Real-time risk ranking of emerging epidemics based on optimized moving average prediction limit-taking the COVID-19 pandemic as an example.

BACKGROUND: Mathematical models to forecast the risk trend of the COVID-19 pandemic timely are of great significance to control the pandemic, but the requirement of manual operation and many parameters hinders their efficiency and value for application. This study aimed to establish a convenient and prompt one for monitoring emerging infectious diseases online and achieving risk assessment in real time. METHODS: The Optimized Moving Average Prediction Limit (Op-MAPL) algorithm model analysed real-time COVID-19 data online and was validated using the data of the Delta variant in India and the Omicron in the United States. Then, the model was utilized to determine the infection risk level of the Omicron in Shanghai and Beijing. RESULTS: The Op-MAPL model can predict the epidemic peak accurately. The daily risk ranking was stable and predictive, with an average accuracy of 87.85% within next 7 days. Early warning signals were issued for Shanghai and Beijing on February 28 and April 23, 2022, respectively. The two cities were rated as medium-high risk or above from March 27 to April 20 and from April 24 to May 5, indicating that the pandemic had entered a period of rapid increase. After April 21 and May 26, the risk level was downgraded to medium and became stable by the algorithm, indicating that the pandemic had been controlled well and mitigated gradually. CONCLUSIONS: The Op-MAPL relies on nothing but an indicator to assess the risk level of the COVID-19 pandemic with different data sources and granularities. This forward-looking method realizes real-time monitoring and early warning effectively to provide a valuable reference to prevent and control infectious diseases.

A neutralizing bispecific single-chain antibody against SARS-CoV-2 Omicron variant produced based on CR3022.

Introduction: The constantly mutating SARS-CoV-2 has been infected an increasing number of people, hence the safe and efficacious treatment are urgently needed to combat the COVID-19 pandemic. Currently, neutralizing antibodies (Nabs), targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein are potentially effective therapeutics against COVID-19. As a new form of antibody, bispecific single chain antibodies (BscAbs) can be easily expressed in E. coli and exhibits broad-spectrum antiviral activity. Methods: In this study, we constructed two BscAbs 16-29, 16-3022 and three single chain variable fragments (scFv) S1-16, S2-29 and S3022 as a comparison to explore their antiviral activity against SARS-CoV-2. The affinity of the five antibodies was characterized by ELISA and SPR and the neutralizing activity of them was analyzed using pseudovirus or authentic virus neutralization assay. Bioinformatics and competitive ELISA methods were used to identify different epitopes on RBD. Results: Our results revealed the potent neutralizing activity of two BscAbs 16-29 and 16-3022 against SARS-CoV-2 original strain and Omicron variant infection. In addition, we also found that SARS-CoV RBD-targeted scFv S3022 could play a synergistic role with other SARS-CoV-2 RBD-targeted antibodies to enhance neutralizing activity in the form of a BscAb or in cocktail therapies. Discussion: This innovative approach offers a promising avenue for the development of subsequent antibody therapies against SARSCoV-2. Combining the advantages of cocktails and single-molecule strategies, BscAb therapy has the potential to be developed as an effective immunotherapeutic for clinical use to mitigate the ongoing pandemic.

Protein-based nano-vaccines against SARS-CoV-2: Current design strategies and advances of candidate vaccines

The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shaken the global health system. Various nanotechnology-based strategies for vaccine development have played pivotal roles in fighting against SARS-CoV-2. Among them, the safe and effective protein-based nanoparticle (NP) platforms display a highly repetitive array of foreign antigens on their surface, which is urgent for improving the immunogenicity of vaccines. These platforms greatly improved antigen uptake by antigen presenting cells (APCs), lymph node trafficking, and B cell activation, due to the optimal size, multivalence, and versatility of NPs. In this review, we summarize the advances of protein-based NP platforms, strategies of antigen attachment, and the current progress of clinical and preclinical trials in the development of SARS-CoV-2 vaccines based on protein-based NP platforms. Importantly, the lessons learnt and design approaches developed for these NP platforms against SARS-CoV-2 also provide insights into the development of protein-based NP strategies for preventing other epidemic diseases. Graphical abstract Unlabelled Image

Iontophoresis-driven microneedle patch for the active transdermal delivery of vaccine macromolecules.

