Impact of comorbidities on the serological response to COVID-19 vaccination in Taiwan (preprint)

Background/Aims Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best policies to control COVID-19 pandemic. The serological response to COVID-19 vaccination in Taiwanese patients with different comorbidities is elusive. Methods Uninfected subjects who received 3 doses of mRNA vaccines (BNT162b2 [Pfizer-BioNTech, BNT] and mRNA-1273 [Moderna]), viral vector-based vaccines (ChAdOx1-S (AZD1222, AZ) or protein subunit vaccines (Medigen COVID-19 vaccine) were prospectively enrolled. The SARS-CoV-2-IgG spike antibody level was determined within three months after the 3rd dose of vaccination. The Charlson Comorbidity Index (CCI) was applied to determine the association between vaccine titers and underlying comorbidities. Results A total of 824 subjects were enrolled in the current study. The proportions of CCI scores of 0-1, 2-3 and >4 were 52.8% (n=435), 31.3% (n=258) and 15.9% (n=131), respectively. The most commonly used vaccination combination was AZ-AZ-Moderna (39.2%), followed by Moderna-Moderna-Moderna (27.8%). The mean vaccination titer was 3.11 log BAU/mL after a median of 48 days after the 3rd dose. Factors associated with potentially effective neutralization capacity included an age ≥60 years (odds ratio [OR]/95% confidence interval [CI], 0.49/0.34–0.72; P <0.001), female gender (OR/CI, 1.78/1.26–2.53; P =0.001), Moderna-based vaccination (compared to AZ-based vaccination; OR/CI, 6.49/3.90–10.82; P <0.001) and a CCI score ≥4 (OR/CI, 0.55/0.35–0.85; P =0.01). There was a decreasing trend in antibody titers with increasing CCI scores (trend P<0.001). Linear regression analysis revealed that AZ-based vaccination (β: 0.341, CI: 0.144, 0.21, P<0.001) and higher CCI scores (β: -0.055, CI: -0.096, -0.014, P=0.009) independently correlated with low IgG spike antibody levels. Conclusions Subjects with more comorbidities had a poor response to 3 doses of COVID-19 vaccination.

The impact of COVID-19 lockdown on maternal and neonatal outcomes of uninfected woman in late pregnancy: A multicenter study in China (preprint)

Background COVID-19 pandemic has had direct and indirect impacts on health-care system and maternal and neonatal health, but no multicenter evidence from China of this effects has been undertaken. The purpose of this study was to investigate the impacts of COVID-19 lockdown on maternal and fetal outcomes in China.Methods This retrospective cohort study included 3540 women in their late pregnancy without COVID-19 who received perinatal healthcare in three hospitals in Wuhan, Shanghai and Haikou during COVID-19 lockdown period in 2020 or the non-lockdown period in 2019. Propensity-score matching was used to compare preterm birth (< 37 weeks) and its classification, very preterm birth (< 34 weeks), caesarean section and its indications, the length of hospital stay, birth weight and other pregnancy outcomes between two groups.Results Preterm births before 37 weeks’ gestation (5.4% vs. 5.3%, P = 0.83) and very preterm birth (0.7% vs. 0.8%, P = 0.58) were not significantly changed overall. But medical-induced preterm birth before 37 weeks’ gestation in Wuhan was decreased (0.8% vs. 1.7%, P = 0.04). The cesarean section for maternal factors was decreased (21.4% vs. 24.3%, P = 0.003). The length of maternal (4.2d vs 4.5d, P < 0.001) and neonatal (3.4d vs 3.7d, P < 0.001) hospital stay was shortened. No overall significant effects were identified for other outcomes included in the quantitative analysis: maternal gestational diabetes; pregnancy-induced hypertension; preterm birth with premature rupture of membranes; low birthweight (< 2500 g); neonatal intensive care unit admission; or abnormal Apgar score.Conclusions This study demonstrated that there was protective impact of the COVID-19 lockdown on maternal and neonatal outcomes among women in their late pregnancy in China.

