The medicinal value of tea drinking in the management of COVID-19.

Corona Virus Disease 2019 (COVID-19) is presently the largest international public health event, individuals infected by the virus not only have symptoms such as fever, dry cough, and lung infection at the time of onset, but also possibly have sequelae in the cardiovascular system, respiratory system, nervous system, mental health and other aspects. However, numerous studies have depicted that the active ingredients in tea show good antiviral effects and can treat various diseases by regulating multiple pathways, and the therapeutic effects are associated with the categories of chemical components in tea. In this review, the differences in the content of key active ingredients in different types of tea are summarized. In addition, we also highlighted their effects on COVID-19 and connected sequelae, further demonstrating the possibility of developing a formulation for the prevention and treatment of COVID-19 and its sequelae through tea extracts. We have a tendency to suggest forestalling and treating COVID-19 and its sequelae through scientific tea drinking.

A study on differences about the influencing factors of depressive symptoms between medical staff and residents during 2022 city-wide temporary static management period to fighting against COVID-19 pandemic in Shanghai.

Objectives: Our study aimed to identify the latent class of depressive symptoms in the Shanghai population during the city-wide temporary static management period and compare differences in the factors influencing depressive symptoms between medical staff and residents. Methods: An online cross-sectional survey was conducted with 840 participants using questionnaires, including Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Pittsburgh Sleep Quality Index (PSQI), and self-compiled questionnaire (demographic characteristics and internet usage time). Latent class analysis (LCA) was performed based on participants' depressive symptoms. The latent class subgroups were compared using the chi-square test and t-test. Logistic regression was used in our study to analyze the factors influencing depressive symptoms within the medical staff group and residents group and then compare their differences. Results: Two distinct subgroups were identified based on the LCA: the group with low-depressive symptoms and the group with high-depressive symptoms. There were significant differences between the two groups (P < 0.05) on age, education level, marital status, internet usage time, identity characteristics (medical staff or residents), family income level, living style, overall quality of sleep, and anxiety levels. Furthermore, logistic regression analysis results showed that compared with the residents group, the participants in the group of medical staff with "increasing internet usage time" and the "daytime dysfunction" would have nearly two times the possibility of getting serious depressive symptoms. Conclusions: There are differences in the factors influencing depression symptoms between medical staff and residents during the 2022 city-wide temporary static management period to fighting against the COVID-19 pandemic in Shanghai. We should pay special attention to those with increasing internet usage time and daytime dysfunction in medical staff working in a special environment such as the COVID-19 pandemic.

A study on differences about the influencing factors of depressive symptoms between medical staff and residents during 2022 city-wide temporary static management period to fighting against COVID-19 pandemic in Shanghai

Objectives Our study aimed to identify the latent class of depressive symptoms in the Shanghai population during the city-wide temporary static management period and compare differences in the factors influencing depressive symptoms between medical staff and residents. Methods An online cross-sectional survey was conducted with 840 participants using questionnaires, including Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Pittsburgh Sleep Quality Index (PSQI), and self-compiled questionnaire (demographic characteristics and internet usage time). Latent class analysis (LCA) was performed based on participants' depressive symptoms. The latent class subgroups were compared using the chi-square test and t-test. Logistic regression was used in our study to analyze the factors influencing depressive symptoms within the medical staff group and residents group and then compare their differences. Results Two distinct subgroups were identified based on the LCA: the group with low-depressive symptoms and the group with high-depressive symptoms. There were significant differences between the two groups (P < 0.05) on age, education level, marital status, internet usage time, identity characteristics (medical staff or residents), family income level, living style, overall quality of sleep, and anxiety levels. Furthermore, logistic regression analysis results showed that compared with the residents group, the participants in the group of medical staff with "increasing internet usage time” and the "daytime dysfunction” would have nearly two times the possibility of getting serious depressive symptoms. Conclusions There are differences in the factors influencing depression symptoms between medical staff and residents during the 2022 city-wide temporary static management period to fighting against the COVID-19 pandemic in Shanghai. We should pay special attention to those with increasing internet usage time and daytime dysfunction in medical staff working in a special environment such as the COVID-19 pandemic.

