Case report: COVID-19-associated refractory thrombotic thrombocytopenic purpura complicated with Guillain-Barré syndrome.

Thrombotic thrombocytopenic purpura (TTP), a rare and lethal thrombotic microangiopathy, is an autoimmune disease that can be triggered by viral infections such as COVID-19. This condition is characterized by hemolytic microangiopathy, thrombocytopenia, and neurologic alterations, possibly accompanied by fever and renal damage. Moreover, more than 220 patients with Guillain-Barré syndrome (GBS) have been reported in association with the COVID-19 infection. In this report, we present a case of a patient who developed refractory TTP complicated by GBS following a SARS-CoV-2 infection. We aimed to highlight the importance of accurately diagnosing neurological complications associated with a COVID-19 infection and to demonstrate our strategies for treating a patient with COVID-19 infection-related refractory TTP complicated by GBS.

A Nomogram Model for Predicting the Polyphenol Content of Pu-Erh Tea.

To investigate different contents of pu-erh tea polyphenol affected by abiotic stress, this research determined the contents of tea polyphenol in teas produced by Yuecheng, a Xishuangbanna-based tea producer in Yunnan Province. The study drew a preliminary conclusion that eight factors, namely, altitude, nickel, available cadmium, organic matter, N, P, K, and alkaline hydrolysis nitrogen, had a considerable influence on tea polyphenol content with a combined analysis of specific altitudes and soil composition. The nomogram model constructed with three variables, altitude, organic matter, and P, screened by LASSO regression showed that the AUC of the training group and the validation group were respectively 0.839 and 0.750, and calibration curves were consistent. A visualized prediction system for the content of pu-erh tea polyphenol based on the nomogram model was developed and its accuracy rate, supported by measured data, reached 80.95%. This research explored the change of tea polyphenol content under abiotic stress, laying a solid foundation for further predictions for and studies on the quality of pu-erh tea and providing some theoretical scientific basis.

Influenza surveillance in Ezhou city, Hubei Province, 2016-2021

ObjectiveTo analyze the influenza surveillance data in Ezhou City, Hubei Province from 2016 to 2021, determine the epidemiological characteristics and etiological trend of influenza like illness (ILI), and to provide scientific evidence for influenza prevention and control. MethodsThe ILI surveillance data were reported by Ezhou influenza sentinel hospitals and etiological examination results were collected by network laboratory. Influenza surveillance data from 2016 to 2021 were analyzed. ResultsFrom 2016 to 2021, the percentage of ILI visits (ILI%) in Ezhou city was 2.81% and increased over years. Majority (55.55%) of ILI cases were 0-4 years. A total of 7 716 ILI samples were examined from 2016 to 2021, of which 1 467 tested positive with a positive rate of 19.01%. Influenza A H1N1 was mainly concentrated in January-April, A H3N2 mainly in August-December, B Victoria mainly in April-July and December-March, and B Yamagata mainly in December-February. Influenza network laboratory isolated influenza virus from the 1 467 positive samples by using MDCK cells and SPF chicken embryos. The overall isolation rate was 32.78%, which was 26.93% by MDCK cells and 5.86% by SPF chicken embryos. From 2016 to 2021, a total of 13 ILI outbreaks were reported in Ezhou City. Temporally, the outbreaks mainly occurred in winter and spring. Spatially, they were mainly in primary schools, middle schools and kindergartens. ConclusionThe winter and spring are the key time period of influenza prevention and control in Ezhou City, as they are susceptible to influenza outbreaks. Children aged 0-14 are the key population of prevention and control. Diverse subtypes of influenza virus alternate by years, which warrants continually strengthening monitoring. Additionally, certain countermeasures against COVID-19 may be recommended in the prevention and control of influenza.

Advanced Nitric Oxide Generating Nanomedicine for Therapeutic Applications.

