MIL-101(CuFe) Nanozymes with Excellent Peroxidase-like Activity for Simple, Accurate, and Visual Naked-Eye Detection of SARS-CoV-2.

The COVID-19 pandemic has spread to every corner of the world and seriously affected our health and daily activities in the past three years; thereby, it is still urgent to develop various simple, quick, and accurate methods for early detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Nanozymes, a kind of nanomaterial with intrinsic enzyme-mimicking activity, have emerged as a suitable alternative for both therapy and diagnosis of SARS-CoV-2. Here, ultrasensitive and ultrafast MIL-101(CuFe)-CD147 biosensors are established for the detection of SARS-CoV-2 by a simple colorimetric method. A MIL-101(CuFe) metal-organic framework has excellent peroxidase-like activity due to the synergistic effect of Fe and Cu atoms. In addition, the MIL-101(CuFe)-CD147 biosensor shows great potential to detect the various variants of SARS-CoV-2 due to the universal receptor of CD147. The enzyme-based biosensor for the detection of SARS-CoV-2 achieves a very low limit of detection (about 3 PFU/mL) within 30 min. Therefore, the present method provides a new generation of an alternative approach for highly sensitive and visual diagnosis of COVID-19.

Development of a three-panel multiplex real-time PCR assay for simultaneous detection of nine canine respiratory pathogens.

Infectious respiratory disease is one of the most common diseases in dogs worldwide. Several bacterial and viral pathogens can serve as causative agents of canine infectious respiratory disease (CIRD), including Mycoplasma cynos, Mycoplasma canis, Bordetella bronchiseptica, canine adenovirus type 2 (CAdV-2), canine herpesvirus 1 (CHV-1), canine parainfluenza virus (CPIV), canine distemper virus (CDV), canine influenza virus (CIA) and canine respiratory coronavirus (CRCoV). Since these organisms cause similar clinical symptoms, disease diagnosis based on symptoms alone can be difficult. Therefore, a quick and accurate test is necessary to rapidly identify the presence and relative concentrations of causative CIRD agents. In this study, a multiplex real-time PCR panel assay was developed and composed of three subpanels for detection of the aforementioned pathogens. Correlation coefficients (R2) were >0.993 for all singleplex and multiplex real-time PCR assays with the exception of one that was 0.988; PCR amplification efficiencies (E) were between 92.1% and 107.8% for plasmid DNA, and 90.6-103.9% for RNA templates. In comparing singular and multiplex PCR assays, the three multiplex reactions generated similar R2 and E values to those by corresponding singular reactions, suggesting that multiplexing did not interfere with the detection sensitivities. The limit of detection (LOD) of the multiplex real-time PCR for DNA templates was 5, 2, 3, 1, 1, 1, 4, 24 and 10 copies per microliter for M. cynos, M. canis, B. brochiseptica, CAdV-2, CHV-1, CPIV, CDV, CIA and CRCoV, respectively; and 3, 2, 6, 17, 4 and 8 copies per microliter for CAdV-2, CHV-1, CPIV, CDV, CIA and CRCoV, respectively, when RNA templates were used for the four RNA viruses. No cross-detection was observed among the nine pathogens. For the 740 clinical samples tested, the newly designed PCR assay showed higher diagnostic sensitivity compared to an older panel assay; pathogen identities from selected samples positive by the new assay but undetected by the older assay were confirmed by Sanger sequencing. Our data showed that the new assay has higher diagnostic sensitivity while maintaining the assay's specificity, as compared to the older version of the panel assay.

A Quantitative Approach of Subway Station Passengers’ Heterogeneity of Decision Preference Considering Personality Traits during Emergency Evacuation

