A systematical association analysis of 25 common virus infection and genetic susceptibility of COVID-19 infection.

OBJECTIVES: Previous studies identified a number of diseases were associated with 2019 coronavirus disease (COVID-19). However, the associations between these diseases related viral infections and COVID-19 remains unknown now. METHODS: In this study, we utilized single nucleotide polymorphisms (SNPs) related to COVID-19 from genome-wide association study (GWAS) and individual-level genotype data from the UK biobank to calculate polygenic risk scores (PRS) of 487,409 subjects for eight COVID-19 clinical phenotypes. Then, multiple logistic regression models were established to assess the correlation between serological measurements (positive/negative) of 25 viruses and the PRS of eight COVID-19 clinical phenotypes. And we performed stratified analyses by age and gender. RESULTS: In whole population, we identified 12 viruses associated with the PRS of COVID-19 clinical phenotypes, such as VZV seropositivity for Varicella Zoster Virus (Unscreened/Exposed_Negative: ß = 0.1361, P = 0.0142; Hospitalized/Unscreened: ß = 0.1167, P = 0.0385) and MCV seropositivity for Merkel Cell Polyomavirus (Unscreened/Exposed_Negative: ß = -0.0614, P = 0.0478). After age stratification, we identified seven viruses associated with the PRS of eight COVID-19 clinical phenotypes. After gender stratification, we identified five viruses associated with the PRS of eight COVID-19 clinical phenotypes in the women group. CONCLUSION: Our study findings suggest that the genetic susceptibility to different COVID-19 clinical phenotypes is associated with the infection status of various common viruses.

Combined effects of inflammation and coronavirus disease 2019 (COVID-19) on the risks of anxiety and depression: A cross-sectional study based on UK Biobank.

Infection-induced perturbation of immune homeostasis could promote psychopathology. Psychiatric sequelae have been observed after previous coronavirus outbreaks. However, limited studies were conducted to explore the potential interaction effects of inflammation and coronavirus disease 2019 (COVID-19) on the risks of anxiety and depression. In this study, first, polygenic risk scores (PRS) were calculated for eight COVID-19 clinical phenotypes using individual-level genotype data from the UK Biobank. Then, linear regression models were developed to assess the effects of COVID-19 PRS, C-reactive protein (CRP), systemic immune inflammation index (SII), and their interaction effects on the Generalized Anxiety Disorder-7 (GAD-7, 104 783 individuals) score and the Patient Health Questionnaire-9 (PHQ-9, 104 346 individuals) score. Several suggestive interactions between inflammation factors and COVID-19 clinical phenotypes were detected for PHQ-9 score, such as CRP/SII × Hospitalized/Not_Hospitalized in women group and CRP × Hospitalized/Unscreened in age >65 years group. For GAD-7 score, we also found several suggestive interactions, such as CRP × Positive/Unscreened in the age ≤65 years group. Our results suggest that not only COVID-19 and inflammation have important effects on anxiety and depression but also the interactions of COVID-19 and inflammation have serious risks for anxiety and depression.

Adverse reactions to inactivated COVID-19 vaccination in patients with chronic liver disease: The effect of anxiety.

Studies have shown that patients with chronic liver disease are at a higher risk of contracting novel coronavirus pneumonia than healthy individuals, and many guidelines state that patients with chronic liver disease should be prioritized for COVID-19 vaccination, but there are a few studies on its safety in CLD patients. We aimed to evaluate the safety of the inactivated COVID-19 vaccine in patients with chronic liver disease, and the effect of anxiety on adverse reactions. A questionnaire survey for self-administered post-vaccination adverse reaction monitoring was conducted from June 17, 2021, to August 11, 2021, in patients with chronic liver disease attending a tertiary care hospital in Taizhou, China. We analyzed the data from of a total of 160 participants who scanned the QR code on social media to respond to the questionnaire. The overall incidence of adverse reactions after COVID-19 vaccination in patients with chronic liver disease was 44.4% (71/160), and the most common adverse reaction was local injection site reaction, accounting for 80.3% of adverse reactions (57/71). No serious adverse reactions were reported. Approximately 53.1% of the patients had anxiety about vaccination, and 51.8% of those who felt anxious reported adverse reactions. The safety of COVID-19 vaccination in patients with chronic liver disease is good, and there is a strong association between adverse reactions and vaccine anxiety. Pre-vaccination education for patients with vaccine anxiety and psychological counseling may reduce reports of adverse reactions and improve patients' confidence in the vaccine.

