Combining virtual screening with cis-/trans-cleavage enzymatic assays effectively reveals broad-spectrum inhibitors that target the main proteases of SARS-CoV-2 and MERS-CoV.

The main protease (Mpro) of SARS-CoV-2 is essential for viral replication, which suggests that the Mpro is a critical target in the development of small molecules to treat COVID-19. This study used an in-silico prediction approach to investigate the complex structure of SARS-CoV-2 Mpro in compounds from the United States National Cancer Institute (NCI) database, then validate potential inhibitory compounds against the SARS-CoV-2 Mpro in cis- and trans-cleavage proteolytic assays. Virtual screening of ∼280,000 compounds from the NCI database identified 10 compounds with highest site-moiety map scores. Compound NSC89640 (coded C1) showed marked inhibitory activity against the SARS-CoV-2 Mpro in cis-/trans-cleavage assays. C1 strongly inhibited SARS-CoV-2 Mpro enzymatic activity, with a half maximal inhibitory concentration (IC50) of 2.69 µM and a selectivity index (SI) of >74.35. The C1 structure served as a template to identify structural analogs based on AtomPair fingerprints to refine and verify structure-function associations. Mpro-mediated cis-/trans-cleavage assays conducted with the structural analogs revealed that compound NSC89641 (coded D2) exhibited the highest inhibitory potency against SARS-CoV-2 Mpro enzymatic activity, with an IC50 of 3.05 µM and a SI of >65.57. Compounds C1 and D2 also displayed inhibitory activity against MERS-CoV-2 with an IC50 of <3.5 µM. Thus, C1 shows potential as an effective Mpro inhibitor of SARS-CoV-2 and MERS-CoV. Our rigorous study framework efficiently identified lead compounds targeting the SARS-CoV-2 Mpro and MERS-CoV Mpro.

Peimine inhibits variants of SARS‐CoV‐2 cell entry via blocking the interaction between viral spike protein and ACE2

Coronavirus disease 2019 (COVID‐19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Several vaccines against SARS‐CoV‐2 have been approved;however, variants of concern (VOCs) can evade vaccine protection. Therefore, developing small compound drugs that directly block the interaction between the viral spike glycoprotein and ACE2 is urgently needed to provide a complementary or alternative treatment for COVID‐19 patients. We developed a viral infection assay to screen a library of approximately 126 small molecules and showed that peimine inhibits VOCs viral infections. In addition, a fluorescence resonance energy transfer (FRET) assay showed that peimine suppresses the interaction of spike and ACE2. Molecular docking analysis revealed that peimine exhibits a higher binding affinity for variant spike proteins and is able to form hydrogen bonds with N501Y in the spike protein. These results suggest that peimine, a compound isolated from Fritillaria, may be a potent inhibitor of SARS‐CoV‐2 variant infection. PRACTICAL APPLICATIONS: In this study, we identified a naturally derived compound of peimine, a major bioactive alkaloid extracted from Fritillaria, that could inhibit SARS‐CoV‐2 variants of concern (VOCs) viral infection in 293T/ACE2 and Calu‐3 lung cells. In addition, peimine blocks viral entry through interruption of spike and ACE2 interaction. Moreover, molecular docking analysis demonstrates that peimine has a higher binding affinity on N501Y in the spike protein. Furthermore, we found that Fritillaria significantly inhibits SARS‐CoV‐2 viral infection. These results suggested that peimine and Fritillaria could be a potential functional drug and food for COVID‐19 patients.

Using temporal heatmaps to identify worthwhile articles on immune checkpoint blockade for melanoma (ICBM) in Mainland China, Hong Kong, and Taiwan since 2000: A bibliometric analysis.

BACKGROUND: Melanoma is a life-threatening form of skin cancer. Due to its remarkable effectiveness, the immune checkpoint blockade is widely used to treat melanoma (ICBM). No research has been conducted on ICBM for identifying the most readable articles. A bibliometric analysis of 100 top-cited ICBM (T100ICBM) in recent decades is required to highlight articles worth reading. METHODS: Based on the Web of Science Core Collection, we summarized the articles on ICBM published in each year from 2000 to 2022, with first authors from Mainland China, Hong Kong, and Taiwan (CHT). Using the CJAL score, data extraction and visualization of the distribution of ICBM publications were conducted on 2718, and 100 top-cited articles, respectively. We used the temporal heatmap to identify the most readable articles. Four descriptive, diagnostic, predictive, and prescriptive analytics (called DDPP model) were applied to describe the features of T100ICBM articles. The absolute advantage coefficient was used to determine the dominance extent of the most influential region, institute, department, and author. RESULTS: A total of 2718 publications was included after removing first or corresponding authors who were not affiliated with CHT. Publications by year showed a sharp increase from 2014 onward and either peaked in 2022 or have not yet peaked. It was evident that there was a large difference between the number of publications in provinces/metropolitan cities/regions on CHT. Beijing, Sichuan University, Oncology, and Guo Jun from Beijing are the most prolific and influential region, institute, department, and author. When comparing research achievements to the next productive authors based on the CJAL score, only Dr Jun has a medium effect of dominance (=0.60). On the basis of their consecutive growth in citations over the past 4 years, 20 T100ICBM articles were recommended for readers. CONCLUSION: The field of ICBM is growing rapidly, and Beijing and Sichuan University are taking the lead in CHT. Furthermore, the study provides references for worth-reading articles using the temporal heatmap. Future research hot spots may focus on these 4 themes of immunotherapy, melanoma, metastatic melanoma, regulatory T cells, cells, and activation, which may pave the way for additional study.