COVID-19 has seriously threatened public health, and transdermal vaccination is an effective way to prevent pathogen infection. Microneedles (MNs) can damage the stratum corneum to allow passive diffusion of vaccine macromolecules, but the delivery efficiency is low, while iontophoresis can actively promote transdermal delivery but fails to transport vaccine macromolecules due to the barrier of the stratum corneum. Herein, we developed a wearable iontophoresis-driven MN patch and its iontophoresis-driven device for active and efficient transdermal vaccine macromolecule delivery. Polyacrylamide/chitosan hydrogels with good biocompatibility, excellent conductivity, high elasticity, and a large loading capacity were prepared as the key component for vaccine storage and active iontophoresis. The transdermal vaccine delivery strategy of the iontophoresis-driven MN patch is "press and poke, iontophoresis-driven delivery, and immune response". We demonstrated that the synergistic effect of MN puncture and iontophoresis significantly promoted transdermal vaccine delivery efficiency. In vitro experiments showed that the amount of ovalbumin delivered transdermally using the iontophoresis-driven MN patch could be controlled by the iontophoresis current. In vivo immunization studies in BALB/c mice demonstrated that transdermal inoculation of ovalbumin using an iontophoresis-driven MN patch induced an effective immune response that was even stronger than that of traditional intramuscular injection. Moreover, there was little concern about the biosafety of the iontophoresis-driven MN patch. This delivery system has a low cost, is user-friendly, and displays active delivery, showing great potential for vaccine self-administration at home.

Impaired autophagy-accelerated senescence of alveolar type II epithelial cells drives pulmonary fibrosis induced by single-walled carbon nanotubes.

BACKGROUND: The rapid increase in production and application of carbon nanotubes (CNTs) has led to wide public concerns in their potential risks to human health. Single-walled CNTs (SWCNTs), as an extensively applied type of CNTs, have shown strong capacity to induce pulmonary fibrosis in animal models, however, the intrinsic mechanisms remain uncertain. RESULTS: In vivo experiments, we showed that accelerated senescence of alveolar type II epithelial cells (AECIIs) was associated with pulmonary fibrosis in SWCNTs-exposed mice, as well as SWCNTs-induced fibrotic lungs exhibited impaired autophagic flux in AECIIs in a time dependent manner. In vitro, SWCNTs exposure resulted in profound dysfunctions of MLE-12 cells, characterized by impaired autophagic flux and accelerated cellular senescence. Furthermore, the conditioned medium from SWCNTs-exposed MLE-12 cells promoted fibroblast-myofibroblast transdifferentiation (FMT). Additionally, restoration of autophagy flux with rapamycin significantly alleviated SWCNTs-triggered senescence and subsequent FMT whereas inhibiting autophagy using 3-MA aggravated SWCNTs-triggered senescence in MLE-12 cells and FMT. CONCLUSION: SWCNTs trigger senescence of AECIIs by impairing autophagic flux mediated pulmonary fibrosis. The findings raise the possibility of senescence-related cytokines as potential biomarkers for the hazard of CNTs exposure and regulating autophagy as an appealing target to halt CNTs-induced development of pulmonary fibrosis.

Effects of Resveratrol on Pulmonary Fibrosis via TGF-ß/Smad/ERK Signaling Pathway.

Pulmonary fibrosis (PF) is a progressive pulmonary disease with no effective treatment and high mortality. Resveratrol has shown promising benefits in the treatment of PF. However, the probable efficacy and underlying mechanism of resveratrol in PF treatment remain unclear. This study investigates the intervention effects and potential mechanisms underpinning the treatment of PF with resveratrol. The histopathological analysis of lung tissues in PF rats showed that resveratrol improved collagen deposition and reduced inflammation. Resveratrol decreased the levels of collagen, glutathione, superoxide dismutase, myeloperoxidase, and hydroxyproline, lowered total anti-oxidant capacity, and suppressed the migration of TGF-[Formula: see text]1 and LPS-induced 3T6 fibroblasts. With resveratrol intervention, the protein and RNA expressions of TGF-[Formula: see text]1, a-SMA, Smad3/4, p-Smad3/4, CTGF, and p-ERK1/2 were markedly downregulated. Similarly, the protein and RNA expression levels of Col-1 and Col-3 were significantly downregulated. However, Smad7 and ERK1/2 were evidently upregulated. The protein and mRNA expression levels of TGF-[Formula: see text], Smad, and p-ERK correlated positively with the lung index, while the protein and mRNA expression levels of ERK correlated negatively with the lung index. These results reveal that resveratrol may have therapeutic effects on PF by reducing collagen deposition, oxidation, and inflammation. The mechanism is associated with the regulation of the TGF-[Formula: see text]/Smad/ERK signaling pathway.

