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.

Construction and immunogenicity of an mRNA vaccine against chikungunya virus.

Chikungunya fever (CHIKF) has spread to more than 100 countries worldwide, with frequent outbreaks in Europe and the Americas in recent years. Despite the relatively low lethality of infection, patients can suffer from long-term sequelae. Until now, no available vaccines have been approved for use; however, increasing attention is being paid to the development of vaccines against chikungunya virus (CHIKV), and the World Health Organization has included vaccine development in the initial blueprint deliverables. Here, we developed an mRNA vaccine using the nucleotide sequence encoding structural proteins of CHIKV. And immunogenicity was evaluated by neutralization assay, Enzyme-linked immunospot assay and Intracellular cytokine staining. The results showed that the encoded proteins elicited high levels of neutralizing antibody titers and T cell-mediated cellular immune responses in mice. Moreover, compared with the wild-type vaccine, the codon-optimized vaccine elicited robust CD8+ T-cell responses and mild neutralizing antibody titers. In addition, higher levels of neutralizing antibody titers and T-cell immune responses were obtained using a homologous booster mRNA vaccine regimen of three different homologous or heterologous booster immunization strategies. Thus, this study provides assessment data to develop vaccine candidates and explore the effectiveness of the prime-boost approach.

Epidemiological characteristics of 3 054 COVID-19 patients with mild symptoms/asymptomatic infection in makeshift hospitals of Shanghai in 2022

OBJECTIVE: To analyze the epidemiological characteristics of Omicron subvariant BA.2 represented mild/asymptomatic COVID-19 cases in makeshift hospitals. METHODS: The data of COVID-19 patients who were mild and asymptomatic admitted to Shanghai Shilong Road Temporary Capsule Hospital from Apr 8 to May 13, 2022 were retrospectively collected. The epidemiological history, general situation, length of stay, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) vaccination, and cycle threshold (Ct) values of N and ORF1ab genes in the cases were analyzed. Univariate analysis and multivariate Logistic regression were used to analyze the risk factors for hospitalization > 14 days and the risk of not being vaccinated. RESULTS: A total of 2896 patients with Omicron variant infection were collected in this study. The average length of hospital stay was (10.79+or-4.31)days. The average Ct values of N gene and ORF1ab gene on admission were 28.63+or-6.55 and 29.45+or-5.50, respectively, and 13.05% of the patients were not vaccinated against COVID-19. The length of hospital stay of the patients with old age was more likely to surpass 14 days. The patients with more times of vaccination were more likely to discharge within 14 days. Nucleic acid testing for COVID-19 showed that the Ct values of the N and ORF1ab genes in the juvenile patients were higher than those in the adult patients, and the Ct values of the genes in the patients with common chronic diseases were lower than those in the uncomplicated patients. Correlation analysis showed that the length of hospital stay was negatively correlated with the Ct values of N gene (r=-0.362,P<0.001) and ORF1ab gene (r=-0.391, P<0.001). CONCLUSION: The age of Omicron subvariant BA.2 infection patients, co-morbidity, times of vaccination, and Ct values of SARS-CoV-2 nucleic acid are the risk factors for the length of stay in hospital. Isolation of asymptomatic and mild COVID-19 patients in makeshift hospitals can effectively control the social spread of the epidemic.

The dose- and time-dependent effectiveness and safety associated with COVID-19 vaccination during pregnancy: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to provide guidance for clinical treatment and increase public confidence in COVID-19 vaccines. METHODS: The Cochrane Library, Embase, PubMed, Web of Science, ClinicalKey, and other COVID-19 datasets were searched from December 2019 to May 2022. Case-control studies and prospective cohort studies of COVID-19 vaccine effectiveness and safety in pregnant women were included. RESULTS: From day 11 to day 13, after the first dose of the COVID-19 messenger RNA vaccine, the effectiveness was 54% (95% confidence interval: 0.33-0.69). On days 14 to 27, the effectiveness was 59%. There was a 14% increase in vaccine effectiveness 28 days after the first dose was given. The inactivated vaccines showed similar effectiveness. The proportions of placental abruptions, postpartum hemorrhages, miscarriages, stillbirths, premature births, and small for gestational age infants were not significantly different between vaccinated and nonvaccinated pregnant women. Fatigue and fever were also not associated with pregnancy. CONCLUSION: Our findings affirm that the effectiveness varies for different types of vaccines and is significantly and positively correlated with time in the pregnant population. COVID-19 vaccines have also been deemed safe for pregnant women. Thus, we developed a comprehensive understanding of the role of vaccines in pregnant women.

