Sensitive Detection of SARS-CoV-2 Spike Protein based on Electrochemical Impedance Spectroscopy of Fe3O4@SiO2-Au/GCE Biosensor

Highly contagious COVID-19 disease is caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which poses a serious threat to global public health. Therefore, the development of a fast and reliable method for the detection of SARS-CoV-2 is an urgent research need. The Fe3O4@SiO2-Au is enriched with a variety of functional groups, which can be used to fabricate a sensitive electrochemical biosensor by biofunctionalization with angiotensin-converting enzyme 2 (ACE2). Accordingly, we developed a novel electrochemical sensor by chemically modifying a glassy carbon electrode (GCE) with Fe3O4@SiO2-Au nanocomposites (hereafter Fe3O4@SiO2-Au/GCE) for the rapid detection of S-protein spiked SARS-CoV-2 by electrochemical impedance spectroscopy (EIS). The new electrochemical sensor has a low limit detection (viz., 4.78 pg/mL) and a wide linear dynamic range (viz., 0.1 ng/mL to 10 μg/mL) for detecting the EIS response signal of S-protein. The robust Fe3O4@SiO2-Au/GCE biosensor has high selectivity, stability, and reproducibility for the detection of S-protein with good recovery of saliva samples.

Amino‐terminated hyperbranched polymer functionalized graphene oxide with in situ trapped silver nanoparticles for high‐performance antibacterial nonwoven fabric

Antibacterial fabric with high thermal stability and mechanical strength is important for personalized protection, especially under the background of coronavirus pandemic (COVID‐19). This paper presents a facile approach toward high‐efficient antibacterial polypropylene spunbonded nonwoven fabrics (SNFs), which are decorated by a composite of graphene oxide embedded with silver nanoparticles (AgNPs/GO) through dip‐coating and in situ reduction effect of pre‐introduced amino‐terminated hyperbranched polymer (HBP‐NH2). Typically, HBP‐NH2 was grafted onto the GO nanosheets, then silver ions were trapped and self‐reduced by the HBP‐NH2 to generate silver nanoparticles decorated GO. The produced AgNPs are uniformly dispersed on the GO with a size of 13 nm. As an antibacterial coating, the Ag/GO composite could tightly wrap the SNFs fibers through the dip‐padding method, capable of enhancing the thermal stability and mechanical property of SNFs. The treated SNFs exhibited excellent antibacterial activities (~99.9%) against both Echerisia coli and Staphylococcus aureus, promising important potential for biomedical and personal protection applications.

The S protein of a novel recombinant PEDV strain promotes the infectivity and pathogenicity of PEDV in mid-west China.

Porcine epidemic diarrhoea virus (PEDV) is an emerging and re-emerging swine enterovirus that causes highly contagious diarrhoea and mortality in piglets. To better understand the current prevalence of PEDV in mid-west China, and to find out the reason for the re-emergence of PEDV from the viral genomic characteristics. Herein, we firstly investigated epidemiology of PEDV in mid-west China from 2019 to 2020. A total of 62.23% (257/413) of diarrhoea samples were positive for PEDV, and the PEDV-positive cases were mainly detected in winter. Then, we selected the SXSL strain as a representative strain to study the genetic and pathogenic characterization of PEDV pandemic strains in mid-west China. The recombination analysis showed that SXSL strain was a recombinant strain, and the major and minor parent strains of the recombination are CH/SCZJ/2018 strain and GDS48 strain, respectively. Complete genome sequencing and homology analysis showed that the S protein of SXSL strain contained multiple amino acid indels and mutations compared to the PEDV representative strains. Furthermore, we evaluated the effect of S protein on the infectivity and pathogenicity of PEDV by the PEDV reverse genetics system, and results showed that SXSL S protein increased the infectivity and pathogenicity of chimeric virus. Overall, our findings provided important information for understanding the roles of S protein in the prevalence of PEDV in mid-west China and developing vaccines based on PEDV pandemic strains.