Impact of Music Education on Mental Health of Higher Education Students: Moderating Role of Emotional Intelligence

Music education is one of human kind most universal forms of expression and communication, and it can be found in the daily lives of people of all ages and cultures all over the world. As university life is a time when students are exposed to a great deal of stress, it can have a negative impact on their mental health. Therefore, it is critical to intervene at this stage in their life so that they are prepared to deal with the pressures they will face in the future. The aim of this study was to see how music education affects university students’ mental health, with emotional intelligence functioning as a moderator. The participants in this research were graduate students pursuing degrees in music education. Non probability convenience sampling technique was used to collect and evaluate the data from 265 students studying in different public and private Chinese universities. The data was gathered at a time, and therefore, the study is cross-sectional. The data was collected from January 2022 till the end of March 2022. Many universities have been closed because to COVID-19, therefore data was also gathered online through emails. The data was analyzed quantitatively using the partial least squares (PLS)–structural equation modeling (SEM) technique. The findings backed up the hypotheses. The results revealed that there is a significant effect of music education on student’s mental health. Also, emotional intelligence as a moderator significantly and positively moderates the relationship between music education and students’ mental health. Music has numerous physiological aspects, and listening to it on a daily basis may be beneficial to your general health and well-being. Furthermore, musicians and music students with a high level of emotional intelligence have a better chance of not just performing well in school, college and university or in the music industry, but also of maintaining mental health and improving it.

NLRP3 Inflammasome: Mechanism of Action, Role, and Therapeutics in Liver Diseases (preprint)

Liver inflammation is a universal characteristic of chronic liver diseases. NLRP3 is an intracellular sensor that recognizes various endogenous danger signals and environmental irritants, contributing to the formation and activation of the NLRP3 inflammasome. NLRP3 inflammasome is closely related to the progression of various liver diseases and is strongly associated with replicating COVID-19, which is still spreading globally. The assembly and activation of NLRP3 inflammasome in the liver diseases aggravate inflammation and subsequent fibrosis, and this effect is abolished by genetic or pharmacologic deletion of NLRP3 inflammasome. Here, we summarized the latest advances in the critical regulatory role of NLRP3 inflammasome in a variety of liver diseases, including COVID-19 induced liver diseases, NAFLD, ALD, and ischemia-reperfusion (I/R) injury. Additionally, we also discuss small-molecule inhibitors identifying the NLRP3 inflammasome signaling are novel therapeutic targets in treating liver diseases. Our review provides novel insights into the underlying mechanisms of NLRP3 inflammasome in liver diseases and may offer a potential therapeutic strategy for treating liver diseases by targeting NLRP3 inflammasome.

A human monoclonal antibody potently pan-neutralizes SARS-CoV-2 VOCs by targeting RBD invariant sites (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.

Oil futures volatility predictability: Evidence based on Twitter-based uncertainty

This paper explores the influence of the Twitter-based uncertainty index on oil futures market volatility. The Twitter-based Market Uncertainty (TMU) index, based on the novel Markov-regime GARCH-MIDAS model, may significantly improve prediction accuracy for oil futures volatility. Moreover, the TMU was still useful in predicting oil volatility during the COVID-19 pandemic. Furthermore, when the alternative Twitter-based uncertainty index, Twitter-based Economic Uncertainty (TEU), is adopted, these results are also robust. This paper highlights the importance of the Twitter-based uncertainty index for oil futures market.

Epidemiology and clinical re-positivity evaluation of SARS-CoV-2 cases in Wuxi

This study aimed to analyze the relationship between SARS-CoV-2 spreading and clinical classification to evaluate the transmission and pathogenicity characteristics of the local virus, and to understand the clinical characteristics of SARS-CoV-2 reactivation, on the basis of the clinical manifestations in Wuxi. We collected information on the SARS-CoV-2 positive cases admitted to The Fifth People's Hospital of Wuxi from January 23 to November 20, 2020. According to epidemiological and clinical characteristics, we analyzed the changes in the transmission and pathogenicity of the virus and the clinical manifestations of SARS-CoV-2 reactivation cases. The severe and critical COVID-19 cases appeared only before the second-generation, whereas the third-generation cases were all mild. The rate of severe illness in the second-generation (7.1%) was significantly lower than that in the first-generation (17.5%), and the overseas imported cases (n-generation cases) were asymptomatic and mild. The presence of antibodies (IgM and IgG) in partially asymptomatic and mild cases appeared to become negative. The clinical features of SARS-CoV-2 first-positive and reactivation cases showed that some cases (2/3) developed lung inflammation, but their blood clinical indicators were normal. The proportion of severe cases of SARS-CoV-2 infection in Wuxi has decreased gradually, and asymptomatic or mild cases may become a high-risk group of viral re-yang. Immunological indicators can help predict clinical re-positivity.