Nitric oxide (NO), a gaseous transmitter extensively present in the human body, regulates vascular relaxation, immune response, inflammation, neurotransmission, and other crucial functions. Nitrite donors have been used clinically to treat angina, heart failure, pulmonary hypertension, and erectile dysfunction. Based on NO's vast biological functions, it further can treat tumors, bacteria/biofilms and other infections, wound healing, eye diseases, and osteoporosis. However, delivering NO is challenging due to uncontrolled blood circulation release and a half-life of under five seconds. With advanced biotechnology and the development of nanomedicine, NO donors packaged with multifunctional nanocarriers by physically embedding or chemically conjugating have been reported to show improved therapeutic efficacy and reduced side effects. Herein, we review and discuss recent applications of NO nanomedicines, their therapeutic mechanisms, and the challenges of NO nanomedicines for future scientific studies and clinical applications. As NO enables the inhibition of the replication of DNA and RNA in infectious microbes, including COVID-19 coronaviruses and malaria parasites, we highlight the potential of NO nanomedicines for antipandemic efforts. This review aims to provide deep insights and practical hints into design strategies and applications of NO nanomedicines.

Exploring Potential Biomarkers and Molecular Mechanisms of Ischemic Cardiomyopathy and COVID-19 Comorbidity Based on Bioinformatics and Systems Biology.

Cardiovascular complications combined with COVID-19 (SARS-CoV-2) lead to a poor prognosis in patients. The common pathogenesis of ischemic cardiomyopathy (ICM) and COVID-19 is still unclear. Here, we explored potential molecular mechanisms and biomarkers for ICM and COVID-19. Common differentially expressed genes (DEGs) of ICM (GSE5406) and COVID-19 (GSE164805) were identified using GEO2R. We performed enrichment and protein-protein interaction analyses and screened key genes. To confirm the diagnostic performance for these hub genes, we used external datasets (GSE116250 and GSE211979) and plotted ROC curves. Transcription factor and microRNA regulatory networks were constructed for the validated hub genes. Finally, drug prediction and molecular docking validation were performed using cMAP. We identified 81 common DEGs, many of which were enriched in terms of their relation to angiogenesis. Three DEGs were identified as key hub genes (HSP90AA1, HSPA9, and SRSF1) in the protein-protein interaction analysis. These hub genes had high diagnostic performance in the four datasets (AUC > 0.7). Mir-16-5p and KLF9 transcription factor co-regulated these hub genes. The drugs vindesine and ON-01910 showed good binding performance to the hub genes. We identified HSP90AA1, HSPA9, and SRSF1 as markers for the co-pathogenesis of ICM and COVID-19, and showed that co-pathogenesis of ICM and COVID-19 may be related to angiogenesis. Vindesine and ON-01910 were predicted as potential therapeutic agents. Our findings will contribute to a deeper understanding of the comorbidity of ICM with COVID-19.

Exploring hospitality workers' career choices in the wake of COVID-19: Insights from a phenomenological inquiry.

The COVID-19 pandemic severely hit the hospitality industry and caused employees concerns over health, finance, and well-being. These challenges may trigger their decisions to leave the profession, leading to major talent crises in the industry. Guided by the transactional model of stress and coping and the career construction theory, this study explored how their experiences with the pandemic affected their career choices moving on. A phenomenological approach was adopted, and 31 current and past hospitality employees were interviewed. The findings supported the conceptual model and addressed the connection between stress management and career decisions among the participants. It is also noted that, besides generational differences, most participants' career decisions at this critical moment were influenced by their personality traits, industry involvement, and employer-employee relationships. Thus, to create a sustainable, resilient, and engaged workforce, hospitality practitioners must commit to crafting positive relationships with their employees both in regular and crisis times.

Forecasting method of highway freight volume based on GC-rBPNN model during COVID-19 epidemic

Under the COVID-19 epidemic situation, the volume of road freight has declined significantly, and road operations have changed complexly. It is urgent to scientifically predict the volume of road freight. Through gray correlation analysis, the main factors affecting road freight volume during the epidemic period are determined, and a road freight volume forecast method based on the gray combination(GC)-revised BP neural network(rBPNN) model is constructed. The BP neural network is trained and tested based on the statistical data of China's road freight volume from July 2017 to May 2020 as the original data, and the "correction coefficient" HM is introduced to modify the predicting result. Based on the data of the past five months during the epidemic, the gray combined model is used to predict the value of the main factors affecting the road freight volume in the next month, and the BP neural network is used to predict China's road freight volume in June 2020. Compared the GC-rBPNN model with other prediction methods, the PE and MAPE of the GC-rBPNN model are 0.21% and 3.21%, respectively. The results show that the prediction accuracy of the GC-rBPNN model is higher, and the method has certain feasibility and effectiveness.

