Traditional Chinese Medicine Syndrome Differentiation of Delta and Omicron Variants of SARS-CoV-2 Carriers in Changsha,Hunan.

Objective: To summarize and compare the main traditional Chinese medicineTCMsyndromes of Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2SARS-CoV-2 carriers to provide references for the syndrome evolution and syndrome differentiation of SARS-CoV-2 infection. Method(s):The TCM medical records of imported and local cases of infection with Delta and Omicron variants of SARS-CoV-2 in Changsha since September 23,2021 to March 27,2022 were collected,including 18 Delta variant cases and 36 Omicron variant cases. Their TCM diagnosis information and TCM pathogenesis were analyzed and compared. Result(s): The common manifestations in Delta variant cases were cough,fever,chest distress/shortness of breath,sore muscles,nausea,dry mouth,dry or sore throat,thick and greasy tongue coating,and rapid and slippery pulse. The predominant pathogenesis was dampness-heat in the upper-energizer and heat stagnation in the lesser Yang combined with dampness. The occurrence of chest distress/shortness of breath,greasy tongue coating,slippery pulse,and the proportion of dampness-heat in the upper-energizer syndrome were higher in Delta variant cases than in Omicron variant cases P<0.05. The common manifestations in Omicron variant cases were itchy and sore throat,nasal congestion,running nose,fever,mild aversion to cold,dry mouth,dizziness,slightly reddish tongue with thin white coating,and rapid or wiry pulse. The predominant pathogenesis was wind-dryness invading defensive exterior,and heat stagnation in the lesser Yang. The occurrence of white-coated tongue and the proportion of wind-dryness invading defensive exterior syndrome were higher in Omicron variant cases than in Delta variant casesP<0.05. Conclusion(s): There are certain differences in TCM syndromes and the corresponding pathogenesis between Delta variant and Omicron variant cases in Changsha,Hunan. The Delta variant of SARS-COV-2 tends to induce dampness-heat syndrome, whereas Omicron variant infection tends to elicit wind-dampness syndrome,which is expected to provide a reference for the pathogenesis evolution of SARS-COV-2 infection.Copyright © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Dynamic correlations of renewable-energy companies: Evidence from a multilayer network model

Against the background of seeking to achieve carbon neutrality, relationships among renewable-energy companies around the world have become multiple and complex. In this work, the Pearson, Kendall, tail, and partial correlation coefficients were applied to 51 global companies - including solar and wind firms, independent power plants, and utilities - to explore the linear, nonlinear, extreme-risk, and direct relations between them. Sample data from 7 August 2015 to 6 August 2021 were considered, and three sub-periods were extracted from these sample data by analysis of the evolution of multiple correlations combined with event analysis. A four-layer correlation network model was then constructed. The main results are as follows. (1) The multiple relations among the selected firms underwent dramatic changes during two external shocks (the China-US trade war and the COVID-19 pandemic). (2) The extreme-risk network layer verified that the trade war mainly affected the relationships among companies in the solar industries of China and the US. (3) During the COVID-19 pandemic period, the linear and direct relationships among wind firms from Canada, Spain, and Germany were significantly increased. In this sub-period, edge-weight distributions of the four different layers were heterogeneous and varied from power-law features to Gaussian distributions. (4) During all the sub-periods, most companies had similar numbers of neighbors, while the numbers of neighbors of a few companies varied greatly in the four different layers. These findings provide a useful reference for stakeholders and may help them understand the connectedness and evolution of global renewable-energy markets. © 2023 Author(s).