Protein-based nano-vaccines against SARS-CoV-2: Current design strategies and advances of candidate vaccines.

The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shaken the global health system. Various nanotechnology-based strategies for vaccine development have played pivotal roles in fighting against SARS-CoV-2. Among them, the safe and effective protein-based nanoparticle (NP) platforms display a highly repetitive array of foreign antigens on their surface, which is urgent for improving the immunogenicity of vaccines. These platforms greatly improved antigen uptake by antigen presenting cells (APCs), lymph node trafficking, and B cell activation, due to the optimal size, multivalence, and versatility of NPs. In this review, we summarize the advances of protein-based NP platforms, strategies of antigen attachment, and the current progress of clinical and preclinical trials in the development of SARS-CoV-2 vaccines based on protein-based NP platforms. Importantly, the lessons learnt and design approaches developed for these NP platforms against SARS-CoV-2 also provide insights into the development of protein-based NP strategies for preventing other epidemic diseases.

Characterization of a Vesicular Stomatitis Virus-Vectored Recombinant Virus Bearing Spike Protein of SARS-CoV-2 Delta Variant.

The frequent emergence of SARS-CoV-2 variants thwarts the prophylactic and therapeutic countermeasures confronting COVID-19. Among them, the Delta variant attracts widespread attention due to its high pathogenicity and fatality rate compared with other variants. However, with the emergence of new variants, studies on Delta variants have been gradually weakened and ignored. In this study, a replication-competent recombinant virus carrying the S protein of the SARS-CoV-2 Delta variant was established based on the vesicular stomatitis virus (VSV), which presented a safe alternative model for studying the Delta variant. The recombinant virus showed a replication advantage in Vero E6 cells, and the viral titers reach 107.3 TCID50/mL at 36 h post-inoculation. In the VSV-vectored recombinant platform, the spike proteins of the Delta variant mediated higher fusion activity and syncytium formation than the wild-type strain. Notably, the recombinant virus was avirulent in BALB/c mice, Syrian hamsters, 3-day ICR suckling mice, and IFNAR/GR-/- mice. It induced protective neutralizing antibodies in rodents, and protected the Syrian hamsters against the SARS-CoV-2 Delta variant infection. Meanwhile, the eGFP reporter of recombinant virus enabled the visual assay of neutralizing antibodies. Therefore, the recombinant virus could be a safe and convenient surrogate tool for authentic SARS-CoV-2. This efficient and reliable model has significant potential for research on viral-host interactions, epidemiological investigation of serum-neutralizing antibodies, and vaccine development.

