Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in our previous randomized, double-blind, placebo-controlled clinical trial (NCT04288102). METHODS: A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4 × 107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. Outcomes measured included: 6-min walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire (SF-36), COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, tumor markers, and MSC-related adverse events (AEs). FINDINGS: Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). At month 18, the general health score from the SF-36 was higher in the MSC group than in the placebo group (50.00 vs. 35.00, 95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.018). Total severity score of lung imaging and the titer of neutralizing antibodies were similar between the two groups at months 18 and 24. There was no difference in AEs or tumor markers at the 2-year follow-up between the two groups. INTERPRETATION: Long-term safety was observed for the COVID-19 patients who received MSC treatment. However, efficacy of MSC treatment was not significantly sustained through the end of the 2-year follow-up period. FUNDING: The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900, 2022YFC2304401), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRC-ID202105,413FZT6).

Analysis of risk correlations among stock markets during the COVID-19 pandemic.

The outbreak of the COVID-19 pandemic significantly negatively impacted the global economy and stock markets. This paper investigates the stock-market tail risks caused by the COVID-19 pandemic and how the pandemic affects the risk correlations among the stock markets worldwide. The conditional autoregressive value at risk (CAViaR) model is used to measure the tail risks of 28 selected stock markets. Furthermore, risk correlation networks are constructed to describe the risk correlations among stock markets during different periods. Through dynamic analysis of the risk correlations, the influence of the COVID-19 pandemic on stock markets worldwide is examined quantitatively. The results show the following: (i) The COVID-19 pandemic has caused significant tail risks in stock markets in most countries, while the stock markets of a few countries have been unaffected by the pandemic. (ii) The topology of risk correlation networks has become denser during the COVID-19 pandemic. The impact of the COVID-19 pandemic makes it easier for risk to transfer among stock markets. (iii) The increase in the closeness of the risk relationship between countries with lower economic correlation has become much higher than that between counties with higher economic correlation during the COVID-19 pandemic. For researchers and policy-makers, these findings reveal practical implications of the risk correlations among stock markets.

Dynamics of SARS-CoV-2 Antibody Responses up to 9 Months Post-Vaccination in Individuals with Previous SARS-CoV-2 Infection Receiving Inactivated Vaccines.

Humoral immunity confers protection against COVID-19. The longevity of antibody responses after receiving an inactivated vaccine in individuals with previous SARS-CoV-2 infection is unclear. Plasma samples were collected from 58 individuals with previous SARS-CoV-2 infection and 25 healthy donors (HDs) who had been vaccinated with an inactivated vaccine. The neutralizing antibodies (NAbs) and S1 domain-specific antibodies against the SARS-CoV-2 wild-type and Omicron strains and nucleoside protein (NP)-specific antibodies were measured using a chemiluminescent immunoassay. Statistical analysis was performed using clinical variables and antibodies at different timepoints after SARS-CoV-2 vaccination. NAbs targeting the wild-type or Omicron strain were detected in individuals with previous SARS-CoV-2 infection at 12 months after infection (wild-type: 81%, geometric mean (GM): 20.3 AU/mL; Omicron: 44%, GM: 9.4 AU/mL), and vaccination provided further enhancement of these antibody levels (wild-type: 98%, GM: 53.3 AU/mL; Omicron: 75%, GM: 27.8 AU/mL, at 3 months after vaccination), which were significantly higher than those in HDs receiving a third dose of inactivated vaccine (wild-type: 85%, GM: 33.6 AU/mL; Omicron: 45%, GM: 11.5 AU/mL). The level of NAbs in individuals with previous infection plateaued 6 months after vaccination, but the NAb levels in HDs declined continuously. NAb levels in individuals with previous infection at 3 months post-vaccination were strongly correlated with those at 6 months post-vaccination, and weakly correlated with those before vaccination. NAb levels declined substantially in most individuals, and the rate of antibody decay was negatively correlated with the neutrophil-to-lymphocyte ratio in the blood at discharge. These results suggest that the inactivated vaccine induced robust and durable NAb responses in individuals with previous infection up to 9 months after vaccination.

Fixing China's humanitarian aid architecture: what are the lessons from the European Union and the United States?