Traditional Chinese Medicine Syndrome Differentiation of Delta and Omicron Variants of SARS-CoV-2 Carriers in Changsha，Hunan

Objective： To summarize and compare the main traditional Chinese medicine（TCM）syndromes of Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2（SARS-CoV-2） carriers to provide references for the syndrome evolution and syndrome differentiation of SARS-CoV-2 infection. Method：The TCM medical records of imported and local cases of infection with Delta and Omicron variants of SARS-CoV-2 in Changsha since September 23，2021 to March 27，2022 were collected，including 18 Delta variant cases and 36 Omicron variant cases. Their TCM diagnosis information and TCM pathogenesis were analyzed and compared. Result： The common manifestations in Delta variant cases were cough，fever，chest distress/shortness of breath，sore muscles，nausea，dry mouth，dry or sore throat，thick and greasy tongue coating，and rapid and slippery pulse. The predominant pathogenesis was dampness-heat in the upper-energizer and heat stagnation in the lesser Yang combined with dampness. The occurrence of chest distress/shortness of breath，greasy tongue coating，slippery pulse，and the proportion of dampness-heat in the upper-energizer syndrome were higher in Delta variant cases than in Omicron variant cases （P<0.05）. The common manifestations in Omicron variant cases were itchy and sore throat，nasal congestion，running nose，fever，mild aversion to cold，dry mouth，dizziness，slightly reddish tongue with thin white coating，and rapid or wiry pulse. The predominant pathogenesis was wind-dryness invading defensive exterior，and heat stagnation in the lesser Yang. The occurrence of white-coated tongue and the proportion of wind-dryness invading defensive exterior syndrome were higher in Omicron variant cases than in Delta variant cases（P<0.05）. Conclusion： There are certain differences in TCM syndromes and the corresponding pathogenesis between Delta variant and Omicron variant cases in Changsha，Hunan. The Delta variant of SARS-COV-2 tends to induce dampness-heat syndrome， whereas Omicron variant infection tends to elicit wind-dampness syndrome，which is expected to provide a reference for the pathogenesis evolution of SARS-COV-2 infection. © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Baicalin Ameliorates Preeclampsia In Vitro by Regulating the miRNA-19a/PTEN Axis

Baicalin is a kind of extraction from herb, and had treatment effects in some disease, however, it has been unclear that it's effects in preeclampsia (PE). The aim of our work was to evaluate baicalin's effects in PE treatment and relative mechanisms in vivo. Using hypoxia to make PE cell model. First step, using difference baicalin concentration to treat. Next step, transfecting si-miRNA-19a to discuss miRNA-19a's effects in baicalin's treatment to PE. Measuring cell proliferation, apoptosis, invasion and migration by CCK-8, flow cytometer, transwell and wound healing assay. Relative protein and gene expression by WB and RT-qPCR assay. Analysis correlation between miRNA-19a and PTEN by dual-luciferase reporter gene assay. Compared with NC, cell proliferation was significantly depressed with apoptosis significantly increasing and invasion cell number and wound healing rates were significantly down-regulation. miRNA-19a expression was significantly down-regulation, PTEN expression was significantly up-regulation, and p-AKT and p-PI3K expressions were significantly down-regulation. With baicalin supplement, the cell's biological activities including cell proliferation, invasion and migration were significantly up-regulation with miRNA-19a increasing. Meanwhile, PTEN protein expression was significantly depressed and p-AKT and p-PI3K proteins expression were significantly increased (p < 0.001, respectively). By dual-luciferase reporter gene assay, miRNA-19a could target PTEN in cell lines. Baicalin had effects to improve PE with miRNA-19a/PTEN axis in vivo study.

Research Progress and Implication of Wastewater Surveillance of SARS-CoV-2

Since the outbreak of the coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been found in wastewater frequently worldwide. Based on the wastewater-based epidemiology (WBE), wastewater surveillance of SARS-CoV-2 can complement population surveillance for COVID-19. Quantification of viral load and genome sequencing of SARS-CoV-2 can help early warning of COVID-19 outbreaks, early identification of asymptomatic cases, assessment of infection scale, prediction of pandemic trend status, and identification of virus sources to provide scientific basis for polices for the prevention and control. Accordingly, here, the sources of SARS-CoV-2 in wastewater at home and abroad and the major factors affecting the survival of virus were reviewed. Common methods to concentrate, detect and quantify SARS-CoV-2 were reviewed, with an overview of global surveillance projects, progresses, and remaining scientific issues. Some shortcomings of the current procedures, including the lack of sufficient information on distribution characteristics and infectivity of SARS-CoV-2 in wastewater and limited development and application of prediction models were also discussed. WBE can provide insight into the scientific prevention and control of COVID-19 in the face of current or future pandemics in China, and enhance China′s ability to deal with the surveillance and early warning, epidemic scale assessment, and accurate policy-making for the infectious and non-infectious diseases. © 2022 Editorial Board, Research of Environmental Sciences. All rights reserved.