Phillyrin (KD-1) exerts anti-viral and anti-inflammatory activities against novel coronavirus (SARS-CoV-2) and human coronavirus 229E (HCoV-229E) by suppressing the nuclear factor kappa B (NF-κB) signaling pathway.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has extensively and rapidly spread in the world, causing an outbreak of acute infectious pneumonia. However, no specific antiviral drugs or vaccines can be used. Phillyrin (KD-1), a representative ingredient of Forsythia suspensa, possesses anti-inflammatory, anti-oxidant, and antiviral activities. However, little is known about the antiviral abilities and mechanism of KD-1 against SARS-CoV-2 and human coronavirus 229E (HCoV-229E). PURPOSE: The study was designed to investigate the antiviral and anti-inflammatory activities of KD-1 against the novel SARS-CoV-2 and HCoV-229E and its potential effect in regulating host immune response in vitro. METHODS: The antiviral activities of KD-1 against SARS-CoV-2 and HCoV-229E were assessed in Vero E6 cells using cytopathic effect and plaque-reduction assay. Proinflammatory cytokine expression levels upon infection with SARS-CoV-2 and HCoV-229E infection in Huh-7 cells were measured by real-time quantitative PCR assays. Western blot assay was used to determine the protein expression of nuclear factor kappa B (NF-κB) p65, p-NF-κB p65, IκBα, and p-IκBα in Huh-7 cells, which are the key targets of the NF-κB pathway. RESULTS: KD-1 could significantly inhibit SARS-CoV-2 and HCoV-229E replication in vitro. KD-1 could also markedly reduce the production of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, MCP-1, and IP-10) at the mRNA levels. Moreover, KD-1 could significantly reduce the protein expression of p-NF-κB p65, NF-κB p65, and p-IκBα, while increasing the expression of IκBα in Huh-7 cells. CONCLUSIONS: KD-1 could significantly inhibit virus proliferation in vitro, the up-regulated expression of proinflammatory cytokines induced by SARS-CoV-2 and HCoV-229E by regulating the activity of the NF-кB signaling pathway. Our findings indicated that KD-1 protected against virus attack and can thus be used as a novel strategy for controlling the coronavirus disease 2019.

Thickness-Sensing Sandwiched Plasmonic Biosensors Enable Label-Free Naked-Eye Antibody Quantification.

Clinical serology assays for detecting the antibodies of the virus are time-consuming, are less sensitive/selective, or rely on sophisticated detection instruments. Here, we develop a sandwiched plasmonic biosensor (SPB) for supersensitive thickness-sensing via utilizing the distance-dependent electromagnetic coupling in sandwiched plasmonic nanostructures. SPBs quantitatively amplify the thickness changes on the nanoscale range (sensitivity: ∼2% nm-1) into macroscopically visible signals, thereby enabling the rapid, label-free, and naked-eye detection of targeted biomolecular species (via the thickness change caused by immunobinding events). As a proof of concept, this assay affords a broad dynamic range (7 orders of magnitude) and a low LOD (∼0.3 pM), allowing for the extremely accurate SARS-CoV-2 antibody quantification (sensitivity/specificity: 100%/∼99%, with a portable optical fiber device). This strategy is suitable for high-throughput multiplexed detection and smartphone-based sensing at the point-of-care, which can be expanded for various sensing applications beyond the fields of viral infections and vaccination.

Traditional Chinese medicine combined with Moxibustion in the treatment of "long-COVID": A protocol for systematic review and meta-analysis.

BACKGROUND: From the end of 2019 to now, COVID-19 is still prevalent, which poses a great threat to international public health. With the increasing number of people infected, the number of patients with COVID-19 sequelae is also increasing, but there is no specific drug for COVID-19 sequelae. In China, traditional Chinese medicine combined with acupuncture has been widely used in COVID-19 sequelae, but there is still a lack of evidence-based medicine evaluation. The purpose of this study was to evaluate the efficacy and safety of traditional Chinese medicine combined with moxibustion in the treatment of COVID-19 sequelae. METHODS: According to the retrieval strategy, the "long COVID" randomized controlled trial of traditional Chinese medicine combined with moxibustion will be search in eight databases composed of PubMed, Embase, Web of Science, China National knowledge Infrastructure Database, China Biomedical Database and China Science and Technology Journal Database, regardless of publication date or language. The study was screened according to the inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the study. Meta-analysis was carried out using RevMan5.3 and STATA12.0 software. Finally, the level of evidence of the results will be evaluated. RESULTS: This study will evaluate whether traditional Chinese medicine combined with moxibustion can effectively treat the symptoms of COVID-19 sequelae. CONCLUSION: This study will provide evidence whether there is benefit of traditional Chinese medicine combined with moxibustion in the treatment of COVID-19 sequelae. At the same time, our research results will provide a reference for clinical decision-making and guiding development in the future.

Traditional Chinese Medicine in Treating Children With Coronavirus Disease 2019: A Scoping Review.