The global humanitarian situation has deteriorated drastically since the outbreak of COVID-19 and the Russian–Ukrainian war. The European Union and the United States are forerunners to providing global humanitarian aid, but China's visibility and role in global humanitarian affairs has significantly increased. Although China has been contributing more, its humanitarian aid concept remains vague, its aid mechanism is fragmented, and its approach to providing aid is rigid. These factors make China unprepared for tackling future humanitarian challenges. There are notable divergences in terms of concepts and mechanisms for and approaches to humanitarian aid among the European Union, the United States and China. Despite the pitfalls in the humanitarian aid architectures of the European Union and United States, China can learn from them to strive for an architecture that can help it aid more effectively. In particular, China should build coherence and consistency among aid concept, mechanism and approach, streamline aid mechanism, and give full play of non-governmental actors. [ABSTRACT FROM AUTHOR] Copyright of Third World Quarterly is the property of Routledge and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A potent, broadly protective vaccine against SARS-CoV-2 variants of concern.

Since the first outbreak in December 2019, SARS-CoV-2 has been constantly evolving and five variants have been classified as Variant of Concern (VOC) by the World Health Organization (WHO). These VOCs were found to enhance transmission and/or decrease neutralization capabilities of monoclonal antibodies and vaccine-induced antibodies. Here, we successfully designed and produced a recombinant COVID-19 vaccine in CHO cells at a high yield. The vaccine antigen contains four hot spot substitutions, K417N, E484K, N501Y and D614G, based on a prefusion-stabilized spike trimer of SARS-CoV-2 (S-6P) and formulated with an Alum/CpG 7909 dual adjuvant system. Results of immunogenicity studies showed that the variant vaccine elicited robust cross-neutralizing antibody responses against SARS-CoV-2 prototype (Wuhan) strain and all 5 VOCs. It further, stimulated a TH1 (T Helper type 1) cytokine profile and substantial CD4+ T cell responses in BALB/c mice and rhesus macaques were recorded. Protective efficacy of the vaccine candidate was evaluated in hamster and rhesus macaque models of SARS-CoV-2. In Golden Syrian hamsters challenged with Beta or Delta strains, the vaccine candidate reduced the viral loads in nasal turbinates and lung tissues, accompanied by significant weight gain and relieved inflammation in the lungs. In rhesus macaque challenged with prototype SARS-CoV-2, the vaccine candidate decreased viral shedding in throat, anal, blood swabs over time, reduced viral loads of bronchus and lung tissue, and effectively relieved the lung pathological inflammatory response. Together, our data demonstrated the broadly neutralizing activity and efficacy of the variant vaccine against both prototype and current VOCs of SARS-CoV-2, justifying further clinical development.

Characterization of RNA G-quadruplexes in porcine epidemic diarrhea virus genome and the antiviral activity of G-quadruplex ligands.

Porcine epidemic diarrhea virus (PEDV), an enteropathogenic coronavirus, has catastrophic impacts on the global pig industry. However, there are still no anti-PEDV drugs with accurate targets. G-quadruplexes (G4s) are non-canonical secondary structures formed within guanine-rich regions of DNA or RNA, and have attracted great attention as potential targets for antiviral strategy. In this study, we reported two putative G4-forming sequences (PQS) in S and Nsp5 genes of PEDV genome based on bioinformatic analysis, and identified that S-PQS and Nsp5-PQS were enabled to fold into G4 structure by using circular dichroism spectroscopy and fluorescence turn-on assay. Furthermore, we verified that both S-PQS and Nsp5-PQS PQS could form G4 structure in live cells by immunofluorescence microscopy. In addition, G4-specific compounds, such as TMPyP4 and PDS, could significantly inhibit transcription, translation and proliferation of PEDV in vitro. Importantly, these compounds exert antiviral activity at the post-entry step of PEDV infection cycle, by inhibiting viral genome replication and protein expression. Lastly, we demonstrated that TMPyP4 can inhibit reporter gene expression by targeting G4 structure in Nsp5. Taken together, these findings not only reinforce the presence of viral G-quadruplex sequences in PEDV genome but also provide new insights into developing novel antiviral drugs targeting PEDV RNA G-quadruplexes.