Specific Immune Phenotypes Protect Individuals Against COVID-19 Susceptibility and Severity: A Mendelian Randomization Study (preprint)

Identifying the host factors influencing the COVID-19 outcome is critical to overcome the global pandemic. The associations between immune phenotypes and the risk of COVID-19 are still poorly understood. We sought to systematically evaluate the causal impact of multiple immune cell traits on COVID-19 susceptibility and its severity using two-sample Mendelian randomization (MR). Genetic variants associated with each immune phenotypes at P < 5×10-8 from genome-wide association studies (GWAS). The GWAS statistics of COVID-19 is from COVID-19 Host Genetics Initiative. Susceptibility and severity were defined as COVID-19 positive and hospitalization versus population controls, respectively. Inverse-variance weighted (IVW) method was used as the main MR analysis, and comprehensive sensitivity analyses were conducted for estimating the robustness. The MR estimates showed that genetically predicted high expression of BAFF-R on B cell was strongly associated with a lower risk of COVID-19 severity. In addition, BAFF-R expression on B cell subsets showed consistent causal relationship with COVID-19 severity, such as its expression on transitional B cell and naïve-mature B cell. Evidence from all sensitivity analyses further supported these associations. In MR analysis for COVID-19 susceptibility, we observed a highly consistent protective role of BAFF-R expression, although the P value was not significant. Moreover, in multivariable MR analyses, adjusting for the effects of other B cell biomarkers displayed similar MR findings. This study provides genetic evidence that the genetically high expression of BAFF-R on B cells decreases the risk of COVID-19 severity.

Periodontal Disease Increases the Host Susceptibility to COVID-19 and its Severity: A Mendelian Randomization Study (preprint)

Background: Emerging evidence shows that periodontal disease (PD) may increase the risk of Coronavirus disease 2019 (COVID-19) complications. Here, we undertook a two-sample Mendelian randomization (MR) study, and investigated for the first time the possible causal impact of PD on host susceptibility to COVID-19 and its severity.Methods: Summary statistics of COVID-19 susceptibility and severity was retrieved from the COVID-19 Host Genetics Initiative and used as outcomes in this study. As for exposures, Single Nucleotide Polymorphisms (SNPs) with genome-wide significant variants from genome wide association study (GWAS) of PD were included in the MR analysis. Inverse-variance weighted (IVW) method was employed as the main approach to analyzing the causal relationships between PD and COVID-19. Three additional methods were adopted, allowing the existence of horizontal pleiotropy including MR-Egger regression, weighted median and weighted mode methods. Comprehensive sensitivity analyses were also conducted for estimating the robustness of the identified associations.Findings: The MR estimates showed that PD was markedly associated with a higher susceptibility to COVID-19 using IVW (OR = 1.024, P = 0.017) and weighted median method (OR = 1.029, P = 0.024). Furthermore, it revealed that PD was significantly linked to COVID-19 severity based on the comparison of hospitalization versus population controls (IVW: OR = 1.025, P = 0.039; weighted median, OR = 1.030, P = 0.027). No such association was observed in the cohort of highly severe cases confirmed versus those not hospitalized due to COVID-19.Interpretation: This study provides genetic evidence on the possible causality of periodontal disease accounting for the host susceptibility to COVID-19 and its severity, thereby highlighting the importance of disease prevention and oral/periodontal healthcare for general wellbeing during the pandemic and beyond.Funding Information: This work was supported by the Natural Science Foundation of Zhejiang Province (LY18H160050, LQ20H140002), Medical and Health Science and Technology Planning Project of Zhejiang Province (2018KY518), National Natural Science Foundation of China (31771390, 81972261, 32070151), Wenzhou Science and Technology Bureau (ZY2020007, 2020Y0536, Y20190147).Declaration of Interests: The authors declare that no competing interests exist.Ethics Approval Statement: This study only used publicly available data and the relevant ethical approval can be found in the corresponding studies referenced in the Methods section.