Chimeric mRNA-based COVID-19 vaccine induces protective immunity against Omicron and Delta variants.

The emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the effectiveness of currently approved mRNA vaccines. To achieve wider coverage of VOCs, we first constructed a cohort of mRNAs harboring a furin cleavage mutation in the spike (S) protein of predominant VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). The mutation abolished the cleavage between the S1 and S2 subunits. Systematic evaluation in vaccinated mice discovered that individual VOC mRNAs elicited strong neutralizing activity in a VOC-specific manner. In particular, the neutralizing antibodies (nAb) produced by immunization with Beta-Furin and Washington (WA)-Furin mRNAs showed potent cross-reactivity with other VOCs. However, neither mRNA elicited strong neutralizing activity against the Omicron variant. Hence, we further developed an Omicron-specific mRNA vaccine that restored protection against the original Omicron variant and some sublineages. Finally, to broaden the protection spectrum of the new Omicron mRNA vaccine, we engineered an mRNA-based chimeric immunogen by introducing the receptor-binding domain of Delta variant into the entire S antigen of Omicron. The resultant chimeric mRNA induced potent and broadly nAbs against Omicron and Delta, which paves the way to developing new vaccine candidates to target emerging variants in the future.

Synergistic Immunity and Protection in Mice by Co-Immunization with DNA Vaccines Encoding the Spike Protein and Other Structural Proteins of SARS-CoV-2.

The emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated recurring worldwide infection outbreaks. These highly mutated variants reduce the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines, which are designed to target only the spike (S) protein of the original virus. Except for the S of SARS-CoV-2, the immunoprotective potential of other structural proteins (nucleocapsid, N; envelope, E; membrane, M) as vaccine target antigens is still unclear and worthy of investigation. In this study, synthetic DNA vaccines encoding four SARS-CoV-2 structural proteins (pS, pN, pE, and pM) were developed, and mice were immunized with three doses via intramuscular injection and electroporation. Notably, co-immunization with two DNA vaccines that expressed the S and N proteins induced higher neutralizing antibodies and was more effective in reducing the SARS-CoV-2 viral load than the S protein alone in mice. In addition, pS co-immunization with either pN or pE + pM induced a higher S protein-specific cellular immunity after three immunizations and caused milder histopathological changes than pS alone post-challenge. The role of the conserved structural proteins of SARS-CoV-2, including the N/E/M proteins, should be investigated further for their applications in vaccine design, such as mRNA vaccines.

Research progress on the phase separation of SARS - CoV - 2 nucleocapsid protein

COVID-19 pandemic, caused by infection Of severe acute respiratory syndrome Coronavirus 2 (SARS -CoV-2), is an ongoing and severe threat to public health and safety. The Coronavirus nucleoeapsid(N) protein mainly functions as a key structural protein, responsible for binding and packaging viral genome RNA into nucleocapsid and recruiting membrane(M) protein for virion assembly. In addition. the N protein functions as a regulatory protein and plays important roles in suppression of the host innate immune response, and localization with replication transcription complex (RTC) to facilitate Viral transcription and replication. Accumulating evidences have emerged recently that SARS-CoV-2 N protein undergoes liquid-liquid phase separation (LLPS) with RNA or other proteins. Importantly, phase separation of the N protein has been Shown to be essential for its structural and regulatory roles. Here, we summarize recent research progress on the phase separation of SARS-CoV-2 N protein. The potential of the phase separation of the N protein as a therapeutic drug targets is also discussed.

Porcine deltacoronavirus E protein induces interleukin-8 production via NF-κB and AP-1 activation.