Coronavirus disease 2019 (COVID-19) is currently widely spread across the world. Traditional Chinese Medicine (TCM) plays an important role in the overall treatment process. As a special group of population, the treatment outcome of children with COVID-19 has attracted much attention. Our study summarizes the current situation of TCM treatment of children with COVID-19. The results showed that TCM displayed a positive role in the treatment process, and that no significant adverse reactions were found. Our findings provide analytical evidence for the efficacy and safety of TCM participation in the treatment of COVID-19 in children.

Fermented natural product targeting gut microbiota regulate immunity and anti-inflammatory activity: A possible way to prevent COVID-19 in daily diet.

Low immune function makes the body vulnerable to being invaded by external bacteria or viruses, causing influenza and inflammation of various organs, and this trend is shifting to the young and middle-aged group. It has been pointed out that natural products fermented by probiotic have benign changes about their active ingredients in some studies, and it have shown strong nutritional value in anti-oxidation, anti-aging, regulating lipid metabolism, anti-inflammatory and improving immunity. In recent years, the gut microbiota plays a key role and has been extensively studied in improving immunity and anti-inflammation activity. By linking the relationship between natural products fermented by probiotic, gut microbiota, immunity, and inflammation, this review presents the modulating effects of probiotics and their fermented natural products on the body, including immunity-enhancing and anti-inflammatory activities by modulating gut microbiota, and it is discussed that the current understanding of its molecular mechanisms. It may become a possible way to prevent COVID-19 through consuming natural products fermented by probiotic in our daily diet.

Analysis of correlation between occupational stress and influencing factors of employees of a power supply company in Guangdong: based on effort-reward imbalance model

[Background] With the rapid development of China's economy, the working pressure of occupational population has increased rapidly, and the impacts of occupational stress on the physical and mental health of occupational population are becoming an important public health issue. Power supply companies are high risk industries of occupational stress covering many stressors. At present, no systematic research on occupational stress among workers in power supply companies has been reported, especially the impacts of occupational hazardous factors on occupational stress of workers. [Objective] The study aims to obtain the current status of occupational stress, explore the correlation between occupational stress and influencing factors, and provide a basis for formulating occupational stress intervention measures through a questionnaire survey of employees of a power supply company in Guangdong. [Methods] A cross-sectional study design was adopted and 1 091 employees of a power supply company in Guangdong were selected in May 2019. A general information questionnaire tailored to power supply companies was designed and distributed to collect basic information of the subjects. Occupational stress was assessed by effort-reward imbalance (ERI) index[ERI=effort score/(reward scorex0.545 4)] of ERI scale, and ERI index > 1 was defined as having high occupational stress. Chi-square test was used to compare the differences of occupational stress rate among groups with different individual characteristics, occupational characteristics, lifestyles, and exposures to occupational hazardous factors. Multiple logistic regression was used to analyze the influencing factors of high occupational stress. [Results] A total of 1 091 questionnaires were distributed in this survey, and 972 (89.1%) valid questionnaires were returned. The respondents included 859 men (88.4%) and 113 women (11.6%). There were 514 (52.9%) subjects with high occupational stress. The prevalence rate of high occupational stress were higher in men than in women, higher among married employees than among single employees, higher in employees at and over 30 years of age than in those below 30 years, higher in dispatching and maintenance workers than in other types of workers, higher in high-income-level employees than in low-income-level employees, higher in employees with < 6h sleeping time than in those with >7 h, higher in employees with alcohol consumption than in those without, and higher in those exposed to noise, electromagnetic radiation, high temperature and high altitude, and visual display terminal than in those not;these differences were all statistically significant (P < 0.05). The logistic regression analysis results showed that compared with the workers at the age of < 30 years, those at the age of 30-years and 40-years had a higher risk for high occupational stress (OR=2.438, 95% CI:1.507-3.943;OR=2.407, 95% CI:1.472-3.934, respectively);compared with customer service and other types of workers, the maintenance and dispatching workers had a higher risk for high occupational stress (OR=1.841, 95% CI:1.140-2.973;OR=2.417, 95% CI:1.149-5.083, respectively);compared with the employees who slept >7h every day, those who slept < 6h and 6-7h every day had a higher risk for high occupational stress (OR=1.735, 95% CI:1.182-2.547;OR=1.518, 95% CI:1.069-2.115, respectively);compared with those without visual display terminal exposure, the employees with such exposure had a higher risk for high occupational stress (OR=1.419, 95% CI:1.043-1.932). [Conclusion] The employees of the selected power supply company generally have a high rate of high occupational stress. Aged above 30 years, at maintenance and dispatch positions, with short sleeping duration, and with exposure to visual display terminal are risk factors of high occupational stress.