Pulmonary Lesion Subtypes Recognition of COVID-19 From Radiomics Data With Three Dimensional Texture Characterization in CT Images (preprint)

Background: The COVID-19 disease is putting unprecedented pressure on the global healthcare system. The CT examination as a auxiliary confirmed diagnostic method can help clinicians quickly detect lesions locations of COVID-19 once screening by PCR test. Furthermore, the lesion subtypes classification plays a critical role in the consequent treatment decision. Identifying the subtypes of lesions accurately can help doctors discover changes in lesions in time and better assess the severity of COVID-19. Method: The most four typical lesion subtypes of COVID-19 are discussed in this paper, which are ground-glass opacity (GGO), cord, solid and subsolid. A computer aided diagnosis approach of lesion subtype is proposed in this paper. The radiomics data of lesions are segmented from COVID-19 patients CT images with diagnosis and lesions annotations by radiologists. Then the three dimensional texture descriptors are applied on the volume data of lesions as well as shape and First order features. The massive feature data are selected by hybrid adaptive selection algorithm and a classification model is trained at the same time. The classifier is used to predict lesion subtypes as side decision information for radiologists. Results: There are 3734 lesions extracted from the dataset with 319 patients collection and then 189 radiomics features are obtained finally. The random forest classifier is trained with data augmentation that the number of different subtypes of lesions is imbalanced in initial dataset. The experimental results show that the accuracy of the four subtypes of lesions is (0.9306, 0.9684, 0.9958, and 0.9430), the recall is (0.9552, 0.9158, 0.9580 and 0.8075) and the f-score is (0.93.84, 0.92.37, 0.95.47, and 84.42). Conclusion: The method is evaluated in multiple sufficient experiments. The results show that the 3D radiomics features chosen by hybrid adaptive selection algorithm can better express the advanced information of the lesion data. The classification model obtains a good performance and is compared the models of COVID-19 in the stat of art, which can help clinicians more accurately identify the subtypes of COVID-19 lesions and provide help for further research.

Molecular Insights into Small‐Molecule Drug Discovery for SARS‐CoV‐2

The mainstream approach to antiviral drugs against COVID‐19 is to focus on key stages of the SARS‐CoV‐2 life cycle. The vast majority of candidates under investigation are repurposed from agents of other indications. Understanding protein–inhibitor interactions at the molecular scale will provide crucial insights for drug discovery to stop this pandemic. In this article, we summarize and analyze the most recent structural data on several viral targets in the presence of promising inhibitors for COVID‐19 in the context of the perspective of modes of action (MOA) to unravel insightful mechanistic features with atomistic resolution. The targets include spike glycoprotein and various host proteases mediating the entry of the virus into the cells, viral chymotrypsin‐ and papain‐like proteases, and RNA‐dependent RNA polymerase. The main purpose of this review is to present detailed MOA analysis to inspire fresh ideas for both de novo drug design and optimization of known scaffolds to combat COVID‐19.

How fear and collectivism influence public's preventive intention towards COVID-19 infection: A study based on big data from the social media (preprint)

Background: Despite worldwide calls for precautionary measures to combat COVID-19, the public's preventive intention still varies significantly among different regions. Exploring the influencing factors of the public's preventive intention is very important to curtail the spread of COVID-19. Previous studies have found that fear can effectively improve the public's preventive intention, but they ignore the impact of differences in cultural values. The present study examines the combined effect of fear and collectivism on the public's preventive intention towards COVID-19 through the analysis of social media big data. Methods: : The Sina microblog posts of 108,914 active users from Chinese mainland 31 provinces were downloaded. The data was retrieved from January 11 to February 21 2020. Afterwards, we conducted a province-level analysis of the contents of downloaded posts. Three lexicons were applied to automatically recognise the scores of fear, collectivism, and preventive intention of 31 provinces. After that, a multiple regression model was established to examine the combined effect of fear and collectivism on the public's preventive intention towards COVID-19. The simple slope test and the Johnson-Neyman technique were used to test the interaction of fear and collectivism on preventive intention. Results: : The study reveals that: (a) both fear and collectivism can positively predict people's preventive intention and (b) there is an interaction of fear and collectivism on people's preventive intention, where fear and collectivism reduce each other's positive influence on people's preventive intention. Conclusion: The promotion of fear on people's preventive intention may be limited and conditional, and values of collectivism can well compensate for the promotion of fear on preventive intention. These results provide scientific inspiration on how to enhance the public's preventive intention towards COVID-19 effectively.

