A SARS-CoV-2-specific CAR-T-cell model identifies felodipine, fasudil, imatinib, and caspofungin as potential treatments for lethal COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this "two-cell" (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.

Quinazolinone-Peptido-Nitrophenyl-Derivatives as Potential Inhibitors of SARS-CoV-2 Main Protease.

The severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2-Mpro) plays an essential role in viral replication, transcription, maturation, and entry into host cells. Furthermore, its cleavage specificity for viruses, but not humans, makes it a promising drug target for the treatment of coronavirus disease 2019 (COVID-19). In this study, a fragment-based strategy including potential antiviral quinazolinone moiety and glutamine- or glutamate-derived peptidomimetic backbone and positioned nitro functional groups was used to synthesize putative Mpro inhibitors. Two compounds, G1 and G4, exhibited anti-Mpro enzymatic activity in a dose-dependent manner, with the calculated IC50 values of 22.47 ± 8.93 µM and 24.04 ± 0.67 µM, respectively. The bio-layer interferometer measured real-time binding. The dissociation kinetics of G1/Mpro and G4/Mpro also showed similar equilibrium dissociation constants (KD) of 2.60 × 10-5 M and 2.55 × 10-5 M, respectively, but exhibited distinct association/dissociation curves. Molecular docking of the two compounds revealed a similar binding cavity to the well-known Mpro inhibitor GC376, supporting a structure-function relationship. These findings may open a new avenue for developing new scaffolds for Mpro inhibition and advance anti-coronavirus drug research.

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.

Scientific planning of urban cordon sanitaire for desired queuing time.

The outbreak of the COVID-19 pandemic disrupted ofur normal life. Many cities enforced a cordon sanitaire as a countermeasure to protect densely inhabited areas. Travelers can only cross the cordon after being checked. To minimize the waiting time in the queue, this paper proposes a method to determine the scientific planning of urban cordon sanitaire for desired queuing time, which is a significant problem that has not been explored. A novel two-stage optimization model is proposed where the first stage is the transportation system equilibrium problem to predict traffic inflow, and the second stage is the queuing network design problem to determine the allocation of test stations. This method aims to minimize the total health infrastructure investment for the desired maximum queuing time. Note that queuing theory is used to represent the queuing phenomenon at each urban entrance. A heuristic algorithm is designed to solve the proposed model where the Method of Successive Averages (MSA) is adopted for the first stage, and the Genetic Algorithm (GA) with elite strategy is adopted for the second stage. An experimental study with sensitivity analysis is conducted to demonstrate the effectiveness of the proposed methods. The results show that the methods can find a good heuristic optimal solution. This research is helpful for policymakers to determine the optimal investment and planning of cordon sanitaire for disease prevention and control, as well as other criminal activities such as drunk driving, terrorists, and smuggling.

Pathogenic and metagenomic evaluations reveal the correlations of porcine epidemic diarrhea virus, porcine kobuvirus and porcine astroviruses with neonatal piglet diarrhea.

Porcine epidemic diarrhea virus (PEDV) frequently causes diarrhea outbreaks. However, whether newly discovered enteric viruses such as porcine kobuvirus (PKV) and porcine astroviruses (PAstVs) are also correlated with diarrhea is still unclear. Diarrhea outbreaks were reported in a PEDV-vaccinated pig farm in Xinjiang Uygur Autonomous Region of China from 2019 to 2020. PEDV was a common pathogen detected in fecal samples by routine RT-PCR assays. The PEDV positive fecal sample was used for pathogenic analysis due to the failure isolation of PEDV. The challenged neonatal piglets appeared watery diarrhea within one day post infection (dpi) and all died within 6 dpi. Histopathological and immunohistochemical examinations supported that PEDV is a major pathogen causing intestinal lesions. To further explore enteric viruses associated with neonatal piglet diarrhea, metagenomics sequencing was performed for the diarrheic piglets. Remarkably, PKV was the most abundant virus (58.33%) followed by PEDV (34.45%) and PAstVs (7.22%), which were also confirmed by real-time RT-PCR assays. Significant in vivo replications of PEDV and PKV could only be observed in challenged piglets whilst PAstVs maintained similar virus loads in both challenged and mock infected piglets. Overall, this study provides first pathogenic and metagenomic evidence that significant proliferations of PEDV and PKV are closely associated with severe diarrhea in neonatal piglets, while PAstVs likely play limited roles in neonatal piglet diarrhea.

