A surface molecularly imprinted electrochemical biosensor for the detection of SARS-CoV-2 spike protein by using Cu7S4-Au as built-in probe.

Sensitive detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein (S protein) is of significant clinical importance in the diagnosis of COVID-19 pandemic. In this work, a surface molecularly imprinted (SMI) electrochemical biosensor is fabricated for the detection of SARS-CoV-2 S protein. Cu7S4-Au is used as the built-in probe and modified on the surface of a screen-printed carbon electrode (SPCE). 4-Mercaptophenylboric acid (4-MPBA) is anchored to the surface of the Cu7S4-Au through Au-SH bonds, which can be used for the immobilization of the SARS-CoV-2 S protein template through boronate ester bonds. After that, 3-aminophenylboronic acid (3-APBA) is electropolymerized on the electrode surface and used as the molecularly imprinted polymers (MIPs). The SMI electrochemical biosensor is obtained after the elution of the SARS-CoV-2 S protein template with an acidic solution by the dissociation of the boronate ester bonds, which can be utilized for sensitive detection of the SARS-CoV-2 S protein. The developed SMI electrochemical biosensor displays high specificity, reproducibility and stability, which might be a potential and promising candidate for the clinical diagnosis of COVID-19.

Factors associated with weight gain during COVID-19 pandemic: A global study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in changes in lifestyle habits and experiences of mental health outcomes, some of which were possibly related to weight gain, leading to an increase in the prevalence of obesity, which is associated with the development of several severe diseases. Concerns regarding weight gain and its impact on health outcomes are prevalent worldwide, with obesity being one of the highest causes of mortality in current society. METHODS: A self-reported questionnaire collected data from participants aged 18 years of age and above from 26 countries and regions worldwide. Post-hoc multiple logistic regression analyses have been done to evaluate the association between demographic and socioeconomic factors, and the perspectives that were identified to be associated with weight gain. RESULTS: Participants belonging to a younger age group; with a higher level of education; living in an urban area; living with family members; employed full-time; and had obesity were found to be more vulnerable to weight gain. After adjusting for socio-demographic factors, participants who were quarantined; exercised less prior to the pandemic; consumed unhealthy foods; and reported negative thoughts such as helplessness and the perceived risk of COVID-19, were more likely to experience weight gain; while negative thoughts such as having no means of control over the COVID-19 pandemic and the consequences of the COVID-19 pandemic will have great personal effect were associated with females, students, and people living in the rural area. CONCLUSIONS: Weight gain risk during the pandemic was significantly associated with certain socio-demographic and COVID-19 related factors. To improve public health outcomes, future research should conduct a longitudinal evaluation on the effects of COVID-19 experiences upon health choices. Streamlined mental support should also be provided to the vulnerable groups which were prone to negative thoughts that were associated with weight gain.

Molecularly imprinted miniature electrochemical biosensor for SARS-CoV-2 spike protein based on Au nanoparticles and reduced graphene oxide modified acupuncture needle.

Accurate detection of SARS-CoV-2 spike (SARS-CoV-2-S) protein is of clinical significance for early diagnosis and timely treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, a surface molecularly imprinted miniature biosensor was fabricated. Au nanoparticles (AuNPs), reduced graphene oxide (rGO), poly(methylene blue)/poly(ionic liquids) and poly(ionic liquids) were successively electrodeposited onto the pinpoint of an acupuncture needle (AN). The molecularly imprinted miniature biosensor was obtained after the template of SARS-CoV-2-S protein was removed, which could be used for sensitive detection of SARS-CoV-2-S protein. The linear range and limit of detection (LOD) were 0.1 âˆ¼ 1000 ng mL-1 and 38 pg mL-1, respectively, which were superior to other molecularly imprinted biosensors previously reported. The developed miniature biosensor also exhibited high specificity and stability. The reliability of the biosensor was evaluated by the detection of SARS-CoV-2-S protein in clinical serum samples.