A Vicious Cycle: In Severe and Critically Ill COVID-19 Patients.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is one of the fastest-evolving viral diseases that has instigated a worldwide pandemic. Severe inflammatory syndrome and venous thrombosis are commonly noted in COVID-19 patients with severe and critical illness, contributing to the poor prognosis. Interleukin (IL)-6, a major complex inflammatory cytokine, is an independent factor in predicting the severity of COVID-19 disease in patients. IL-6 and tumor necrosis factor (TNF)-α participate in COVID-19-induced cytokine storm, causing endothelial cell damage and upregulation of plasminogen activator inhibitor-1 (PAI-1) levels. In addition, IL-6 and PAI-1 form a vicious cycle of inflammation and thrombosis, which may contribute to the poor prognosis of patients with severe COVID-19. Targeted inhibition of IL-6 and PAI-1 signal transduction appears to improve treatment outcomes in severely and critically ill COVID-19 patients suffering from cytokine storms and venous thrombosis. Motivated by studies highlighting the relationship between inflammatory cytokines and thrombosis in viral immunology, we provide an overview of the immunothrombosis and immunoinflammation vicious loop between IL-6 and PAI-1. Our goal is that understanding this ferocious circle will benefit critically ill patients with COVID-19 worldwide.

Correction:The Associations Between Racially/Ethnically Stratified COVID-19 Tweets and COVID-19 Cases and Deaths: Cross-sectional Study.

[This corrects the article DOI: 10.2196/30371.].

GCN-based stock relations analysis for stock market prediction.

Most stock price predictive models merely rely on the target stock's historical information to forecast future prices, where the linkage effects between stocks are neglected. However, a group of prior studies has shown that the leverage of correlations between stocks could significantly improve the predictions. This article proposes a unified time-series relational multi-factor model (TRMF), which composes a self-generating relations (SGR) algorithm that can extract relational features automatically. In addition, the TRMF model integrates stock relations with other multiple dimensional features for the price prediction compared to extant works. Experimental validations are performed on the NYSE and NASDAQ data, where the model is compared with the popular methods such as attention Long Short-Term Memory network (Attn-LSTM), Support Vector Regression (SVR), and multi-factor framework (MF). Results show that compared with these extant methods, our model has a higher expected cumulative return rate and a lower risk of return volatility.

How should designated COVID-19 hospitals in megacities implement a precise management strategy in response to Omicron?

As a new variant of COVID-19 with varied mutations, Omicron is more transmissible, more rapidly contagious, and has a greater risk of reinfection. Given those facts, a precise manage strategy needs to be formulated and implemented in designated megacities. Here, the precise COVID-19 prevention and control strategy for a designated hospital in Shenzhen, China is summarized, including implementation of a two-wing "On duty/On standby" approach based on busy and calm periods, an identification, classification, and grading system for the occupational exposure risks of medical staff, classification of patient transmission risks, separate admission, and an innovative treatment (nasal irrigation). The strategy has enabled the efficient and orderly integration of resources, it has resulted in zero infections among medical staff even during the peak hours of the pandemic at the hospital (1,930 patients admitted to both wings in a single day), and it has significantly reduced the initial period of no virus detection when patients infected with Omicron received saline nasal irrigation (P < 0.001). This strategy has provided evidence of precise prevention and control in a hospital, infection control, and efficient patient treatment in an era when Omicron is widespread.

A Vicious Cycle: In Severe and Critically Ill COVID-19 Patients

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is one of the fastest-evolving viral diseases that has instigated a worldwide pandemic. Severe inflammatory syndrome and venous thrombosis are commonly noted in COVID-19 patients with severe and critical illness, contributing to the poor prognosis. Interleukin (IL)-6, a major complex inflammatory cytokine, is an independent factor in predicting the severity of COVID-19 disease in patients. IL-6 and tumor necrosis factor (TNF)-α participate in COVID-19-induced cytokine storm, causing endothelial cell damage and upregulation of plasminogen activator inhibitor-1 (PAI-1) levels. In addition, IL-6 and PAI-1 form a vicious cycle of inflammation and thrombosis, which may contribute to the poor prognosis of patients with severe COVID-19. Targeted inhibition of IL-6 and PAI-1 signal transduction appears to improve treatment outcomes in severely and critically ill COVID-19 patients suffering from cytokine storms and venous thrombosis. Motivated by studies highlighting the relationship between inflammatory cytokines and thrombosis in viral immunology, we provide an overview of the immunothrombosis and immunoinflammation vicious loop between IL-6 and PAI-1. Our goal is that understanding this ferocious circle will benefit critically ill patients with COVID-19 worldwide.

