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.

Protective effect of ursodeoxycholic acid on COVID-19 in patients with chronic liver disease.

Objective: Ursodeoxycholic acid (UDCA) may reduce susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by downregulating angiotensin-converting enzyme 2 (ACE2), based on recent experimental investigation. This study aimed to determine the potential protective effect of UDCA against SARS-CoV-2 infection in patients with chronic liver disease. Methods: Patients with chronic liver disease receiving UDCA (taking UDCA ≥1 month) at Beijing Ditan Hospital between January 2022 and December 2022 were consecutively enrolled. These patients were matched in a 1:1 ratio to those with liver disease not receiving UDCA during the same period by using a propensity score matching analysis with nearest neighbor matching algorithm. We conducted a phone survey of coronavirus disease 2019 (COVID-19) infection during the early phase of the pandemic liberation (from 15 December 2022 to 15 January 2023). The risk of COVID-19 was compared in two matched cohorts of 225 UDCA users and 225 non-UDCA users based on patient self-report. Results: In the adjusted analysis, the control group was superior to the UDCA group in COVID-19 vaccination rates and liver function indicators, including γ-glutamyl transpeptidase and alkaline phosphatase (p < 0.05). UDCA was associated with a lower incidence of SARS-CoV-2 infection (UDCA 85.3% vs. control 94.2%, p = 0.002), more mild cases (80.0% vs. 72.0%, p = 0.047), and shorter median time from infection to recovery (5 vs. 7 days, p < 0.001). Logistic regression analysis showed that UDCA was a significant protective factor against COVID-19 infection (OR: 0.32, 95%CI: 0.16-0.64, p = 0.001). Furthermore, diabetes mellitus (OR: 2.48, 95%CI: 1.11-5.54, p = 0.027) and moderate/severe infection (OR: 8.94, 95%CI: 1.07-74.61, p = 0.043) were more likely to prolong the time from infection to recovery. Conclusion: UDCA therapy may be beneficial in reducing COVID-19 infection risk, alleviating symptoms, and shortening the recovery time in patients with chronic liver disease. However, it should be emphasized that the conclusions were based on patient self-report rather than classical COVID-19 detection by experimental investigations. Further large clinical and experimental studies are needed to validate these findings.

Recent development of surface-enhanced Raman scattering for biosensing.

Surface-Enhanced Raman Scattering (SERS) technology, as a powerful tool to identify molecular species by collecting molecular spectral signals at the single-molecule level, has achieved substantial progresses in the fields of environmental science, medical diagnosis, food safety, and biological analysis. As deepening research is delved into SERS sensing, more and more high-performance or multifunctional SERS substrate materials emerge, which are expected to push Raman sensing into more application fields. Especially in the field of biological analysis, intrinsic and extrinsic SERS sensing schemes have been widely used and explored due to their fast, sensitive and reliable advantages. Herein, recent developments of SERS substrates and their applications in biomolecular detection (SARS-CoV-2 virus, tumor etc.), biological imaging and pesticide detection are summarized. The SERS concepts (including its basic theory and sensing mechanism) and the important strategies (extending from nanomaterials with tunable shapes and nanostructures to surface bio-functionalization by modifying affinity groups or specific biomolecules) for improving SERS biosensing performance are comprehensively discussed. For data analysis and identification, the applications of machine learning methods and software acquisition sources in SERS biosensing and diagnosing are discussed in detail. In conclusion, the challenges and perspectives of SERS biosensing in the future are presented.

NPInter v5.0: ncRNA interaction database in a new era.