Seven bacterial response-related genes are biomarkers for colon cancer.

BACKGROUND: Colon cancer (CC) is a common tumor that causes significant harm to human health. Bacteria play a vital role in cancer biology, particularly the biology of CC. Genes related to bacterial response were seldom used to construct prognosis models. We constructed a bacterial response-related risk model based on three Molecular Signatures Database gene sets to explore new markers for predicting CC prognosis. METHODS: The Cancer Genome Atlas (TCGA) colon adenocarcinoma samples were used as the training set, and Gene Expression Omnibus (GEO) databases were used as the test set. Differentially expressed bacterial response-related genes were identified for prognostic gene selection. Univariate Cox regression analysis, least absolute shrinkage and selection operator-penalized Cox regression analysis, and multivariate Cox regression analysis were performed to construct a prognostic risk model. The individual diagnostic effects of genes in the prognostic model were also evaluated. Moreover, differentially expressed long noncoding RNAs (lncRNAs) were identified. Finally, the expression of these genes was validated using quantitative polymerase chain reaction (qPCR) in cell lines and tissues. RESULTS: A prognostic signature was constructed based on seven bacterial response genes: LGALS4, RORC, DDIT3, NSUN5, RBCK1, RGL2, and SERPINE1. Patients were assigned a risk score based on the prognostic model, and patients in the TCGA cohort with a high risk score had a poorer prognosis than those with a low risk score; a similar finding was observed in the GEO cohort. These seven prognostic model genes were also independent diagnostic factors. Finally, qPCR validated the differential expression of the seven model genes and two coexpressed lncRNAs (C6orf223 and SLC12A9-AS1) in 27 pairs of CC and normal tissues. Differential expression of LGALS4 and NSUN5 was also verified in cell lines (FHC, COLO320DM, SW480). CONCLUSIONS: We created a seven-gene bacterial response-related gene signature that can accurately predict the outcomes of patients with CC. This model can provide valuable insights for personalized treatment.

Isothermal nucleic acid amplification technology for rapid detection of virus.

While the research field and industrial market of in vitro diagnosis (IVD) thrived during and post the COVID-19 pandemic, the development of isothermal nucleic acid amplification test (INAAT) based rapid diagnosis was engendered in a global wised large measure as a problem-solving exercise. This review systematically analyzed the recent advances of INAAT strategies with practical case for the real-world scenario virus detection applications. With the qualities that make INAAT systems useful for making diagnosis relevant decisions, the key performance indicators and the cost-effectiveness of enzyme-assisted methods and enzyme-free methods were compared. The modularity of nucleic acid amplification reactions that can lead to thresholding signal amplifications using INAAT reagents and their methodology design were examined, alongside the potential application with rapid test platform/device integration. Given that clinical practitioners are, by and large, unaware of many the isothermal nucleic acid test advances. This review could bridge the arcane research field of different INAAT systems and signal output modalities with end-users in clinic when choosing suitable test kits and/or methods for rapid virus detection.

New cardiovascular events in the convalescent period among survivors of SARS-CoV-2 infection.

BACKGROUND: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may have an increased risk of acute cardiovascular events in the convalescent period. AIMS: To determine whether patients with SARS-CoV-2 infection have an increased risk of cardiovascular events during the convalescent period. METHODS: We analyzed 10,691 hospitalized adult pneumonia patients with SARS-CoV-2 infection and contemporary matched controls of pneumonia patients without SARS-CoV-2 infection. The risk of new cardiovascular events following >30 days pneumonia admission (convalescent period) was ascertained using Cox proportional hazards regression analysis to adjust for potential confounders. RESULTS: Among 10,691 pneumonia patients with SARS-CoV-2 infection, 697 patients (5.8%; 95% CI, 5.4-6.2%) developed new cardiovascular events (median time interval of 218 days post pneumonia admission; interquartile range Q1 = 117 days, Q3 = 313 days). The risk of new cardiovascular events was not significantly higher among pneumonia patients with SARS-CoV-2 infection compared with those with pneumonia without SARS-CoV-2 infection (hazard ratio (HR), 0.90, 95% CI, 0.80-1.02) after adjustment for potential confounders. In addition, no significant difference in the rate of a new ischemic stroke (HR, 0.84; 95% CI, 0.70-1.02) or ischemic heart disease (HR, 1.00; 95% CI, 0.87-1.15) was observed between the pneumonia patients with and without SARS-CoV-2 infection. CONCLUSION: Our study suggests that new cardiovascular events rate in the convalescent period among pneumonia patients with SARS-CoV-2 infection was not significantly higher than the rate seen with other pneumonias.