Infection induces the production of proinflammatory cytokines and chemokines such as interleukin-8 (IL-8) and interleukin-6 (IL-6). Although they facilitate local antiviral immunity, their excessive release leads to life-threatening cytokine release syndrome, exemplified by the severe cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present study, we found that interleukin-8 (IL-8) was upregulated by PDCoV infection. We then demonstrated that PDCoV E protein induced IL-8 production and that the TM domain and the C-terminal domain of the E protein were important for IL-8 production. Subsequently, we showed here that deleting the AP-1 and NF-κB binding motif in porcine IL-8 promoter abrogated its activation, suggesting that IL-8 expression was dependent on AP-1 and NF-κB. Furthermore, PDCoV E induced IL-8 production, which was also dependent on the NF-κB pathway through activating nuclear factor p65 phosphorylation and NF-κB inhibitor alpha (IκBα) protein phosphorylation, as well as inducing the nuclear translocation of p65, eventually resulting in the promotion of IL-8 production. PDCoV E also activated c-fos and c-jun, both of which are members of the AP-1 family. These findings provide new insights into the molecular mechanisms of PDCoV-induced IL-8 production and help us further understand the pathogenesis of PDCoV infection.

Research on Emergency Response Policy for Public Health Emergencies in China-Based on Content Analysis of Policy Text and PMC-Index Model.

Policy is an important support for risk society to prevent and resolve crises. Based on the content analysis of the policy text and PMC-Index model, this paper takes texts of 327 public health emergency response policies (PHERP) at the central level in China from 1989 to 2022 as the analysis object, designs an indicator system, and combines qualitative and quantitative methods to evaluate the existing policies. The results of content analysis indicate that current policy focuses on emergency rather than preventive control, the main policy-making and issuing authority is the Ministry of Health and policies are mostly issued in the form of notice. The PMC-Index of ten selected policies is all ranked above acceptable, which means that the overall quality of policy text is relatively high. However, the PMC-Surface shows that there is still considerable variability in the scores of the main indicators for each policy. The top three main scoring indicators are policy nature, policy evaluation and policy instrument, while the bottom three are policy time, policy release agency and policy target groups, which reminds us that the design of policy text can still be improved in terms of optimizing policy time, policy issuing institutions and expanding policy target groups. In response to these problems, this paper puts forward six suggestions for optimization.

Stromal Antigen 2 Deficiency Induces Interferon Responses and Restricts Porcine Deltacoronavirus Infection.

Porcine deltacoronavirus (PDCoV) is a recently discovered enteropathogenic coronavirus and has caused significant economic impacts on the pork industry. Although studies have partly uncovered the molecular mechanism of PDCoV-host interaction, it requires further research. In this study, we explored the roles of Stromal Antigen 2 (STAG2) in PDCoV infection. We found that STAG2-deficient cells inhibited infection with vesicular stomatitis virus (VSV) and PDCoV, whereas restoration of STAG2 expression in STAG2-depleted (STAG2-/-) IPEC-J2 cells line restored PDCoV infection, suggesting that STAG2 is involved in the PDCoV replication. Furthermore, we found that STAG2 deficiency results in robust interferon (IFN) expression. Subsequently, we found that STAG2 deficiency results in the activation of JAK-STAT signaling and the expression of IFN stimulated gene (ISG), which establish an antiviral state. Taken together, the depletion of STAG2 activates the JAK-STAT signaling and induces the expression of ISG, thereby inhibiting PDCoV replication. Our study provides new insights and potential therapeutic targets for unraveling the mechanism of PDCoV replication.

Factors Associated With the Vaccination Behavior Among COVID-19 Vaccine Hesitant College Students in Wuhan, China: A Survey Based on Social Psychological Dimension.

