Four new eudesmane-type and one new eremophilane-type sesquiterpenes from the whole plant of Carpesium abrotanoides L.

The extract of the whole plant of Carpesium abrotanoides L. yielded five new sesquiterpenes including four eudesmanes (1-4) and one eremophilane (5). The new compounds were characterized by spectroscopic analysis especially 1D and 2D NMR spectroscopy and HRESIMS data. Structurally, both compounds 1 and 2 were sesquiterpene epoxides and 2 owned an epoxy group at C-4/C-15 position to form a spiro skeleton. Compounds 4 and 5 were two sesquiterpenes without lactones and 5 possessed a carboxy group in the molecule. Additionally, all the isolated compounds were preliminarily evaluated for the inhibitory activity against SARS-CoV-2 main protease. As a result, compound 2 showed moderate activity with an IC50 value of 18.79 µM, while other compounds were devoid of noticeable activity (IC50 > 50 µM).

Epidemiological characteristics of respiratory syncytial virus in hospitalized patients in Guangzhou from 2018 to 2022

Objective To analyze the epidemiological characteristics of respiratory syncytial virus（RSV） before and after the COVID-19 epidemic in Guangzhou in recent years. Methods Nasopharynx swabs from hospitalized patients with acute respiratory infection were collected from two sentinel hospitals in Guangzhou（Guangdong Maternal and Child Health Hospital and Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University） from 2018 to 2022. Luminex respiratory multi-pathogen detection technology was used to detect and type RSV in samples. Results A total of 1 243 nasopharyngeal swab samples were collected. The overall positive rate of RSV was 6. 11%（76/1 243）, including 39 RSV-A（51. 32%, 39/76） and 37 RSV-B（48. 68%, 37/76）. The highest detection rate of RSV in children under 3 years old was 8. 79%（66 cases）. Compared with 2018（8. 30%, 22/265） and 2020（14. 78%, 30/203）, the positive rate of RSV decreased significantly in 2019（3. 13%, 10/319）, 2021（4. 08%, 10/245） and 2022（1. 90%, 4/211）. Compared with 2018（8. 30%,22/265） and 2020（14. 78%,30/203）,the positive rate of RSV decreased significantly in 2019（3. 13%,10/319）, 2021（4. 08%,10/245） and 2022（1. 90%,4/211）. Type A prevailed in 2018（19/22） and 2022（4/4）, type B（25/30） prevailed in 2020, type A and type B coexisted in 2019 and 2021. The detection rate showed had no statistically significant seasonal difference except for 2020 [7. 14%（3/42）, 16. 39%（10/61）, 27. 12%（16/59）, 0（0/42）,χ~2= 16. 975,P＜0. 001]. Among all the 76 RSV positive samples, 17（22. 37%） showed multiple infections. Among them, human rhinovirus was the most common virus causing mixed infection, accounting for 58. 83%（10/17） of the mixed infection. Conclusion RSV is a common respiratory virus prevalent in Guangzhou, and children under 3 years old are the main population infected with RSV. RSV infection is prevalent every other year, with the characteristics of alternating epidemic of type A and type B, and the anti-seasonal epidemic appeared after the COVID-19. After the outbreak of COVID-19, the detection rate of RSV increased significantly in 2020. With the change of the national COVID-19 epidemic prevention and control policy, the detection rate of RSV declined significantly during 2021-2022.

Successful clearance of persistent SARS-CoV-2 asymptomatic infection following a single dose of Ad5-nCoV vaccine.

Persistent asymptomatic (PA) SARS-CoV-2 infections have been identified. The immune responses in these patients are unclear, and the development of effective treatments for these patients is needed. Here, we report a cohort of 23 PA cases carrying viral RNA for up to 191 days. PA cases displayed low levels of inflammatory and interferon response, weak antibody response, diminished circulating follicular helper T cells (cTfh), and inadequate specific CD4+ and CD8+ T-cell responses during infection, which is distinct from symptomatic infections and resembling impaired immune activation. Administration of a single dose of Ad5-nCoV vaccine to 10 of these PA cases elicited rapid and robust antibody responses as well as coordinated B-cell and cTfh responses, resulting in successful viral clearance. Vaccine-induced antibodies were able to neutralize various variants of concern and persisted for over 6 months, indicating long-term protection. Therefore, our study provides an insight into the immune status of PA infections and highlights vaccination as a potential treatment for prolonged SARS-CoV-2 infections.