Efficacy of high-flow nasal oxygenation compared with laryngeal mask airway in children undergoing ambulatory oral surgery under deep sedation: A randomized controlled non-inferiority trial.

Background: High-flow nasal oxygenation (HFNO) has been suggested as an alternative oxygenation method during procedural sedation. This randomized, non-inferiority trial evaluated the safety and efficacy of HFNO compared with laryngeal mask airway (LMA) in pediatric ambulatory oral surgery under deep sedation. Methods: In total, 120 children aged 2-7 years (weight: 10-30 kg) were equally assigned into two groups, namely, HFNO with propofol total intravenous anesthesia infusion (HFNO-IV) or LMA with propofol total intravenous anesthesia infusion (LMA-IV). The primary objective was to monitor carbon dioxide (CO2) accumulation during perioperative surgery. Secondary objectives included monitoring transcutaneous oxygen saturation, grade exposure to the surgical field, perioperative adverse events, or other events. The predefined non-inferiority margin was 7 mmHg. During the COVID-19 pandemic, a novel WeChat applet was implemented to gather follow-up data after discharge. Results: Non-inferiority could be declared for HFNO relative to LMA (mean difference in transcutaneous CO2 (TcCO2) = -1.4 mmHg, 95% CI: -2.9, 0.1 mmHg; P > 0.05). The pre-surgical TcCO2 of the HFNO-IV group (45.4 ± 4.5 mmHg) was similar to that of the LMA-IV group (44.0 ± 3.5 mmHg), within the clinically acceptable normal range. All the children maintained SpO2 levels of >97%. The surgical field exposure score of the HFNO group was significantly better than that of the LMA group. There was no significant difference between the two groups regarding risk or adverse events. Conclusion: HFNO was not inferior to LMA for maintaining oxygenation and ventilation in patients undergoing pediatric ambulatory oral surgery under deep sedation under strict isolation from the oral cavity to the upper airway.

Response of Algal-Bacterial Regrowth Characteristics to the Hypochlorite in Landscape Ponds Replenished with Reclaimed Water

Sodium hypochlorite was widely used as a supplementary disinfectant in reclaimed water (RW) production during the COVID-19 epidemic. It is well known that the chlorination of RW results in a relatively high bacterial regrowth potential in pipeline systems. However, the algal growth and algal-bacterial interactions would be another concern in RW-replenished surface water with light irradiation. In this study, microcosmic experiments were used to explore the impact of hypochlorite on the algae-bacteria community, including the influence of hypochlorite on algal-bacterial regrowth, microbial community structure, and the specific bacteria that can survive chlorination. Results demonstrated that algal growth potential could be promoted after chlorination of the RW, and bacteria abundance increased along with an increase in algal density, which is probably related to DOM decomposition by chlorine oxidation. Additionally, the characteristics of the bacterial community were altered. It is more likely that phytospheric bacteria will survive chlorination. It was discovered that the secondary risks of chlorine disinfection include the growth of algae in addition to bacterial regeneration, which is an extension of the common perception. As a consequence, when chlorinated reclaimed water is used as a supplement for urban landscape ponds, particular attention should be paid to controlling bio-available organic matter induced by reactive chlorine, as well as the algal bloom, to decrease the risk of pathogen transmission.

Source tracing of the COVID-19 infection case in Guangxi, China

The study describing the process of discovery and source tracing of a native case of coronavirus disease 2019 (COVID-19) infection on Jan 2021, in Guangxi, China, to provide methodology for source investigation better in the future. Following the Epidemiological Investigation Plan for COVID-19 (version 7), information of the native COVID-19 case and related close contacts were collected. Real time reverse transcription-quantitative polymerase chain reaction was performed to detect the nucleic acids of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in samples collected from the infection case, related close contacts, and the environment, combined with serum specific antibody detection. The positive nucleic acid samples were undergone whole genome sequencing, phylogenetic analysis and analyses of variation of amino acids. The whole genome sequence from the native case and the imported asymptomatic infected case from Indonesia containing 25 nucleotide mutation sites belong to L-Lineage European Branch II. 3. The imported asymptomatic case was the source of infection of this native case. The possible route of infection was that native case was exposed to contaminated environment by imported case, due to improper personal protective equipment. A focus on local outbreaks of COVID-19 caused by SARS-CoV-2-infected people from outside China is needed.