Background: During the COVID-19 pandemic, vaccine hesitancy (VH) on COVID-19 vaccination still exists in different populations, which has a negative impact on epidemic prevention and control. The objectives were to explore college students' willingness to vaccinate, determine the factors influencing the vaccination behavior of students with COVID-19 vaccine hesitancy, and provide a basis for improving the compliance of college students with COVID-19 vaccination. Methods: The universities in Wuhan are categorized into three levels according to their comprehensive strength and randomly sampled at each level, of which ten universities were selected. A self-designed anonymous electronic questionnaire was distributed online from May 12 to 31, 2021 to investigate the hesitancy, vaccination status, and influencing factors of COVID-19 vaccination among college students in Wuhan. Results: Of the 1,617 participants (1,825 students received the electronic questionnaire) surveyed, 19.0% reported COVID-19 vaccine hesitancy. Among the vaccine-hesitant students, 40.1% were vaccinated against COVID-19. The binary logistic regression analysis shows that families' attitudes "Uncertain" (odds ratio (OR) = 0.258 [0.132-0.503]), vaccination risk psychology (OR = 0.242 [0.079-0.747]) and wait-and-see mentality (OR = 0.171 [0.068-0.468]) are negative factors for the vaccination behavior of hesitant students, while herd mentality (OR = 7.512 [2.718-20.767]) and uncertainty of free policy's impact on vaccine trust (OR = 3.412 [1.547-7.527]) are positive factors. Conclusion: The vaccine hesitancy among college students in Wuhan was relatively high. Family support, herd mentality and free vaccination strategies can help improve vaccination among hesitant students, while vaccination risk psychology and "wait-and-see" psychology reduce the possibility of vaccination. The vaccination strategy of college students should be strengthened from the perspective of social psychological construction.

Influence of COVID-19 vaccines on endocrine system.

The COVID-19 pandemic has posed a significant health threat globally. Timely and appropriate vaccination is a key step to reduce the morbidity and mortality from COVID-19. The clinical course of COVID-19 infection and the effects of COVID-19 vaccination are influenced by patients' health situations and involve a systemic physiological reaction. Just like an "endocrine phenotype" of COVID-19 infection, endocrine dysfunction after COVID-19 vaccination also acquired clinical concerns. In the present review, we briefly introduce the commonly available vaccines against SARS-CoV-2, summarize the influence of COVID-19 vaccines on the endocrine system, and explore the underlying pathogenic mechanisms.

Death in a farmer with underlying diseases carrying Vibrio cholerae non-O1/non-O139 producing zonula occludens toxin.

OBJECTIVES: The non-O1/non-O139 Vibrio cholerae caused outbreaks or sporadic cases of gastroenteritis that was rarely seen in good sanitary condition. It was described a case of systemic multiple organ lesions that worsened because of non-O1/non-O139 V. cholerae, suggesting that serogroups have a potential virulence in enhancing pathogenicity with patients with underlying diseases compared with a healthy population. DESIGN OR METHODS: Samples are identified by strain culture, polymerase chain reaction (PCR) virulence identification, and whole genome sequencing. RESULTS: A middle-aged man was diagnosed with cytotoxin-producing and nontoxin V. cholerae non-O1/non-O139 serogroups. Although lacking the CT toxin encoded by ctxAB gene, the pathogenesis of cholera relies on the synergistic action of many other genes, especially virulence genes. CONCLUSIONS: This case suggested that the laborers engaging in agricultural production are at potential risk of V. cholerae infection by exposure of open wounds to contaminated water . However, epidemiological investigation should focus on the objective cause of the change of working environment. Furthermore, common diseases can possibly enhance the virulence of non-O1/non-O139 serogroups by attacking the tight junction of small intestinal epithelial cells, further triggering bacteremia, a process that may lead to death within 48-72 hours, which requires great attention.

Aspulvins A-H, Aspulvinone Analogues with SARS-CoV-2 Mpro Inhibitory and Anti-inflammatory Activities from an Endophytic Cladosporium sp.