Neutrophil extracellular traps primed intercellular communication in cancer progression as a promising therapeutic target.

In addition to the anti-infection response, neutrophils are linked to tumor progression through the secretion of inflammation components and neutrophil extracellular traps (NETs) formation. NET is a web-like structure constituted by a chromatin scaffold coated with specific nuclear and cytoplasmic proteins, such as histone and granule peptides. Increasing evidence has demonstrated that NETs are favorable factors to promote tumor growth, invasion, migration, and immunosuppression. However, the cell-cell interaction between NETs and other cells (tumor cells and immune cells) is complicated and poorly studied. This work is the first review to focus on the intercellular communication mediated by NETs in cancer. We summarized the complex cell-cell interaction between NETs and other cells in the tumor microenvironment. We also address the significance of NETs as both prognostic/predictive biomarkers and molecular targets for cancer therapy. Moreover, we presented a comprehensive landscape of cancer immunity, improving the therapeutic efficacy for advanced cancer in the future.

Are vehicle on-demand and shared services a favorable solution for the first and last-mile mobility: Evidence from China

Vehicle on-demand and shared services (VDSS), such as Uber, Lyft, Didi and Car2go, have experienced rapid growth over the last decade. While these emerging mobility services have advantages, such as serving as an alternative mode for public transit, it remains unclear to what extent the services are adopted by different user groups, particularly in the context of first and last-mile mobility and how demand varies in different periods. To fill this research gap, we conducted a comprehensive travel survey of 1,420 railway passengers in China, to examine how VDSS were utilized for the first and last-mile connection with train stations. Using binary and multinomial logit modeling analysis, the study shows that the attitude toward VDSS was influenced by various factors and the outcomes varied substantially before and after the outbreak of the COVID-19 pandemic. Based on the research findings, we recommend that transportation planning and operation agencies should add ride-sourcing waiting and car-sharing parking sites at railway stations to further improve their advantages of flexibility and convenience. Meanwhile, attention should be paid to maintaining a healthy, safe and relaxed riding environment to facilitate VDSS usage. The equity issue of VDSS should also be addressed through strategies, such as providing special discounts or subsidies to certain lower-income user groups so that wider social groups may also enjoy such services. In terms of mitigating the impact of the COVID-19 pandemic, further attention should be paid to improving a healthy and clean riding environment in VDSS to reduce the risk to public health.

A Novel Deep Learning Model for Medical Report Generation by Inter-Intra Information Calibration.

Automatic generation of medical reports can provide diagnostic assistance to doctors and reduce their workload. To improve the quality of the generated medical reports, injecting auxiliary information through knowledge graphs or templates into the model is widely adopted in previous methods. However, they suffer from two problems: 1) The injected external information is limited in amount and difficult to adequately meet the information needs of medical report generation in content. 2) The injected external information increases the complexity of model and is hard to be reasonably integrated into the generation process of medical reports. Therefore, we propose an Information Calibrated Transformer (ICT) to address the above issues. First, we design a Precursor-information Enhancement Module (PEM), which can effectively extract numerous inter-intra report features from the datasets as the auxiliary information without external injection. And the auxiliary information can be dynamically updated with the training process. Secondly, a combination mode, which consists of PEM and our proposed Information Calibration Attention Module (ICA), is designed and embedded into ICT. In this method, the auxiliary information extracted from PEM is flexibly injected into ICT and the increment of model parameters is small. The comprehensive evaluations validate that the ICT is not only superior to previous methods in the X-Ray datasets, IU-X-Ray and MIMIC-CXR, but also successfully be extended to a CT COVID-19 dataset COV-CTR.

