Bioinformatics analysis to identify intersection genes, associated pathways and therapeutic drugs between COVID-19 and Oral candidiasis.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a serious threat to human health. Oral candidiasis (OC) may be one of the causes of morbidity in severe COVID-19 patients. However, there is currently no treatment for oral candidiasis and COVID-19 (OC/COVID-19). The purpose of this study was to use text mining and data analysis to investigate the target genes for treatment and explore potential therapeutic drugs for OC/COVID-19. METHODS: We used the text mining tool pubmed2ensembl to detect genes associated with OC, and the dataset GSE164805 was used for the data analysis. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the two intersection genes using the Database of Annotation, Visualization and Integrated Discovery (DAVID) platform. The protein-protein interaction (PPI) networks were constructed by STRING software, and gene module analysis was performed using Molecular Complex Detection (MCODE), a plug-in in Cytoscape. The most significant genes were selected as hub genes and their functions and pathways were analyzed using Metascape. We revealed the upstream pathway activity of the hub genes. The drug-gene interaction database (DGIdb) and the traditional Chinese medicines integrated database (TCMID) were used to discover potential drugs for the treatment of OC/COVID-19. RESULTS: The analysis indicated that there were 2869 differentially expressed genes (DEGs) in GSE164805. We identified 161 unique genes associated with oral candidiasis through text mining. A total of 20 intersection genes were identified as the therapeutic targets for OC/COVID-19. Based on the bioinformatics analysis, nine genes (TNF, IL1B, IFNG, CSF2, ELANE, CCL2, MMP9, CXCR4, and IL1A) were identified as hub genes that were mainly enriched in the IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications and NOD-like receptor signaling pathway. We identified four of the nine genes that target five existing drugs, including BKT140, mavorixafor, sivelestat, canakinumab, and rilonacept. Furthermore, twenty herb ingredients were also screened as potential drugs. CONCLUSION: In this study, TNF, IL1B, IFNG, CSF2, ELANE, CCL2, MMP9, CXCR4, and IL1A were potentially key genes involved in the treatment of OC/COVID-19. Taken together five drugs and twenty herb ingredients were identified as potential therapeutic agents for OC/COVID-19 treatment and management.

Assessing vaccine literacy and exploring its association with vaccine hesitancy: A validation of the vaccine literacy scale in China.

BACKGROUND: Assessment of vaccine literacy is essential for understanding people's ability to access various vaccine information to meet health demands. Few studies have examined the role of vaccine literacy in vaccine hesitancy, which is a psychological state. This study aimed to validate the applicability of the HLVa-IT (Vaccine Health Literacy of Adults in Italian) scale in Chinese settings and to explore the association between vaccine literacy and vaccine hesitancy. METHODS: From May to June 2022, we conducted an online cross-sectional survey in mainland China. Potential factor domains were obtained by the exploratory factor analysis. Cronbach's alpha coefficient, composite reliability values, and square root values of average variances extracted were calculated to determine the internal consistency and discriminant validity. The association between vaccine literacy, vaccine acceptance, with vaccine hesitancy was assessed using logistic regression analysis. RESULTS: Totally, 12,586 participants completed the survey. Two potential dimensions, the functional and the interactive/critical, were identified. Cronbach's alpha coefficient and composite reliability values were >0.90. The square root values of average variances extracted exceeded the related correlations. The functional dimension (adjusted odds ratio (aOR): 0579; 95 % Confidence Interval (CI); 0.529, 0.635), interactive (aOR: 0.654; 95%CI: 0.531, 0.806)/critical (aOR: 0.709; 95%CI: 0.575, 0.873) dimension were significantly and negatively associated with vaccine hesitancy. Similar results were also found in different vaccines acceptance subgroups. LIMITATIONS: This report is limited by the convenience sampling method. CONCLUSIONS: The modified HLVa-IT is suitable for use in Chinese settings. Vaccine literacy was negatively associated with vaccine hesitancy.