Subway station emergencies are gradually increasing in China. The aim of this research is to study the effects of “Dist”, “Pedestrian flow” and “Crowd density” on the heterogeneity of passengers’ decision-making preference and explore the relationship between heterogeneity and personality. Firstly, a questionnaire of 20 emergency evacuation scenarios, that includes the Eysenck Personality Questionnaire, is designed. Secondly, the heterogeneity of passengers’ decision preference is quantified by the random parameter logit model. Finally, personality traits and influencing factors are used as abscissa and ordinate respectively, to study the relationship between personality traits and preference heterogeneity. The results show that the coefficients of “Dist”, “Pedestrian flow” and “Crowd density” are −0.101, 0.236 and −0.442 respectively, which are statistically significant. The proportion of extroverted passengers of the exit is 9% higher than that of introverted passengers when “Pedestrian flow” of the exit is greater than the average value, while the proportion of introverted passengers is 7% higher than that of extroverted passengers when “Crowd density” is smaller than the average value. The conclusion is that the three influence factors are random variables, and “Dist” shows the lowest level of heterogeneity. Extroverted passengers are more likely to follow a large crowd for evacuation, but introverted passengers are more likely to avoid crowded exits.

Prophylactic vaccine delivery systems against epidemic infectious diseases.

Prophylactic vaccines have evolved from traditional whole-cell vaccines to safer subunit vaccines. However, subunit vaccines still face problems, such as poor immunogenicity and low efficiency, while traditional adjuvants are usually unable to meet specific response needs. Advanced delivery vectors are important to overcome these barriers; they have favorable safety and effectiveness, tunable properties, precise location, and immunomodulatory capabilities. Nevertheless, there has been no systematic summary of the delivery systems to cover a wide range of infectious pathogens. We herein summarized and compared the delivery systems for major or epidemic infectious diseases caused by bacteria, viruses, fungi, and parasites. We also included the newly licensed vaccines (e.g., COVID-19 vaccines) and those close to licensure. Furthermore, we highlighted advanced delivery systems with high efficiency, cross-protection, or long-term protection against epidemic pathogens, and we put forward prospects and thoughts on the development of future prophylactic vaccines.

Robust neutralization assay based on SARS-CoV-2 S-protein-bearing vesicular stomatitis virus (VSV) pseudovirus and ACE2-overexpressing BHK21 cells.

The global pandemic of coronavirus disease 2019 (COVID-19) is a disaster for human society. A convenient and reliable neutralization assay is very important for the development of vaccines and novel drugs. In this study, a G protein-deficient vesicular stomatitis virus (VSVdG) bearing a truncated spike protein (S with C-terminal 18 amino acid truncation) was compared to that bearing the full-length spike protein of SARS-CoV-2 and showed much higher efficiency. A neutralization assay was established based on VSV-SARS-CoV-2-Sdel18 pseudovirus and hACE2-overexpressing BHK21 cells (BHK21-hACE2 cells). The experimental results can be obtained by automatically counting the number of EGFP-positive cells at 12 h after infection, making the assay convenient and high-throughput. The serum neutralizing titer measured by the VSV-SARS-CoV-2-Sdel18 pseudovirus assay has a good correlation with that measured by the wild type SARS-CoV-2 assay. Seven neutralizing monoclonal antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 S protein were obtained. This efficient and reliable pseudovirus assay model could facilitate the development of new drugs and vaccines.

Factors contributing to healthcare professional burnout during the COVID-19 pandemic: A rapid turnaround global survey.

BACKGROUND: Healthcare professionals (HCPs) on the front lines against COVID-19 may face increased workload and stress. Understanding HCPs' risk for burnout is critical to supporting HCPs and maintaining the quality of healthcare during the pandemic. METHODS: To assess exposure, perceptions, workload, and possible burnout of HCPs during the COVID-19 pandemic we conducted a cross-sectional survey. The main outcomes and measures were HCPs' self-assessment of burnout, indicated by a single item measure of emotional exhaustion, and other experiences and attitudes associated with working during the COVID-19 pandemic. FINDINGS: A total of 2,707 HCPs from 60 countries participated in this study. Fifty-one percent of HCPs reported burnout. Burnout was associated with work impacting household activities (RR = 1·57, 95% CI = 1·39-1·78, P<0·001), feeling pushed beyond training (RR = 1·32, 95% CI = 1·20-1·47, P<0·001), exposure to COVID-19 patients (RR = 1·18, 95% CI = 1·05-1·32, P = 0·005), and making life prioritizing decisions (RR = 1·16, 95% CI = 1·02-1·31, P = 0·03). Adequate personal protective equipment (PPE) was protective against burnout (RR = 0·88, 95% CI = 0·79-0·97, P = 0·01). Burnout was higher in high-income countries (HICs) compared to low- and middle-income countries (LMICs) (RR = 1·18; 95% CI = 1·02-1·36, P = 0·018). INTERPRETATION: Burnout is present at higher than previously reported rates among HCPs working during the COVID-19 pandemic and is related to high workload, job stress, and time pressure, and limited organizational support. Current and future burnout among HCPs could be mitigated by actions from healthcare institutions and other governmental and non-governmental stakeholders aimed at potentially modifiable factors, including providing additional training, organizational support, and support for family, PPE, and mental health resources.