A review of epidemic investigation on cold‐chain food‐mediated SARS‐CoV‐2 transmission and food safety consideration during COVID‐19 pandemic

COVID‐19 has brought speculations on potential transmission routes of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the causal agent of the pandemic. It is reported that the main route of virus transmission to be person‐to‐person by respiratory droplets;however, people have raised concerns on the possible transmission of SARS‐CoV‐2 to humans via food and packaging and its potential effects on food safety. This review discusses food safety issues in the COVID‐19 pandemic and reveals its possible transmission in cold‐chain food. The first outbreak of COVID‐19 in late 2019 was associated with a seafood market in Wuhan, China, while the second outbreak of COVID‐19 in June 2020 was also related to a seafood market in Beijing, China. As of 2020, several frozen seafood products linked with SARS‐CoV‐2 have been reported in China. According to the current survey and scientific studies, the risk of infection by SARS‐CoV‐2 from cold‐chain food, food products, and food packaging is thought to be very low. However, studies on food cold chain contamination have shown that SARS‐CoV‐2 remained highly stable under refrigerated (4°C) and even in freezing conditions (−10 to −80°C). Since one mode of SARS‐CoV‐2 transmission appears to be touching contaminated surfaces, it is important to clean and sanitize food contact surfaces properly. Understanding food safety hazard risks is essential to avoid potential negative health effects and SARS‐CoV‐2 transmission in the food supply chain during the COVID‐19 pandemic.

A study of glycemic perturbations following two doses of COVID-19 vaccination for patients with diabetes: the impacts of vaccine type and anti-diabetes drugs.

BACKGROUND: Glycemic monitoring has become critical during the COVID-19 pandemic because of poor prognosis in diabetes. Vaccines were key in reducing the spread of infection and disease severity but data were lacking on effects on blood sugar levels. The aim of the current study was to investigate the impact of COVID-19 vaccination on glycemic control. METHODS: We performed a retrospective study of 455 consecutive patients with diabetes who completed two doses of COVID-19 vaccination and attended a single medical center. Laboratory measurements of metabolic values were assessed before and after vaccination, while the type of vaccine and administrated anti-diabetes drugs were analyzed to find independent risks associated with elevated glycemic levels. RESULTS: One hundred and fifty-nine subjects received ChAdOx1 (ChAd) vaccines, 229 received Moderna vaccines, and 67 received Pfizer-BioNtech (BNT) vaccines. The average HbA1c was raised in the BNT group from 7.09 to 7.34% (P = 0.012) and non-significantly raised in ChAd (7.13 to 7.18%, P = 0.279) and Moderna (7.19 to 7.27%, P = 0.196) groups. Both Moderna and BNT groups had around 60% of patients with elevated HbA1c following two doses of COVID-19 vaccination, and the ChAd group had only 49%. Under logistic regression modeling, the Moderna vaccine was found to independently predict the elevation of HbA1c (Odds ratio 1.737, 95% Confidence interval 1.12-2.693, P = 0.014), and sodium-glucose co-transporter 2 inhibitor (SGLT2i) was negatively associated with elevated HbA1c (OR 0.535, 95% CI 0.309-0.927, P = 0.026). CONCLUSIONS: Patients with diabetes might have mild glycemic perturbations following two doses of COVID-19 vaccines, particularly with mRNA vaccines. SGLT2i showed some protective effect on glycemic stability. Hesitancy in having vaccinations should not be indicated for diabetic patients with respect to manageable glycemic change. TRIAL REGISTRATION: Not applicable.

LAMP-Based Point-of-Care Biosensors for Rapid Pathogen Detection.