Using Grounded Theory to Identify Online Public Opinion in China to Improve Risk Management-The Case of COVID-19.

BACKGROUND: During the outbreak of COVID-19, online public opinion related to the epidemic was rapidly generated and developed rapidly. If some online public opinions cannot be effectively responded to and guided, it will bring risks to social order. The government should understand how to use information on social media to grasp public demands, provide useful information in a timely manner and take countermeasures. Studying the formation mechanism of online public opinion during the outbreak can help the government make scientific decisions and improve risk management capabilities. METHODS: The research selects the public opinion information of online platforms represented by WeChat, online communities, Sina Weibo and search engines, involving 75 relevant texts (1 January to 31 March 2022). According to the grounded theory method, using the QSR NVivo12 qualitative research software, the collected network texts were successively researched using open coding, axial coding and theoretical coding. RESULTS: The structure of online public opinion during the COVID-19 epidemic was obtained. The operation mechanism of the online public opinion system about COVID-19 was mainly affected by the interaction of online public opinion objects, online public opinion subjects, online public opinion intermediaries and government forces. It was based on social facts and citizens' appeals as the starting point, subject behaviors and prevention and control measures as the focus, government's governance as macro-control and citizens' evaluation as the guide. CONCLUSIONS: Scientific analysis of online public opinion is an important tool to identify and manage risks and improve the quality of government activities. Online public opinion has the function of assisting government decision-making, and the government can identify the important information reflected in it, especially the mainstream public opinion, as a reference for decision-making. By taking effective measures and properly responding to citizens' reasonable demands, the government can prevent social risks and avoid new negative public opinions. Contributions: According to the characteristics of the basic model of online public opinion, this study provides risk mitigation suggestions for Chinese public sectors to use online public opinion, optimize epidemic prevention policies and formulate strategic measures.

Prolonged Viral Shedding in Three Young Adult Cases of COVID-19

Severe acute respiratory syndrome coronavirus-2 infection is usually self-limited, with a short duration for viral shedding within several weeks. However, prolonged viral shedding has been observed in severe or immune-compromised coronavirus disease 2019 (COVID-19) cases. Here, we reported that three young adult cases of COVID-19 patients, who were either immunosuppressed nor severe, showed prolonged viral RNA shedding from the upper respiratory tract for 58, 81, and 137 days since initial diagnosis. To our knowledge, this is the longest duration of viral shedding reported to date in young adult patients. Further studies on factors relevant to prolonged viral positivity, as well as the correlation between viral positivity and transmission risk are needed for the optimal management of COVID-19 patients with prolonged nucleic acid positive.

IrriMap_CN: Annual irrigation maps across China in 2000–2019 based on satellite observations, environmental variables, and machine learning

Agricultural irrigation, as an important practice to protect crops from drought and promote grain yield, has a long history in China. A timely and precise dataset about the extent and dynamics of irrigated areas is necessary for water allocation and agricultural management but is scarce in China. Here we developed annual irrigated cropland maps across China (IrriMap_CN) at 500-m resolution from 2000 to 2019, using MODIS data, machine-learning method, and Google Earth Engine platform. First, we generated annual nationwide training samples by strictly screening the existing irrigation maps downscaled from the statistical data. Second, we implemented locally adaptive random forest classifiers in 511 nominal 1° × 1° grid cells across China with MODIS vegetation indices, climatic factors, and topography variables. Third, we conducted nationwide pixel-wise validation of the IrriMap_CN using independent samples. The validation results based on more than 3000 ground truth points revealed that IrriMap_CN had high accuracies ranging from 77.2% to 85.9%. The time series of IrriMap_CN detected substantial expansion of irrigated areas in Xinjiang and Heilongjiang (more than 50% in total) and pronounced decreases in Sichuan, Jiangsu, and Hebei. The analyses of irrigation frequency, start time, and end time implied that North China Plain was the most intensive irrigated area;but the irrigation area showed a decreasing trend since 2000, consistent with the reduced agricultural water consumption. The annual irrigation datasets allow us to understand the spatiotemporal dynamics of irrigated croplands in China and are expected to contribute to the improvement of earth system models and facilitate sustainable agricultural water management. • Annual irrigation maps (IrriMap_CN) were generated for China in 2000–2019. • Nationwide training samples were extracted from existing irrigation maps. • IrriMap_CN highlights the declining irrigation area in North China Plain. • Cropland reclamation/occupation and water supply are key to irrigation area changes. [ FROM AUTHOR] Copyright of Remote Sensing of Environment is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