Emergency Response Measures for Anesthesia Nursing During the COVID-19 Pandemic: West China Hospital Experiences.

During the COVID-19 pandemic, ensuring the gradual recovery of anesthesia nursing unit and avoiding cross-infection between surgical patients and staff are difficult problems for hospital managers. We outlined the emergency response measures and the transition to normal operation of the anesthesia nursing unit in West China Hospital, which is a large teaching hospital. This mainly included hospital and operating room channel management, three-level screening management of patients and medical staff, classification management of patients undergoing anesthesia and recovery, training management of medical personnel, strict environmental management, and online teaching management.

Molecular mechanism of Bufei Huoxue Capsule on COVID-2019 based on network pharmacology and molecular docking

Objective: To explore the potential mechanism of Bufei Huoxue Capsule (BHC) on coronavirus disease 2019 (COVID-19), and provide a theoretical basis for the clinical application of BHC. Methods: TCMSP, BATMAN-TCM, CNKI and Pubmed databases were used to search the compounds and targets of BHC and GeneCards database was used to search the targets of COVID-19;The intersection method was used to obtain the targets related to the therapeutic effect of BHC. Cytoscape 3.7.2 software was applied for the construction of CMM-compounds-targets network map. Protein-protein interaction (PPI) network was constructed by STRING database. Gene ontology (GO) functional enrichment analysis and KEGG pathway enrichment analysis were conducted by DAVID. AutoDock Tools 1.5.6 and AutoDock vina 1.1.2 were used for molecular docking. Results: A total of 32 potential active components were screened from BHC, corresponding to 203 targets. Among them, there were 11 core compounds and 52 core targets. PPI network analysis showed that there were 25 key targets intervening COVID-19 by BHC. A total of 251 biological processes (P < 0.05) and 93 pathways (P < 0.05) were obtained by GO analysis and KEGG analysis, respectively. The results of molecular docking showed that the key compounds had good affinity with SARS-CoV-2 3CL hydrolase and angiotensin converting enzyme II. Conclusion: The active compounds of BHC can target IL6, MAPK8, PTGS2, PTGS1 and NCOA2 to regulate multiple signal pathways, and play a therapeutic role in the recovery period of COVID-19.

Serology characteristics of SARS-CoV-2 infection since exposure and post symptom onset

BACKGROUND: Timely diagnosis of SARS-CoV-2 infection is a prerequisite for treatment and prevention. The serology characteristics and complement diagnosis value of the antibody test to RNA test need to be demonstrated. METHOD: Serial sera of 80 patients with PCR-confirmed COVID-19 were collected at the First Affiliated Hospital of Zhejiang University, China. Total antibody (Ab), IgM and IgG antibodies against SARS-CoV-2 were detected, and the antibody dynamics during the infection were described. RESULTS: The seroconversion rates for Ab, IgM and IgG were 98.8%, 93.8% and 93.8%, respectively. The first detectible serology marker was Ab, followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 days post exposure (d.p.e) or 9, 10 and 12 days post onset (d.p.o), respectively. The antibody levels increased rapidly beginning at 6 d.p.o. and were accompanied by a decline in viral load. For patients in the early stage of illness (0-7 d.p.o), Ab showed the highest sensitivity (64.1%) compared to IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG increased to 100%, 96.7% and 93.3% 2 weeks later, respectively. When the same antibody type was detected, no significant difference was observed between enzyme-linked immunosorbent assays and other forms of immunoassays. CONCLUSIONS: A typical acute antibody response is induced during SARS-CoV-2 infection. Serology testing provides an important complement to RNA testing in the later stages of illness for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patients.