Combining intramuscular and intranasal homologous prime-boost with a chimpanzee adenovirus-based COVID-19 vaccine elicits potent humoral and cellular immune responses in mice.

The efficacy of many coronavirus disease 2019 (COVID-19) vaccines has been shown to decrease to varying extents against new severe acute respiratory syndrome coronavirus 2 variants, which are responsible for the continuing COVID-19 pandemic. Combining intramuscular and intranasal vaccination routes is a promising approach for achieving more potent immune responses. We evaluated the immunogenicity of prime-boost protocols with a chimpanzee adenovirus serotype 68 vector-based vaccine, ChAdTS-S, administered via both intranasal and intramuscular routes in BALB/c mice. Intramuscular priming followed by an intranasal booster elicited the highest levels of IgG, IgA, and pseudovirus neutralizing antibody titres among all the protocols tested at day 42 after prime immunization compared with the intranasal priming/intramuscular booster and prime-boost protocols using only one route. In addition, intramuscular priming followed by an intranasal booster induced high T-cell responses, measured using the IFN-γ ELISpot assay, that were similar to those observed upon intramuscular vaccination. All ChAdTS-S vaccination groups induced Th1-skewing of the T-cell response according to intracellular cytokine staining and Meso Scale Discovery cytokine profiling assays on day 56 after priming. This study provides reference data for assessing vaccination schemes of adenovirus-based COVID-19 vaccines with high immune efficacy.

The Associations Between Racially/Ethnically Stratified COVID-19 Tweets and COVID-19 Cases and Deaths: Cross-sectional Study.

BACKGROUND: The COVID-19 pandemic exacerbated existing racial/ethnic health disparities in the United States. Monitoring nationwide Twitter conversations about COVID-19 and race/ethnicity could shed light on the impact of the pandemic on racial/ethnic minorities and help address health disparities. OBJECTIVE: This paper aims to examine the association between COVID-19 tweet volume and COVID-19 cases and deaths, stratified by race/ethnicity, in the early onset of the pandemic. METHODS: This cross-sectional study used geotagged COVID-19 tweets from within the United States posted in April 2020 on Twitter to examine the association between tweet volume, COVID-19 surveillance data (total cases and deaths in April), and population size. The studied time frame was limited to April 2020 because April was the earliest month when COVID-19 surveillance data on racial/ethnic groups were collected. Racially/ethnically stratified tweets were extracted using racial/ethnic group-related keywords (Asian, Black, Latino, and White) from COVID-19 tweets. Racially/ethnically stratified tweets, COVID-19 cases, and COVID-19 deaths were mapped to reveal their spatial distribution patterns. An ordinary least squares (OLS) regression model was applied to each stratified dataset. RESULTS: The racially/ethnically stratified tweet volume was associated with surveillance data. Specifically, an increase of 1 Asian tweet was correlated with 288 Asian cases (P<.001) and 93.4 Asian deaths (P<.001); an increase of 1 Black tweet was linked to 47.6 Black deaths (P<.001); an increase of 1 Latino tweet was linked to 719 Latino deaths (P<.001); and an increase of 1 White tweet was linked to 60.2 White deaths (P<.001). CONCLUSIONS: Using racially/ethnically stratified Twitter data as a surveillance indicator could inform epidemiologic trends to help estimate future surges of COVID-19 cases and potential future outbreaks of a pandemic among racial/ethnic groups.

Safety and immunogenicity of a live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine in adults: randomised, double-blind, placebo-controlled, phase 1 and 2 trials.