Risk of Myocarditis and Pericarditis Following Coronavirus Disease 2019 Messenger RNA Vaccination—A Nationwide Study

Background An extended interval between the two primary doses may reduce the risk of myocarditis/pericarditis after COVID-19 mRNA vaccination. Taiwan has implemented a two-dose regimen with a 12-week interval for adolescents. Here we present nationwide data of myocarditis/pericarditis following COVID-19 vaccinations. Methods Data on adverse events of myocarditis/pericarditis were from the Taiwan Vaccine Adverse Events Reporting System between March 22, 2021, and February 9, 2022. The reporting rates according to sex, age, and vaccine type were calculated. We investigated the rates among young individuals under different two-dose intervals and among those who received two doses of different vaccines. Results Among 204 cases who met the case definition of myocarditis/pericarditis, 75 cases occurred after the first dose and 129 after the second. The rate of myocarditis/pericarditis after COVID-19 vaccination varied across sex and age groups and was highest after the second dose in males aged 12–17 years (126.79 cases per million vaccinees) for the BNT162b2 vaccine and in males aged 18–24 years (93.84 cases per million vaccinees) for the mRNA-1273 vaccine. The data did not suggest an association between longer between-dose interval and lower rate of myocarditis/pericarditis among males and females aged 18–24 or 25–29 years who received two doses of the BNT162b2 or mRNA-1273 vaccine. Rates of myocarditis/pericarditis in males and females aged 18–49 years after receiving ChAdOx1-S - mRNA-1273 vaccination was significantly higher than after ChAdOx1-S - ChAdOx1-S vaccination. Conclusions Myocarditis and pericarditis are rare following mRNA vaccination, with higher risk occurring in young males after the second dose.

Exosome-Based Carrier for RNA Delivery: Progress and Challenges.

In the last few decades, RNA-based drugs have emerged as a promising candidate to specifically target and modulate disease-relevant genes to cure genetic defects. The key to applying RNA therapy in clinical trials is developing safe and effective delivery systems. Exosomes have been exploited as a promising vehicle for drug delivery due to their nanoscale size, high stability, high biocompatibility, and low immunogenicity. We reviewed and summarized the progress in the strategy and application of exosome-mediated RNA therapy. The challenges of exosomes as a carrier for RNA drug delivery are also elucidated in this article. RNA molecules can be loaded into exosomes and then delivered to targeted cells or tissues via various biochemical or physical approaches. So far, exosome-mediated RNA therapy has shown potential in the treatment of cancer, central nervous system disorders, COVID-19, and other diseases. To further exploit the potential of exosomes for RNA delivery, more efforts should be made to overcome both technological and logistic problems.

Monocytic HLA-DR Expression in Immune Responses of Acute Pancreatitis and COVID-19.

Acute pancreatitis is a common gastrointestinal disease with increasing incidence worldwide. COVID-19 is a potentially life-threatening contagious disease spread throughout the world, caused by severe acute respiratory syndrome coronavirus 2. More severe forms of both diseases exhibit commonalities with dysregulated immune responses resulting in amplified inflammation and susceptibility to infection. Human leucocyte antigen (HLA)-DR, expressed on antigen-presenting cells, acts as an indicator of immune function. Research advances have highlighted the predictive values of monocytic HLA-DR (mHLA-DR) expression for disease severity and infectious complications in both acute pancreatitis and COVID-19 patients. While the regulatory mechanism of altered mHLA-DR expression remains unclear, HLA-DR-/low monocytic myeloid-derived suppressor cells are potent drivers of immunosuppression and poor outcomes in these diseases. Future studies with mHLA-DR-guided enrollment or targeted immunotherapy are warranted in more severe cases of patients with acute pancreatitis and COVID-19.