Resilience level and its association with maladaptive coping behaviours in the COVID-19 pandemic: a global survey of the general populations.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has induced a significant global concern on mental health. However few studies have measured the ability of individuals to "withstand setbacks, adapt positively, and bounce back from adversity" on a global scale. We aimed to examine the level of resilience, its determinants, and its association with maladaptive coping behaviours during the pandemic. METHODS: The Association of Pacific Rim Universities (APRU) conducted a global survey involving 26 countries by online, self-administered questionnaire (October 2020-December 2021). It was piloted-tested and validated by an expert panel of epidemiologists and primary care professionals. We collected data on socio-demographics, socioeconomic status, clinical information, lifestyle habits, and resilience levels measured by the Brief Resilience Scale (BRS) among adults aged ≥ 18 years. We examined factors associated with low resilience level, and evaluated whether low resilience was correlated with engagement of maladaptive coping behaviours. RESULTS: From 1,762 surveys, the prevalence of low resilience level (BRS score 1.00-2.99) was 36.4% (America/Europe) and 24.1% (Asia Pacific). Young age (18-29 years; adjusted odds ratio [aOR] = 0.31-0.58 in older age groups), female gender (aOR = 1.72, 95% C.I. = 1.34-2.20), poorer financial situation in the past 6 months (aOR = 2.32, 95% C.I. = 1.62-3.34), the presence of one (aOR = 1.56, 95% C.I. = 1.19-2.04) and more than two (aOR = 2.32, 95% C.I. = 1.59-3.39) medical conditions were associated with low resilience level. Individuals with low resilience were significantly more likely to consume substantially more alcohol than usual (aOR = 3.84, 95% C.I. = 1.62-9.08), take considerably more drugs (aOR = 12.1, 95% C.I. = 2.72-54.3), buy supplements believed to be good for treating COVID-19 (aOR = 3.34, 95% C.I. = 1.56-7.16), exercise less than before the pandemic (aOR = 1.76, 95% C.I. = 1.09-2.85), consume more unhealthy food than before the pandemic (aOR = 2.84, 95% C.I. = 1.72-4.67), self-isolate to stay away from others to avoid infection (aOR = 1.83, 95% C.I. = 1.09-3.08), have an excessive urge to disinfect hands for avoidance of disease (aOR = 3.08, 95% C.I. = 1.90-4.99) and transmission (aOR = 2.54, 95% C.I. = 1.57-4.10). CONCLUSIONS: We found an association between low resilience and maladaptive coping behaviours in the COVID-19 pandemic. The risk factors identified for low resilience in this study were also conditions known to be related to globalization-related economic and social inequalities. Our findings could inform design of population-based, resilience-enhancing intervention programmes.

Tracing production carbon emission transfer through global value chains: Towards a top gainer principle.

This study proposes the top gainer principle (TGP) and builds a calculation model based on the TGP to measure production carbon emissions transfer (PCET) in the context of global value chains. Compared with embodied carbon research, the innovative TGP model establishes a traceability mechanism based on the difference between responsibility and actual emissions from the perspective of the value chain, avoiding the endless debate between producer and consumer responsibility, which makes the TGP model more reasonable and fairer. In addition, using long-term input-output data, this study measures spatiotemporal patterns and the network evolution of global PCET. The results show that the total amount of global PCET has increased, and the regions with high outflows of PCET mainly include East Asia, North America, Central and Western Europe, and Russia. Among these regions, the United States and China accounted for the largest proportion of PCET outflow. By contrast, South America and Africa are typical low-outflow regions. From North America via central Europe, Turkey, Iran, South Asia to China, is a "W"-shaped high net outflow belt. The overall concentration of the global PCET network first decreased and then increased, and the network structure evolved into a bipolar network group with China and the United States as the core. Under the shock of the COVID-19 pandemic, the network structure showed a trend towards decentralization. This study suggests that efforts should be made to strengthen the responsibility of major countries, enhance the supervision of lead firms, establish a carbon emission transfer compensation system within value chains, and promote the development and spread of carbon emission reduction technologies to facilitate the reduction of global carbon emissions.