Global influenza vaccination rates and factors associated with influenza vaccination.

OBJECTIVES: Influenza vaccination is an effective method for preventing influenza virus infection. Herein, we performed a meta-analysis to quantify global influenza vaccination rates (IVRs) and the factors influencing its uptake in the general population, individuals with chronic diseases, pregnant women, and healthcare workers. METHODS: Related articles were obtained from online databases and screened according to the inclusion criteria. The pooled IVRs were calculated using the random effects model. Subgroup analyses and multivariate meta-regression were performed to determine the factors associated with influenza vaccine uptake. RESULTS: e included 522 studies from 68 countries/regions. Most studies were conducted in the European region (247 studies), followed by the Western Pacific (135 studies) and American regions (100 studies). The IVRs with 95% confidence intervals (CIs) in the general population were lower (24.96%, 23.45%-26.50%) than in individuals with chronic diseases (41.65%, 40.08%-43.23%), healthcare workers (36.57%, 33.74%-39.44%), and pregnant women (25.92%, 23.18%-28.75%). The IVRs in high-income countries/regions were significantly higher than that in middle-income countries/regions. A free national or regional vaccination policy, perception of influenza vaccine efficacy and disease severity, a recommendation from healthcare workers, and having a history of influenza vaccination were positive factors for vaccine uptake (P <0.01). CONCLUSION: Overall, global IVRs were low, especially in the general population. The studies on the IVRs, especially for priority populations, should be strengthened in Eastern Mediterranean, South-East Asian, and African regions. Free vaccination policies and the dissemination of continuous awareness campaigns are effective measures to enhance vaccination uptake.

Low infectious risk of re-positive COVID-19 patients: a single-center study.

OBJECTIVE: The aim of this study was to investigate the infectiousness of re-positive coronavirus disease 2019 (COVID-19) patients. METHODS: All nucleic acid testing (NAT) was performed using throat swabs, nasopharyngeal swabs, and anal swabs, which were tested by Fluorescent quantitative realtime PCR. Re-positive cases were defined as a discharged patient who re-tested positive by NAT. Micro-neutralization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was performed based on the methods for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) viruses. IgM and IgG against the N protein of SARS-CoV-2 were determined by ELISA. RESULTS: A total 255 (16.04%) of 1590 COVID-19 patients were re-positive. The re-positive cases were more likely to occur in patients in the 20-39 years age group and in patients with disease of moderate severity. Quantitative PCR showed that cycle threshold (Ct) values and viral loads were both far lower than in the hospitalized COVID-19 patients. The viral load in re-positive cases was very low. Viral culture of the samples from re-positive patients showed no cytopathic effect, and NAT of the culture medium of viral cultures all exhibited negative results. CONCLUSION: The viral load in re-positive cases was very low; patients were not infectious and the risk of human-to-human transmission was extremely low. Discharged COVID-19 patients should undergo home health management for 3 weeks.

Hom-Complex-Based Machine Learning (HCML) for the Prediction of Protein-Protein Binding Affinity Changes upon Mutation.

Protein-protein interactions (PPIs) are involved in almost all biological processes in the cell. Understanding protein-protein interactions holds the key for the understanding of biological functions, diseases and the development of therapeutics. Recently, artificial intelligence (AI) models have demonstrated great power in PPIs. However, a key issue for all AI-based PPI models is efficient molecular representations and featurization. Here, we propose Hom-complex-based PPI representation, and Hom-complex-based machine learning models for the prediction of PPI binding affinity changes upon mutation, for the first time. In our model, various Hom complexes Hom(G1, G) can be generated for the graph representation G of protein-protein complex by using different graphs G1, which reveal G1-related inner connections within the graph representation G of protein-protein complex. Further, for a specific graph G1, a series of nested Hom complexes are generated to give a multiscale characterization of the PPIs. Its persistent homology and persistent Euler characteristic are used as molecular descriptors and further combined with the machine learning model, in particular, gradient boosting tree (GBT). We systematically test our model on the two most-commonly used data sets, that is, SKEMPI and AB-Bind. It has been found that our model outperforms all the existing models as far as we know, which demonstrates the great potential of our model for the analysis of PPIs. Our model can be used for the analysis and design of efficient antibodies for SARS-CoV-2.