Regorafenib in patients (pts) with unresectable hepatocellular carcinoma (uHCC) in real-world practice in Asia: Final analysis of the prospective, observational REFINE study

Background: In an interim analysis of Asian pts with uHCC in the observational REFINE study of regorafenib (NCT03289273), treatment-emergent adverse events (TEAEs) were consistent with those reported in the global, phase 3 RESORCE trial. Here, we present the final analysis of Asian pts with uHCC in REFINE. Method(s): REFINE is an international, prospective, multicenter study that enrolled pts with uHCC for whom a decision to treat with regorafenib was made by the treating physician prior to enrollment, according to the local health authority approved label. The primary objective is safety, including the incidences of TEAEs and dose modifications due to TEAEs (NCI-CTCAE v4.03). Secondary endpoints include overall survival, progression-free survival, and treatment duration. Result(s): Of the 1005 evaluable pts, 557 (55%) were from Asia (Korea [31%], Japan [26%], Taiwan [24%], China [18%], Thailand [1%]) and 82% were male. At baseline, median age was 65 years (range 21-94) and the most common HCC etiology in Asian pts was hepatitis B (60%) and in non-Asian pts was alcohol use (36%;Table). More Asian pts (71%) had received prior transarterial chemoembolization vs non-Asian pts (42%). The initial daily regorafenib dose was 160/120/80/40 mg in 51%/12%/35%/3% of Asian pts and 42%/9%/45%/4% of non-Asian pts. The median treatment duration was 3.7 months (range 0-34.4) in Asian pts and 3.6 months (range 0-38.9) in non-Asian pts. The most common TEAEs in Asian pts were hand-foot skin reaction (40%), diarrhea (27%), and decreased appetite (17%). TEAEs led to dose modification in 44% of Asian pts. [Formula presented]. Conclusion(s): These final data from REFINE confirm the safety and effectiveness of regorafenib in Asian pts with uHCC from a broad population in real-world practice. Final analyses from REFINE are ongoing and will be presented at the conference. Clinical trial identification: NCT03289273. Editorial acknowledgement: Editorial assistance in the preparation of this manuscript was provided by Matthew Reynolds of OPEN Health Communications (London, UK), with financial support from Bayer. Legal entity responsible for the study: Bayer. Funding(s): Bayer. Disclosure: Y.J. Kim: Financial Interests, Personal, Advisory Role: Bayer, Bristol Myers Squibb, Samil, PharmaKing, Celltrion, Bukwang;Financial Interests, Personal, Invited Speaker: Roche, AbbVie, Eisai, Ipsen, Boston Scientific, Bristol Myers Squibb, BTG, Bayer, MSD, Gilead Sciences, Novo Nordisk, Green Cross Cell, Boehringer Ingelheim, AstraZeneca;Financial Interests, Personal, Funding: BTG, Bayer, Boston Scientific, AstraZeneca, Gilead Sciences, Samjin, BL&H. M. Kurosaki: Financial Interests, Personal, Speaker's Bureau: Gilead Sciences, AbbVie, Eisai, Chugai, Lilly, Takeda. H.Y. Lim: Financial Interests, Personal, Advisory Role: Bayer, Eisai, Roche, Ipsen. M. Ikeda: Financial Interests, Personal, Advisory Board: AstraZeneca, Chugai, Eli Lilly Japan, Eisai, Nihon Servier, Novartis, Ono, Takeda, GlaxoSmithKline;Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Eli