Eight new aspulvinone analogues, aspulvins A-H (1-8) and aspulvinones D, M, O, and R (9-12), were isolated from cultures of the endophytic fungus Cladosporium sp. 7951. Detailed spectroscopic analyses were conducted to determine the structures of the new compounds. All isolates displayed different degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) at 10 µM. Notably, compounds 9, 10, and 12 showed potential SARS-CoV-2 Mpro inhibition with IC50 values of 10.3 ± 0.6, 9.4 ± 0.6, and 7.7 ± 0.6 µM, respectively. For all compounds except 3 and 4, the anti-inflammatory activity occurred by inhibiting the release of lactate dehydrogenase (LDH) with IC50 values ranging from 0.7 to 7.4 µM. Compound 10 showed the most potent anti-inflammatory activity by inhibiting Casp-1 cleavage, IL-1ß maturation, NLRP3 inflammasome activation, and pyroptosis. The findings reveal that the aspulvinone analogues 9, 10, and 12 could be promising candidates for coronavirus disease 2019 (COVID-19) treatment as they inhibit SARS-CoV-2 infection and reduce inflammatory reactions caused by SARS-CoV-2.

Serious Cardiovascular Adverse Events Associated with Hydroxychloroquine/Chloroquine Alone or with Azithromycin in Patients with COVID-19: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: The use of hydroxychloroquine or chloroquine (HCQ/CQ) as monotherapy or combined with azithromycin for the treatment of coronavirus disease 2019 (COVID-19) may increase the risk of serious cardiovascular adverse events (SCAEs). OBJECTIVE: Our objective was to describe and evaluate the risk of SCAEs with HCQ/CQ as monotherapy or combined with azithromycin compared with that for therapeutic alternatives. METHODS: We performed a disproportionality analysis and descriptive case series using the US FDA Adverse Event Reporting System. RESULTS: Compared with remdesivir, HCQ/CQ was associated with increased reporting of SCAEs (reporting odds ratio [ROR] 2.1; 95% confidence interval [CI] 1.8-2.5), torsade de pointes (TdP)/QTc prolongation (ROR 35.4; 95% CI 19.4-64.5), and ventricular arrhythmia (ROR 2.5; 95% CI 1.6-3.9); similar results were found in comparison with other therapeutic alternatives. Compared with lopinavir/ritonavir, HCQ/CQ was associated with increased reporting of ventricular arrhythmia (ROR 10.5; 95% CI 3.3-33.4); RORs were larger when HCQ/CQ was used in combination with azithromycin. In 2020, 312 of the 575 reports of SCAEs listed concomitant use of HCQ/CQ and azithromycin, including QTc prolongation (61.4%), ventricular arrhythmia (12.0%), atrial fibrillation (8.2%), TdP (4.9%), and cardiac arrest (4.4%); 88 (15.3%) cases resulted in hospitalization and 79 (13.7%) resulted in death. In total, 122 fatal QTc prolongation-related cardiovascular reports were associated with 1.4 times higher odds of reported death than those induced by SCAEs; 87 patients received more than one QTc-prolonging agent. CONCLUSIONS: Patients treated with HCQ/CQ monotherapy or HCQ/CQ + azithromycin may be at increased risk of SCAEs, TdP/QTc prolongation, and ventricular arrhythmia. Cardiovascular risks need to be considered when evaluating the benefit/harm balance of treatment with HCQ/CQ, especially with the concurrent use of QTc-prolonging agents and cytochrome P450 3A4 inhibitors when treating COVID-19.

DNA Vaccines Expressing the Envelope and Membrane Proteins Provide Partial Protection Against SARS-CoV-2 in Mice.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency of international concern, and an effective vaccine is urgently needed to control the pandemic. Envelope (E) and membrane (M) proteins are highly conserved structural proteins among SARS-CoV-2 and SARS-CoV and have been proposed as potential targets for the development of cross-protective vaccines. Here, synthetic DNA vaccines encoding SARS-CoV-2 E/M proteins (called p-SARS-CoV-2-E/M) were developed, and mice were immunised with three doses via intramuscular injection and electroporation. Significant cellular immune responses were elicited, whereas no robust humoral immunity was detected. In addition, novel H-2d-restricted T-cell epitopes were identified. Notably, although no drop in lung tissue virus titre was detected in DNA-vaccinated mice post-challenge with SARS-CoV-2, immunisation with either p-SARS-CoV-2-E or p-SARS-CoV-2-M provided minor protection and co-immunisation with p-SARS-CoV-2-E+M increased protection. Therefore, E/M proteins should be considered as vaccine candidates as they may be valuable in the optimisation of vaccination strategies against COVID-19.