The Role of the Vascular Niche in Organ Fibrosis and COVID-19-Related Organ Damage and the Countermeasures adopted by Chinese and Western Medicine

The vascular niche is a microenvironment located around capillaries and is mainly composed of endothelial cells, pericytes, macrophages, lymphocytes, mesenchymal stem cells, and hematopoietic stem cells. Studies have found that the vascular niche not only functions to regulate cell growth and differentiation in normal tissues, but also has an important role in regulating fibrosis in various organs and tissues in disease states. Coronavirus disease 2019 (COVID-19) is a systemic disease that broke out in 2019, caused by SARS-CoV-2 infection, which results in pulmonary inflammation, systemic multi-organ damage, and an inflammatory cytokine storm. Recently, the vascular niche has been found to play a role in COVID-19-related multi-organ damage. In this review, we introduce the important role of the vascular niche in organ fibrosis and COVID-19-related organ damage, summarize some of the cellular signaling pathways in the vascular niche that promote fibrosis, and discuss the treatment of organ fibrosis in Traditional Chinese medicine and Western medicine.

Association of COVID-19 vaccination with herpes zoster: a systematic review and meta-analysis.

BACKGROUND: Following COVID-19 vaccination, several herpes zoster cases have been reported, making it critical to explore the association between herpes zoster and COVID-19 vaccination. This is especially true in the context of increasing the number of participants enrolled to receive COVID-19 vaccination. RESEARCH DESIGN AND METHODS: Three databases, including the Cochrane Library, PubMed, and EMBASE, were searched for relevant studies before 25 December 2021 according to preliminarily determined inclusion and exclusion criteria without any language limitations. Four cohort studies were included in this systematic review and meta-analysis. RESULTS: Compared with the placebo group, there was no evidence that the COVID-19 vaccination group was associated with increased incidence of herpes zoster (Risk ratio [RR]: 1.06; 95% confidence interval [CI]: 0.91 to 1.24). There is no evidence that the COVID-19 vaccination from Moderna is associated with the incidence of herpes zoster compared with vaccination from Pfizer (RR: 0.20; 95% CI: 0.01 to 2.99). CONCLUSIONS: To date, there is no evidence of an association between covid-19 vaccination and herpes zoster.

Generation of a single-cell B cell atlas of antibody repertoires and transcriptomes to identify signatures associated with antigen-specificity (preprint)

Murine models of immunization have played a major role in discovering antibody candidates against therapeutic targets. It nevertheless remains time-consuming and expensive to identify antibodies with diverse binding modalities against druggable candidate molecules. Although new genomics-based pipelines have potential to augment antibody discovery, these methods remain in their infancy due to an incomplete understanding of the selection process that governs B cell clonal selection, expansion and antigen specificity. Furthermore, it remains unknown how factors such as aging and reduction of tolerance influence B cell selection in murine models of immunization. Here we perform single-cell sequencing of antibody repertoires and transcriptomes of B cells following immunizations with a model therapeutic antigen target (human Tumor necrosis factor receptor 2, TNFR2). We determine the relationship between antibody repertoires, gene expression signatures and antigen specificity across 100,000 B cells. Recombinant expression and characterization of 227 monoclonal antibodies revealed the existence of clonally expanded and class-switched antigen-specific B cells that were more frequent in young mice. Although integrating multiple repertoire features such as germline gene usage, somatic hypermutation, and transcriptional signatures failed to distinguish antigen-specific from non-specific B cells, other features such as IgG-subtype and sequence composition correlated with antigen-specificity. This work provides a single-cell resource for B cells relating antibody repertoires, transcriptomes and antigen specificity.

