewage virus detection robot, ShenNong No.1 robot, was developed, showing a high degree of agreement with experimental data, offering the possibility of large-scale multi-point surveillance. Overall, our results illustrated the clear indicative role of wastewater surveillance in combating COVID-19 and provided a practical basis for rapidly expanding the feasibility and value of routine wastewater surveillance for future emerging infectious diseases.
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Fine particulate matter (PM2.5) chemical composition has strong and diverse impacts on the planetary environment, climate, and health. These effects are still not well understood due to limited surface observations and uncertainties in chemical model simulations. We developed a four-dimensional spatiotemporal deep forest (4D-STDF) model to estimate daily PM2.5 chemical composition at a spatial resolution of 1 km in China since 2000 by integrating measurements of PM2.5 species from a high-density observation network, satellite PM2.5 retrievals, atmospheric reanalyses, and model simulations. Cross-validation results illustrate the reliability of sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and chloride (Cl-) estimates, with high coefficients of determination (CV-R2) with ground-based observations of 0.74, 0.75, 0.71, and 0.66, and average root-mean-square errors (RMSE) of 6.0, 6.6, 4.3, and 2.3 µg/m3, respectively. The three components of secondary inorganic aerosols (SIAs) account for 21% (SO42-), 20% (NO3-), and 14% (NH4+) of the total PM2.5 mass in eastern China; we observed significant reductions in the mass of inorganic components by 40-43% between 2013 and 2020, slowing down since 2018. Comparatively, the ratio of SIA to PM2.5 increased by 7% across eastern China except in Beijing and nearby areas, accelerating in recent years. SO42- has been the dominant SIA component in eastern China, although it was surpassed by NO3- in some areas, e.g., Beijing-Tianjin-Hebei region since 2016. SIA, accounting for nearly half (â¼46%) of the PM2.5 mass, drove the explosive formation of winter haze episodes in the North China Plain. A sharp decline in SIA concentrations and an increase in SIA-to-PM2.5 ratios during the COVID-19 lockdown were also revealed, reflecting the enhanced atmospheric oxidation capacity and formation of secondary particles.
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Infection with porcine epidemic diarrhea virus (PEDV) causes severe watery diarrhea in newborn piglets, leading to substantial financial losses for the swine industry. In this study, we screened small molecule drugs targeting 3 C-like protease (3CLpro) by molecular docking, and further evaluated the antiviral activity of the screened drugs against PEDV. Results showed that octyl gallate (OG), a widely used food additive, exhibited strong binding affinity with the 3CLpro active sites of PEDV. Bio-layer interferometry and fluorescence resonance energy transfer revealed that OG directly interacts with PEDV 3CLpro (KD = 549 nM) and inhibits 3CLpro activity (IC50 = 22.15 µM). OG showed a strong inhibition of PEDV replication in vitro. Virus titers were decreased by 0.58 and 0.71 log10 TCID50/mL for the CV777 and HM2017 strains, respectively. In vivo, all piglets in the PEDV-infected group died at 48 h post-infection (hpi), while 75% of piglets in the OG treatment group showed significant relief from the clinical symptoms, pathological damage, and viral loads in the jejunum and ileum. Moreover, the western blotting results showed that OG also has strong antiviral activity against other swine enteric coronaviruses, including transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV). Our findings revealed that OG could be developed as a novel antiviral drug against PEDV. The OG exhibited a potential broad-spectrum antiviral drug for control of other swine enteric coronaviruses.