Discovery of inhibitors against SARS-CoV-2 main protease using fragment-based drug design.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 2019 (COVID-19), in which the main protease (Mpro) plays an important role in the virus's life cycle. In this work, two representative peptide inhibitors (11a and PF-07321332) were selected, and their interaction mechanisms of non-covalently bound with Mpro were firstly investigated by means of molecular dynamical simulation. Then, using the fragment-based drug design method, some fragments from the existing SARS-CoV and SARS-CoV-2 inhibitors were selected to replace the original P2 and P3 fragments, resulting in some new molecules. Among them, two molecules (O-74 and N-98) were confirmed by molecular docking and molecular dynamics simulation, and ADMET properties prediction was employed for further verification. The results shown that they presented excellent activity and physicochemical properties, and had the potential to be new inhibitors for SARS-CoV-2 main protease.

Inspiration of SARS-CoV-2 envelope protein mutations on pathogenicity of Omicron XBB (preprint)

Predicting pathogenicity of Omicron sub-variants is critical for assessing disease dynamics and developing public health strategies. As an important virulence factor, SARS-CoV-2 envelope protein (2-E) causes cell death and acute respiratory distress syndrome (ARDS)-like pathological damages. Evaluation of 2-E mutations might offer clues to pathogenicity forecast. Here, the frequency and cell lethality of 92 mutations of 2-E in five early "variants of concern" (VOCs, Alpha, Beta, Gamma, Delta, and Omicron BA.1, BA.2, BA.3, BA.4, and BA.5) were analyzed, which could be divided into three classes. Most (87) mutations belong to Class I, no obvious frequency changes. Class II consists of 2 mutations, exhibiting enhanced cell lethality but decreased frequency. The rest 3 mutations in Class III were characterized by attenuated cell lethality and increased frequency. Remarkably, the Class II mutations are always observed in the VOCs with high disease severity while the Class III mutations are highly conserved in the VOCs with weakened pathogenicity. For example, P71L, the most lethal mutation, dropped to nearly 0.00% in the milder Omicrons from 99.12% in Beta, while the less lethal mutation T9I, sharply increased to 99.70% in BA.1 and is highly conserved in BA.1-5. Accordingly, we proposed that some key 2-E mutations are pathogenicity markers of the virus. Notably, the highly contagious Omicron XBB retained T9I also. In addition, XBB gained a new dominant-negative mutation T11A with frequency 90.52%, exhibiting reduced cell lethality, cytokine induction and viral production capabilities in vitro, and particularly weakened lung damages in mice. No mutations with enhanced cell lethality were observed in XBB. These clues imply a further weakened pathogenicity of XBB among Omicron sub-variants.

Is indoor and outdoor greenery associated with fewer depressive symptoms during COVID-19 lockdowns? A mechanistic study in Shanghai, China.

Increasing numbers of studies have observed that indoor and outdoor greenery are associated with fewer depressive symptoms during COVID-19 lockdowns. However, most of these studies examined direct associations without sufficient attention to underlying pathways. Furthermore, few studies have combined different types of indoor and outdoor greenery to examine their effects on the alleviation of depressive symptoms. The present study hypothesized that indoor and outdoor exposure to greenery increased the perceived restorativeness of home environments, which, in turn, reduced loneliness, COVID-related fears, and, ultimately, depressive symptoms. To test our hypotheses, we conducted an online survey with 386 respondents in Shanghai, China, from April to May 2022, which corresponded to strict citywide lockdowns that resulted from the outbreak of the Omicron variant. Indoor greenery measures included the number of house plants, gardening activities, and digital nature exposure as well as semantic image segmentation applied to photographs from the most viewed windows to quantify indoor exposure to outdoor trees and grass. Outdoor greenery measures included total vegetative cover (normalized difference vegetation index [NDVI]) within a 300 m radius from the home and perceived quality of the community's greenery. Associations between greenery and depressive symptoms/clinical levels of depression, as measured by the Patient Health Questionnaire-9 (PHQ-9), were examined using generalized linear and logistic regression models. Structural equation modeling (SEM) was used to test pathways between greenery exposure, restorativeness, loneliness, fear of COVID-19, and depressive symptoms. The results showed that: 1) indoor and outdoor greenery were associated with fewer depressive symptoms; 2) greenery could increase the restorativeness of the home environment, which, in turn, was associated with fewer COVID-related mental stressors (i.e., loneliness and fear of COVID-19), and ultimately depressive symptoms; and 3) gender, education, and income did not modify associations between greenery and depressive symptoms. These findings are among the first to combine objective and subjective measures of greenery within and outside of the home and document their effects on mental health during lockdowns. Comprehensive enhancements of greenery in living environments could be nature-based solutions for mitigating COVID-19 related mental stressors.