Chlorine poisoning caused by improper mixing of household disinfectants during the COVID-19 pandemic: Case series.

BACKGROUND: Misuse of disinfectants during the coronavirus disease 2019 pandemic has led to several poisoning incidents. However, there are few clinical case reports on poisoning caused by improper mixing of household disinfectants. AIM: To summarize the clinical characteristics and treatment effects of chlorine poisoning caused by improper mixing of hypochlorite bleach with acidic cleaning agents.METHODSWe retrospectively analyzed baseline and clinical data, clinical symptoms, and treatment methods of seven patients with chlorine poisoning who were admitted to the National Army Poisoning Treatment Center. RESULTS: Among the seven patients, the average poisoning time (exposure to admission) was 57 h (4-240 h). All patients were involved in cleaning bathrooms. Chest computed tomography scans revealed bilateral lung effusions or inflammatory changes in five patients. The partial pressure of oxygen decreased in six patients, and respiratory failure occurred in one. Five patients had different degrees of increase in white blood cell count. Humidified oxygen therapy, non-invasive mechanical ventilation, anti-inflammatory corticosteroids, antioxidants, and antibiotics were administered for treatment. The average length of hospital stay was 7 d (4-9 d). All seven patients recovered and were discharged. CONCLUSION: Improper mixing of household disinfectants may cause damage to the respiratory system due to chlorine poisoning. Corticosteroids may improve lung exudation in severe cases, and symptomatic supportive treatment should be performed early.

Chemiluminescent Imaging Assay of SARS-CoV-2 Protein with Target-Induced Enzyme Activity Regulation.

Simple but robust testing assays are essential for screening and diagnosis of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in COVID-19 pandemic. Here, we described a chemiluminescent imaging assay (CLIA) for sensitive and convenient detection of SARS-CoV-2 nucleocapsid protein (NP) by a target-induced enzyme activity regulation (T-EAR) strategy. The T-EAR used a pair of antibody-DNA probes to recognize SARS-CoV-2 NP and proximity-induce rolling circle amplification for mass-production of pyrophosphate to coordinate with Cu2+ , which prevented the reduction of Cu2+ to Cu+ by sodium ascorbate as well as the Cu+ -caused inactivation of horseradish peroxidase (HRP). The activity retention of HRP produced strong CL signal for the detection of SARS-CoV-2 NP by catalyzing the oxidation of luminol by H2 O2 . The T-EAR based CLIA showed a wide detection range from 1 pg/mL to 100 ng/mL (13 fM to 1.3 nM) with the requirement of only 0.75 µL of sample. This CLIA had advantages of good sensitivity, simple wash-free operation, acceptable accuracy, and high-throughput imaging detection, displaying potential applicability in screening assay of COVID-19 infection.

Unusual global outbreak of monkeypox: what should we do?

Recently, monkeypox has become a global concern amid the ongoing COVID-19 pandemic. Monkeypox is an acute rash zoonosis caused by the monkeypox virus, which was previously concentrated in Africa. The re-emergence of this pathogen seems unusual on account of outbreaks in multiple nonendemic countries and the incline to spread from person to person. We need to revisit this virus to prevent the epidemic from getting worse. In this review, we comprehensively summarize studies on monkeypox, including its epidemiology, biological characteristics, pathogenesis, and clinical characteristics, as well as therapeutics and vaccines, highlighting its unusual outbreak attributed to the transformation of transmission. We also analyze the present situation and put forward countermeasures from both clinical and scientific research to address it.