Noncoding RNAs (ncRNAs) play key regulatory roles in biological processes by interacting with other biomolecules. With the development of high-throughput sequencing and experimental technologies, extensive ncRNA interactions have been accumulated. Therefore, we updated the NPInter database to a fifth version to document these interactions. ncRNA interaction entries were doubled from 1 100 618 to 2 596 695 by manual literature mining and high-throughput data processing. We integrated global RNA-DNA interactions from iMARGI, ChAR-seq and GRID-seq, greatly expanding the number of RNA-DNA interactions (from 888 915 to 8 329 382). In addition, we collected different types of RNA interaction between SARS-CoV-2 virus and its host from recently published studies. Long noncoding RNA (lncRNA) expression specificity in different cell types from tumor single cell RNA-seq (scRNA-seq) data were also integrated to provide a cell-type level view of interactions. A new module named RBP was built to display the interactions of RNA-binding proteins with annotations of localization, binding domains and functions. In conclusion, NPInter v5.0 (http://bigdata.ibp.ac.cn/npinter5/) provides informative and valuable ncRNA interactions for biological researchers.

Futures hedging in crude oil markets: A trade-off between risk and return

Risk and return are two fundamentals that have an impact on an investor’s or hedger’s investing choices. Based on the proposed synchronous movement intensity index, this paper aims to improve the hedging performance by adjusting the model-driven hedge ratio and realize the trade-off between return and risk in futures hedging. First, without loss of generality, we forecast crude oil spot and futures volatility using 10 GARCH-type models, including three linear models and seven nonlinear models, to obtain the ex-ante hedging ratio under the minimum variance framework. Then, we develop a novel and tractable method to identify the market state based on the index of consistency intensity, in which the index portrays the synchronous degree of stock price movements in the energy sector. Last but not least, we propose the hedge ratio adjustment criteria based on the identified state, and adjust the ratio driven by GARCH-type models of futures in accordance with the market state. Empirical results of crude oil futures markets indicate that the proposed state-dependent hedging model is superior to the commonly used models in terms of three criteria including mean of returns, variance, and ratio of mean to variance of returns for measuring hedging effect. We apply the DM test to make a statistical inference and discover that while the mean and the ratio of mean to variance of returns are increasing, the variance and hedging effectiveness of the hedged portfolio based on the modified methods are not significantly affected. Furthermore, the superiority of the proposed method is robust to different market conditions, including significant rising or falling trends, large basis, and COVID-19 pandemic. We also test the robustness of the proposed method with respect to the baseline model, quantile, and evaluation window. Overall, this paper provides a more realistic approach for crude oil risk managers to hedge crude oil price risk, some corresponding implications are also concluded.

Evaluating the performance of futures hedging using factors-driven realized volatility

The complexity and uncertainty of the financial market mainly stem from the rich market internal transaction information and a wide range effect of external factors. To this end, this paper proposes the combination factors-driven forecasting method to predict realized volatilities of the CSI 300 index and index futures. Based on the volatilities predicted by the proposed method, we further evaluate the ex-ante hedging performance in comparison to the conventional HAR model as well as GARCH-type models. The empirical results indicate that the factors-driven realized volatility model significantly dominates the other commonly used models in terms of hedging effectiveness. Furthermore, the superiority of the proposed method is robust in different market conditions, including significant rising or falling and abnormal market fluctuations in the COVID-19 pandemic, and in different index markets. Therefore, this paper improves the prediction accuracy of volatility by integrating market internal transaction information and external factor information, and the proposed method in this paper can be used by investors to obtain an excellent hedging effect.

Recent Advances of Representative Optical Biosensors for Rapid and Sensitive Diagnostics of SARS-CoV-2.

The outbreak of Corona Virus Disease 2019 (COVID-19) has again emphasized the significance of developing rapid and highly sensitive testing tools for quickly identifying infected patients. Although the current reverse transcription polymerase chain reaction (RT-PCR) diagnostic techniques can satisfy the required sensitivity and specificity, the inherent disadvantages with time-consuming, sophisticated equipment and professional operators limit its application scopes. Compared with traditional detection techniques, optical biosensors based on nanomaterials/nanostructures have received much interest in the detection of SARS-CoV-2 due to the high sensitivity, high accuracy, and fast response. In this review, the research progress on optical biosensors in SARS-CoV-2 diagnosis, including fluorescence biosensors, colorimetric biosensors, Surface Enhancement Raman Scattering (SERS) biosensors, and Surface Plasmon Resonance (SPR) biosensors, was comprehensively summarized. Further, promising strategies to improve optical biosensors are also explained. Optical biosensors can not only realize the rapid detection of SARS-CoV-2 but also be applied to judge the infectiousness of the virus and guide the choice of SARS-CoV-2 vaccines, showing enormous potential to become point-of-care detection tools for the timely control of the pandemic.