A System Dynamics Model of Multi-Airport Logistics System under the Impact of COVID-19: A Case of Jing-Jin-Ji Multi-Airport System in China

The development of a multi-airport logistics system (MLS) is closely linked to factors such as regional economy, international and domestic trade, competitive synergies between airports, and the impact of unforeseen events such as the COVID-19 outbreak. There are various causal relationships and feedback loops within the MLS, and it is always in a dynamic state of change, so it is ideal to use a system dynamics model to depict the MLS. Taking the Jing-Jin-Ji MLS as an example, a system dynamics model consisting of an economy subsystem, a trade subsystem, and an airport cluster subsystem is constructed, and the sustainable development of the MLS is studied by simulating three pandemic scenarios with different impact levels. At the same time, different policy simulations and sensitivity analyses are used to find effective strategies to enhance the sustainable development of the Jing-Jin-Ji MLS. The results can provide an effective method for forecasting air cargo volumes in the MLS under the COVID-19 pandemic and provide a basis for the relevant departments to formulate policies for the development of the MLS.

Big Data Enabled the Development of Public Sports Health Emergency Corpus: Taking MACPHE as an Example.

This study aims to make public sports health emergency corpus as a way to deal with public health emergency such as COVID-19, reducing the losses affected by an illness or health condition that has occurred frequently in recent years. On this basis, this paper analyzes the research status of emergency language services at home and abroad, discusses the significance and principles of Multimodal Aligned Corpus Public Health Emergency (shorted for MACPHE) construction, and develops technical processing paths and building procedures for MACPHE. Finally, it was emphasized that the construction of MACPHE and emergency language resources are important parts of the national language service capacity. Furthermore, on the basis of big data, a modal architecture of MACPHE was given and analyzed in the field of public health service.

The role of different transportation modes in China's national economy: An input–output analysis

This study aims to analyse the role of different transportation modes in China's national economy and provide a reference for transportation policy. To this end, we use input–output analysis to evaluate the inter-industry linkage effect, production-inducing effect, supply shortage effect, and employment-inducing effect of five transportation modes (rail, road, water, air, and pipeline) in China from 2007 to 2020. The contributions of these different transportation modes to China's economy and their evolution are quantitatively investigated. The results reveal that the forward linkage effect of road transportation in China is the highest and shows an upward trend. The backward linkage effect of air transportation is the highest but shows a declining trend while the supply shortage effect of pipeline transportation is the highest. COVID-19 had a significant effect on transportation in 2020, with only rail and water maintaining growth in their production-inducing and supply shortage effects on the economy. Meanwhile, road, air, and pipeline transportation all showed varying degrees of decline in their contributions to the economy in 2020. Regarding employment, the employment-inducing effect multipliers of the five transportation modes are all gradually decreasing, showing that the transportation industry is shifting from a labour-intensive orientation toward a technology-intensive one. These results have significance for understanding the economic contribution and evolution of China's transportation industries. They can provide a reference for related policy formulation and for improving transportation management.

The More Natural the Window, the Healthier the Isolated People-A Pathway Analysis in Xi'an, China, during the COVID-19 Pandemic.