DeepSARS: simultaneous diagnostic detection and genomic surveillance of SARS-CoV-2 (preprint)

The continued spread of SARS-CoV-2 and emergence of new variants with higher transmission rates and/or partial resistance to vaccines has further highlighted the need for large-scale testing and genomic surveillance. However, current diagnostic testing (e.g., PCR) and genomic surveillance methods (e.g., whole genome sequencing) are performed separately, thus limiting the detection and tracing of SARS-CoV-2 and emerging variants. Here, we developed DeepSARS, a high-throughput platform for simultaneous diagnostic detection and genomic surveillance of SARS-CoV-2 by the integration of molecular barcoding, targeted deep sequencing, and computational phylogenetics. DeepSARS enables highly sensitive viral detection, while also capturing genomic diversity and viral evolution. We show that DeepSARS can be rapidly adapted for identification of emerging variants, such as alpha, beta, gamma, and delta strains, and profile mutational changes at the population level. DeepSARS sets the foundation for quantitative diagnostics that capture viral evolution and diversity. Abstract Figure Graphical abstract DeepSARS uses molecular barcodes (BCs) and multiplexed targeted deep sequencing (NGS) to enable simultaneous diagnostic detection and genomic surveillance of SARS-CoV-2.

Effect of COVID-19 on hospital visits in Ningbo, China: an interrupted time-series analysis.

OBJECTIVE: Unprecedented rigorous public health measures were implemented during the coronavirus disease 2019 (COVID-19) epidemic, but it is still unclear how the intervention influenced hospital visits for different types of diseases. We aimed to evaluate the impact of the intervention on hospital visits in Yinzhou District, Ningbo, Zhejiang province, China. METHODS: We conducted an interrupted time-series analysis from 1 January 2017 to 6 September 2020 based on the Yinzhou Health Information System in Ningbo, Zhejiang province. The beginning of the intervention was on 23 January 2020, and thus, there were 160 weeks before the intervention and 32 weeks after the implementation of the intervention. Level changes between expected and observed hospital visits in the post-intervention period were estimated using quasi-Poisson regression models. RESULTS: Compared with the expected level, there was an estimated decrease of -22.60% (95% confidence interval (CI): -27.53%, -17.36%) in the observed total hospital visits following the intervention. Observed hospital visits for diseases of the respiratory system were found to be decreased dramatically (-62.25%; 95% CI: -65.62%, -58.60%). However, observed hospital visits for certain diseases were estimated to be increased, including diseases of the nervous system (+11.17%; 95% CI: +3.21%, +19.74%); diseases of pregnancy, childbirth and the puerperium (+27.01%; 95% CI: +17.89%, +36.85%); certain conditions originating in the perinatal period (+45.05%; 95% CI: +30.24%, +61.56%); and congenital malformation deformations and chromosomal abnormalities (+35.50%; 95% CI: +21.24%, +51.45%). CONCLUSIONS: Our findings provided scientific evidence that cause-specific hospital visits evolve differently following the intervention during the COVID-19 epidemic.

Single-Cell Sequencing of Plasma Cells from COVID-19 Patients Reveals Highly Expanded Clonal Lineages Produce Specific and Neutralizing Antibodies to SARS-CoV-2 (preprint)

Isolation and characterization of antibodies in COVID-19 patients has largely focused on memory B cells, however it is the antibody-secreting plasma cells that are directly responsible for the production of serum antibodies, which play a critical role in controlling and resolving SARS-CoV-2 infection. To date there is little known about the specificity of plasma cells in COVID-19 patients. This is largely because plasma cells lack surface antibody expression, which complicates their screening. Here, we describe a technology pipeline that integrates single-cell antibody repertoire sequencing and high-throughput mammalian display screening to interrogate the specificity of plasma cells from 16 convalescent COVID-19 patients. Single-cell sequencing allows us to profile antibody repertoire features in these patients and identify highly expanded clonal lineages. Mammalian display screening is employed to reveal that 37 antibodies (out of 132 candidates) derived from expanded plasma cell clonal lineages are specific for SARS-CoV-2 antigens, including antibodies that target the receptor binding domain (RBD) with high affinity and exhibit potent neutralization of SARS-CoV-2.Funding: This work was supported by the European Research Grant CoroNAb (to S.T.R. and B.M.), Personalized Health and Related Technologies (to S.T.R. and R.V-L.), Botnar Research Centre for Child Health (to S.T.R.).Conflict of Interest: The authors have no competing interests to declare.Ethical Approval: Ethics permission was granted by the ethics board “Ethikkommission Nordwest- und. Zentralschweiz (EKNZ)”. Every participant has signed a written informed consent as described previously (Kaltenbach et al., 2020).