The Effect of Group Identification on Death Anxiety: The Chain Mediation Role of Close Relationships and Self-Esteem.

Based on the terror management theory (TMT), this study integrated self-esteem and close relationships to explore the effects of group identification on death anxiety. Five hundred and four participants completed the Death Anxiety, Rosenberg Self-Esteem, Social Identity, and Inclusion of Other in the Self scales via online platforms. There were significant correlations among group identification, close relationship, self-esteem, and death anxiety. Group identification had a significant negative predictive effect on death anxiety. Specifically, group identification affects death anxiety through two pathways: the separate mediating role of self-esteem and the serial mediation pathway of close relationships → self-esteem. Our study provides direct evidence that group identification relieves death anxiety. The results showed that the alleviating function of group identification was mediated by self-esteem and close relationships. This study provides a new perspective concerning TMT as a defense mechanism against death anxiety.

Construct and Validate a Predictive Model for Surgical Site Infection after Posterior Lumbar Interbody Fusion Based on Machine Learning Algorithm.

Purpose: Surgical site infection is one of the serious complications after lumbar fusion. Early prediction and timely intervention can reduce the harm to patients. The aims of this study were to construct and validate a machine learning model for predicting surgical site infection after posterior lumbar interbody fusion, to screen out the most important risk factors for surgical site infection, and to explore whether synthetic minority oversampling technique could improve the model performance. Method: This study reviewed 584 patients who underwent posterior lumbar interbody fusion for degenerative lumbar disease at our center from January 2019 to August 2021. Clinical information and laboratory test data were collected from the electronic medical records. The original dataset was divided into training set and validation set in a 1 : 1 ratio. Seven machine learning algorithms were used to develop predictive models; the training set of each model was resampled using synthetic minority oversampling technique. Finally, the model performance was assessed in the validation set. Results: Of the 584 patients, 33 (5.65%) occurred surgical site infection. Stepwise logistic regression showed that preoperative albumin level (OR 0.659, 95% CI 0.563-0.756), diabetes (OR 9.129, 95% CI 3.816-23.126), intraoperative dural tear (OR 8.436, 95% CI 2.729-25.334), and rheumatic disease (OR 8.471, 95% CI 1.743-39.567) were significant predictors associated with surgical site infection. The performance of the AdaBoost Classification Trees model was the best among the seven machine learning models, and synthetic minority oversampling technique improved the performance of all models. Conclusion: The prediction model we constructed based on machine learning and synthetic minority oversampling technique can accurately predict surgical site infection, which is conducive to clinical decision-making and optimization of perioperative management.

Habit formation of preventive behaviours during the COVID-19 pandemic: a longitudinal study of physical distancing and hand washing.

BACKGROUND: Since the outbreak of the COVID-19 pandemic, physical distancing and hand washing have been used as effective means to reduce virus transmission in the Netherlands. However, these measures pose a societal challenge as they require people to change their customary behaviours in various contexts. The science of habit formation is potentially useful for informing policy-making in public health, but the current literature largely overlooked the role of habit in predicting and explaining these preventive behaviours. Our research aimed to describe habit formation processes of physical distancing and hand washing and to estimate the influences of habit strength and intention on behavioural adherence. METHODS: A longitudinal survey was conducted between July and November 2020 on a representative Dutch sample (n = 800). Respondents reported their intentions, habit strengths, and adherence regarding six context-specific preventive behaviours on a weekly basis. Temporal developments of the measured variables were visualized, quantified, and mapped onto five distinct phases of the pandemic. Regression models were used to test the effects of intention, habit strength, and their interaction on behavioural adherence. RESULTS: Dutch respondents generally had strong intentions to adhere to all preventive measures and their adherence rates were between 70% and 90%. They also self-reported to experience their behaviours as more automatic over time, and this increasing trend in habit strength was more evident for physical-distancing than for hand washing behaviours. For all six behaviours, both intention and habit strength predicted subsequent adherence (all ps < 2e-16). In addition, the predictive power of intention decreased over time and was weaker for respondents with strong habits for physical distancing when visiting supermarkets (B = -0.63, p <.0001) and having guests at home (B = -0.54, p <.0001) in the later phases of the study, but not for hand washing. CONCLUSIONS: People's adaptations to physical-distancing and hand washing measures involve both intentional and habitual processes. For public health management, our findings highlight the importance of using contextual cues to promote habit formation, especially for maintaining physical-distancing practices. For habit theories, our study provides a unique dataset that covers multiple health behaviours in a critical real-world setting.