Seeking optimized infectious pathogen detection tools is of primary importance to lessen the spread of infections, allowing prompt medical attention for the infected. Among nucleic-acid-based sensing techniques, loop-mediated isothermal amplification is a promising method, as it provides rapid, sensitive, and specific detection of microbial and viral pathogens and has enormous potential to transform current point-of-care molecular diagnostics. In this review, the advances in LAMP-based point-of-care diagnostics assays developed during the past few years for rapid and sensitive detection of infectious pathogens are outlined. The numerous detection methods of LAMP-based biosensors are discussed in an end-point and real-time manner with ideal examples. We also summarize the trends in LAMP-on-a-chip modalities, such as classical microfluidic, paper-based, and digital LAMP, with their merits and limitations. Finally, we provide our opinion on the future improvement of on-chip LAMP methods. This review serves as an overview of recent breakthroughs in the LAMP approach and their potential for use in the diagnosis of existing and emerging diseases.

Digital health literacy and well-being among university students: Mediating roles of fear of COVID-19, information satisfaction, and internet information search.

Background: Digital health literacy (DHL) enables healthy decisions, improves protective behaviors and adherence to COVID-19 measures, especially during the era of the "infodemic", and enhances psychological well-being. Objective: We aimed to explore the mediating roles of fear of COVID-19, information satisfaction, and the importance of online information searching on the association between DHL and well-being. Methods: A cross-sectional web-based survey was conducted among 1631 Taiwanese university students, aged 18 years and above, from June 2021 to March 2022. The collected data include sociodemographic characteristics (sex, age, social status, and financial satisfaction), the importance of online information searching, information satisfaction, fear of COVID-19, DHL, and well-being. A linear regression model was utilized to investigate factors associated with well-being, followed by a pathway analysis to assess the direct and indirect relationship between DHL and well-being. Results: The scores of DHL and overall well-being were 3.1 ± 0.4 and 74.4 ± 19.7, respectively. Social status (B = 2.40, 95% confidence interval (CI) 1.73-3.07, p < 0.001), DHL (B 0.29, 95% CI 0.10-0.49, p < 0.001), importance of online information searching (B = 0.78, 95% CI 0.38-1.17, p < 0.001), and information satisfaction (B = 3.59, 95% CI 2.22-4.94, p < 0.001) were positively associated with well-being, whereas higher fear of COVID-19 scores (B = -0.38, 95% CI -0.55-(-0.21), p < 0.001) and female (B = -2.99, 95% CI -5.02-0.6, p = 0.004) were associated with lower well-being, when compared with lower fear scores and male, respectively. Fear of COVID-19 (B = 0.03, 95% CI 0.016-0.04, p < 0.001), importance of online information searching (B = 0.03, 95% CI 0.01-0.05, p = 0.005), and information satisfaction (B = 0.05, 95% CI 0.023-0.067, p < 0.001) were significantly mediated the relationship between DHL and well-being. Conclusion: Higher DHL scores show direct and indirect associations with higher well-being scores. Fear, importance of online information searching, and information satisfaction significantly contributed to the association.

Risk Factors Surrounding an Increase in Burnout and Depression Among Health Care Professionals in Taiwan During the COVID-19 Pandemic.

OBJECTIVES: This study aimed to investigate the risk factors surrounding an increase in both burnout levels and depression among health care professionals in Taiwan through use of a longitudinal study design. DESIGN: This is a 2-year observational study that took place from January 2019 to December 2020. SETTING AND PARTICIPANTS: Data among health care professionals were extracted from the Overload Health Control System of a tertiary medical center in central Taiwan. METHODS: Burnout was measured through use of the Chinese version of the Copenhagen Burnout Inventory (C-CBI), whereas depression was ascertained by the Taiwanese Depression Questionnaire. Each participant provided both burnout and depression measurements during a nonpandemic period (2019) as well as during the COVID pandemic era (2020). Risk factors surrounding an increase in burnout levels and depression were analyzed through a multivariate logistic regression model with adjusting confounding factors. RESULTS: Two thousand nineteen participants completed the questionnaire over 2 consecutive years, including 132 visiting doctors, 105 resident doctors, 1371 nurses, and 411 medical technicians. After adjustments, sleeplessness, daily working hours >8, and stress due to one's workload were all found to be risk factors for an increase in depression levels, whereas sleeplessness, lack of exercise, and stress due to one's workload were all found to be risk factors for an increase in personal burnout level. Being a member of the nursing staff, a younger age, sleeplessness, and lack of exercise were all risk factors for an increase in work-related burnout levels. CONCLUSIONS AND IMPLICATIONS: Poor sleep, lack of exercise, long working hours, and being a member of the nursing staff were risk factors regarding an increase in personal burnout, work-related burnout levels and depression among health care professionals. Leaders within the hospital should investigate the working conditions and personal habits of all medical staff regularly and systematically during the COVID-19 pandemic and take any necessary preventive measures, such as improving resilience for nursing staff, in order to best care for their employees.