Quality of healthcare and admission rates for acute cardiac events during COVID-19 pandemic: a retrospective cohort study on ST-segment-elevation myocardial infarction in China.

OBJECTIVE: To evaluate changes in admission rates for and quality of healthcare of ST-segment-elevation myocardial infarction (STEMI) during the period of the COVID-19 outbreak and postoutbreak. METHODS: We conducted a retrospective study among patients with STEMI in the outbreak time and the postoutbreak time. DESIGN: To examine the changes in the admission rates and in quality of healthcare, by comparison between periods of the postoutbreak and the outbreak, and between the postoutbreak and the corresponding periods. SETTING: Data for this analysis were included from patients discharge diagnosed with STEMI from all the hospitals of Suzhou in each month of the year until the end of July 2020. PARTICIPANTS: 1965 STEMI admissions. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the number of moecondary outcomnthly STEMI admissions, and the secondary outcomes were the quality metrics of STEMI healthcare. RESULTS: There were a 53% and 38% fall in daily admissions at the phase of outbreak and postoutbreak, compared with the 2019 corresponding. There remained a gap in actual number of postoutbreak admissions at 306 and the predicted number at 497, an estimated 26 deaths due to STEMI would have been caused by not seeking healthcare. Postoutbreak period of 2020 compared with corresponding period of 2019, the percentage of cases transferred by ambulance decreased from 9.3% to 4.2% (p=0.013), the door-to-balloon median time increased from 17.5 to 34.0 min (p=0.001) and the rate of percutaneous coronary intervention (PCI) therapy declined from 71.3% to 60.1% (p=0.002). CONCLUSIONS: The impact of public health restrictions may lead to unexpected out-of-hospital deaths and compromised quality of healthcare for acute cardiac events. Delay or absence in patients should be continuously considered avoiding the secondary disaster of the pandemic. System delay should be modifiable for reversing the worst clinical outcomes from the COVID-19 outbreak, by coordination measures with focus on the balance between timely PCI procedure and minimising contamination of cardiac catheterisation rooms.

Factors Associated with Vaccination Intention against the COVID-19 Pandemic: A Global Population-Based Study.

Several vaccines have been developed for COVID-19 since the pandemic began. This study aimed to evaluate the factors associated with COVID-19 vaccination intention. A global survey was conducted across 26 countries from October, 2020 to December, 2021 using an online self-administered questionnaire. Demographic information, socio-economic status, and clinical information were collected. A logistic regression examined the associations between vaccine intention and factors such as perceptions and the presence of chronic physical and mental conditions. The sample included 2459 participants, with 384 participants (15.7%) expressing lower COVID-19 vaccination intent. Individuals who identified as female; belonged to an older age group; had a higher level of education; were students; had full health insurance coverage; or had a previous history of influenza vaccination were more willing to receive vaccination. Conversely, those who were working part-time, were self-employed, or were receiving social welfare were less likely to report an intention to get vaccinated. Participants with mental or physical health conditions were more unwilling to receive vaccination, especially those with sickle cell disease, cancer history within the past five years, or mental illness. Stronger vaccination intent was associated with recommendations from the government or family doctors. The presence of chronic conditions was associated with lower vaccine intention. Individuals with health conditions are especially vulnerable to health complications and may experience an increased severity of COVID-19 symptoms. Future research should evaluate the effectiveness of interventions targeting the vaccine perceptions and behaviours of at-risk groups. As such, public awareness campaigns conducted by the government and proactive endorsement from health physicians may help improve COVID-19 vaccination intention.

Aggregation-Induced Emission Fluorophore-Incorporated Curcumin-Based Ratiometric Nanoprobe for Hypochlorite Detection in Food Matrices.