Risk of myocarditis and pericarditis following coronavirus disease 2019 messenger RNA Vaccination-A nationwide study.

BACKGROUND: An extended interval between the two primary doses may reduce the risk of myocarditis/pericarditis after COVID-19 mRNA vaccination. Taiwan has implemented a two-dose regimen with a 12-week interval for adolescents. Here we present nationwide data of myocarditis/pericarditis following COVID-19 vaccinations. METHODS: Data on adverse events of myocarditis/pericarditis were from the Taiwan Vaccine Adverse Events Reporting System between March 22, 2021, and February 9, 2022. The reporting rates according to sex, age, and vaccine type were calculated. We investigated the rates among young individuals under different two-dose intervals and among those who received two doses of different vaccines. RESULTS: Among 204 cases who met the case definition of myocarditis/pericarditis, 75 cases occurred after the first dose and 129 after the second. The rate of myocarditis/pericarditis after COVID-19 vaccination varied across sex and age groups and was highest after the second dose in males aged 12-17 years (126.79 cases per million vaccinees) for the BNT162b2 vaccine and in males aged 18-24 years (93.84 cases per million vaccinees) for the mRNA-1273 vaccine. The data did not suggest an association between longer between-dose interval and lower rate of myocarditis/pericarditis among males and females aged 18-24 or 25-29 years who received two doses of the BNT162b2 or mRNA-1273 vaccine. Rates of myocarditis/pericarditis in males and females aged 18-49 years after receiving ChAdOx1-S - mRNA-1273 vaccination was significantly higher than after ChAdOx1-S - ChAdOx1-S vaccination. CONCLUSIONS: Myocarditis and pericarditis are rare following mRNA vaccination, with higher risk occurring in young males after the second dose.

Enhancing COVID-19 Epidemic Forecasting Accuracy by Combining Real-time and Historical Data From Multiple Internet-Based Sources: Analysis of Social Media Data, Online News Articles, and Search Queries.

BACKGROUND: The SARS-COV-2 virus and its variants pose extraordinary challenges for public health worldwide. Timely and accurate forecasting of the COVID-19 epidemic is key to sustaining interventions and policies and efficient resource allocation. Internet-based data sources have shown great potential to supplement traditional infectious disease surveillance, and the combination of different Internet-based data sources has shown greater power to enhance epidemic forecasting accuracy than using a single Internet-based data source. However, existing methods incorporating multiple Internet-based data sources only used real-time data from these sources as exogenous inputs but did not take all the historical data into account. Moreover, the predictive power of different Internet-based data sources in providing early warning for COVID-19 outbreaks has not been fully explored. OBJECTIVE: The main aim of our study is to explore whether combining real-time and historical data from multiple Internet-based sources could improve the COVID-19 forecasting accuracy over the existing baseline models. A secondary aim is to explore the COVID-19 forecasting timeliness based on different Internet-based data sources. METHODS: We first used core terms and symptom-related keyword-based methods to extract COVID-19-related Internet-based data from December 21, 2019, to February 29, 2020. The Internet-based data we explored included 90,493,912 online news articles, 37,401,900 microblogs, and all the Baidu search query data during that period. We then proposed an autoregressive model with exogenous inputs, incorporating real-time and historical data from multiple Internet-based sources. Our proposed model was compared with baseline models, and all the models were tested during the first wave of COVID-19 epidemics in Hubei province and the rest of mainland China separately. We also used lagged Pearson correlations for COVID-19 forecasting timeliness analysis. RESULTS: Our proposed model achieved the highest accuracy in all 5 accuracy measures, compared with all the baseline models of both Hubei province and the rest of mainland China. In mainland China, except for Hubei, the COVID-19 epidemic forecasting accuracy differences between our proposed model (model i) and all the other baseline models were statistically significant (model 1, t198=-8.722, P<.001; model 2, t198=-5.000, P<.001, model 3, t198=-1.882, P=.06; model 4, t198=-4.644, P<.001; model 5, t198=-4.488, P<.001). In Hubei province, our proposed model's forecasting accuracy improved significantly compared with the baseline model using historical new confirmed COVID-19 case counts only (model 1, t198=-1.732, P=.09). Our results also showed that Internet-based sources could provide a 2- to 6-day earlier warning for COVID-19 outbreaks. CONCLUSIONS: Our approach incorporating real-time and historical data from multiple Internet-based sources could improve forecasting accuracy for epidemics of COVID-19 and its variants, which may help improve public health agencies' interventions and resource allocation in mitigating and controlling new waves of COVID-19 or other relevant epidemics.