Lilly Japan, Eisai, Nihon Servier, Novartis, Taiho, Yakult, Teijin Pharma, AbbVie, Abbott Japan, Fujifilm Toyama Chemical, Incyte Biosciences Japan, ASLAN, Chugai, Nihon Servier, Takeda;Financial Interests, Institutional, Invited Speaker: Bayer, Bristol Myers Squibb, Eisai, AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, Merck Serono, MSD, Ono, Yakult, Novartis, Takeda, J-Pharma, Pfizer, Chiome Bioscience, Nihon Servier, Delta-Fly Pharma, Syneos Health, Merus.N.V. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Liiy, Bayer, Takeda, MSD;Financial Interests, Institutional, Research Grant: Otsuka, Sumitomo Dainippon Pharma, EA Pharma, Taiho, Eisai, AbbVie, Gilead Sciences, Takeda, GE Healthcare, Chugai. Y. Huang: Financial Interests, Personal, Advisory Role: Eisai, Bayer, BMS, Ono, Gilead, Lilly, AbbVie, Roche;Financial Interests, Personal, Invited Speaker: Eisai, Bayer, BMS, Ono, Gilead, Lilly, AbbVie, Roche;Financial Inte ests, Personal, Speaker's Bureau: Eisai, Bayer, BMS, Ono, Gilead, Lilly, AbbVie, Roche;Financial Interests, Institutional, Funding: Gilead. N. Kato: Financial Interests, Personal, Invited Speaker: Gilead Sciences Inc., AbbVie G.K., Ohtsuka Pharmaceutical Co., Ltd., Bayer Yakuhin Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Zeria Pharmaceutical Co., Ltd., Olympus Corporation, Eisai Co., Ltd., Aska Pharmaceutical Co., Ltd., Tsumura & Co., Mochida Pharmaceutical Co., Ltd., Miyarisan Pharmaceutical Co., Ltd., Covidien Japan Inc., Eli Lilly Japan K.K., Nobelpharma Co., Ltd., Kowa Company, Ltd., Incyte Biosciences Japan GK, Yakult Honsha Co.,Ltd., Olympus Marketing, Inc., Taisho Pharmaceutical Co.,Ltd., Janssen Pharmaceutical K.K.;Financial Interests, Institutional, Research Grant: AbbVie G.K., Ohtsuka Pharmaceutical Co., Ltd., Bayer Yakuhin Ltd., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., Shionogi & Co., Ltd., Eisai Co., Ltd., Tsumura & Co., Nippon Kayaku Co., Ltd., JIMRO Co., Ltd., Kowa Company, Ltd. C. Hsu: Financial Interests, Personal, Speaker's Bureau: Bristol Myers Squibb, Ono Pharmaceutical, Merck Sharp & Dohme, Roche, Eisai;Financial Interests, Institutional, Funding: Ono Pharmaceutical, AstraZeneca, MSD, Merck Serono, Taiho Pharmaceutical, Bristol Myers Squibb, BeiGene, NuCana BioMed, Johnson & Johnson, Roche/Genentech, BeiGene;Financial Interests, Personal, Advisory Role: Ono Pharmaceutical, MSD, Bristol Myers Squibb, Merck Serono, Roche/Genentech. B. Chewaskulyong: Financial Interests, Personal, Advisory Role: Pfizer, STADA;Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, DKSH, Janssen, BMS, MSD, Roche, TAIHO;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Pfizer, DKSH, Janssen, BMS, MSD, Roche, TAIHO;Financial Interests, Institutional, Funding: Bayer. J. Khan: Financial Interests, Institutional, Full or part-time Employment: Bayer. K. Ozgurdal: Financial Interests, Institutional, Full or part-time Employment: Bayer;Financial Interests, Personal, Stocks/Shares: Bayer. All other authors have declared no conflicts of interest. Copyright © 2022

Detection of the SARS-CoV-2 Delta Variant in the Transboundary Rivers of Yunnan, China