Mental health and preventive behaviour of pregnant women in China during the early phase of the COVID-19 period.

BACKGROUND: The COVID-19 has caused significant toll over the globe. Pregnant women are at risk of infection. The present study examined the frequency of washing hands with soap and wearing face mask when going out, prevalence of depression and anxiety, and identified their associated factors among pregnant women during the early phase of COVID-19 outbreak in China. METHODS: A cross-sectional online survey was conducted between 24 February and 3 March 2020. A total of 15 428 pregnant women who were using maternal health care services in China completed a questionnaire which assessed their socio-demographic and pregnancy-related characteristics, contextual, cognitive and social factors related to COVID-19, frequency of washing hands and wearing face masks, and depression and anxiety. Logistics regression analyses were performed to identify the associated factors of preventive behaviours and mental health. RESULTS: The prevalence of probable anxiety and depression was 28.2% and 43.6% respectively. 19.8% reported always wearing face mask when going out, and 19.1% reported washing hands with soap for more than 10 times per day. Results from logistic regression analyses showed that older age was associated with lower levels of depression and anxiety (OR = 0.42-0.67) and higher frequency of washing hands (OR = 1.57-3.40). Higher level of education level was associated with probable depression (OR = 1.31-1.45) and higher frequency of wearing face mask (OR = 1.50-1.57). After adjusting for significant socio-demographic and pregnancy-related factors, place of residence being locked down (aOR = 1.10-1.11), being quarantined (aOR = 1.42-1.57), personally knowing someone being infected with COVID-19 (aOR = 1.80-1.92), perception that COVID-19 would pose long term physical harm to human (aOR = 1.25-1.28) were associated with higher levels of depression and anxiety, while the perception that the disease will be under control in the coming month was associated with lower levels of depression and anxiety (aOR = 0.59-0.63) and lower tendency of always wearing face mask (aOR = 0.85). Social support was associated with lower levels of depression and anxiety (aOR = 0.86-0,87) and higher frequency of washing hands (aOR = 1.06). CONCLUSIONS: The mental health and preventive behaviours of pregnant women during COVID-19 outbreak was associated with a range of socio-demographic, pregnancy-related, contextual, cognitive and social factors. Interventions to mitigate their mental health problems and to promote preventive behaviours are highly warranted.

Sewage Treatment Project Design of Wuhan Huoshenshan and Leishenshan Hospitals

The Huoshenshan hospital and Leishenshan hospital are special infectious diseases hospitals that were designed to focus on the treatment of patients infected by new Coronavirus pneumonia( COVID-19). The design of sewage treatment system was "pre-disinfection contact tank + septic tank + lifting pump station( including crushed grille) + regulating tank + MBBR biochemical tank +coagulation sedimentation tank + contact disinfection tank ". MBBR process could achieve efficient removal of pollutants in sewage at low temperature. Two-stage disinfection process guaranteed 100% virus elimination. At the same time,HDPE membrane was laid under the sewage station according to the landfill standard to ensure the full collection,disinfection and discharge of rainwater and sewage. The sludge was collected and transported as hazardous waste after disinfection and dehydration. The waste gas was collected,deodorized and disinfected in a unified way,so as to realize the full collection and treatment of rainwater,sewage,sludge and waste gas. At present,the operations of the sewage stations of Huoshenshan and Leishenshan hospitals had kept stable,and the relevant effluent indexes met the design requirements. COD concentration was stable below 50 mg/L,ammonia nitrogen was stable below 2 mg/L,residual chlorine was stable near 13 mg/L. Therefore,the pollutant removal and disinfection effect were stable during the whole operation.