First isolation and identification of SARS-CoV-2 in Guangdong Province, China

In January 2020, Guangdong Province, China imported several suspected cases with SARS-CoV-2 from Wuhan City, Hubei Province. China, which were detected as SARS-CoV-2 positive in laboratory. To further understand the SARS-CoV-2 virulence, as well as drug development and epidemic prevention and control needs, we established a SARS-CoV-2 isolation procedure. Vero-E6 cells were infected with the positive bronchoalveolar-lavage sample. The cells were monitored daily for cytopathic effects using light microscopy. The presence of viral nucleic acid in the supernatant was detected by RT-PCR. RNA extracted from culture supernatants were used as a template to clone and sequence the genome. We used Illumina sequencing to characterize the virus genome and results showed that the isolated virus was SARS-CoV-2.

Evaluating the Response and Safety of Inactivated COVID-19 Vaccines in Liver Transplant Recipients.

Purpose: To evaluate the response and safety of an inactivated vaccine (Sinovac Life Sciences Co., Ltd., Beijing, China) for coronavirus disease 2019 (COVID-19) in liver transplant (LTx) recipients from China. Patients and Methods: Thirty-five recipients post LTx from the First Affiliated Hospital of Zhejiang University School of Medicine who received inactivated vaccine from June to October 2021 were screened. Information regarding vaccine side effects and clinical data were collected. Results: Thirty-five LTx recipients were enrolled, with a mean age of 46 years, and most patients were male (30, 85.71%). All the participants had a negative history of COVID-19 infection. Predictors for negative response in the recipients were interleukin-2 receptor (IL-2R) induction during LTx, shorter time post LTx and application of a derivative from mycophenolate acid (MPA). No serious adverse events were observed during the progress of vaccination or after the vaccination. Conclusion: LTx recipients have a substantially partial immunological response to the inactivated vaccine for COVID-19. IL-2R induction during LTx, a shorter time post LTx and the application of a derivative from MPA seem to be predictors for a negative serological immunoglobulin G (IgG) antibody response in recipients. The findings require booster vaccination in these LTx recipients.

Assessment of the Benefits of Targeted Interventions for Pandemic Control in China Based on Machine Learning Method and Web Service for COVID-19 Policy Simulation.

Taking the Chinese city of Xiamen as an example, simulation and quantitative analysis were performed on the transmissions of the Coronavirus Disease 2019 (COVID-19) and the influence of intervention combinations to assist policymakers in the preparation of targeted response measures. A machine learning model was built to estimate the effectiveness of interventions and simulate transmission in different scenarios. The comparison was conducted between simulated and real cases in Xiamen. A web interface with adjustable parameters, including choice of intervention measures, intervention weights, vaccination, and viral variants, was designed for users to run the simulation. The total case number was set as the outcome. The cumulative number was 4,614,641 without restrictions and 78 under the strictest intervention set. Simulation with the parameters closest to the real situation of the Xiamen outbreak was performed to verify the accuracy and reliability of the model. The simulation model generated a duration of 52 days before the daily cases dropped to zero and the final cumulative case number of 200, which were 25 more days and 36 fewer cases than the real situation, respectively. Targeted interventions could benefit the prevention and control of COVID-19 outbreak while safeguarding public health and mitigating impacts on people's livelihood.

Evaluation of an intelligent artificial climate chamber for high-throughput crop phenotyping in wheat.