The development of efficient, economic, reliable, and accurate monitoring of hypochlorite (ClO-) in food matrices is in great demand for food safety assessment, particularly during its massive use against the COVID-19 epidemic. Here, we prepared an aggregation-induced emission (AIE) fluorophore tetraphenylethylene (TPE)-incorporated curcumin-based hybrid ratiometric fluorescence nanoprobe (Curcumin/TPE@HyNPs) through amphiphilic phospholipid polymer-powered nanoprecipitation, which exhibited a fast, highly sensitive, and selective response to the residual ClO- in real food matrices. Because of the inner filter effect (IFE) from curcumin toward TPE inside the nanoprobe, the bright fluorescence of TPE aggregation at ∼437 nm was effectively quenched, along with an enhanced fluorescence of curcumin at ∼478 nm. Once there was a ClO- residue in food matrices, ClO- triggered the oxidation of o-methoxyphenol inside curcumin and led to the almost complete absorption collapse, thereby terminating curcumin fluorescence at ∼478 nm and the IFE process. Accordingly, the fluorescence of TPE at ∼437 nm was recovered. In this case, a ratiometric fluorescent response of Curcumin/TPE@HyNPs toward the residual ClO- in food matrices (e.g., milk) was proposed with a low detection limit of 0.353 µM and a rapid response time of 140.0 s. Notably, the phospholipid polymer as the protection layer effectively reduced/evaded the nonspecific binding of signal reporters inside the nanoprobe, facilitating it to directly monitor the residual ClO- in real food matrices. This work provided a novel approach to utilize the unconventional AIE luminophors for constructing the efficient and reliable early warning mechanisms toward various food contaminants.

Stem cell therapy: A promising treatment for COVID-19.

Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. SARS-CoV-2 is an RNA virus and has a glycosylated spike (S) protein used for genome encoding. COVID-19 can lead to a cytokine storm and patients usually have early respiratory signs and further secondary infections, which can be fatal. COVID-19 has entered an emergency phase, but there are still no specific effective drugs for this disease. Mesenchymal stem cells (MSCs) are multipotent stromal cells, which cause antiapoptosis and can repair damaged epithelial cells. Many clinical trials have proved that MSC therapy could be a potential feasible therapy for COVID-19 patients, especially those with acute respiratory distress syndrome, without serious adverse events or toxicities. However, more studies are needed in the future, in order to confirm the effect of this therapy.

PAGEANT: personal access to genome and analysis of natural traits.

GWASs have identified numerous genetic variants associated with a wide variety of diseases, yet despite the wide availability of genetic testing the insights that would enhance the interpretability of these results are not widely available to members of the public. As a proof of concept and demonstration of technological feasibility, we developed PAGEANT (Personal Access to Genome & Analysis of Natural Traits), usable through Graphical User Interface or command line-based version, aiming to serve as a protocol and prototype that guides the overarching design of genetic reporting tools. PAGEANT is structured across five core modules, summarized by five Qs: (i) quality assurance of the genetic data; (ii) qualitative assessment of genetic characteristics; (iii) quantitative assessment of health risk susceptibility based on polygenic risk scores and population reference; (iv) query of third-party variant databases (e.g. ClinVAR and PharmGKB) and (v) quick Response code of genetic variants of interest. Literature review was conducted to compare PAGEANT with academic and industry tools. For 2504 genomes made publicly available through the 1000 Genomes Project, we derived their genomic characteristics for a suite of qualitative and quantitative traits. One exemplary trait is susceptibility to COVID-19, based on the most up-to-date scientific findings reported.

Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms.

The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors - CX3CR1 and L-selectin - were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.

Clinical Characteristics of Coronavirus Disease 2019 in China.

BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).

Synthesis and Biological Evaluation of Honokiol Derivatives Bearing 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones as Potential Viral Entry Inhibitors against SARS-CoV-2.