Understanding Drivers of Vaccine Hesitancy During the COVID-19 Pandemic Among Older Adults in Jiangsu Province, China: Cross-sectional Survey.

BACKGROUND: Older adults are particularly at risk from infectious diseases, including serve complications, hospitalization, and death. OBJECTIVE: This study aimed to explore the drivers of vaccine hesitancy among older adults based on the "3Cs" (confidence, complacency, and convenience) framework, where socioeconomic status and vaccination history played the role of moderators. METHODS: A cross-sectional questionnaire survey was conducted in Jiangsu Province, China, between June 1 and July 20, 2021. Older adults (aged ≥60 years) were recruited using a stratified sampling method. Vaccine hesitancy was influenced by the 3Cs in the model. Socioeconomic status and vaccination history processed through the item parceling method were used to moderate associations between the 3Cs and hesitancy. Hierarchical regression analyses and structural equation modeling were used to test the validity of the new framework. We performed 5000 trials of bootstrapping to calculate the 95% CI of the pathway's coefficients. RESULTS: A total of 1341 older adults participated. The mean age was 71.3 (SD 5.4) years, and 44.7% (599/1341) of participants were men. Confidence (b=0.967; 95% CI 0.759-1.201; P=.002), convenience (b=0.458; 95% CI 0.333-0.590; P=.002), and less complacency (b=0.301; 95% CI 0.187-0.408; P=.002) were positively associated with less vaccine hesitancy. Socioeconomic status weakened the positive effect of low complacency (b=-0.065; P=.03) on low vaccine hesitancy. COVID-19 vaccination history negatively moderated the positive association between confidence (b=-0.071; P=.02) and lower vaccine hesitancy. CONCLUSIONS: Our study identified that confidence was the more influential dimension in reducing vaccine hesitancy among older adults. COVID-19 vaccination history, as well as confidence, had a positive association with less vaccine hesitancy and could weaken the role of confidence in vaccine hesitancy. Socioeconomic status had a substitution relationship with less complacency, which suggested a competitive positive association between them on less vaccine hesitancy.

Low-to-Moderate Dosage and Short-Term Use of Corticosteroids Benefit Patients With Severe COVID-19 Infections.

Although the FDA has given emergency use authorization (EUA) for some antiviral drugs for the treatment of COVID-19, no direct antiviral drugs have been identified for the treatment of critically ill patients, the most important treatment is suppression of the hyperinflammation. The purpose of this study was to evaluate the role of corticosteroids in hospitalized severe or critical patients positive for COVID-19. This is a retrospective single-center descriptive study. Patients classified as having severe or critical COVID-19 infections with acute respiratory dysfunction syndrome in Shenzhen Third People's Hospital were enrolled from January 11th to March 30th, 2020. Ninety patients were classified as having severe or critical COVID-19 infections. The patients were treated with methylprednisolone with a low-to-moderate dosage and short duration. The days from the symptom onset to methylprednisolone were about 8 days. Eighteen patients were treated with invasive ventilation and intensive care unit (ICU) care. All the patients in the severe group and ten in the critical group recovered and were discharged. Three critical cases with invasive ventilation died. Although cases were much more severe in the corticosteroid-treated group, the mortality was not significantly increased. Early use of low-to-moderate dosage and short duration of corticosteroid may be the more accurate immune-modulatory treatment and brings more benefits to severe patients with COVID-19.