Subject(s)
Coronavirus Infections , Porcine epidemic diarrhea virus , Swine Diseases , Animals , Swine , Porcine epidemic diarrhea virus/physiology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Peptide Hydrolases , Coronavirus Infections/drug therapy , Coronavirus Infections/veterinary , Molecular Docking Simulation , Swine Diseases/drug therapyABSTRACT
Objective: During the COVID-19 epidemic, vaccination staff had three main aspects of work: routine vaccination for children and adults, COVID-19 vaccination and COVID-19 prevention and control. All these works significantly increased the workload of vaccination staff. This study aimed to investigate the prevalence and influencing factors of burnout among vaccination staff in Hangzhou, China. Methods: A total of 501 vaccination staff from 201 community/township healthcare centers in Hangzhou were recruited using a cross-sectional survey through WeChat social platform. The Maslach Burnout Inventory-General Scale (MBI-GS) was used to assess the level of burnout. Descriptive statistics were made on the characteristics of participants. Univariate analysis using the chi-square test and multivariable analysis using binary logistic regression were conducted to determine the relative predictors of burnout. Univariate analysis and multiple linear regression were used to determine the relative predictors of exhaustive emotion, cynicism, and personal accomplishment. Results: During the COVID-19 pandemic, 20.8% of the vaccination staff experienced burnout. Educational level above undergraduate education level, medium professional title, and more working time in COVID-19 vaccination work reported a higher degree of job burnout. The vaccination staff was experiencing a high degree of exhaustive emotion, cynicism, and low personal accomplishment. Professional title, working place, and working time for COVID-19 vaccination were associated with exhaustive emotion and cynicism. Professional title and participation time for COVID-19 prevention and control were associated with personal accomplishment. Conclusions: Our findings suggest that the prevalence rate of burnout is high among vaccination staff during the COVID-19 pandemic, especially with a low level of personal accomplishment. Psychological intervention for vaccination staff is urgently needed.
Subject(s)
Burnout, Professional , COVID-19 , Health Personnel , Vaccination , Humans , Burnout, Professional/epidemiology , Burnout, Professional/psychology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Cross-Sectional Studies , East Asian People , Job Satisfaction , Pandemics , Surveys and Questionnaires , Health Personnel/psychologyABSTRACT
SARS-CoV-2 is still wreaking havoc all over the world with surging morbidity and high mortality. The main protease (Mpro ) is essential in the replication of SARS-CoV-2, enabling itself an active target for antiviral development. Herein, we reported the design and synthesis of a new class of peptidomimetics-constrained α, γ-AA peptides, based on which a series of aldehyde and ketoamide inhibitors of the Mpro of SARS-CoV-2 were prepared. The lead compounds showed excellent inhibitory activity in the FRET-based Mpro enzymatic assay not only for the Mpro of SARS-CoV-2 but also for SARS-CoV and MERS-CoV, along with HCoVs like HCoV-OC43, HCoV-229E, HCoV-NL63 and HKU1. The X-ray crystallographic results demonstrated that our compounds form a covalent bond with the catalytic Cys145. They also demonstrated effective antiviral activity against live SARS-CoV-2. Overall, the results suggest that α, γ-AA peptide could be a promising molecular scaffold in designing novel Mpro inhibitors of SARS-CoV-2 and other coronaviruses.
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Importance: In 2022, Omicron variants circulated globally, and Urumqi, China, experienced a COVID-19 outbreak seeded by Omicron BA.5 variants, resulting in the highest number of infections in the city's record before the exit of the zero COVID-19 strategy. Little was known about the characteristics of Omicron variants in mainland China. Objective: To evaluate transmission characteristics of Omicron BA.5 variants and the effectiveness of inactivated vaccine (mainly BBIBP-CorV) against their transmission. Design, Setting, and Participants: This cohort study was conducted using data from an Omicron-seeded COVID-19 outbreak in Urumqi from August 7 to September 7, 2022. Participants included all individuals with confirmed SARS-CoV-2 infections and their close contacts identified between August 7 and September 7, 2022 in Urumqi. Exposures: A booster dose was compared vs 2 doses (reference level) of inactivated vaccine and risk factors were evaluated. Main Outcomes and Measures: Demographic characteristics, timeline records from exposure to laboratory testing outcomes, contact tracing history, and contact setting were obtained. The