Nasal Mucosa Exploited by SARS-CoV-2 for Replicating and Shedding during Reinfection.

Reinfection risk is a great concern with regard to the COVID-19 pandemic because a large proportion of the population has recovered from an initial infection, and previous reports found that primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques without viral presence and pathological injury; however, a high possibility for reinfection at the current stage of the pandemic has been proven. We found the reinfection of SARS-CoV-2 in Syrian hamsters with continuous viral shedding in the upper respiratory tracts and few injuries in the lung, and nasal mucosa was exploited by SARS-CoV-2 for replication and shedding during reinfection; meanwhile, no viral replication or enhanced damage was observed in the lower respiratory tracts. Consistent with the mild phenotype in the reinfection, increases in mRNA levels in cytokines and chemokines in the nasal mucosa but only slight increases in the lung were found. Notably, the high levels of neutralizing antibodies in serum could not prevent reinfection in hamsters but may play roles in benefitting the lung recovery and symptom relief of COVID-19. In summary, Syrian hamsters could be reinfected by SARS-CoV-2 with mild symptoms but with obvious viral shedding and replication, and both convalescent and vaccinated patients should be wary of the transmission and reinfection of SARS-CoV-2.

Longitudinal analyses reveal distinct immune response landscapes in lung and intestinal tissues from SARS-CoV-2-infected rhesus macaques.

The pathological and immune response of individuals with COVID-19 display different dynamics in lung and intestine. Here, we depict the single-cell transcriptional atlas of longitudinally collected lung and intestinal tissue samples from SARS-CoV-2-infected monkeys at 3 to 10 dpi. We find that intestinal enterocytes are degraded at 3 days post-infection but recovered rapidly, revealing that infection has mild effects on the intestine. Crucially, we observe suppression of the inflammatory response and tissue damage related to B-cell and Paneth cell accumulation in the intestines, although T cells are activated in the SARS-CoV-2 infection. Compared with that in the lung, the expression of interferon response-related genes is inhibited, and inflammatory factor secretion is reduced in the intestines. Our findings indicate an imbalance of immune dynamic in intestinal mucosa during SARS-CoV-2 infection, which may underlie ongoing rectal viral shedding and mild tissue damage.

High-sensitivity and point-of-care detection of SARS-CoV-2 from nasal and throat swabs by magnetic SERS biosensor.

The outbreak of COVID-19 caused by SARS-CoV-2 urges the development of rapidly and accurately diagnostic methods. Here, one high-sensitivity and point-of-care detection method based on magnetic SERS biosensor composed of Fe3O4-Au nanocomposite and Au nanoneedles array was developed to detect SARS-CoV-2 directly. Among, the magnetic Fe3O4-Au nanocomposite is applied to capture and separate virus from nasal and throat swabs and enhance the Raman signals of SARS-CoV-2. The magnetic SERS biosensor possessed high sensitivity by optimizing the Fe3O4-Au nanocomposite. More significantly, the on-site detection of inactivated SARS-CoV-2 virus was achieved based on the magnetic SERS biosensor with ultra-low limit of detection of 100 copies/mL during 15 mins. Furthermore, the contaminated nasal and throat swabs samples were identified by support vector machine, and the diagnostic accuracy of 100% was obtained. The magnetic SERS biosensor combined with support vector machine provides giant potential as the point-of-care detection tool for SARS-CoV-2.

Three doses of prototypic SARS-CoV-2 inactivated vaccine induce cross-protection against its variants of concern.