Low-to-Moderate Dosage and Short-Term Use of Corticosteroids Benefit Patients With Severe COVID-19 Infections

Although the FDA has given emergency use authorization (EUA) for some antiviral drugs for the treatment of COVID-19, no direct antiviral drugs have been identified for the treatment of critically ill patients, the most important treatment is suppression of the hyperinflammation. The purpose of this study was to evaluate the role of corticosteroids in hospitalized severe or critical patients positive for COVID-19. This is a retrospective single-center descriptive study. Patients classified as having severe or critical COVID-19 infections with acute respiratory dysfunction syndrome in Shenzhen Third People’s Hospital were enrolled from January 11th to March 30th, 2020. Ninety patients were classified as having severe or critical COVID-19 infections. The patients were treated with methylprednisolone with a low-to-moderate dosage and short duration. The days from the symptom onset to methylprednisolone were about 8 days. Eighteen patients were treated with invasive ventilation and intensive care unit (ICU) care. All the patients in the severe group and ten in the critical group recovered and were discharged. Three critical cases with invasive ventilation died. Although cases were much more severe in the corticosteroid-treated group, the mortality was not significantly increased. Early use of low-to-moderate dosage and short duration of corticosteroid may be the more accurate immune-modulatory treatment and brings more benefits to severe patients with COVID-19.

Vaccination Intention and Behavior of the General Public in China: Cross-sectional Survey and Moderated Mediation Model Analysis.

BACKGROUND: Promoting vaccination and eliminating vaccine hesitancy are key measures for controlling vaccine-preventable diseases. OBJECTIVE: We aimed to understand the beliefs surrounding and drivers of vaccination behavior, and their relationships with and influence on vaccination intention and practices. METHODS: We conducted a web-based survey in 31 provinces in mainland China from May 24, 2021 to June 15, 2021, with questions pertaining to vaccination in 5 dimensions: attitude, subjective norms, perceived behavioral control, intention, and behavior. We performed hierarchical regression analysis and structural equation modeling based on the theory of planned behavior-in which, the variables attitude, subjective norms, and intention each affect the variable intention; the variable intention mediates the relationships of attitude and subjective norms with behavior, and the variable perceived behavioral control moderates the strength of this mediation-to test the validity of the theoretical framework. RESULTS: A total of 9924 participants, aged 18 to 59 years, were included in this study. Vaccination intention mediated the relationships of attitude and subjective norms with vaccination behavior. The indirect effect of attitude on vaccination behavior was 0.164 and that of subjective norms was 0.255, and the difference was statistically significant (P<.001). The moderated mediation analysis further indicated that perceived behavioral control would affect the mediation when used as moderator, and the interaction terms for attitude (ß=-0.052, P<.001) and subjective norms (ß=-0.028, P=.006) with perceived behavioral control were significant. CONCLUSIONS: Subjective norms have stronger positive influences on vaccination practices than attitudes. Perceived behavioral control, as a moderator, has a substitution relationship with attitudes and subjective norms and weakens their positive effects on vaccination behavior.

Changes in Parental Attitudes Toward COVID-19 Vaccination and Routine Childhood Vaccination During the COVID-19 Pandemic: Repeated Cross-sectional Survey Study.

BACKGROUND: It was reported that one in four parents were hesitant about vaccinating their children in China. Previous studies have revealed a declining trend in the vaccine willingness rate in China. There is a need to monitor the level of parental vaccine hesitancy toward routine childhood vaccination and hesitancy toward the COVID-19 vaccine during the ongoing COVID-19 pandemic. OBJECTIVE: This study aims to assess changes in trends of parental attitudes toward routine childhood vaccines and COVID-19 vaccinations across different time periods in China. METHODS: Three waves of cross-sectional surveys were conducted on parents residing in Wuxi City in Jiangsu Province, China from September to October 2020, February to March 2021, and May to June 2021. Participants were recruited from immunization clinics. Chi-square tests were used to compare the results of the three surveys, controlling for sociodemographic factors. Binary and multivariable logistic regression analysis was used to examine factors related to parental vaccine hesitancy and COVID-19 vaccine willingness. RESULTS: Overall, 2881, 1038, and 1183 participants were included in the survey's three waves. Using the Vaccine Hesitancy Scale, 7.8% (225/2881), 15.1% (157/1038), and 5.5% (65/1183) of parents showed hesitancy to childhood vaccination (P<.001), and 59.3% (1709/2881), 64.6% (671/1038), and 92% (1088/1183) of parents agreed to receive a COVID-19 vaccine themselves in the first, second, and third surveys, respectively (P<.001). In all three surveys, "concerns about vaccine safety and side effects" was the most common reason for refusal. CONCLUSIONS: There has been an increasing acceptance of COVID-19 vaccination in Wuxi City, China. Effective interventions are needed to mitigate public concerns about vaccine safety.