This study explores how windows with a green view might affect the mental health (i.e., depressive/anxiety symptoms) of home-isolated populations. An online survey was conducted among 508 adults isolated under government quarantine policies for COVID-19 emergency pandemic control between 10 and 20 January 2022 in Xi'an, China. Structural equation modeling was employed to identify the pathways from green view through windows to isolated people's depressive/anxiety symptoms. The relative frequency of plant/water exposure through windows was associated with fewer depressive/anxiety symptoms. Home-isolated people during COVID-19 reported better mental health when they were exposed to more natural settings. These findings could inspire public health authorities to adopt nature-based solutions to mitigate the adverse mental health consequences of isolated populations during the pandemic.

Changing characteristics of the industrial correlation and economic contribution of air transport in China: An input–output analysis

To investigate changing characteristics of the industrial correlation and economic contribution of air transport in China in different periods, the industry linkage effect and the industry ripple effect of air transport were assessed based on an input–output analysis over the period 2007–2020. Taking the air transport sector as an exogenous variable, the production-inducing effect and the supply shortage effect were calculated, and their changing characteristics were analyzed. The result shows that China's air transport industry is gradually changing its close linkages with secondary industries, and is instead strengthening its interaction with some tertiary industries. Before the COVID-19 outbreak in 2020, the production-inducing multiplier of air transport was trending downwards and the supply shortage multiplier was trending upwards. After the COVID-19 outbreak, China's air transport industry was hit hard and both the production-inducing effect and the supply shortage effect decreased significantly. The results of this paper are of great significance in the evaluation of the industrial correlation and economic contribution of air transport and can serve as a reference for formulating policies and improving the management of the air transport industry.

Innovative Application of SERS in Food Quality and Safety: A Brief Review of Recent Trends.

Innovative application of surface-enhanced Raman scattering (SERS) for rapid and nondestructive analyses has been gaining increasing attention for food safety and quality. SERS is based on inelastic scattering enhancement from molecules located near nanostructured metallic surfaces and has many advantages, including ultrasensitive detection and simple protocols. Current SERS-based quality analysis contains composition and structural information that can be used to establish an electronic file of the food samples for subsequent reference and traceability. SERS is a promising technique for the detection of chemical, biological, and harmful metal contaminants, as well as for food poisoning, and allergen identification using label-free or label-based methods, based on metals and semiconductors as substrates. Recognition elements, including immunosensors, aptasensors, or molecularly imprinted polymers, can be linked to SERS tags to specifically identify targeted contaminants and perform authenticity analysis. Herein, we highlight recent studies on SERS-based quality and safety analysis for different foods categories spanning the whole food chain, 'from farm to table' and processing, genetically modified food, and novel foods. Moreover, SERS detection is a potential tool that ensures food safety in an easy, rapid, reliable, and nondestructive manner during the COVID-19 pandemic.

Low molecular weight heparin reduces arterial blood lactic acid content and increases estimated glomerular filtration rate in patients with moderate Covid-19 pneumonia.

BACKGROUND: Coronavirus disease 2019 (Covid-19) remains a serious health threat worldwide. We aimed to investigate whether low molecular weight heparin (LMWH) can promote organ function recovery in moderate Covid-19 pneumonia patients. METHODS: We initiated an LMWH protocol in Covid-19 patients with increased D-dimer, body mass index >30 kg/m2 or a history of diabetes from January 18, 2020 at Shanghai Public Health Clinical Center. In this retrospective study, we assigned moderate Covid- 19 pneumonia patients admitted between January 18th and April 18, 2020 receiving the LMWH protocol to the LMWH group. Moderate patients who met the inclusion criteria but did not receive LMWH protocol were included in the control group by 1:2 propensity score matching. General clinical information, indicators for renal function, arterial blood gas analyses, arterial blood lactic acid content (mmol/L), and coagulation indexes at 0 day, 3 days, 7 days, and 11 days after admission were recorded and compared between the two groups. RESULTS: There were 41 patients in the LMWH group and 82 patients in the control group. General information in both groups were similar. Compared to the control group, the arterial blood lactic acid content (mmol/L) at day 11 (1.3 [1.1, 1.7] vs. 1.2 [0.9, 1.3], P = 0.016) was reduced in the LMWH group. The estimated glomerular filtration rate (eGFR) in the LMWH group was higher than that in the control group at day 7 (108.54 [89.11, 128.17] vs. 116.85 [103.39, 133.47], P = 0.039) and day 11 (113.74 [94.49, 126.34] vs. 128.31 [112.75, 144, 12], P  = 0.003). The serum creatinine levels (Scr) in the LMWH group were lower than that in the control group at day 7 (62.13 [51.47, 77.64] vs. 55.49 [49.50, 65.75], P = 0.038) and day 11 (63.35 [50.17, 75.73] vs. 51.62 [44.62, 61.24], P = 0.005). CONCLUSIONS: LMWH treatment can reduce arterial blood lactic acid levels and improve eGFR in moderate Covid-19 pneumonia patients. Randomized controlled trials are warranted to further investigate this issue. TRIAL REGISTRATION: ChiCTR.org.cn, ChiCTR2000034796.