BACKGROUND: All currently available SARS-CoV-2 vaccines are administered by intramuscular injection. We aimed to evaluate the safety and immunogenicity of a live-attenuated influenza virus vector-based SARS-CoV-2 vaccine (dNS1-RBD) administered by intranasal spray in healthy adults. METHODS: We did double-blind, randomised, placebo-controlled phase 1 and 2 trials, followed by a phase 2 extension trial, at a single centre in Jiangsu, China. Healthy adults (≥18 years) who had negative serum or fingertip blood total antibody tests for SARS-CoV-2 (in phases 1 and 2), with no prevalent SARS-CoV-2 infection or history of infection and no SARS-CoV-2 vaccination history (in all three trials reported here), were enrolled. Participants were randomly allocated (4:1 in phase 1, 2:1 in phase 2, and 1:1 in the extension trial) to receive two intranasal doses of the dNS1-RBD vaccine or placebo on days 0 and 14 or, for half of the participants in phase 2, on days 0 and 21. To avoid cross-contamination during administration, vaccine and placebo recipients were vaccinated in separate rooms in the extension trial. The phase 1 primary outcome was safety (adverse events recorded on days 0-44; serious adverse events recorded from day 0 until 12 months after the second dose). In the phase 2 and extension trials, the primary immunogenicity outcomes were SARS-CoV-2-specific T-cell response in peripheral blood (measured by IFN-γ ELISpot), proportion of participants with positive conversion for SARS-CoV-2 receptor-binding domain (RBD)-specific IgG and secretory IgA (s-IgA) antibodies, and concentration of SARS-CoV-2 RBD IgG in serum and SARS-CoV-2 RBD s-IgA in the nasopharynx (measured by ELISA) at 1 month after the second dose in the per-protocol set for immunogenicity. χ2 test and Fisher's exact test were used to analyse categorical data, and t test and Wilcoxon rank sum test to compare the measurement data between groups. These trials were registered with the Chinese Clinical Trial Registry (ChiCTR2000037782, ChiCTR2000039715, and ChiCTR2100048316). FINDINGS: Between Sept 1, 2020, and July 4, 2021, 63, 724, and 297 participants without a history of SARS-CoV-2 vaccination were enrolled in the phase 1, phase 2, and extension trials, respectively. At least one adverse reaction after vaccination was reported in 133 (19%) of 684 participants in the vaccine groups. Most adverse reactions were mild. No vaccine-related serious adverse event was noted. Specific T-cell immune responses were observed in 211 (46% [95% CI 42-51]) of 455 vaccine recipients in the phase 2 trial, and in 48 (40% [31-49]) of 120 vaccine recipients compared with one (1% [0-5]) of 111 placebo recipients (p<0·0001) in the extension trial. Seroconversion for RBD-specific IgG was observed in 48 (10% [95% CI 8-13]) of 466 vaccine recipients in the phase 2 trial (geometric mean titre [GMT] 3·8 [95% CI 3·4-4·3] in responders), and in 31 (22% [15-29]) of 143 vaccine recipients (GMT 4·4 [3·3-5·8]) and zero (0% [0-2]) of 147 placebo recipients (p<0·0001) in the extension trial. 57 (12% [95% CI 9-16]) of 466 vaccine recipients had positive conversion for RBD-specific s-IgA (GMT 3·8 [95% CI 3·5-4·1] in responders) in the phase 2 trial, as did 18 (13% [8-19]) of 143 vaccine recipients (GMT 5·2 [4·0-6·8]) and zero (0% [0-2]) of 147 placebo recipients (p<0·0001) in the extension trial. INTERPRETATION: dNS1-RBD was well tolerated in adults. Weak T-cell immunity in peripheral blood, as well as weak humoral and mucosal immune responses against SARS-CoV-2, were detected in vaccine recipients. Further studies are warranted to verify the safety and efficacy of intranasal vaccines as a potential supplement to current intramuscular SARS-CoV-2 vaccine pools. Steps should be taken in future studies to reduce the potential for cross-contamination caused by the vaccine strain aerosol during administration. FUNDING: National Key Research and Development Program of China, National Science, Fujian Provincial Science, CAMS Innovation Fund for Medical Sciences, and Beijing Wantai Biological Pharmacy Enterprise.

A live attenuated virus-based intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2.

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 d after single-dose vaccination or 9 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants, especially for the latest Omicron variant. In addition, this vaccine also provides cross-protection against H1N1 and H5N1 influenza viruses. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to the fight against the ongoing coronavirus disease 2019 pandemic and influenza infection, compensating limitations of current intramuscular vaccines.

A glucose-like metabolite deficient in diabetes inhibits cellular entry of SARS-CoV-2.