mean and variance of the key time-to-event intervals of transmission were estimated for individuals with known information. Transmission risks and contact patterns were assessed under different disease-control measures and in different contact settings. The effectiveness of inactivated vaccine against the transmission of Omicron BA.5 was estimated using multivariate logistic regression models. Results: Among 1139 individuals diagnosed with COVID-19 (630 females [55.3%]; mean [SD] age, 37.4 [19.9] years) and 51â¯323 close contacts who tested negative for COVID-19 (26â¯299 females [51.2%]; mean [SD] age, 38.4 [16.0] years), the means of generation interval, viral shedding period, and incubation period were estimated at 2.8 days (95% credible interval [CrI], 2.4-3.5 days), 6.7 days (95% CrI, 6.4-7.1 days), and 5.7 days (95% CrI, 4.8-6.6 days), respectively. Despite contact tracing, intensive control measures, and high vaccine coverage (980 individuals with infections [86.0%] received ≥2 doses of vaccine), high transmission risks were found in household settings (secondary attack rate, 14.7%; 95% CrI, 13.0%-16.5%) and younger (aged 0-15 years; secondary attack rate, 2.5%; 95% CrI, 1.9%-3.1%) and older age (aged >65 years; secondary attack rate, 2.2%; 95% CrI, 1.5%-3.0%) groups. Vaccine effectiveness against BA.5 variant transmission for the booster-dose vs 2 doses was 28.9% (95% CrI, 7.7%-45.2%) and 48.5% (95% CrI, 23.9%-61.4%) for 15-90 days after booster dose. No protective outcome was detected beyond 90 days after the booster dose. Conclusions and Relevance: This cohort study revealed key transmission characteristics of SARS-CoV-2 as they evolved, as well as vaccine effectiveness against variants. These findings suggest the importance of continuously evaluating vaccine effectiveness against emerging SARS-CoV-2 variants.
Subject(s)
COVID-19 , SARS-CoV-2 , Female , Humans , Adult , Cohort Studies , Vaccine Efficacy , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Vaccines, InactivatedABSTRACT
The current monkeypox outbreaks during the COVID-19 pandemic have reignited interest in orthopoxvirus antivirals. Monkeypox belongs to the Orthopoxvirus genus of the Poxviridae family, which also includes the variola virus, vaccinia virus, and cowpox virus. Two orally bioavailable drugs, tecovirimat and brincidofovir, have been approved for treating smallpox infections. Given their human safety profiles and in vivo antiviral efficacy in animal models, both drugs have also been recommended to treat monkeypox infection. To facilitate the development of additional orthopoxvirus antivirals, we summarize the antiviral activity, mechanism of action, and mechanism of resistance of orthopoxvirus antivirals. This perspective covers both direct-acting and host-targeting antivirals with an emphasis on drug candidates showing in vivo antiviral efficacy in animal models. We hope to speed the orthopoxvirus antiviral drug discovery by providing medicinal chemists with insights into prioritizing proper drug targets and hits for further development.
Subject(s)
COVID-19 , Monkeypox , Orthopoxvirus , Variola virus , Animals , Humans , Monkeypox virus , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Monkeypox/drug therapy , PandemicsABSTRACT
Objective: According to the WHO, compared to before the COVID-19 pandemic, young people showed a significant increase in depressive symptoms. In light of the recent coronavirus pneumonia pandemic, this study was conducted to determine how social support, coping style, parent-child relationships, and depression are associated. We investigated how these factors interacted and affected the prevalence of depression during this challenging and unheard-of time. Our research may help both individuals and healthcare professionals better comprehend and assist those who are coping with the pandemic's psychological effects. Design and main outcome measures: 3,763 students from a medical college in Anhui Province were investigated with Social Support Rate Scale, Trait Coping Style Questionnaire, and Self-rating Depression Scale. Results: When the pandemic situation was normalizing, social support was associated with depression and the coping style of college students (p < 0.01). During the period of pandemic normalization, the parent-child relationship moderated the relationship between social support and positive coping (t = -2.45, p < 0.05); the parent-child relationship moderated the relationship between social support and negative coping (t = -4.29, p < 0.01); and the parent-child relationship moderated the association between negative coping and depression (t = 2.08, p < 0.05). Conclusion: Social support has an impact on depression in the period of the regular prevention and control of COVID-19 through the mediating role of coping style and the moderating effect of the parent-child relationship.