Defense of COVID-19 by Human Organoids.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has created an immense menace to public health worldwide, exerting huge effects on global economic and political conditions. Understanding the biology and pathogenesis mechanisms of this novel virus, in large parts, relies on optimal physiological models that allow replication and propagation of SARS-CoV-2. Human organoids, derived from stem cells, are three-dimensional cell cultures that recapitulate the cellular organization, transcriptional and epigenetic signatures of their counterpart organs. Recent studies have indicated their great values as experimental virology platforms, making human organoid an ideal tool for investigating host-pathogen interactions. Here, we summarize research developments for SARS-CoV-2 infection of various human organoids involved in multiple systems, including lung, liver, brain, intestine, kidney and blood vessel organoids. These studies help us reveal the pathogenesis mechanism of COVID-19, and facilitate the development of effective vaccines and drugs as well as other therapeutic regimes.

Risk of ischemic stroke in patients with COVID-19 infection: A systematic review and meta-analysis.

An ongoing global pandemic, the coronavirus disease 2019 is posing threat to people all over the world. The association between COVID-19 and the risk of ischemic stroke remains unclear. This study systematically reviewed published studies and conducted meta-analysis to evaluate the association between the risk of ischemic stroke and COVID-19. This study was conducted according to guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The protocol used in this study had been registered in the International Prospective Register of Systematic Reviews. EMBASE, PubMed, Cochrane Library and Web of Science were searched from 1st December 2019-19th February 2021. This systematic review and meta-analysis analysed the combined effect estimations based on odds ratios (OR) with the random-effects model. Four studies were screened from 31,634 participants including 171 COVID-19 positive patients with ischemic stroke were included. The mean age of COVID-19 positive patients with ischemic stroke was 69.45 years (Range: 63-77 years) and the male patients were 56%. Countries covered by these articles were USA, Italy and France. Three of the articles were retrospective cohort studies and one was prospective cohort study. Our analysis revealed that the risk of ischemic stroke (combined OR: 2.41; 95% CI: 1.08-5.38) was significantly increased. Four included studies were significantly heterogeneous (I2 = 75.2%, P = 0.007). Significant association between the risk of ischemic stroke and COVID-19 was observed in the North America group (combined OR: 2.90; 95% CI: 0.45-18.80, I2 = 89.60%, P = 0.002). This study found that the risk for ischemic stroke was increased in COVID-19 patients, especially in patients from North America. Further studies with larger sample sizes that include different ethnic populations are required to confirm our analysis.

Discovery of SARS-CoV-2-E channel inhibitors as antiviral candidates.