Willingness of Older Adults with Chronic Diseases to Receive a Booster Dose of Inactivated Coronavirus Disease 2019 Vaccine: A Cross-Sectional Study in Taizhou, China.

Vaccination is an important measure to control the spread of COVID-19 among elderly high-risk groups; however, the propensity to receive COVID-19 vaccine boosters has not been evaluated in these populations. Here, we aimed to investigate the willingness to receive a COVID-19 vaccine booster among the elderly chronic disease population in Taizhou, China. A cross-sectional, hospital-based survey was conducted in the outpatient department of a tertiary care hospital between 6 July and 11 August 2021 in Taizhou, China, and the data were uploaded to Wen-Juan-Xing, one of the largest online platforms used to collect survey data in China. The targeted population was non-oncology chronic disease patients aged 60 years and above. The minimum sample size was 229, determined by the G*Power software (v3.1.9.2, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany). A total of 254 patients with valid data were enrolled in this study, with a response rate of 82.5% (254/308). Chi-square tests and one-way binary regression were used to compare the proportions and the degree of influence of categorical factors. The magnitude of the effect for the comparisons was measured by Gramer's V. A multivariate binary logistic regression model was used to correct for confounders and to identify factors. All data were analyzed using SPSS v24.0 (IBM Corporation, Armonk, NY, USA). A total of 198 respondents (77.9%) were willing to receive a COVID-19 vaccine booster dose, and 77.6% of respondents were willing to receive the primary dose. Age < 70 years (OR 2.82), stable disease control (OR 2.79), confidence in the effectiveness of the COVID-19 vaccine (OR 3.11), and vaccine recipient (OR 5.02) were significantly associated with the willingness to receive a COVID-19 vaccine booster dose. Promoting primary dose vaccination is essential for advancing booster vaccination, and it is important to focus on elderly patients' confidence in the vaccine, in addition to strengthening health management and promoting disease stability. Follow-up studies should focus on elderly patients who belong to specific disease groups.

Relationship between knowledge, attitudes, and practices and COVID-19 vaccine hesitancy: A cross-sectional study in Taizhou, China.

Objective: This study aimed to explore COVID-19 vaccine hesitancy in Chinese adults and analyzed the relationship between knowledge, attitudes, practices (KAP), and COVID-19 vaccine hesitancy. Methods: A population-based self-administered online survey was conducted in Taizhou, China to evaluate the population's hesitancy to receive COVID-19 vaccination. A total of 2.463 adults received the invitation for the survey through WeChat (A Chinese app that is used for chat, social media, and mobile payment), and 1.788 interviewees answered the structured questionnaire. The overall response rate was 72.6%. Results: Total 45.2% of people were hesitant about the COVID-19 vaccination. Using binary logistic regression analysis, we found low perception of safety (Model 3: Odds ratio = 2.977, Confidence interval: 2.237-3.963) and efficacy (Model 3: OR = 1.904, 95%CI: 1.462-2.479) of the COVID-19 vaccine in adults is the most important risk factor for COVID-19 vaccine hesitation. People who know more about COVID-19 vaccination are less hesitant (Model 2: OR = 0.967, 95% CI: 0.951-0.983). People who did not seek information independently about the COVID-19 vaccine are more likely to be skeptical (Model 4: OR = 1.300, 95% CI: 1.058-1.598, P = 0.013). Conclusion: In China, the population had higher levels of COVID-19 vaccine hesitation, and their knowledge of the COVID-19 vaccine, perceptions of safety and efficacy, and physical health status were significantly associated with vaccine hesitation. These results provide ideas for promoting COVID-19 vaccination and intervention and have far-reaching implications for further strengthening research on vaccine hesitancy in COVID-19 and exploring strategies for COVID-19 vaccine promotion.