Traditional Chinese Medicine in Treating Children With Coronavirus Disease 2019: A Scoping Review

Coronavirus disease 2019 (COVID-19) is currently widely spread across the world. Traditional Chinese Medicine (TCM) plays an important role in the overall treatment process. As a special group of population, the treatment outcome of children with COVID-19 has attracted much attention. Our study summarizes the current situation of TCM treatment of children with COVID-19. The results showed that TCM displayed a positive role in the treatment process, and that no significant adverse reactions were found. Our findings provide analytical evidence for the efficacy and safety of TCM participation in the treatment of COVID-19 in children.

Clinical Characteristics of Immune Response in Asymptomatic Carriers and Symptomatic Patients With COVID-19.

The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major public health challenge worldwide. A comprehensive understanding of clinical characteristics and immune responses in asymptomatic carriers and symptomatic patients with COVID-19 is of great significance to the countermeasures of patients with COVID-19. Herein, we described the clinical information and laboratory findings of 43 individuals from Hunan Province, China, including 13 asymptomatic carriers and 10 symptomatic patients with COVID-19, as well as 20 healthy controls in the period from 25 January to 18 May 2020. The serum samples of these individuals were analyzed to measure the cytokine responses, receptor-binding domain (RBD), and nucleocapsid (N) protein-specific antibody titers, as well as SARS-CoV-2 neutralizing antibodies (nAbs). For cytokines, significantly higher Th1 cytokines including IL-2, IL-8, IL-12p70, IFN-γ, and TNF-α, as well as Th2 cytokines including IL-10 and IL-13 were observed in symptomatic patients compared with asymptomatic carriers. Compared with symptomatic patients, higher N-specific IgG4/IgG1 ratio and RBD-specific/N-specific IgG1 ratio were observed in asymptomatic carriers. Comparable nAbs were detected in both asymptomatic carriers and symptomatic patients with COVID-19. In the symptomatic group, nAbs in patients with underlying diseases were weaker than those of patients without underlying diseases. Our retrospective study will enrich and verify the clinical characteristics and serology diversities in asymptomatic carriers and symptomatic patients with COVID-19.

Influence of epidemic situation on COVID-19 vaccination between urban and rural residents in China-Vietnam border area: A cross-sectional survey.

BACKGROUND: The situation of the COVID-19 outbreak in the border areas of China and Vietnam is complex, and its progress may affect the willingness of urban and rural residents to receive the vaccine. OBJECTIVE: This study aims to understand the influence of the COVID-19 epidemic situation on the willingness of urban and rural residents in China-Vietnam border areas to get vaccinated and the factors that affect the vaccinations. METHODS: A cross-sectional survey was conducted in Hani-Yi Autonomous Prefecture of Honghe, a border area between China and Vietnam, using online and paper questionnaires from April 1 to June 4, 2021. A total of 8849 valid questionnaires were surveyed to compare the differences in the willingness of urban and rural residents to receive the COVID-19 vaccine. Single factor analysis and multivariate logistic regression analysis were used to explore the influence of the epidemic situation on the willingness to be vaccinated. RESULTS: In the border areas between China and Vietnam in Yunnan Province, both urban and rural residents had a high willingness (> 90%) to receive the COVID-19 vaccination, with a higher level of willingness in urban than in rural areas and a higher willingness among residents aged ≥ 56 years. Rural residents mainly concerned about the vaccination were different from urban residents (p< 0.05). About 54.8% of urban respondents and 59.2% of rural respondents indicated that their willingness to get COVID-19 vaccine would be affected by new COVID-19 cases. Respondents who were divorced, had an occupation other than farming, had contraindications to vaccination, were concerned about the safety of vaccines and worried about virus mutation, thought that the epidemic situation would not affect their willingness to get vaccinated (p< 0.05). CONCLUSION: The prevention and control of epidemics in border areas is of considerable importance. It is necessary to conduct targeted health education and vaccine knowledge popularization among urban and rural residents to increase the vaccination rate and consolidate the epidemic prevention and control at the border.