Lack of efficiency has been a major problem shared by all currently developed anti-SARS-CoV-2 therapies. Our previous study shows that SARS-CoV-2 structural envelope (2-E) protein forms a type of cation channel, and heterogeneously expression of 2-E channels causes host cell death. In this study we developed a cell-based high throughput screening (HTS) assay and used it to discover inhibitors against 2-E channels. Among 4376 compounds tested, 34 hits with cell protection activity were found. Followed by an anti-viral analysis, 15 compounds which could inhibit SARS-CoV-2 replication were identified. In electrophysiological experiments, three representatives showing inhibitory effect on 2-E channels were chosen for further characterization. Among them, proanthocyanidins directly bound to 2-E channel with binding affinity (KD) of 22.14 µM in surface plasmon resonance assay. Molecular modeling and docking analysis revealed that proanthocyanidins inserted into the pore of 2-E N-terminal vestibule acting as a channel blocker. Consistently, mutations of Glu 8 and Asn 15, two residues lining the proposed binding pocket, abolished the inhibitory effects of proanthocyanidins. The natural product proanthocyanidins are widely used as cosmetic, suggesting a potential of proanthocyanidins as disinfectant for external use. This study further demonstrates that 2-E channel is an effective antiviral drug target and provides a potential antiviral candidate against SARS-CoV-2.

Index and First-Generation Cases in a COVID-19 Outbreak - Jilin Province, China, 2021.

What is already known on this topic? Contact tracing and testing with isolated medical care of identified cases is a key strategy for interrupting chains of transmission of COVID-19 and reducing mortality associated with COVID-19. At the early phases of the COVID-19 pandemic, due to test capacity limitations, case finding often started from suspected cases. What is added by this report? The index patient infected 74 individuals who were close contacts that were identified through contact tracing, and exposed individuals were monitored in quarantine with daily polymerase chain reaction (PCR) testing. All individuals were asymptomatic initially, but all PCR-positive individuals eventually developed symptoms. Infectivity was documented up to 8 days before being confirmed as a symptomatic case, approximately 4 days before turning PCR positive. What are the implications for public health practice? During an outbreak, we suggest tracing close contacts from both PCR-positive individuals and suspected cases, rather than from suspected cases alone. Due to the long period of infectivity before turning PCR positive or developing symptoms, close contacts that had contact with a newly PCR positive case within 4 days should be judged as at risk of being infected; close contacts that had contact within 8 days of a newly symptomatic case should be judged as at risk being infected.

High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study.

Background: Coronavirus disease 2019 (COVID-19) pandemic is continuing to impact multiple countries worldwide and effective treatment options are still being developed. In this study, we investigate the potential of high-dose intravenous vitamin C (HDIVC) in the prevention of moderate COVID-19 disease aggravation. Methods: In this retrospective before-after case-matched clinical study, we compare the outcome and clinical courses of patients with moderate COVID-19 patients who were treated with an HDIVC protocol (intravenous injection of vitamin C, 100 mg/kg/day, 1 g/h, for 7 days from admission) during a one-month period (between March 18 and april 18, 2020, HDIVC group) with a control group treated without the HDIVC protocol during the preceding two months (January 18 to March 18, 2020). Patients in the two groups were matched in a 1:1 ratio according to age and gender. Results: The HDIVC and control groups each comprised 55 patients. For the primary outcomes, there was a significant difference in the number of patients that evolved from moderate to severe type between the two groups (HDIVC: 4/55 vs. control: 12/55, relative risk [RR] = 0.28 [0.08, 0.93], P = 0.03). Compared to the control group, there was a shorter duration of systemic inflammatory response syndrome (SIRS) (P = 0.0004) during the first week and lower SIRS occurrence (2/21 vs 10/22, P = 0.0086) on Day 7 (6-7 days after admission). In addition, HDIVC group had lower C-reactive protein levels (P = 0.005) and higher number of CD4+ T cells from Day 0 (on admission) to Day 7 (P = 0.04)." The levels of coagulation indicators, including activated partial thromboplastin time and D-dimer were also improved in the HDIVC compared to the control group on Day 7. Conclusion: HDIVC may be beneficial in limiting disease aggravation in the early stage of COVID-19 pneumonia, which may be related to its improvements on the inflammatory response, immune function and coagulation function. Further randomized controlled trials are required to augment these findings.