Spatiotemporal variations of public opinion on social distancing in the Netherlands: Comparison of Twitter and longitudinal survey data

Background Social distancing has been implemented by many countries to curb the COVID-19 pandemic. Understanding public support for this policy calls for effective and efficient methods of monitoring public opinion on social distancing. Twitter analysis has been suggested as a cheaper and faster-responding alternative to traditional survey methods. The current empirical evidence is mixed in terms of the correspondence between the two methods. Objective We aim to compare the two methods in the context of monitoring the Dutch public's opinion on social distancing. For this comparison, we quantified the temporal and spatial variations in public opinion and their sensitivities to critical events using data from both Dutch Twitter users and respondents from a longitudinal survey. Methods A longitudinal survey on a representative Dutch sample (n = 1,200) was conducted between July and November 2020 to measure opinions on social distancing weekly. From the same period, near 100,000 Dutch tweets were categorized as supporting or rejecting social distancing based on a model trained with annotated data. Average stances for the 12 Dutch provinces and over the 20 weeks were computed from the two data sources and were compared through visualizations and statistical analyses. Results Both data sources suggested strong support for social distancing, but public opinion was much more varied among tweets than survey responses. Both data sources showed an increase in public support for social distancing over time, and a strong temporal correspondence between them was found for most of the provinces. In addition, the survey but not Twitter data revealed structured differences among the 12 provinces, while the two data sources did not correspond much spatially. Finally, stances estimated from tweets were more sensitive to critical events happened during the study period. Conclusions Our findings indicate consistencies between Twitter data analysis and survey methods in describing the overall stance on social distancing and temporal trends. The lack of spatial correspondence may imply limitations in the data collections and calls for surveys with larger regional samples. For public health management, Twitter analysis can be used to complement survey methods, especially for capturing public's reactivities to critical events amid the current pandemic.

The Depleting and Buffering Effects of Telecommuting on Wellbeing: Evidence From China During COVID-19.

Meta-analytical research has demonstrated the benefits brought by telecommuting to wellbeing. However, we argue that such a setup in the course of the coronavirus disease pandemic exerts negative effects. On the basis of conservation of resources theory, this study determined how telecommuting depletes wellbeing (defined by job satisfaction and emotional exhaustion) through obstructing psychological detachment from work. Moreover, we incorporated family interfering with work and family-work enrichment as moderators that can buffer the negative effect of telecommuting on psychological detachment from work. Time-lagged field research was conducted with 350 Chinese employees, and findings largely supported our theoretical hypotheses. The elevated level of telecommuting results in minimal psychological detachment from work, which then leads to low wellbeing. Meanwhile, the negative effect of the extent of telecommuting on psychological detachment from work is reduced by family interfering with work. These findings extend the literature on telecommuting and psychological detachment from work through revealing why teleworkers present negative feelings during the pandemic.