Ruili and Longchuan, two border counties in southwestern China, are facing epidemic control challenges due to the high rate of COVID-19 infections originating from neighboring Myanmar. Here, we aimed to establish the applicability of wastewater and environmental water surveillance of SARS-CoV-2 and conduct whole-genome sequencing (WGS) to trace the possible infection origin. In August 2021, total 72 wastewater and river water samples were collected from 32 sampling sites. SARS-CoV-2 ORF1ab and N genes were measured by RT-qPCR. We found that 19 samples (26.39%) were positive, and the viral loads of ORF1ab and N genes were 6.62 × 102–2.55×105 and 1.86 × 103–2.32 × 105 copies/L, respectively. WGS further indicated the sequences in two transboundary river samples, and one hospital wastewater sample belonged to the delta variant, suggesting that the infection source might be areas with high COVID-19 delta variant incidence in Southeast Asia (e.g., Myanmar). We reported for the first time the detection and quantification of SARS-CoV-2 RNA in the transboundary rivers of Myanmar–China. Our findings demonstrate that wastewater and environmental water may provide independent and nonintrusive surveillance points to monitor the global spread of emerging COVID-19 variants of concern, particularly in high-risk regions or border areas with considerable epidemic challenges and poor wastewater treatment facilities.

A Neural Predictive Model of Negative Emotions for COVID-19

The long-lasting global pandemic of Coronavirus disease 2019 (COVID-19) has changed our daily life in many ways and put heavy burden on our mental health. Having a predictive model of negative emotions during COVID-19 is of great importance for identifying potential risky population. To establish a neural predictive model achieving both good interpretability and predictivity, we have utilized a large-scale (n =542) longitudinal dataset, alongside two independent samples for external validation. We built a predictive model based on psychologically meaningful resting state neural activities. The whole-brain resting-state neural activity and social-psychological profile of the subjects were obtained from Sept. to Dec. 2019 (Time 1). Their negative emotions were tracked and re-assessed twice, on Feb 22 (Time 2) and Apr 24 (Time 3), 2020, respectively. We first applied canonical correlation analysis on both the neural profiles and psychological profiles collected on Time 1, this step selects only the psychological meaningful neural patterns for later model construction. We then trained the neural predictive model using those identified features on data obtained on Time 2. It achieved a good prediction performance (r =0.44, p =8.13 ×10-27). The two most important neural predictors are associated with self-control and social interaction. This study established an effective neural prediction model of negative emotions, achieving good interpretability and predictivity. It will be useful for identifying potential risky population of emotional disorders related to COVID-19. IEEE

Development of Ultrapure and Potent Tannic Acids as a Pan-coronal Antiviral Therapeutic

The rampageous transmission of SARS-CoV-2 has been devastatingly impacting human life and public health since late 2019. The waves of pandemic events caused by distinct coronaviruses at present and over the past decades have prompted the need to develop broad-spectrum antiviral drugs against them. In this study, our Pentarlandir ultrapure and potent tannic acids (UPPTA) showed activities against two coronaviral strains, SARSCoV-2 and HCoV-OC43, the earliest-known coronaviruses. The mode of inhibition of Pentarlandir UPPTA is likely to act on 3-chymotrypsin-like protease (3CLpro) to prevent viral replication, as supported by results of biochemical analysis, a 3CLpro assay, and a "gain-of-function" 3CLpro overexpressed cell-based method. Even in the 3CLpro overexpressed environment, Pentarlandir UPPTA remained its antiviral characteristic. Utilizing cell-based virucidal and cytotoxicity assays, the 50% effective concentrations (EC50) and 50% cytotoxicity concentration (CC50) of Pentarlandir UPPTA were determined to be similar to 0.5 and 52.5 mu M against SARS-CoV-2, while they were 1.3 and 205.9 mu M against HCoV-OC43, respectively. In the pharmacokinetic studies, Pentarlandir UPPTA was distributable at a high level to the lung tissue with no accumulation in the body, although the distribution was affected by the food effect. With further investigation in toxicology, Pentarlandir UPPTA demonstrated an overall safe toxicology profile. Taking these findings together, Pentarlandir UPPTA is considered to be a safe and efficacious pancoronal antiviral drug candidate that has been advanced to clinical development.