Transmissibility and pathogenicity of the severe acute respiratory syndrome coronavirus 2: A systematic review and meta-analysis of secondary attack rate and asymptomatic infection.

BACKGROUND: Understanding the transmissibility and pathogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for control policies, but evidence remains limited. METHODS: We presented a systematic and meta-analytic summary concerning the transmissibility and pathogenicity of COVID-19. RESULTS: A total of 105 studies were identified, with 35042 infected cases and 897912 close contacts. 48.6% (51/105) of studies on secondary transmissions were from China. We estimated a total SIR of 7.8% (95% confidence interval [CI], 6.8%-8.8%), SAR of 6.6% (95% CI, 5.7%-7.5%), and symptomatic infection ratio of 86.9% (95%CI, 83.9%-89.9%) with a disease series interval of 5.84 (95%CI, 4.92-6.94) days. Household contacts had a higher risk of both symptomatic and asymptomatic infection, and transmission was driven between index cases and second-generation cases, with little transmission occurring in second-to-later-generation cases (SIR, 12.4% vs. 3.6%). The symptomatic infection ratio was not significantly different in terms of infection time, generation, type of contact, and index cases. CONCLUSIONS: Our results suggest a higher risk of infection among household contacts. Transmissibility decreased with generations during the intervention. Pathogenicity of SARS-CoV-2 varied among territories, but didn't change over time. Strict isolation and medical observation measures should be implemented.

Using an extended protection motivation theory to explain vaccine hesitancy: a cross-sectional study among Chinese adults.

BACKGROUND: Vaccine hesitancy was listed as one of the top 10 issues threatening global health in 2019. The objectives of this study were to (a) use an extended protection motivation theory (PMT) with an added trust component to identify predictors of vaccine hesitancy and (b) explore the predictive ability of vaccine hesitancy on vaccination behavior. METHODS: We conducted an online questionnaire from February 9 to April 9, 2021, in China. The target population was Chinese residents aged 18 and over. A total of 14,236 responses were received. Structural equation modeling was used to test the extended PMT model hypotheses. RESULTS: A total of 10,379 participants were finally included in this study, of whom 52.0% showed hesitancy toward vaccination. 2854 (27.5%) participants reported that they got flu shots in the past year, and 2561 (24.7%) participants were vaccinated against COVID-19. 2857 (27.5%) participants engaged in healthcare occupation. The model explained 85.7% variance of vaccine hesitancy. Self-efficacy was the strongest predictor, negatively associated with vaccine hesitancy (ß = -0.584; p < .001). Response efficacy had a negative effect on vaccine hesitancy (ß = -0.372; p < .001), while threat appraisal showed a positive effect (ß = 0.104; p < .001). Compared with non-health workers, health workers showed more vaccine hesitancy, and response efficacy was the strongest predictor (ß = -0.560; p < .001). Vaccine hesitancy had a negative effect on vaccination behavior (ß = -0.483; p < .001), and the model explained 23.4% variance of vaccination behavior. CONCLUSIONS: This study demonstrates that the extended PMT model is efficient in explaining vaccine hesitancy. However, the predictive ability of vaccine hesitancy on vaccination behavior is limited.

Cost-Effectiveness of Public Health Measures to Control COVID-19 in China: A Microsimulation Modeling Study.