The severity and mortality of COVID-19 are associated with pre-existing medical comorbidities such as diabetes mellitus. However, the underlying causes for increased susceptibility to viral infection in patients with diabetes is not fully understood. Here we identify several small-molecule metabolites from human blood with effective antiviral activity against SARS-CoV-2, one of which, 1,5-anhydro-D-glucitol (1,5-AG), is associated with diabetes mellitus. The serum 1,5-AG level is significantly lower in patients with diabetes. In vitro, the level of SARS-CoV-2 replication is higher in the presence of serum from patients with diabetes than from healthy individuals and this is counteracted by supplementation of 1,5-AG to the serum from patients. Diabetic (db/db) mice undergo SARS-CoV-2 infection accompanied by much higher viral loads and more severe respiratory tissue damage when compared to wild-type mice. Sustained supplementation of 1,5-AG in diabetic mice reduces SARS-CoV-2 loads and disease severity to similar levels in nondiabetic mice. Mechanistically, 1,5-AG directly binds the S2 subunit of the SARS-CoV-2 spike protein, thereby interrupting spike-mediated virus-host membrane fusion. Our results reveal a mechanism that contributes to COVID-19 pathogenesis in the diabetic population and suggest that 1,5-AG supplementation may be beneficial to diabetic patients against severe COVID-19.

Protection Duration of COVID-19 Vaccines: Waning Effectiveness and Future Perspective.

The coronavirus disease 2019 (COVID-19) vaccines have very successfully decreased the disease risk as we know; some key information remains unknown due to the short development history and the lack of long-term follow-up studies in vaccinated populations. One of the unanswered issues is the protection duration conferred after COVID-19 vaccination, which appears to play a pivotal role in the future impact of pathogens and is critical to inform the public health response and policy decisions. Here, we review current information on the long-term effectiveness of different COVID-19 vaccines, persistence of immunogenicity, and gaps in knowledge. Meanwhile, we also discuss the influencing factors and future study prospects on this topic.

Advances in COVID-19 mRNA vaccine development.

To date, the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has determined 399,600,607 cases and 5,757,562 deaths worldwide. COVID-19 is a serious threat to human health globally. The World Health Organization (WHO) has declared COVID-19 pandemic a major public health emergency. Vaccination is the most effective and economical intervention for controlling the spread of epidemics, and consequently saving lives and protecting the health of the population. Various techniques have been employed in the development of COVID-19 vaccines. Among these, the COVID-19 messenger RNA (mRNA) vaccine has been drawing increasing attention owing to its great application prospects and advantages, which include short development cycle, easy industrialization, simple production process, flexibility to respond to new variants, and the capacity to induce better immune response. This review summarizes current knowledge on the structural characteristics, antigen design strategies, delivery systems, industrialization potential, quality control, latest clinical trials and real-world data of COVID-19 mRNA vaccines as well as mRNA technology. Current challenges and future directions in the development of preventive mRNA vaccines for major infectious diseases are also discussed.

Protection Duration of COVID-19 Vaccines: Waning Effectiveness and Future Perspective

The coronavirus disease 2019 (COVID-19) vaccines have very successfully decreased the disease risk as we know;some key information remains unknown due to the short development history and the lack of long-term follow-up studies in vaccinated populations. One of the unanswered issues is the protection duration conferred after COVID-19 vaccination, which appears to play a pivotal role in the future impact of pathogens and is critical to inform the public health response and policy decisions. Here, we review current information on the long-term effectiveness of different COVID-19 vaccines, persistence of immunogenicity, and gaps in knowledge. Meanwhile, we also discuss the influencing factors and future study prospects on this topic.

Search query and tourism forecasting during the pandemic: When and where can digital footprints be helpful as predictors?

During the COVID-19 pandemic, daily tourism demand forecasting provides actionable insight on tourism operations amid intense uncertainty. This paper applies the lasso method to predict daily tourism demand across 74 countries in 2020. We evaluate the usefulness of online search queries in boosting forecasting accuracy. The lasso method is used to select appropriate predictors and their lag orders. Results indicate that, in general, no evidence supports the usefulness of Google Trends data in generating more accurate forecasts. However, in some countries, the data can be useful for reducing the forecasting errors. Regression analysis further demonstrates that the relative usefulness of online search queries is associated with pandemic severity, the dominance of inbound tourism, and island geography. Lastly, implications are provided.