The Impact of Pandemic Management Strategies on Staff Mental Health, Work Behaviours, and Resident Care in One Long-Term Care Facility in British Columbia: A Mixed Method Study

Context: To slow the spread of COVID-19 within the Canadian long-term residential care (LTRC) sector, a series of pandemic management strategies were introduced, including restricted visitation and single site employment. These strategies were enacted to prevent and control infection, resulting in unknown impact on direct care staff and staff capacity to deliver quality care or service. Objective: To explore staff reports of outcomes associated with LTRC pandemic management strategies, particularly their impact on LTRC staff mental health, work behaviours and quality of care or service provision. Method: This was a case study using mixed methods including a longitudinal survey and interviews with staff from one LTRC site in British Columbia. Survey data from 68 staff who participated in both survey times were analyzed using regressions with relative weight analysis. Semi-structured interviews were conducted with 26 LTRC staff and analyzed using content analysis. Findings: Survey data demonstrated that staff perceived the sick time policy and staffing levels as the most inadequate pandemic management strategies. Survey data also showed the visitation policy, the sick time policy and the single site employment policy were most significantly associated with negative outcomes to staff mental health, work behaviours and quality of care or service delivery. Qualitative data suggested connections between these policies and inadequate staffing levels and heavy workloads. Limitations: The study design along with the low response rate and the small sample size limits the generalizability of the findings to other settings. Implications: The development and implementation of pandemic management strategies must be informed by and give consideration to working conditions of LTRC staff including long standing systemic issues such as staffing shortages and heavy workloads. © 2022 The Author(s).

Overview and applications of master protocol in clinical trials

Master protocol is a novel and more efficient design for clinical trial research than the traditional clinical trials. Usually a master protocol includes several sub-protocols which could investigate treatment effects of a single drug on several diseases or multiple drugs targeting a single disorder. This review compared master protocol with traditional trials in terms of the research design principle, application, and procedure flow as well as advantages and limitations. We also presented some examples of ongoing applications of master protocol designs including treatment of COVID-19 related illness. Finally, we discussed about potential implementation of master protocol in China especially under the COVID-19 pandemic with an evaluation on the relevant opportunities and challenges. © 2021, Chinese Journal of New Drugs Co. Ltd. All right reserved.

[Influence of SARS-CoV-2 vaccination on the epidemiological and clinical characteristics of imported COVID-19 cases in Chengdu].

Objective: To analyze the epidemiological and clinical characteristics of imported COVID-19 cases after SARS-CoV-2 vaccination and to provide evidence for the prevention and control of COVID-19. Methods: The imported COVID-19 cases in Chengdu as of April 15, 2021 were divided into the vaccinated group and unvaccinated group according to the history of SARS-CoV-2 vaccination. The epidemiological and clinical data of the cases were collected retrospectively, and the differences in epidemiological and clinical characteristics of the two groups were compared. Laboratory tests consisted of nucleic acid test, clinical index test, serum antibody test and lymphocyte test. Software WPS2019 was used for data management and software R 4.0.3 was used for statistical analysis. Results: A total of 75 COVID-19 cases were included in the analysis, in which 20 had received SARS-CoV-2 vaccination and only 4 with clinical symptoms, 55 patients did not receive SARS-CoV-2 vaccination, and 16 had clinical symptoms. In vaccinated group, the first injection time of vaccination ranged from July to November 2020, and 10 cases received two doses of vaccine simultaneously and 10 cases received two doses of vaccine at intervals of 14-57 days. The intervals between the completion of vaccination and the onset ranged from 87 days to 224 days. The differences in classification and clinical type between the two groups were significant. Significant differences were observed in case classification and clinical type between vaccinated group and unvaccinated group (P<0.05). The vaccinated group had a relatively high proportion of asymptomatic infections (40.00%, 8/20), while mild infections were mainly observed in the unvaccinated group(76.36%,42/55). The differences in Ct values (ORF1ab gene and N gene) at the diagnosis were not significant between vaccinated group and unvaccinated group (P>0.05), similar results were also observed in lymphocyte subtypes, procalcitonin and C-reactive protein level comparisons. Serum amyloid A level was higher in unvaccinated group than in vaccinated group (P<0.05). However, the SARS-CoV-2 related serum antibody of IgM, IgG and total antibody levels were significantly higher in vaccinated group (P<0.05). Conclusions: Risk of infection still exists with SARS-CoV-2 after vaccination, which can facilitate the production of specific serum antibody of IgM and IgG when people are exposed to the virus. It has a certain protective effect on SARS-CoV-2 infected persons. Vaccination can reduce the clinical symptoms and mitigate disease severity.