This study aimed to assess the cost-effectiveness of various public health measures in dealing with coronavirus disease 2019 (COVID-19) in China. A stochastic agent-based model was used to simulate the progress of the COVID-19 outbreak in scenario I (imported one case) and scenario II (imported four cases) with a series of public health measures. The main outcomes included the avoided infections and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed to assess uncertainty. The results indicated that isolation-and-quarantine averted the COVID-19 outbreak at the lowest ICERs. The joint strategy of personal protection and isolation-and-quarantine averted one more case than only isolation-and-quarantine with additional costs. The effectiveness of isolation-and-quarantine decreased with lowering quarantine probability and increasing delay time. The strategy that included community containment would be cost-effective when the number of imported cases was >65, or the delay time of the quarantine was more than 5 days, or the quarantine probability was below 25%, based on current assumptions. In conclusion, isolation-and-quarantine was the most cost-effective intervention. However, personal protection combined with isolation-and-quarantine was the optimal strategy for averting more cases. The community containment could be more cost-effective as the efficiency of isolation-and-quarantine drops and the imported cases increases.

Delays in routine childhood vaccinations and their relationship with parental vaccine hesitancy: a cross-sectional study in Wuxi, China.

OBJECTIVES: This study aimed to examine childhood vaccination delay, explore the association between vaccination delay and parental vaccine hesitancy, and assess childhood vaccination delays during the coronavirus disease (COVID)-19 pandemic in China. METHODS: This cross-sectional survey was conducted in Wuxi City. Participants were recruited from local vaccination clinics. Questionnaires were used to collect information about socio-demographics, vaccine hesitancy, and immunization clinic evaluations. Vaccination records were obtained from the Jiangsu Information Management System of Vaccination Cases. RESULTS: Overall, 2728 participants were included. The coverage for seven category A vaccines (Expanded Program on Immunization (EPI)) was more than 95% at 24 months. The proportion of children vaccinated in a timely manner was the highest for the first dose of the hepatitis B vaccine (91.6%) and the lowest for the Bacillus-Calmette-Guerin vaccine (44.6%). More than 50% of the planned vaccinations were delayed in February and March 2020. The Vaccine Hesitancy Scale scores were not associated with vaccination delay (P = 0.842). Children's vaccination delays were negatively associated with parents who reported convenient access to clinics and satisfaction with immunization services (P = 0.020, P = 0.045). CONCLUSIONS: EPI is highly successful in China. Despite vaccination delays due to the COVID-19 pandemic, coverage was recovered after lockdown restrictions were eased.

Vaccination against COVID-19: A systematic review and meta-analysis of acceptability and its predictors.

We aimed to estimate the coronavirus disease 2019 (COVID-19) vaccine acceptance rate and identify predictors associated with acceptance. To this end, we searched PubMed, Web of Science, Cochrane Library, and Embase databases until November 4, 2020. Meta-analyses were performed to estimate the rate with 95% confidence intervals (CI). Predictors were identified to be associated with vaccination intention based on the health belief model framework. Thirty-eight articles, with 81,173 individuals, were included. The pooled COVID-19 vaccine acceptance rate was 73.31% (95%CI: 70.52, 76.01). Studies using representative samples reported a rate of 73.16%. The pooled acceptance rate among the general population (81.65%) was higher than that among healthcare workers (65.65%). Gender, educational level, influenza vaccination history, and trust in the government were strong predictors of COVID-19 vaccination willingness. People who received an influenza vaccination in the last year were more likely to accept COVID-19 vaccination (odds ratio: 3.165; 95%CI: 1.842, 5.464). Protecting oneself or others was the main reason for willingness, and concerns about side effects and safety were the main reasons for unwillingness. National- and individual-level interventions can be implemented to improve COVID-19 vaccine acceptance before large-scale vaccine rollout. Greater efforts could be put into addressing negative predictors associated with willingness.

Reporting of coronavirus disease 2019 prognostic models: the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis statement.