Effects of physical activity and use of digital devices on visual acuity in children and adolescents during the COVID-19 pandemic: A cross-sectional study.

Purpose: To determine the association between poor visual acuity, the use of digital devices and physical activity (PA) during the COVID-19 pandemic. Methods: A total of 327,646 Chinese children and adolescents were included in the analysis using a cluster random sampling method; this is a case-control study, of those 144,708 children and adolescents with poor visual acuity were included in the case group, while 182,938 who did not have poor visual acuity were included in the control group. A logistic regression model was used to assess the contribution of PA and the use of digital devices to poor visual acuity. Results: A total of 144,708 children and adolescents experienced poor visual acuity during the COVID-19 pandemic; 54.8% were male, and 55.2% live in rural areas. Compared to controls, children and adolescents with poor visual acuity exhibited more time for the use of digital devices (4.51 ± 2.44 vs. 3.79 ± 2.34 for cases and controls, respectively; P < 0.001) and PA (3.07 ± 0.92 vs. 2.85 ± 1.00 for cases and controls, respectively; P < 0.001). During the COVID-19 pandemic, risk factors related to poor visual acuity among children and adolescents included the use of digital devices (OR 1.135; 95% CI 1.132-1.139), and PA (OR 1.269; 95%CI 1.259-1.278). The results of interaction analysis show that for children and adolescents aged 12 to 17, the positive association between the use of digital devices and poor visual acuity decreased. The interaction effect between PA and digital devices is 0.987. Conclusions: Children and adolescents were at risk of poor visual acuity during the COVID-19 pandemic. Extended use of the digital devices increased the risk of poor visual acuity, especially for children aged 6-11 years. But the risk of poor visual acuity among children and adolescents decreases as the time spent on PA increases.

Electrochemical biosensors based on saliva electrolytes for rapid detection and diagnosis.

In recent years, electrochemical biosensors (ECBSs) have shown significant potential for real-time disease diagnosis and in situ physical condition monitoring. As a multi-constituent oral fluid comprising various disease signaling biomarkers, saliva has drawn much attention in the field of point-of-care (POC) testing. In particular, during the outbreak of the COVID-19 pandemic, ECBSs which hold the simplicity of a single-step assay compared with the multi-step assay of traditional testing methods are expected to relieve the human and economic burden caused by the massive and long-term sample testing process. Noteworthily, ECBSs for the detection of SARS-CoV-2 in saliva have already been developed and may replace current testing methods. Furthermore, the detection scope has expanded from routine indices such as sugar and uric acid to abnormal biomarkers for early-stage disease detection and drug level monitoring, which further facilitated the evolution of ECBSs in the last 5 years. This review is divided into several main sections. First, we discussed the latest advancements and representative research on ECBSs for saliva testing. Then, we focused on a novel kind of ECBS, organic electrochemical transistors (OECTs), which hold great advantages of high sensitivity and signal-to-noise ratio and on-site detection. Finally, application of ECBSs with integrated portable platforms in oral cavities, which lead to powerful auxiliary testing means for telemedicine, has also been discussed.

Interim analysis from a phase 2 randomized trial of EuCorVac-19: a recombinant protein SARS-CoV-2 RBD nanoliposome vaccine.