Single-cell sequencing of plasma cells from COVID-19 patients reveals highly expanded clonal lineages produce specific and neutralizing antibodies to SARS-CoV-2 (preprint)

Isolation and characterization of antibodies in COVID-19 patients has largely focused on memory B cells, however it is the antibody-secreting plasma cells that are directly responsible for the production of serum antibodies, which play a critical role in controlling and resolving SARS-CoV-2 infection. To date there is little known about the specificity of plasma cells in COVID-19 patients. This is largely because plasma cells lack surface antibody expression, which complicates their screening. Here, we describe a technology pipeline that integrates single-cell antibody repertoire sequencing and high-throughput mammalian display screening to interrogate the specificity of plasma cells from 16 convalescent COVID-19 patients. Single-cell sequencing allows us to profile antibody repertoire features in these patients and identify highly expanded clonal lineages. Mammalian display screening is employed to reveal that 37 antibodies (out of 132 candidates) derived from expanded plasma cell clonal lineages are specific for SARS-CoV-2 antigens, including antibodies that target the receptor binding domain (RBD) with high affinity and exhibit potent neutralization of SARS-CoV-2. One Sentence SummarySingle-cell antibody repertoire sequencing and high-throughput screening identifies highly expanded plasma cells from convalescent COVID-19 patients that produce SARS-CoV-2-specific antibodies capable of potent neutralization.

Exploring the role of online efl learners' perceived social support in their learning engagement: A structural equation model

ABSTRACT During the COVID-19 pandemic period, a growing number of learning activities are taking place in online contexts. Along with the adversity in the online course of target language learning, student engagement has been considered important to improve learners' academic achievements of the target language. Although there has been a growing interest in the relationship between students' perceived social support and their online learning engagement, the literature lacks an in-depth investigation of the intricate relations between these two constructs in an online English as a foreign language (EFL) learning setting during the pandemic. To address this gap, this study attempts to develop a model which depicts the relationships between students' perceived social support and their online English learning engagement. A total of 615 university students in China were invited to take part in the study. By conducting structural equation modeling, the results confirmed the mediational model in which behavioral engagement completely mediated the relationships between social support (teacher support and peer support) and three other types of student engagement (cognitive, emotional and social engagement). These findings suggest designing effective instruction and developing support strategies in online teaching to enhance EFL learners' engagement during the COVID-19 lockdown. (PsycInfo Database Record (c) 2020 APA, all rights reserved)

Response of Chinese Anesthesiologists to the COVID-19 Outbreak.

The coronavirus disease 2019, named COVID-19 officially by the World Health Organization (Geneva, Switzerland) on February 12, 2020, has spread at unprecedented speed. After the first outbreak in Wuhan, China, Chinese anesthesiologists encountered increasing numbers of infected patients since December 2019. Because the main route of transmission is via respiratory droplets and close contact, anesthesia providers are at a high risk when responding to the devastating mass emergency. So far, actions have been taken including but not limited to nationwide actions and online education regarding special procedures of airway management, oxygen therapy, ventilation support, hemodynamic management, sedation, and analgesia. As the epidemic situation has lasted for months (thus far), special platforms have also been set up to provide free mental health care to all anesthesia providers participating in acute and critical caring for COVID-19 patients. The current article documents the actions taken, lesson learned, and future work needed.

[Practice and System Construction of Telemedicine for Coronavirus Disease 2019 Epidemic Prevention and Control].

Telemedicine is one of the five key components of the "Internet Plus Healthcare".Due to its high speed,real-timeness,low cost,and wide spread,telemedicine is highly feasible in the prevention and control of major infectious diseases.This article introduces the practiceof telemedicine in Peking Union Medical College Hospital during the cornavirus disease 2019(COVID-19)epidemic,during which the network resources were applied to break geographical restrictions and resolve communication barriers between hospitals and departments.This article summarizes the telemedicine application before,during and after COVID-19 control and elucidates how to build a telemedicine prevention and control system for infectious diseases,with an attempt to further improve telemedicine and is application in the public health emergency system in China.

The severe COVID-19: A sepsis induced by viral infection? And its immunomodulatory therapy.

COVID-19 is known for its magical infectivity, fast transmission and high death toll based on the large number of infected people. From the perspective of the clinical manifestation, autopsy examination and pathophysiology, the essence of COVID-19 should be viewed as a sepsis induced by viral infection, and has the essential characteristics as sepsis induced by other pathogens. Therefore, in addition to etiological and supportive treatment, immunomodulatory therapy is also appropriate to severe COVID-19. Although there is still a lack of consensus on immunotherapy for sepsis so far, relatively rich experiences have been accumulated in the past decades, which will help us in the treatment of severe COVID-19. This article will elaborate immunotherapy of sepsis, though it may not be consistent.