The 2019 coronavirus disease (COVID-19) caused by SARS-CoV-2 virus infection has posed a serious danger to global health and the economy. However, SARS-CoV-2 medications that are specific and effective are still being developed. Honokiol is a bioactive component from Magnoliae officinalis Cortex with damp-drying effect. To develop new potent antiviral molecules, a series of novel honokiol analogues were synthesized by introducing various 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones to its molecule. In a SARS-CoV-2 pseudovirus model, all honokiol derivatives were examined for their antiviral entry activities. As a result, 6a and 6p demonstrated antiviral entry effect with IC50 values of 29.23 and 9.82 µM, respectively. However, the parental honokiol had a very weak antiviral activity with an IC50 value more than 50 µM. A biolayer interfero-metry (BLI) binding assay and molecular docking study revealed that 6p binds to human ACE2 protein with higher binding affinity and lower binding energy than the parental honokiol. A competitive ELISA assay confirmed the inhibitory effect of 6p on SARS-CoV-2 spike RBD's binding with ACE2. Importantly, 6a and 6p (TC50 > 100 µM) also had higher biological safety for host cells than honokiol (TC50 of 48.23 µM). This research may contribute to the discovery of potential viral entrance inhibitors for the SARS-CoV-2 virus, although 6p's antiviral efficacy needs to be validated on SARS-CoV-2 viral strains in a biosafety level 3 facility.

Current therapeutic strategies for respiratory diseases using mesenchymal stem cells.

Mesenchymal stromal/stem cells (MSCs) have a great potential to proliferate, undergo multi-directional differentiation, and exert immunoregulatory effects. There is already much enthusiasm for their therapeutic potentials for respiratory inflammatory diseases. Although the mechanism of MSCs-based therapy has been well explored, only a few articles have summarized the key advances in this field. We hereby provide a review over the latest progresses made on the MSCs-based therapies for four types of inflammatory respiratory diseases, including idiopathic pulmonary fibrosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and asthma, and the uncovery of their underlying mechanisms from the perspective of biological characteristics and functions. Furthermore, we have also discussed the advantages and disadvantages of the MSCs-based therapies and prospects for their optimization.

COVID-19 Home Quarantine Accelerated the Progression of Myopia in Children Aged 7 to 12 Years in China.

Purpose: To investigate the effect of home quarantine during the COVID-19 pandemic on myopia progression in children and its associated factors. Methods: Myopic children aged 7 to 12 years with regular follow-up visits every half a year from April 2019 to May 2020 were included. Cycloplegic refraction was measured at baseline and at two follow-up visits. The first follow-up visit (visit 1) was conducted before the COVID-19 home quarantine, whereas the second (visit 2) was four months after the home quarantine. Myopia progression at visits 1 and 2 were compared. Factors associated with changes in myopia progression were tested with a multiple regression analysis. Results: In total, 201 myopic children were enrolled. There was a significantly greater change in spherical equivalent at visit 2 (-0.98 ± 0.52 D) than at visit 1 (-0.39 ± 0.58 D; P < 0.001). Students were reported to have spent more time on digital devices for online learning (P < 0.001) and less time on outdoor activities (P < 0.001) at visit 2 than at visit 1. Children using television and projectors had significantly less myopic shift than those using tablets and mobile phones (P < 0.001). More time spent on digital screens (ß = 0.211, P < 0.001), but not less time on outdoor activities (ß = -0.106, P = 0.110), was associated with greater myopia progression at visit 2. Conclusions: Changes in behavior and myopic progression were found during the COVID-19 home quarantine. Myopic progression was associated with digital screen use for online learning, but not time spent on outdoor activities. The projector and television could be better choices for online learning.

Rapid Detection of Anti-SARS-CoV-2 Antibody Using a Selenium Nanoparticle-Based Lateral Flow Immunoassay.

Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is highly transmissible. Early and rapid testing is necessary to effectively prevent and control the outbreak. Detection of SARS-CoV-2 antibodies with lateral flow immunoassay can achieve this goal. In this study, SARS-CoV-2 nucleoprotein (NP) was expressed and purified. We used the selenium nanoparticle as the labeling probe coupled with the NP to prepare an antibody (IgM and IgG) detection kit. The detection limit, cross reaction, sensitivity and specificity of the kit is verified. Separate detection of IgM and IgG, such as in this assay, was performed in order to reduce mutual interference and improve the accuracy of the test results.The final purity of NP was 91.83%. Selenium nanoparticle and NP successfully combined with stable effect. The LOD of the kit was 20 ng/mL for anti-NP IgG and 60 ng/mL for anti-NP IgM, respectively. The kit does not cross reaction with RF. The sensitivity of the kit was 94.74% and the specificity was 96.23%. The assay kit does not require any special device for reading the results and the readout is a simple color change that can be evaluated with the naked eye. This kit is suitable for rapid and real-time detection of the SARS-CoV-2 antibody IgG and IgM.

Disparities in COVID-19 Vaccination among Low-, Middle-, and High-Income Countries: The Mediating Role of Vaccination Policy.

Inequity in the access to and deployment of the coronavirus disease 2019 (COVID-19) vaccines has brought about great challenges in terms of resolving the pandemic. Aiming to analyze the association between country income level and COVID-19 vaccination coverage and explore the mediating role of vaccination policy, we conducted a cross-sectional ecological study. The dependent variable was COVID-19 vaccination coverage in 138 countries as of May 31, 2021. A single-mediator model based on structural equation modeling was developed to analyze mediation effects in different country income groups. Compared with high-income countries, upper-middle- (ß = -1.44, 95% CI: -1.86--1.02, p < 0.001), lower-middle- (ß = -2.24, 95% CI: -2.67--1.82, p < 0.001), and low- (ß = -4.05, 95% CI: -4.59--3.51, p < 0.001) income countries had lower vaccination coverage. Vaccination policies mediated 14.6% and 15.6% of the effect in upper-middle- (ß = -0.21, 95% CI: -0.39--0.03, p = 0.020) and lower-middle- (ß = -0.35, 95% CI: -0.56--0.13, p = 0.002) income countries, respectively, whereas the mediation effect was not significant in low-income countries (ß = -0.21, 95% CI: -0.43-0.01, p = 0.062). The results were similar after adjusting for demographic structure and underlying health conditions. Income disparity remains an important cause of vaccine inequity, and the tendency toward "vaccine nationalism" restricts the functioning of the global vaccine allocation framework. Stronger mechanisms are needed to foster countries' political will to promote vaccine equity.

SARS-CoV-2: from its discovery to genome structure, transcription, and replication.

SARS-CoV-2 is an extremely contagious respiratory virus causing adult atypical pneumonia COVID-19 with severe acute respiratory syndrome (SARS). SARS-CoV-2 has a single-stranded, positive-sense RNA (+RNA) genome of ~ 29.9 kb and exhibits significant genetic shift from different isolates. After entering the susceptible cells expressing both ACE2 and TMPRSS2, the SARS-CoV-2 genome directly functions as an mRNA to translate two polyproteins from the ORF1a and ORF1b region, which are cleaved by two viral proteases into sixteen non-structural proteins (nsp1-16) to initiate viral genome replication and transcription. The SARS-CoV-2 genome also encodes four structural (S, E, M and N) and up to six accessory (3a, 6, 7a, 7b, 8, and 9b) proteins, but their translation requires newly synthesized individual subgenomic RNAs (sgRNA) in the infected cells. Synthesis of the full-length viral genomic RNA (gRNA) and sgRNAs are conducted inside double-membrane vesicles (DMVs) by the viral replication and transcription complex (RTC), which comprises nsp7, nsp8, nsp9, nsp12, nsp13 and a short RNA primer. To produce sgRNAs, RTC starts RNA synthesis from the highly structured gRNA 3' end and switches template at various transcription regulatory sequence (TRSB) sites along the gRNA body probably mediated by a long-distance RNA-RNA interaction. The TRS motif in the gRNA 5' leader (TRSL) is responsible for the RNA-RNA interaction with the TRSB upstream of each ORF and skipping of the viral genome in between them to produce individual sgRNAs. Abundance of individual sgRNAs and viral gRNA synthesized in the infected cells depend on the location and read-through efficiency of each TRSB. Although more studies are needed, the unprecedented COVID-19 pandemic has taught the world a painful lesson that is to invest and proactively prepare future emergence of other types of coronaviruses and any other possible biological horrors.