Evaluation of the validity and applicability of published prognostic prediction models for coronavirus disease 2019 (COVID-19) is essential, because determining the patients' prognosis at an early stage may reduce mortality. This study was aimed to utilize the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) to report the completeness of COVID-19-related prognostic models and appraise its effectiveness in clinical practice. A systematic search of the Web of Science and PubMed was performed for studies published until August 11, 2020. All models were assessed on model development, external validation of existing models, incremental values, and development and validation of the same model. TRIPOD was used to assess the completeness of included models, and the completeness of each item was also reported. In total, 52 publications were included, including 67 models. Age, disease history, lymphoma count, history of hypertension and cardiovascular disease, C-reactive protein, lactate dehydrogenase, white blood cell count, and platelet count were the commonly used predictors. The predicted outcome was death, development of severe or critical state, survival time, and length-of-hospital stay. The reported discrimination performance of all models ranged from 0.361 to 0.994, while few models reported calibration. Overall, the reporting completeness based on TRIPOD was between 31% and 83% [median, 67% (interquartile range: 62%, 73%)]. Blinding of the outcome to be predicted or predictors were poorly reported. Additionally, there was little description on the handling of missing data. This assessment indicated a poorly-reported COVID-19 prognostic model in existing literature. The risk of over-fitting may exist with these models. The reporting of calibration and external validation should be given more attention in future research.

The lncRNA Snhg1-Vps13D vesicle trafficking system promotes memory CD8 T cell establishment via regulating the dual effects of IL-7 signaling.

The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection. Recent studies indicated that long-noncoding RNAs expression is highly cell- and stage-specific during T cell development and differentiation, suggesting their potential roles in T cell programs. However, the key lncRNAs playing crucial roles in memory CD8 T cell establishment remain to be clarified. Through CD8 T cell subsets profiling of lncRNAs, this study found a key lncRNA-Snhg1 with the conserved naivehi-effectorlo-memoryhi expression pattern in CD8 T cells of both mice and human, that can promote memory formation while impeding effector CD8 in acute viral infection. Further, Snhg1 was found interacting with the conserved vesicle trafficking protein Vps13D to promote IL-7Rα membrane location specifically. With the deep mechanism probing, the results show Snhg1-Vps13D regulated IL-7 signaling with its dual effects in memory CD8 generation, which not just because of the sustaining role of STAT5-BCL-2 axis for memory survival, but more through the STAT3-TCF1-Blimp1 axis for transcriptional launch program of memory differentiation. Moreover, we performed further study with finding a similar high-low-high expression pattern of human SNHG1/VPS13D/IL7R/TCF7 in CD8 T cell subsets from PBMC samples of the convalescent COVID-19 patients. The central role of Snhg1-Vps13D-IL-7R-TCF1 axis in memory CD8 establishment makes it a potential target for improving the vaccination effects to control the ongoing pandemic.

Rapid Spread of Mutant Alleles in Worldwide SARS-CoV-2 Strains Revealed by Genome-Wide Single Nucleotide Polymorphism and Variation Analysis.

The novel coronavirus (SARS-CoV-2) has become a pandemic and is threatening human health globally. Here, we report nine newly evolved SARS-CoV-2 single nucleotide polymorphism (SNP) alleles those underwent a rapid increase (seven cases) or decrease (two cases) in their frequency for 30-80% in the initial four months, which are further confirmed by intrahost single nucleotide variation analysis using raw sequence data including 8,217 samples. The nine SNPs are mostly (8/9) located in the coding region and are mainly (6/9) nonsynonymous substitutions. The nine SNPs show a complete linkage in SNP pairs and belong to three different linkage groups, named LG_1 to LG_3. Analyses in population genetics show signatures of adaptive selection toward the mutants in LG_1, but no signal of selection for LG_2. Population genetic analysis results on LG_3 show geological differentiation. Analyses on geographic COVID-19 cases and published clinical data provide evidence that the mutants in LG_1 and LG_3 benefit virus replication and those in LG_1 have a positive correlation with the disease severity in COVID-19-infected patients. The mutants in LG_2 show a bias toward mildness of the disease based on available public clinical data. Our findings may be instructive for epidemiological surveys and disease control of COVID-19 in the future.