Factors related to public COVID-19 vaccine hesitancy based on the "3Cs" model: a cross-sectional study

Objective: To understand the current situation of the hesitation of COVID-19 vaccines among Chinese residents, analyze the factors of vaccine hesitancy based on the "3Cs" model, and to provide reference for population intervention. Methods: From Dec 31, 2020 to Jan 11, 2021, a convenience sampling method was adopted to conduct an online survey of residents in 34 provinces, cities and autonomous regions across the country.The survey content included demographic characteristics, vaccine hesitancy, and the dimensions of the "3Cs" (confidence, complacency, and convenience) model.We analyzed the influence of demographic characteristics on vaccine hesitancy by χ2 test.Logistic regression was used to evaluate the effects of "3Cs" variables on vaccine hesitancy. Results: A total of 2 531 respondents were surveyed.Their average age was (33.9±8.9) years old, male to female ratio was 1:1.42, and vaccine hesitating respondents accounted for 44.3%.Logistic regression analysis found that gender (ORfemale=1.33, 95%CI: 1.12-1.58), monthly income (compared with<6 000 yuan, OR>10 000=1.57, 95%CI: 1.25-1.97), healthcare workers(ORno=1.39, 95%CI: 1.12-1.73), and confidence (OR=0.47, 95%CI: 0.40-0.56) and complacency (OR=2.49, 95%CI: 2.10-2.96) in the "3Cs" model showed statistically significant impacts on the hesitation of COVID-19 vaccines. Conclusion: The confidence and complacency dimensions in the "3Cs" model have an impact on the hesitation of COVID-19 vaccines.Future interventions can focus on improving the public's confidence and reducing complacency associated with COVID-19 vaccines to increase the vaccination rate. © 2021, Editorial Department of Fudan University Journal of Medical Sciences. All right reserved.

[Prediction of the epitopes of SARS-CoV-2 by immunoinformatics]

Objective To predict the epitopes of B cells, cytotoxic T lymphocytes (CTL), and T helper (Th) cells of SARS-CoV-2 by immunoinformatics. Methods The SARS-CoV-2 protein sequences were retrieved from NCBI database and screened, and the sequences with antigenicity >=0.5 and amino acid number >=100 were used for epitopes prediction. The Phyre2 server was used to predict the three-dimensional (3D) structure, the GalaxyRefine system to optimize the 3D structure, and the SWISS-MODEL system to evaluate the accuracy of the optimized structure. The CTL, Th cells, and sequential B-cell antigen peptide prediction was based on the sequences of proteins, and the structural B-cell antigen peptide prediction on the 3D structures of proteins. The cytotoxic T lymphocyte (CTL) and Th cell epitopes of SARS-CoV-2 were predicted by the IEDB database. The sequential B-cell antigen peptide prediction and the structural B-cell antigen peptide prediction were performed by BepiPred-2.0: Sequential B-Cell Epitope Predictor and ElliPro-a structure-based tool for the prediction of epitopes, respectively. Results Twenty seven SARS-CoV-2 protein sequences were obtained from the NCBI database. After removing the proteins with antigenicity <0.5 and amino acid number <100, nine proteins were selected for antigen peptide prediction. Finally, 24 epitopes from CTLs, 20 epitopes from Th cells, and 12 sequential epitopes and 16 structural epitopes from B cells were obtained. Conclusion The epitopes obtained can be used for developing multi-epitope SARS-CoV-2 vaccines. Compared with epitopes that only target a single protein, multi-target epitopes have stronger immunogenicity. These epitopes have certain reference value for the development of SARS-CoV-2 vaccine.