Virtual screening of approved clinic drugs with main protease (3CLpro) reveals potential inhibitory effects on SARS-CoV-2.

3CLpro is the main protease of the novel coronavirus (SARS-CoV-2) responsible for their intracellular duplication. Based on virtual screening technology and molecular dynamics simulation, we found 23 approved clinical drugs such as Viomycin, Capastat, Carfilzomib and Saquinavir, which showed high affinity with the 3CLpro active sites. These findings showed that there were potential drugs that inhibit SARS-Cov-2's 3CLpro in the current clinical drug library, and these drugs can be further tested or chemically modified for the treatment of COVID-19.Communicated by Ramaswamy H. Sarma.

Serial Multiple Mediation of the Correlation Between Internet Addiction and Depression by Social Support and Sleep Quality of College Students During the COVID-19 Epidemic.

OBJECTIVE: This cross-sectional study explores the serial multiple mediation of the correlation between internet addiction and depression by social support and sleep quality of college students during the COVID-19 epidemic. METHODS: We enrolled 2,688 students from a certain university in Wuhu, China. Questionnaire measures of internet addiction, social support, sleep quality, depression and background characteristics were obtained. RESULTS: The prevalence of depression, among 2,688 college students (median age [IQR]=20.49 [20.0, 21.0] years) was 30.6%. 32.4% of the students had the tendency of internet addiction, among which the proportion of mild, moderate and severe were 29.8%, 2.5% and 0.1%, respectively. In our normal internet users and internet addiction group, the incidence of depression was 22.6% and 47.2%, respectively. The findings indicated that internet addiction was directly related to college students' depression and indirectly predicted students' depression via the mediator of social support and sleep quality. The mediation effect of social support and sleep quality on the pathway from internet addiction to depression was 41.97% (direct effect: standardized estimate=0.177; total indirect effect: standardized estimate=0.128). The proposed model fit the data well. CONCLUSION: Social support and sleep quality may continuously mediate the link between internet addiction and depression. Therefore, the stronger the degree of internet addiction, the lower the individual's sense of social support and the worse the quality of sleep, which will ultimately the higher the degree of depression. We recommend strengthening monitoring of internet use during the COVID-19 epidemic, increasing social support and improving sleep quality, so as to reduce the risk of depression for college students.

Research capacity of global health institutions in China: a gap analysis focusing on their collaboration with other low-income and middle-income countries.

INTRODUCTION: This paper presented qualitative and quantitative data collected on the research capacity of global health institutions in China and aimed to provide a landscaping review of the development of global health as a new discipline in the largest emerging economy of the world. METHODS: Mixed methods were used and they included a bibliometric analysis, a standardised survey and indepth interviews with top officials of 11 selected global health research and educational institutions in mainland China. RESULTS: The bibliometric analysis revealed that each institution had its own focus areas, some with a balanced focus among chronic illness, infectious disease and health systems, while others only focused on one of these areas. Interviews of key staff from each institution showed common themes: recognition that the current research capacity in global health is relatively weak, optimism towards the future, as well as an emphasis on mutual beneficial networking with other countries. Specific obstacles raised and the solutions applied by each institution were listed and discussed. CONCLUSION: Global health institutions in China are going through a transition from learning and following established protocols to taking a more leading role in setting up China's own footprint in this area. Gaps still remain, both in comparison with international institutions, as well as between the leading Chinese institutions and those that have just started. More investment needs to be made, from both public and private domains, to improve the overall capacity as well as the mutual learning and communication within the academic community in China.

Sleep quality and influencing factors of college students returning to school during COVID-19 epidemic

Objective: To investigate the sleep quality and influencing factors of the first batch of college students returning to school during COVID-19 epidemic, so as to provide scientific basis for taking corresponding measures.

Corrigendum: Multicenter Analysis of Liver Injury Patterns and Mortality in COVID-19.

[This corrects the article DOI: 10.3389/fmed.2020.584342.].