BACKGROUND: The superposition of COVID-19 and climate change has brought great challenges to global food security. As a major economic crop in the world, studying its phenotype to cultivate high-quality wheat varieties is an important way to increase grain yield. However, most of the existing phenotyping platforms have the disadvantages of high construction and maintenance costs, immobile and limited in use by climatic factors, while the traditional climate chambers lack phenotypic data acquisition, which makes crop phenotyping research and development difficult. Crop breeding progress is slow. At present, there is an urgent need to develop a low-cost, easy-to-promote, climate- and site-independent facility that combines the functions of crop cultivation and phenotype acquisition. We propose a movable cabin-type intelligent artificial climate chamber, and build an environmental control system, a crop phenotype monitoring system, and a crop phenotype acquisition system. RESULT: We selected two wheat varieties with different early vigor to carry out the cultivation experiments and phenotype acquisition of wheat under different nitrogen fertilizer application rates in an intelligent artificial climate chamber. With the help of the crop phenotype acquisition system, images of wheat at the trefoil stage, pre-tillering stage, late tillering stage and jointing stage were collected, and then the phenotypic information including wheat leaf area, plant height, and canopy temperature were extracted by the crop type acquisition system. We compared systematic and manual measurements of crop phenotypes for wheat phenotypes. The results of the analysis showed that the systematic measurements of leaf area, plant height and canopy temperature of wheat in four growth periods were highly correlated with the artificial measurements. The correlation coefficient (r) is positive, and the determination coefficient (R2) is greater than 0.7156. The root mean square error (RSME) is less than 2.42. Among them, the crop phenotype-based collection system has the smallest measurement error for the phenotypic characteristics of wheat trefoil stage. The canopy temperature RSME is only 0.261. The systematic measurement values of wheat phenotypic characteristics were significantly positively correlated with the artificial measurement values, the fitting degree was good, and the errors were all within the acceptable range. The experiment showed that the phenotypic data obtained with the intelligent artificial climate chamber has high accuracy. We verified the feasibility of wheat cultivation and phenotype acquisition based on intelligent artificial climate chamber. CONCLUSION: It is feasible to study wheat cultivation and canopy phenotype with the help of intelligent artificial climate chamber. Based on a variety of environmental monitoring sensors and environmental regulation equipment, the growth environment factors of crops can be adjusted. Based on high-precision mechanical transmission and multi-dimensional imaging sensors, crop images can be collected to extract crop phenotype information. Its use is not limited by environmental and climatic factors. Therefore, the intelligent artificial climate chamber is expected to be a powerful tool for breeders to develop excellent germplasm varieties.

Changes in Influenza Activity and Circulating Subtypes During the COVID-19 Outbreak in China.

Background: Non-pharmaceutical interventions (NPIs) to mitigate COVID-19 can impact the circulation of influenza viruses. There is a need to describe the activity of influenza and its subtypes during the COVID-19 pandemic to aid in the development of influenza prevention and control measures in the next influenza season. Method: Data from pathogenic surveillance performed by the Chinese National Influenza Center from January 2016 to August 2021 were extracted and stratified by type and subtype for northern China and southern China. The distribution of influenza activity and circulating subtypes were described during the COVID-19 pandemic, and data from 2016 to 2019 were used for comparisons. Results: Influenza activity declined rapidly and then rose slowly during the COVID-19 pandemic in China. The distribution of influenza subtypes changed from A-dominant to B/Victoria-dominant after the COVID-19 outbreak. Discussion: Whether the B/Yamagata lineage has disappeared from China deserves more attention in future virologic monitoring programs. The influenza vaccination campaign in the 2021-2022 season is an important means by which to reduce the proportion of susceptible people and limit the damage that potentially greater and earlier circulation of the virus could cause.

Numerical investigation of airborne transmission of respiratory infections on the subway platform

Underground subway platforms are among the world’s busiest public transportation systems, but the airborne transmission mechanism of respiratory infections on these platforms has been rarely studied. Here, computational fluid dynamics (CFD) modeling is used to investigate the airflow patterns and infection risks in an island platform under two common ventilation modes: Mode 1- both sides have air inlets and outlets;Mode 2- air inlets are present at the two sides and outlets are present in the middle. Under the investigated scenario, airflow structure is characterized by the ventilation jet and human thermal plumes. Their interaction with the infector’s breathing jet imposes the front passenger under the highest exposure risk by short-range airborne route, with intake fractions up to 2.57% (oral breathing) or 0.63% (nasal breathing) under Mode 1;oral breathing of the infector may impose higher risks for the front passenger compared with nasal breathing. Pathogen are efficiently diluted as they travel further, in particular to adjacent crowds. The maximum and median value of intake fractions of passengers in adjacent crowds are respectively 0.093% and 0.016% (oral breathing), and 0.073% and 0.014% (nasal breathing) under Mode 1. Compared with Mode 1, the 2nd mode minimizes the interaction of ventilation jet and breathing jet, where the maximum intake fraction is only 0.34%, and the median value in the same crowd and other crowds are reduced by 23-63%. Combining published quanta generation rate data of COVID-19 and influenza infectors, the predicted maximum and median infection risks for passengers in the same crowds are respectively 1.46%−40.23% and 0.038%−1.67% during the 3−10 min waiting period, which are more sensitive to ventilation rate and exposure time compared with return air. This study can provide practical guidance for the prevention of respiratory infections in subway platforms.