Patients hospitalized in Eastern North Carolina

Although majority of coronavirus disease 2019 (COVID-19) cases demonstrate mild to asymptomatic disease, COVID-19 can cause serious complica-tions and death. However, risk factors for development of such complications are not well understood. The purpose of this study was to identify risk factors for intubation, cardiac arrest, and death in COVID-19 patients.Methods: A retrospective chart review of COVID-19 subjects was conducted of the first 185 patients for whom we had complete data sets. Subjects were adult inpa-tients with a confirmed COVID-19 diagnosis who were hospitalized between March and May 2020 at Vidant Medical Center in Greenville, NC. Data including demo-graphics, comorbidities, laboratory results, treatments, and outcomes were collected. Data were analyzed using logistic regression models and receiver operating character-istic curves in SAS 9.4.Results: Of the first 185 subjects hospitalized for COVID-19, 26% of patients were intubated, 9% experienced cardiac arrest, and 17% died. Subjects who required intubation were more likely to exhibit elevated triglycerides, sepsis, acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), elevated troponin levels, altered mental status, leukocytosis, lymphopenia and elevated ferritin (P< 0.05) (Table 1). Troponin elevation, ARDS, AKI and thrombocytopenia were risks for cardiac arrest (P< 0.05) (Table 2). Risk of death was increased in those presenting with advanced age, critical or severe disease, lymphopenia or thrombocytopenia, and in those with history of coronary artery disease (CAD) (P< 0.05) (Table 3). Patients presenting with AKI, elevated Troponin, ARDS, pressor requirements, critical disease, and sepsis were at increased risk of intubation, cardiac arrest, and death (P< 0.05) (Tables 1-3).Table 1: Top non-ICU related risk factors for intubation ordered by AUC.Table 2: Top risk factors for cardiac arrest ordered by AUC.Table 3: Top risk factors for death ordered by AUC.Conclusion: In this rapidly evolving pandemic, clinician awareness of risk factors for clinically significant outcomes such as intubation and mortality is essen-tial. Assessment of risk factors like those highlighted in this study can aid in clinical decision-making and predicting patient outcomes. As more data becomes available we aim to develop a validated scoring system to assist clinicians in patient care (Table Presented).

Data-related and methodological obstacles to determining associations between temperature and COVID-19 transmission

More and more studies have evaluated the associations between ambient temperature and coronavirus disease 2019 (COVID-19). However, most of these studies were rushed to completion, rendering the quality of their findings questionable. We systematically evaluated 70 relevant peer-reviewed studies published on or before 21 September 2020 that had been implemented from community to global level. Approximately 35 of these reports indicated that temperature was significantly and negatively associated with COVID-19 spread, whereas 12 reports demonstrated a significantly positive association. The remaining studies found no association or merely a piecewise association. Correlation and regression analyses were the most commonly utilized statistical models. The main shortcomings of these studies included uncertainties in COVID-19 infection rate, problems with data processing for temperature, inappropriate controlling for confounding parameters, weaknesses in evaluation of effect modification, inadequate statistical models, short research periods, and the choices of research areal units. It is our viewpoint that most studies of the identified 70 publications have had significant flaws that have prevented them from providing a robust scientific basis for the association between temperature and COVID-19.

Combating COVID-19 Through Collaborative Governance: Lessons from East Asia

Collaborative governance plays a significant role in crisis management and greatly contributes to the fight against COVID-19. This article demonstrates how East Asia effectively combats COVID-19 through collaboration with enterprises, nonprofit organizations, and citizens. By comparing different countries' responses, this study proposes three different types of collaborative governance models employed in combating the pandemic, namely the Chinese state-led cooperation model, South Korea's state-society synergy model, and Japan's social voluntary cooperation model. The findings demonstrate that there is no one-size-fits-all model to respond to the COVID-19 crisis. The specific response initiative that the government adopts is shaped by its state intervention and coercion capacity, as well as the social voluntary cooperation norm. Each country should take anti-pandemic measures based on its specific conditions. Achieving a balance between preventing the pandemic and maintaining social economic development is a challenge for governments. The three collaboration models drawn from the East Asian experience provide valuable lessons for combating the global pandemic and future crises.