BACKGROUND: Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes. METHODS: Initial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19-75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 µg RBD), 96 received low-dose ECV19 (10 µg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT). RESULTS: Low-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p < 0.001 between groups). Neutralizing antibodies levels of the low-dose and high-dose ECV19 groups had FRNT50 geometric mean values of 129 and 316, respectively. Boosting responses and dose responses were observed. Antibodies against the RBD correlated with antibodies against the Spike and with virus neutralization. CONCLUSIONS: ECV19 was generally well-tolerated and induced antibodies in a dose-dependent manner that neutralized SARS-CoV-2. The unique liposome display approach of ECV19, which lacks any immunogenic protein components besides the antigen itself, coupled with the lack of increased adverse events during boosting suggest the vaccine platform may be amenable to multiple boosting regimes in the future. Taken together, these findings motivate further investigation of ECV19 in larger scale clinical testing that is underway. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov as # NCT04783311.

Recent Advances in Lipid Nanoparticles for Delivery of mRNA.

Messenger RNA (mRNA), which is composed of ribonucleotides that carry genetic information and direct protein synthesis, is transcribed from a strand of DNA as a template. On this basis, mRNA technology can take advantage of the body's own translation system to express proteins with multiple functions for the treatment of various diseases. Due to the advancement of mRNA synthesis and purification, modification and sequence optimization technologies, and the emerging lipid nanomaterials and other delivery systems, mRNA therapeutic regimens are becoming clinically feasible and exhibit significant reliability in mRNA stability, translation efficiency, and controlled immunogenicity. Lipid nanoparticles (LNPs), currently the leading non-viral delivery vehicles, have made many exciting advances in clinical translation as part of the COVID-19 vaccines and therefore have the potential to accelerate the clinical translation of gene drugs. Additionally, due to their small size, biocompatibility, and biodegradability, LNPs can effectively deliver nucleic acids into cells, which is particularly important for the current mRNA regimens. Therefore, the cutting-edge LNP@mRNA regimens hold great promise for cancer vaccines, infectious disease prevention, protein replacement therapy, gene editing, and rare disease treatment. To shed more lights on LNP@mRNA, this paper mainly discusses the rational of choosing LNPs as the non-viral vectors to deliver mRNA, the general rules for mRNA optimization and LNP preparation, and the various parameters affecting the delivery efficiency of LNP@mRNA, and finally summarizes the current research status as well as the current challenges. The latest research progress of LNPs in the treatment of other diseases such as oncological, cardiovascular, and infectious diseases is also given. Finally, the future applications and perspectives for LNP@mRNA are generally introduced.

Immunosenescence is a therapeutic target for frailty in older adults: a narrative review.

Background and Objective: Aging refers to a progressive decrease in functional performance, leading to increased mortality risk. At present, life expectancy is increasing worldwide and is expected to exceed 80 years by 2040. However, this increase in life expectancy also indicates a rise in the incidence and prevalence of diseases, such as cardiovascular, neurological, musculoskeletal, and oncological diseases, which are associated with aging. The exact underlying mechanisms of aging remain unknown, and whether it is a programmed process or the consequence of an accumulation of stress events remains unclear. Thus, more scientific research is needed to improve the management of complex and frail patients. Methods: Several databases were searched with the following key words: immunosenescence, inflamm-aging, frailty, sarcopenia and skeletal muscle, etc. Key Content and Findings: Skeletal muscle is the core phenotype of frailty and sarcopenia. Immune aging and skeletal muscle decline interplay with each other and form a vicious circle. Maintaining muscle health is beneficial for immune function and delays the onset of frailty. Particularly, in the context of the ongoing corona virus disease (COVID)-19 pandemic, studies have shown that the elderly are more prone to the consequences of the SARS-CoV-2 virus. It has been reported that the rates of hospitalization in the 65-74, 75-84, and ≥85 years old group were 5×, 8×, and 10× greater than the 18-29 years old group, with corresponding COVID-19-related deaths being 60×, 140×, and 330× that of the younger reference group, respectively. Considering the above, this review aims to discuss the relationship between immunosenescence, skeletal muscle, and frailty, and to explore immunosenescence as a potential therapeutic target to prevent frailty and extend healthspan, with some emphasis on the effects of the COVID-19 pandemic on the elderly. Conclusions: Immunosenescence is a promising potential therapeutic target for frailty and is worthy of further investigation.