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This study aims to describe COVID-19 vaccination coverage and its influential factors in hypertensive patients who were administered by community general practitioners in China. A cross-sectional survey was carried out using data from electronic health record systems. The subjects were hypertensive patients who had been involved in the health management of the Essential Public Health Service (EPHS) program in Hangzhou City, China. As of Aug 3, 2022, the full and booster vaccination rates were 77.53% and 60.97% in randomly selected 96,498 subjects. There were disparities across regions, age, and gender in the distribution of COVID-19 vaccination coverage. Obesity and daily alcohol consumption were factors in the promotion of COVID-19 vaccination. Current smoking, non-daily physical exercise, irregular medication adherence, and comorbidities were risk factors for COVID-19 vaccination. Coverage rates have decreased depending on the number of risk factors. The ORs (95% CI) were 1.78 (1.61 ~ 1.96) of full vaccination and 1.74 (1.59 ~ 1.89) of booster vaccination in subjects with ≥4 risk factors, compared to those without risk factors. In summary, the progress of COVID-19 vaccination among community hypertensive patients lagged behind that of the general population during the same period. Individuals who lived in urban areas, were elderly, and had an irregular medication adherence, comorbidities, and multiple risk factors should be highlighted in the COVID-19 vaccination campaign.
Subject(s)
COVID-19 , Hypertension , Vaccination Coverage , Humans , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Cross-Sectional Studies , East Asian People , General Practitioners , Hypertension/epidemiologyABSTRACT
BACKGROUND: We aimed to investigate the factors associated with neurological manifestations of post-coronavirus disease 2019 (COVID-19) conditions. METHODS: We retrospectively collected data from 440 patients who visited our post-COVID-19 clinic more than 4 weeks after severe acute respiratory syndrome coronavirus 2 infection. We analyzed the prevalence of different neurological symptoms (brain fog, memory impairment, headache, and dizziness) and assessed the associated factors. RESULTS: Brain fog was the most common symptom, observed in 170 patients (38.6%), followed by headaches (n = 137, 31.1%), dizziness (n = 128, 29%), and memory impairment (n = 104, 23.6%). Brain fog was associated with hyposmia or hypogeusia (odds ratio [OR], 2.54; P < 0.001), Fatigue Severity Scale (FSS) (OR, 1.06; P < 0.001), and Hospital Anxiety and Depression Scale-Anxiety (OR, 1.09; P = 0.037). Memory impairment was associated with sleep problems (OR, 2.83; P < 0.001), FSS (OR, 1.05; P < 0.001), and age (OR, 1.02; P = 0.015). Headache was associated with sleep problems (OR, 2.28; P = 0.001), sex (OR, 1.68; P = 0.042), and FSS (OR, 1.04; P < 0.001). Dizziness was associated with sleep problems (OR, 2.88; P < 0.001), and FSS (OR, 1.04; P < 0.001). The incidence of brain fog (P < 0.001), memory impairment (P < 0.001), dizziness (P = 0.007), and headache (P = 0.045) accompanied by hyposmia and hypogeusia was higher in patients with the aforementioned symptoms than in those without. CONCLUSION: This study suggests that there is a relationship between neurological symptoms and other clinical factors, such as fatigue, depression, anxiety, hyposmia, and hypogeusia.
Subject(s)
Ageusia , COVID-19 , Sleep Wake Disorders , Humans , COVID-19/complications , Dizziness/complications , Retrospective Studies , Ageusia/etiology , Anosmia/etiology , Headache/etiology , Headache/epidemiology , Sleep Wake Disorders/etiology , Sleep Wake Disorders/complications , Fatigue/etiologyABSTRACT
The rapid development of effective vaccines to combat the SARS-CoV-2 virus has been an effective counter measure to decrease hospitalization and the mortality rate in many countries. However, with the risk of mutated strains decreasing the efficacy of the vaccine, there has been an increasing demand for antivirals to treat COVID-19. While antivirals, such as remdesivir, have had some success treating COVID-19 patients in hospital settings, there is a need for orally bioavailable, cost-effective antivirals that can be administered in outpatient settings to minimize COVID-19-related hospitalizations and death. Nirmatrelvir (PF-07321332) is an orally bioavailable Mpro (also called 3CLpro) inhibitor developed by Pfizer. It is administered in combination with ritonavir, a potent CYP3A4 inhibitor that decreases the metabolism of nirmatrelvir. This review seeks to outline the history of the rational design, the target selectivity, synthesis, drug resistance, and future perspectives of nirmatrelvir. Graphical abstract.