Leveraging the Public Health Emergency Operation Center (PHEOC) for pandemic response: opportunities and challenges.

Public Health Emergency Operation Center (PHEOC) was conceptualized and established for coordinating information and resources towards goal-oriented response in large scale public health emergency. Yet, the activities undertaken by PHEOCs and their intended goals have not been fully optimized in current scenario. This paper revisited the collective efforts invested in PHEOC conceptualization and development, identified the opportunities and challenges in compliance with standards and framework, demonstrated the accountability of PHEOC network, thereby promoted best practice guidance for global public health emergency preparedness and response. This review will help navigate emergency response complexities leveraging PHEOC partnerships and advance the ability to detect and respond to public health emergencies in low resource settings. The review shows that the information on how to adapt best practice guidance to local circumstances could incentivize the full implementation of prevention, early detection and response to outbreaks. Identifying and correcting deficiencies in effectiveness evaluation will provide the basis for continuous PHEOC improvement. With the gradually reopening economies and public services in some countries, there is an urgent need to emphasize and validate the collective efforts undertaken by PHEOCs for tackling the COVID-19 pandemic.

A stepped wedge cluster randomized control trial to evaluate the implementation and effectiveness of optimized initiatives in improving quality of care for ST segment elevation myocardial infarction in response to the COVID-19 outbreak.

BACKGROUND: The National Chest Pain Center Accreditation Program (CHANGE) is the first hospital-based, multifaceted, nationwide quality improvement (QI) initiative, to monitor and improve the quality of the ST segment elevation myocardial infarction (STEMI) care in China. The QI initiatives, as implementation strategies, include a bundle of evidence-based interventions adapted for implementation in China. During the pandemic of coronavirus disease 2019 (COVID-19), fear of infection with severe acute respiratory syndrome coronavirus 2, national lockdowns, and altered health care priorities have highlighted the program's importance in improving STEMI care quality. This study aims to minimize the adverse impact of the COVID-19 pandemic on the quality of STEMI care, by developing interventions that optimize the QI initiatives, implementing and evaluating the optimized QI initiatives, and developing scale-up activities of the optimized QI initiatives in response to COVID-19 and other public health emergencies. METHODS: A stepped wedge cluster randomized control trial will be conducted in three selected cities of China: Wuhan, Suzhou, and Shenzhen. Two districts have been randomly selected in each city, yielding a total of 24 registered hospitals. This study will conduct a rollout in these hospitals every 3 months. The 24 hospitals will be randomly assigned to four clusters, and each cluster will commence the intervention (optimized QI initiatives) at one of the four steps. We will conduct hospital-based assessments, questionnaire surveys among health care providers, community-based household surveys, and key informant interviews during the trial. All outcome measures will be organized using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework, including implementation outcomes, service outcomes (e.g., treatment time), and patient outcomes (e.g., in-hospital mortality and 1-year complication). The Consolidated Framework for Implementation Research framework will be used to identify factors that influence implementation of the optimized QI interventions. DISCUSSION: The study findings could be translated into a systematic solution to implementing QI initiatives in response to COVID-19 and future potential major public health emergencies. Such actionable knowledge is critical for implementors of scale-up activities in low- and middle-income settings. TRIAL REGISTRATION: ChiCTR 2100043319 . Registered on 10 February 2021.