The ORF8 Protein of SARS-CoV-2 Mediates Immune Evasion through Potently Downregulating MHC-I (preprint)

SARS-CoV-2 infection have caused global pandemic and claimed over 5,000,000 tolls1-4. Although the genetic sequences of their etiologic viruses are of high homology, the clinical and pathological characteristics of COVID-19 significantly differ from SARS5,6. Especially, it seems that SARS-CoV-2 undergoes vast replication in vivo without being effectively monitored by anti-viral immunity7. Here, we show that the viral protein encoded from open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all the viral proteins, can directly interact with MHC-I molecules and significantly down-regulates their surface expression on various cell types. In contrast, ORF8a and ORF8b of SARS-CoV do not exert this function. In the ORF8-expressing cells, MHC-I molecules are selectively target for lysosomal degradation by an autophagy-dependent mechanism. As a result, CTLs inefficiently eliminate the ORF8-expressing cells. Our results demonstrate that ORF8 protein disrupts antigen presentation and reduces the recognition and the elimination of virus-infected cells by CTLs8. Therefore, we suggest that the inhibition of ORF8 function could be a strategy to improve the special immune surveillance and accelerate the eradication of SARS-CoV-2 in vivo.

The Urgent Countermeasures in Infection Control for Diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Taiwan (preprint)

The emergence of the coronavirus disease 2019 (COVID-19) caused a large-scale outbreak and has rapidly spread across China and multiple countries. We reported countermeasures in infection control for diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) infection and the experiences of point of care diagnostics and medical quarantine for presumed SARS-CoV-2-infected subjects. We conducted a retrospective cohort study on subjects came to Chung Shan Medical University Hospital with suspicion of SARS-CoV-2 infection during January to March, 2020. We performed the real-time reverse-transcription polymerase chain reaction testing (rRT-PCR) for SARS-CoV-2-infection and reported the results of testing and treatment. A total of 212 participants were enrolled due to suspicion of SARS-CoV-2 infection. Five of those were confirmed COVID-19 cases after monitoring for a period of 14 days and were cured. The time to rRT-PCR test conversion after treatment is variate. The infection control measures of home quarantine and mandatory medical quarantine combined with rapid diagnosis seem to postpone the speed of transmission of SARS-CoV-2 infection at once in Taiwan. Due to lack of vaccination and confirmed antiviral therapy, it is important to strictly abide by the infection control measures.

Study on health-related quality of life and influencing factors of pediatric medical staff during the COVID-19 outbreak (preprint)

Aims To evaluate the health-related quality of life (HRQoL) status and explore its associated factors in pediatric medical staff during the COVID-19 epidemic so as to guide hospitals and administrators to formulate suitable interventions.Methods A cross-sectional study was conducted to investigate the HRQoL of pediatric medical staff. Univariable and multivariable logistic regression were used to analyze the associated factors.Results A total of 2,997 participants were recruited. Females scored worse than males in terms of emotional functioning (OR = 1.6, 95%CI: 1.2–2.1) and cognitive functioning (OR = 1.4, 95%CI: 1.1–1.8). The respondents aged 30–39 years and 40–49 years scored worse in nearly all domains of HRQoL compared health care professionals under 30 years old. Respondents with high education had lower scores in physical functioning (OR = 1.3, 95%CI: 1.0-1.7) and emotional functioning (OR = 1.5, 95%CI: 1.2–1.9).Compared with doctors, nurses had higher scores in all domains except for summary score and worry. The respondents whose working places had not set up pediatric fever clinics and isolated observation areas independently had better scores in all domains except for worry. The respondents who had ever treated patients with COVID-19 had lower scores in all domains.Conclusions During the COVID-19 outbreak, the HRQoL of pediatric medical staff decreased. The factors associated with HRQoL can be used to develop intervention to improve HRQoL in pediatric medical staff.