Variants are globally emerging very quickly following pandemic prototypic SARS-CoV-2. To evaluate the cross-protection of prototypic SARS-CoV-2 vaccine against its variants, we vaccinated rhesus monkeys with three doses of prototypic SARS-CoV-2 inactivated vaccine, followed by challenging with emerging SARS-CoV-2 variants of concern (VOCs). These vaccinated animals produced neutralizing antibodies against Alpha, Beta, Delta, and Omicron variants, although there were certain declinations of geometric mean titer (GMT) as compared with prototypic SARS-CoV-2. Of note, in vivo this prototypic vaccine not only reduced the viral loads in nasal, throat and anal swabs, pulmonary tissues, but also improved the pathological changes in the lung infected by variants of Alpha, Beta, and Delta. In summary, the prototypic SARS-CoV-2 inactivated vaccine in this study protected against VOCs to certain extension, which is of great significance for prevention and control of COVID-19.

Immunogenicity and protective efficacy of a recombinant protein subunit vaccine and an inactivated vaccine against SARS-CoV-2 variants in non-human primates.

Emerging SARS-CoV-2 variants and the gradually decreasing neutralizing antibodies over time post vaccination have led to an increase in incidents of breakthrough infection across the world. To investigate the potential protective effect of the recombinant protein subunit COVID-19 vaccine targeting receptor-binding domain (RBD) (PS-RBD) and whole inactivated virus particle vaccine (IV) against the variant strains, in this study, rhesus macaques were immunized with PS-RBD or IV vaccine, followed by a Beta variant (B.1.351) challenge. Although neutralizing activity against the Beta variant was reduced compared with that against the prototype, the decreased viral load in both upper and lower respiratory tracts, milder pathological changes, and downregulated inflammatory cytokine levels in lung tissues after challenge demonstrated that PS-RBD and IV still provided effective protection against the Beta variant in the macaque model. Furthermore, PS-RBD-induced macaque sera possessed general binding and neutralizing activity to Alpha, Beta, Delta, and Omicron variants in our study, though the neutralizing antibody (NAb) titers declined by varying degrees, demonstrating potential protection of PS-RBD against current circulating variants of concern (VOCs). Interestingly, although the IV vaccine-induced extremely low neutralizing antibody titers against the Beta variant, it still showed reduction for viral load and significantly alleviated pathological change. Other correlates of vaccine-induced protection (CoP) like antibody-dependent cellular cytotoxicity (ADCC) and immune memory were both confirmed to be existing in IV vaccinated group and possibly be involved in the protective mechanism.

Common Demand vs. Limited Supply-How to Serve the Global Fight against COVID-19 through Proper Supply of COVID-19 Vaccines.

Vaccination plays an essential role in the fight against Coronavirus Disease 2019 (COVID-19). The currently insufficient vaccine production capacity makes it difficult to balance supply with demand, which has led to a contradiction between command demand and limited supply. According to analysis based on game theory, the attributes of COVID-19 vaccines vary with supply strategies formulated by vaccine-producing countries. This means that vaccine-receiving countries can only be motivated to prepare operable vaccine distribution plans through the supply of COVID-19 vaccines as global public goods. The rational distribution of global public goods must be guaranteed by a global supply institution system. To that end, Elinor Ostrom's eight design principles provide a basis for designing such a global supply system. This paper proposes a nested institution solution for guaranteeing the global supply of COVID-19 vaccines based on the design principles, which include clearly defined boundaries, proportional equivalence between benefits and costs, collective-choice arrangements, monitoring, graduated sanctions, conflict-resolution mechanisms, minimal recognition of rights to organize, and nested enterprises. To win this global fight against COVID-19, COVID-19 vaccines must not only be treated as global public goods, but countries must also be urged to coordinate cooperation in global institutional design, thus ensuring that COVID-19 vaccines can truly benefit all mankind.

How did we protect ourselves during intubation for a COVID-19 patient in the context of PPE shortage?