Microglia Do Not Restrict SARS-CoV-2 Replication following Infection of the Central Nervous System of K18-Human ACE2 Transgenic Mice.

Unlike SARS-CoV-1 and MERS-CoV, infection with SARS-CoV-2, the viral pathogen responsible for COVID-19, is often associated with neurologic symptoms that range from mild to severe, yet increasing evidence argues the virus does not exhibit extensive neuroinvasive properties. We demonstrate SARS-CoV-2 can infect and replicate in human iPSC-derived neurons and that infection shows limited antiviral and inflammatory responses but increased activation of EIF2 signaling following infection as determined by RNA sequencing. Intranasal infection of K18 human ACE2 transgenic mice (K18-hACE2) with SARS-CoV-2 resulted in lung pathology associated with viral replication and immune cell infiltration. In addition, ∼50% of infected mice exhibited CNS infection characterized by wide-spread viral replication in neurons accompanied by increased expression of chemokine (Cxcl9, Cxcl10, Ccl2, Ccl5 and Ccl19) and cytokine (Ifn-λ and Tnf-α) transcripts associated with microgliosis and a neuroinflammatory response consisting primarily of monocytes/macrophages. Microglia depletion via administration of colony-stimulating factor 1 receptor inhibitor, PLX5622, in SARS-CoV-2 infected mice did not affect survival or viral replication but did result in dampened expression of proinflammatory cytokine/chemokine transcripts and a reduction in monocyte/macrophage infiltration. These results argue that microglia are dispensable in terms of controlling SARS-CoV-2 replication in in the K18-hACE2 model but do contribute to an inflammatory response through expression of pro-inflammatory genes. Collectively, these findings contribute to previous work demonstrating the ability of SARS-CoV-2 to infect neurons as well as emphasizing the potential use of the K18-hACE2 model to study immunological and neuropathological aspects related to SARS-CoV-2-induced neurologic disease. IMPORTANCE Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the role of microglia in aiding in host defense following experimental infection of the central nervous system (CNS) of K18-hACE2 with SARS-CoV-2, the causative agent of COVID-19. Neurologic symptoms that range in severity are common in COVID-19 patients and understanding immune responses that contribute to restricting neurologic disease can provide important insight into better understanding consequences associated with SARS-CoV-2 infection of the CNS.

Application of pseudovirus system in the development of vaccine, antiviral-drugs, and neutralizing antibodies.

Pseudoviruses are viral particles coated with a heterologous envelope protein, which mediates the entry of pseudoviruses as efficiently as that of the live viruses possessing high pathogenicity and infectivity. Due to the deletion of the envelope protein gene and the absence of pathogenic genes, pseudoviruses have no autonomous replication ability and can infect host cells for only a single cycle. In addition, pseudoviruses have the desired characteristics of high safety, strong operability, and can be easily used to perform rapid throughput detection. Therefore, pseudoviruses are widely employed in the mechanistic investigation of viral infection, the screening and evaluation of monoclonal antibodies and antiviral drugs, and the detection of neutralizing antibody titers in serum after vaccination. In this review, we will discuss the construction of pseudoviruses based on different packaging systems, their current applications especially in the research of SARS-CoV-2, limitations, and further directions.