Neutralizing Potency of Prototype and Omicron RBD mRNA Vaccines Against Omicron Variant

The newly emerged Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains more than 30 mutations on the spike protein, 15 of which are located within the receptor binding domain (RBD). Consequently, Omicron is able to extensively escape existing neutralizing antibodies and may therefore compromise the efficacy of current vaccines based on the original strain, highlighting the importance and urgency of developing effective vaccines against Omicron. Here we report the rapid generation and evaluation of an mRNA vaccine candidate specific to Omicron, and explore the feasibility of heterologous immunization with WT and Omicron RBD vaccines. This mRNA vaccine encodes the RBD of Omicron (designated as RBD-O) and is formulated with lipid nanoparticle. Two doses of the RBD-O mRNA vaccine efficiently induce neutralizing antibodies in mice;however, the antisera are effective only on the Omicron variant but not on the wildtype and Delta strains, indicating a narrow neutralization spectrum. It is noted that the neutralization profile of the RBD-O mRNA vaccine is opposite to that observed for the mRNA vaccine expressing the wildtype RBD (RBD-WT). Importantly, booster with RBD-O mRNA vaccine after two doses of RBD-WT mRNA vaccine can significantly increase neutralization titers against Omicron. Additionally, an obvious increase in IFN-γ, IL-2, and TNF-α-expressing RBD-specific CD4+ T cell responses was observed after immunization with the RBD-WT and/or RBD-O mRNA vaccine. Together, our work demonstrates the feasibility and potency of an RBD-based mRNA vaccine specific to Omicron, providing important information for further development of heterologous immunization program or bivalent/multivalent SARS-CoV-2 vaccines with broad-spectrum efficacy.

Public awareness, emotional reactions and human mobility in response to the COVID-19 outbreak in China - a population-based ecological study.

BACKGROUND: The outbreak of COVID-19 generated severe emotional reactions, and restricted mobility was a crucial measure to reduce the spread of the virus. This study describes the changes in public emotional reactions and mobility patterns in the Chinese population during the COVID-19 outbreak. METHODS: We collected data on public emotional reactions in response to the outbreak through Weibo, the Chinese Twitter, between 1st January and 31st March 2020. Using anonymized location-tracking information, we analyzed the daily mobility patterns of approximately 90% of Sichuan residents. RESULTS: There were three distinct phases of the emotional and behavioral reactions to the COVID-19 outbreak. The alarm phase (19th-26th January) was a restriction-free period, characterized by few new daily cases, but a large amount public negative emotions [the number of negative comments per Weibo post increased by 246.9 per day, 95% confidence interval (CI) 122.5-371.3], and a substantial increase in self-limiting mobility (from 45.6% to 54.5%, changing by 1.5% per day, 95% CI 0.7%-2.3%). The epidemic phase (27th January-15th February) exhibited rapidly increasing numbers of new daily cases, decreasing expression of negative emotions (a decrease of 27.3 negative comments per post per day, 95% CI -40.4 to -14.2), and a stabilized level of self-limiting mobility. The relief phase (16th February-31st March) had a steady decline in new daily cases and decreasing levels of negative emotion and self-limiting mobility. CONCLUSIONS: During the COVID-19 outbreak in China, the public's emotional reaction was strongest before the actual peak of the outbreak and declined thereafter. The change in human mobility patterns occurred before the implementation of restriction orders, suggesting a possible link between emotion and behavior.

SARS-CoV-2 couples evasion of inflammatory response to activated nucleotide synthesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves rapidly under the pressure of host immunity, as evidenced by waves of emerging variants despite effective vaccinations, highlighting the need for complementing antivirals. We report that targeting a pyrimidine synthesis enzyme restores inflammatory response and depletes the nucleotide pool to impede SARS-CoV-2 infection. SARS-CoV-2 deploys Nsp9 to activate carbamoyl-phosphate synthetase, aspartate transcarbamoylase, and dihydroorotase (CAD) that catalyzes the rate-limiting steps of the de novo pyrimidine synthesis. Activated CAD not only fuels de novo nucleotide synthesis but also deamidates RelA. While RelA deamidation shuts down NF-κB activation and subsequent inflammatory response, it up-regulates key glycolytic enzymes to promote aerobic glycolysis that provides metabolites for de novo nucleotide synthesis. A newly synthesized small-molecule inhibitor of CAD restores antiviral inflammatory response and depletes the pyrimidine pool, thus effectively impeding SARS-CoV-2 replication. Targeting an essential cellular metabolic enzyme thus offers an antiviral strategy that would be more refractory to SARS-CoV-2 genetic changes.