COVID-19 booster vaccine willingness among patients with chronic kidney disease in Taizhou, China (preprint)

Purpose Investgate the willingness of CKD patients to receive a COVID-19 booster vaccine dose and analyze the related factors of COVID-19 booster vaccine willingness in such patients.Methods An online questionnaire investigation addressing participants’ willingness to receive a booster dose of COVID-19 vaccine was organized among patients with chronic kidney disease in Taizhou, China.Result A total of 350 valid copies were retrieved, among which 246 respondents (70.29%) were willing to receive a COVID-19 booster vaccine dose. Binary logistic regression analysis showed that high perceived vaccine safety and effectiveness, non-hemodialysis treatment, and one or two rounds of COVID-19 vaccine were related to COVID-19 booster vaccine willingness of CKD patients. Therefore, enhancing propaganda on safety and efficacy of COVID-19 vaccine for CKD patients, raising their awareness about vaccination, and increasing vaccination of the first and second rounds can help increase the COVID-19 booster vaccination rate.

The impact of the Omicron epidemic on the health behavior in Cape Town, South Africa.

Background: South Africa was the first country with a case of Omicron variant infection diagnosed; therefore, this study aimed to elucidate the impact of the Omicron mutant strain outbreak on the health behavior of the South African population and encourage the population to adopt timely protective behaviors against Omicron mutant strain infection. Study design and methods: This was a population-based, cross-sectional study conducted in Cape Town, South Africa, in December 2021. We distributed 300 questionnaires to adults aged >18 years, and they were all returned. Results: Of the South African population, 60.3% expressed a high level of concern regarding Omicron; 89.3% improved on at least one of the following three health behaviors: mask-wearing, washing hands, and reducing socialization; and only 10.7% exhibited no improvement in health behaviors. Of these, 71.3% and 57.0% increased the length of time they wore a mask and washed their hands, respectively, and 47% decreased the number of times they socialized. Age, residence, education level, chronic disease, and whether they had received the COVID-19 vaccine were significantly different (p < 0.05) between the presence and absence of enhanced health behaviors. The levels of concern and knowledge regarding the Omicron virus significantly influenced health-behavior change (all P < 0.05). Conclusion: There has been a positive change in the South African population toward adopting mask-wearing, hand washing, and reducing socialization in response to the Omicron virus strain epidemic. Based on one health approach, it is important to focus on populations with chronic diseases, those who have not yet received the COVID-19 vaccine, and other populations with low rates of health behavior change.

T-cell receptor repertoires as potential diagnostic markers for patients with COVID-19.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global health emergency. T-cell receptors (TCRs) are crucial mediators of antiviral adaptive immunity. This study sought to comprehensively characterize the TCR repertoire changes in patients with COVID-19. METHODS: A large sample size multi-center randomized controlled trial was implemented to study the features of the TCR repertoire and identify COVID-19 disease-related TCR sequences. RESULTS: It was found that some T-cell receptor beta chain (TCRß) features differed markedly between COVID-19 patients and healthy controls, including decreased repertoire diversity, longer complementarity-determining region 3 (CDR3) length, skewed utilization of the TCRß variable gene/joining gene (TRBV/J), and a high degree of TCRß sharing in COVID-19 patients. Moreover, this analysis showed that TCR repertoire diversity declines with aging, which may be a cause of the higher infection and mortality rates in elderly patients. Importantly, a set of TCRß clones that can distinguish COVID-19 patients from healthy controls with high accuracy was identified. Notably, this diagnostic model demonstrates 100% specificity and 82.68% sensitivity at 0-3 days post diagnosis. CONCLUSIONS: This study lays the foundation for immunodiagnosis and the development of medicines and vaccines for COVID-19 patients.

Transcriptome Analysis of Peripheral Blood Mononuclear Cells Reveals Distinct Immune Response in Asymptomatic and Re-Detectable Positive COVID-19 Patients.