Beginning in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly resulted in a worldwide pandemic. Many patients with coronavirus disease-19 (COVID-19) require invasive ventilation due to severe respiratory failure. However, many medical hospitals experienced shortages of personal protective equipment, increasing the risk of healthcare workers contracting an infection. However, we report a case of acute respiratory distress syndrome during the early stage of COVID-19 treated at a university hospital outside of Wuhan, China. We described the optimization of healthcare worker personal protection and a procedure for airway management in the context of insufficient personal protective equipment. This report may provide a reference for resource-limited settings in low- and middle-income countries, even countries where healthcare systems have been overwhelmed by the pandemic.

Estimating the Effects of the COVID-19 Outbreak on the Reductions in Tuberculosis Cases and the Epidemiological Trends in China: A Causal Impact Analysis.

OBJECTIVE: COVID-19 may have a demonstrable influence on disease patterns. However, it remained unknown how tuberculosis (TB) epidemics are impacted by the COVID-19 outbreak. The purposes of this study are to evaluate the impacts of the COVID-19 outbreak on the decreases in the TB case notifications and to forecast the epidemiological trends in China. METHODS: The monthly TB incidents from January 2005 to December 2020 were taken. Then, we investigated the causal impacts of the COVID-19 pandemic on the TB case reductions using intervention analysis under the Bayesian structural time series (BSTS) method. Next, we split the observed values into different training and testing horizons to validate the forecasting performance of the BSTS method. RESULTS: The TB incidence was falling during 2005-2020, with an average annual percentage change of -3.186 (95% confidence interval [CI] -4.083 to -2.281), and showed a peak in March-April and a trough in January-February per year. The BSTS method assessed a monthly average reduction of 14% (95% CI 3.8% to 24%) in the TB case notifications from January-December 2020 owing to COVID-19 (probability of causal effect=99.684%, P=0.003), and this method generated a highly accurate forecast for all the testing horizons considering the small forecasting error rates and estimated a continued downward trend from 2021 to 2035 (annual percentage change =-2.869, 95% CI -3.056 to -2.681). CONCLUSION: COVID-19 can cause medium- and longer-term consequences for the TB epidemics and the BSTS model has the potential to forecast the epidemiological trends of the TB incidence, which can be recommended as an automated application for public health policymaking in China. Considering the slow downward trend in the TB incidence, additional measures are required to accelerate the progress of the End TB Strategy.

Estimating the Long-Term Epidemiological Trends and Seasonality of Hemorrhagic Fever with Renal Syndrome in China.

OBJECTIVE: We aim to examine the adequacy of an innovation state-space modeling framework (called TBATS) in forecasting the long-term epidemic seasonality and trends of hemorrhagic fever with renal syndrome (HFRS). METHODS: The HFRS morbidity data from January 1995 to December 2020 were taken, and subsequently, the data were split into six different training and testing segments (including 12, 24, 36, 60, 84, and 108 holdout monthly data) to investigate its predictive ability of the TBATS method, and its forecasting performance was compared with the seasonal autoregressive integrated moving average (SARIMA). RESULTS: The TBATS (0.27, {0,0}, -, {<12,4>}) and SARIMA (0,1,(1,3))(0,1,1)12 were selected as the best TBATS and SARIMA methods, respectively, for the 12-step ahead prediction. The mean absolute deviation, root mean square error, mean absolute percentage error, mean error rate, and root mean square percentage error were 91.799, 14.772, 123.653, 0.129, and 0.193, respectively, for the preferred TBATS method and were 144.734, 25.049, 161.671, 0.203, and 0.296, respectively, for the preferred SARIMA method. Likewise, for the 24-, 36-, 60-, 84-, and 108-step ahead predictions, the preferred TBATS methods produced smaller forecasting errors over the best SARIMA methods. Further validations also suggested that the TBATS model outperformed the Error-Trend-Seasonal framework, with little exception. HFRS had dual seasonal behaviors, peaking in May-June and November-December. Overall a notable decrease in the HFRS morbidity was seen during the study period (average annual percentage change=-6.767, 95% confidence intervals: -10.592 to -2.778), and yet different stages had different variation trends. Besides, the TBATS model predicted a plateau in the HFRS morbidity in the next ten years. CONCLUSION: The TBATS approach outperforms the SARIMA approach in estimating the long-term epidemic seasonality and trends of HFRS, which is capable of being deemed as a promising alternative to help stakeholders to inform future preventive policy or practical solutions to tackle the evolving scenarios.