2021-2022 monitoring, early warning, and forecasting of global infectious diseases.

COVID-19 has had a considerable impact on society since 2019, and the disease has high mortality and infection rates. There has been a particular focus on how to best manage COVID-19 and how to analyze and predict the epidemic status of infectious diseases in general. Methods The present study analyzed the COVID-19 epidemic patterns and made predictions of future trends based on the statistics obtained from a global infectious disease network data monitoring and early warning system (OBN, http://27.115.41.130:8888/OBN/). The development trends of other major infectious diseases were also examined. Results The global COVID-19 pandemic showed periodic increases throughout 2021. At present, there is a high incidence in European countries, especially in Eastern Europe, followed by in Africa. The risk of contracting COVID-19 was divided into high, medium-high, medium, medium-low, and low grades depending on the stage of the epidemic in each examined region over the current period. The occurrence and prevalence of major infectious diseases throughout the world did not significantly change in 2021. Conclusions The COVID-19 pandemic has strongly impacted people's lives and the economy. The effects of global infectious diseases can be ameliorated by strengthening monitoring and early warning systems and by facilitating the international exchange of information.

Antiviral efficacy of selective estrogen receptor modulators against SARS-CoV-2 infection in vitro and in vivo reveals bazedoxifene acetate as an entry inhibitor.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the seventh member of the coronavirus family that can infect humans. Recently, more contagious and pathogenic variants of SARS-CoV-2 have been continuously emerging. Clinical candidates with high efficacy and ready availability are still in urgent need. To identify potent anti-SARS-CoV-2 repurposing drugs, we evaluated the antiviral efficacy of 18 selective estrogen receptor modulators (SERMs) against SARS-CoV-2 infection. Six SERMs exhibited excellent anti-SARS-CoV-2 effects in Vero E6 cells and three human cell lines. Clomifene citrate, tamoxifen, toremifene citrate, and bazedoxifene acetate reduced the weight loss of hamsters challenged with SARS-CoV-2, and reduced hamster pulmonary viral load and interleukin-6 expression when assayed at 4 days postinfection. In particular, bazedoxifene acetate was identified to act on the penetration stage of the postattachment step via altering cholesterol distribution and endosome acidification. And, bazedoxifene acetate inhibited pseudoviruses infection of original SARS-CoV-2, Delta variant, Omicron variant, and SARS-CoV. These results offer critical information supporting bazedoxifene acetate as a promising agent against coronaviruses.

Clinical Characteristics of Immune Response in Asymptomatic Carriers and Symptomatic Patients With COVID-19

The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major public health challenge worldwide. A comprehensive understanding of clinical characteristics and immune responses in asymptomatic carriers and symptomatic patients with COVID-19 is of great significance to the countermeasures of patients with COVID-19. Herein, we described the clinical information and laboratory findings of 43 individuals from Hunan Province, China, including 13 asymptomatic carriers and 10 symptomatic patients with COVID-19, as well as 20 healthy controls in the period from 25 January to 18 May 2020. The serum samples of these individuals were analyzed to measure the cytokine responses, receptor-binding domain (RBD), and nucleocapsid (N) protein-specific antibody titers, as well as SARS-CoV-2 neutralizing antibodies (nAbs). For cytokines, significantly higher Th1 cytokines including IL-2, IL-8, IL-12p70, IFN-γ, and TNF-α, as well as Th2 cytokines including IL-10 and IL-13 were observed in symptomatic patients compared with asymptomatic carriers. Compared with symptomatic patients, higher N-specific IgG4/IgG1 ratio and RBD-specific/N-specific IgG1 ratio were observed in asymptomatic carriers. Comparable nAbs were detected in both asymptomatic carriers and symptomatic patients with COVID-19. In the symptomatic group, nAbs in patients with underlying diseases were weaker than those of patients without underlying diseases. Our retrospective study will enrich and verify the clinical characteristics and serology diversities in asymptomatic carriers and symptomatic patients with COVID-19.