The existence of asymptomatic and re-detectable positive coronavirus disease 2019 (COVID-19) patients presents the disease control challenges of COVID-19. Most studies on immune responses in COVID-19 have focused on moderately or severely symptomatic patients; however, little is known about the immune response in asymptomatic and re-detectable positive (RP) patients. Here we performed a comprehensive analysis of the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 48 COVID-19 patients which included 8 asymptomatic, 13 symptomatic, 15 recovered and 12 RP patients. The weighted gene co-expression network analysis (WGCNA) identified six co-expression modules, of which the turquoise module was positively correlated with the asymptomatic, symptomatic, and recovered COVID-19 patients. The red module positively correlated with symptomatic patients only and the blue and brown modules positively correlated with the RP patients. The analysis by single sample gene set enrichment analysis (ssGSEA) revealed a lower level of IFN response and complement activation in the asymptomatic patients compared with the symptomatic, indicating a weaker immune response of the PBMCs in the asymptomatic patients. In addition, gene set enrichment analysis (GSEA) analysis showed the enrichment of TNFα/NF-κB and influenza infection in the RP patients compared with the recovered patients, indicating a hyper-inflammatory immune response in the PBMC of RP patients. Thus our findings could extend our understanding of host immune response during the progression of COVID-19 disease and assist clinical management and the immunotherapy development for COVID-19.

Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics.

Antiviral drugs (AvDs) are the primary resource in the global battle against viruses, including the recent fight against corona virus disease 2019 (COVID-19). Most AvDs require multiple medications, and their use frequently leads to drug resistance, since they have poor oral bioavailability and low efficacy due to their low solubility/low permeability. Characterizing the in vivo metabolism and pharmacokinetic characteristics of AvDs may help to solve the problems associated with AvDs and enhance their efficacy. In this review of AvDs, we systematically investigated their structure-based metabolic reactions and related enzymes, their cellular pharmacology, and the effects of metabolism on AvD pharmacodynamics and pharmacokinetics. We further assessed how delivery systems achieve better metabolism and pharmacology of AvDs. This review suggests that suitable nanosystems may help to achieve better pharmacological activity and pharmacokinetic behavior of AvDs by altering drug metabolism through the utilization of advanced nanotechnology and appropriate administration routes. Notably, such AvDs as ribavirin, remdesivir, favipiravir, chloroquine, lopinavir and ritonavir have been confirmed to bind to the severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) receptor and thus may represent anti-COVID-19 treatments. Elucidating the metabolic and pharmacokinetic characteristics of AvDs may help pharmacologists to identify new formulations with high bioavailability and efficacy and help physicians to better treat virus-related diseases, including COVID-19.

Comparative analysis of Student's live online learning readiness during the coronavirus (COVID-19) pandemic in the higher education sector.

Amid the coronavirus outbreak, many countries are facing a dramatic situation in terms of the global economy and human social activities, including education. The shutdown of schools is affecting many students around the world, with face-to-face classes suspended. Many countries facing the disastrous situation imposed class suspension at an early stage of the coronavirus outbreak, and Asia was one of the earliest regions to implement live online learning. Despite previous research on online teaching and learning, students' readiness to participate in the real-time online learning implemented during the coronavirus outbreak is not yet well understood. This study explored several key factors in the research framework related to learning motivation, learning readiness and student's self-efficacy in participating in live online learning during the coronavirus outbreak, taking into account gender differences and differences among sub-degree (SD), undergraduate (UG) and postgraduate (PG) students. Technology readiness was used instead of conventional online/internet self-efficacy to determine students' live online learning readiness. The hypothetical model was validated using confirmatory factor analysis (CFA). The results revealed no statistically significant differences between males and females. On the other hand, the mean scores for PG students were higher than for UG and SD students based on the post hoc test. We argue that during the coronavirus outbreak, gender differences were reduced because students are forced to learn more initiatively. We also suggest that students studying at a higher education degree level may have higher expectations of their academic achievement and were significantly different in their online learning readiness. This study has important implications for educators in implementing live online learning, particularly for the design of teaching contexts for students from different educational levels. More virtual activities should be considered to enhance the motivation for students undertaking lower-level degrees, and encouragement of student-to-student interactions can be considered.