Stressors Among Chinese Frontline Health Care Workers Exposed to COVID-19 and Associated Mental Health Outcomes.

The current study aimed to identify the main stressors inherent to caring for patients with coronavirus disease 2019 (COVID-19) and associated mental health outcomes among frontline health care workers. Data were collected via an online questionnaire from 651 frontline health care workers providing direct medical services for patients with suspected or confirmed COVID-19. Participants reported the stressors inherent to caring for patients with COVID-19, including depression, anxiety, and insomnia. Data were analyzed using descriptive statistics and multivariable logistic regression analysis. The most common stressors were "Worry about being negligent and endangering coworkers" (76.2%), "Worry about getting infected" (74.7%), and "Protective gear causing physical discomfort" (73.6%). "Conflict between duty and safety" and "Protective gear causing physical discomfort" were linked to high risk of depression, anxiety, and insomnia. Findings suggest that frontline health care workers may develop adverse mental health outcomes in the face of certain stressors, requiring targeted interventions. [Journal of Psychosocial Nursing and Mental Health Services, 60(1), 17-22.].

Psychological Distress and Trust in University Management Among International Students During the COVID-19 Pandemic.

Since the end of 2019, the outbreak of the COVID-19 pandemic has engendered widespread fear and anxiety across China. Nearly half a million international students pursuing their studies in Chinese universities have also been exposed to the psychological distress triggered by the unfolding crisis. In addition to government and medical institutions' efforts, universities have also endeavored to mitigate concerns among these students under quarantine on campus by providing reliable information as well as medical, monetary, and emotional support. In this study, international students' trust in university management teams and its role in remediating their anxieties were evaluated using an online survey conducted after 10 days of the lockdown of Wuhan, China. The empirical analysis incorporates quantitative data from 180 international students. Ordinary least squares regression and probit regression were used in the analysis with the non-robust and robust models. The study found students' perception of trust in university management to be negatively associated with their anxiety levels. Additionally, having trust in university management was found to positively influence students' commitment to the self-quarantine guidelines. These results reinforce the important role of universities and their relationship with international students during public health emergencies.

Self-Assembling Nanoparticle Vaccines Displaying the Receptor Binding Domain of SARS-CoV-2 Elicit Robust Protective Immune Responses in Rhesus Monkeys.

SARS-CoV-2 caused the COVID-19 pandemic that lasted for more than a year. Globally, there is an urgent need to use safe and effective vaccines for immunization to achieve comprehensive protection against SARS-CoV-2 infection. Focusing on developing a rapid vaccine platform with significant immunogenicity as well as broad and high protection efficiency, we designed a SARS-CoV-2 spike protein receptor-binding domain (RBD) displayed on self-assembled ferritin nanoparticles. In a 293i cells eukaryotic expression system, this candidate vaccine was prepared and purified. After rhesus monkeys are immunized with 20 µg of RBD-ferritin nanoparticles three times, the vaccine can elicit specific humoral immunity and T cell immune response, and the neutralizing antibodies can cross-neutralize four SARS-CoV-2 strains from different sources. In the challenge protection test, after nasal infection with 2 × 105 CCID50 SARS-CoV-2 virus, compared with unimmunized control animals, virus replication in the vaccine-immunized rhesus monkeys was significantly inhibited, and respiratory pathology observations also showed only slight pathological damage. These analyses will benefit the immunization program of the RBD-ferritin nanoparticle vaccine in the clinical trial design and the platform construction to present a specific antigen domain in the self-assembling nanoparticle in a short time to harvest stable, safe, and effective vaccine candidates for new SARS-CoV-2 isolates.