Development of Fluorescence-Tagged SARS-CoV-2 Virus-like Particles by a Tri-Cistronic Vector Expression System for Investigating the Cellular Entry of SARS-CoV-2.

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has caused the pandemic that began late December 2019. The co-expression of SARS-CoV-2 structural proteins in cells could assemble into several types of virus-like particles (VLPs) without a viral RNA genome. VLPs containing S proteins with the structural and functional properties of authentic virions are safe materials to exploit for virus-cell entry and vaccine development. In this study, to generate SARS-CoV-2 VLPs (SCoV2-SEM VLPs) composed of three structural proteins including spike (S), envelop (E) protein and membrane (M) protein, a tri-cistronic vector expression system was established in a cell line co-expressing SARS-CoV-2 S, E and M proteins. The SCoV2-SEM VLPs were harvested from the cultured medium, and three structure proteins were confirmed by Western blot assay. A negative-stain TEM assay demonstrated the size of the SCoV2-SEM VLPs with a diameter of about 90 nm. To further characterize the infectious properties of SCoV2-SEM VLPs, the VLPs (atto647N-SCoV2-SEM VLPs) were fluorescence-labeled by conjugation with atto-647N and visualized under confocal microscopy at a single-particle resolution. The results of the infection assay revealed that atto647N-SCoV2-SEM VLPs attached to the surface of the HEK293T cells at the pre-binding phase in a ACE2-dependent manner. At the post-infection phase, atto647N-SCoV2-SEM VLPs either fused with the cellular membrane or internalized into the cytoplasm with mCherry-rab5-positive early endosomes. Moreover, fusion with the cellular membrane and the internalization with early endosomes could be inhibited by the treatment of camostat (a pharmacological inhibitor of TMPRSS2) and chlorpromazine (an endocytosis inhibitor), respectively. These results elucidated that SCoV2-SEM VLPs behave similarly to the authentic live SARS-CoV-2 virus, suggesting that the development of SCoV2-SEM VLPs provide a realistic and safe experimental model for studying the infectious mechanism of SARS-CoV-2.

Association of Digital Health Literacy with Future Anxiety as Mediated by Information Satisfaction and Fear of COVID-19: A Pathway Analysis among Taiwanese Students.

Digital Health Literacy (DHL) helps online users with navigating the infodemic and co-existing conspiracy beliefs to avoid mental distress and maintain well-being. We aimed to investigate the association between DHL and future anxiety (FA); and examine the potential mediation roles of information satisfaction and fear of COVID-19 (F-CoV). A web-based cross-sectional survey was carried out among 1631 Taiwanese university students aged 18 years and above from June 2021 to March 2022. Data collected were socio-demographic characteristics (sex, age, social status, university location), information satisfaction, F-CoV, DHL and FA (using Future Dark scale). The linear regression model was used to explore factors associated with FA. The pathway analysis was further used to evaluate the direct and indirect relationship between DHL and FA. A higher score of DHL (B = -0.21; 95% CI, -0.37, -0.06; p = 0.006), and information satisfaction (B = -0.16; 95% CI, -0.24, -0.08; p < 0.001) were associated with a lower FA score, whereas a higher F-CoV score was associated with a higher FA score (B = 0.43; 95% CI, 0.36, 0.50; p < 0.001). DHL showed the direct impact (B = -0.1; 95% CI, -0.17, -0.04; p = 0.002) and indirect impact on FA as mediated by information satisfaction (B = -0.04; 95% CI, -0.06, -0.01; p = 0.002) and F-CoV (B = -0.06, 95% CI, -0.08, -0.04; p < 0.001). Strategic approaches to promote DHL, information satisfaction, lower F-CoV are suggested to reduce FA among students.

Machine Learning Analyses Revealed Distinct Arterial Pulse Variability According to Side Effects of Pfizer-BioNTech COVID-19 Vaccine (BNT162b2).

Various adverse events and complications have been attributed to COVID-19 (coronavirus disease 2019) vaccinations, which can affect the cardiovascular system, with conditions such as myocarditis, thrombosis, and ischemia. The aim of this study was to combine noninvasive pulse measurements and frequency domain analysis to determine if the Pfizer-BioNTech COVID-19 vaccine (BNT162b2) vaccination and its accompanying cardiovascular side effects will induce changes in arterial pulse transmission and waveform. Radial blood pressure waveform and photoplethysmography signals were measured noninvasively for 1 min in 112 subjects who visited Shuang-Ho Hospital for a BNT162b2 vaccination. Based on side effects, each subject was assigned to Group N (no side effects), Group CV (cardiac or vascular side effects), Group C (cardiac side effects only), or Group V (vascular side effects only). Two classification methods were used: (1) machine-learning (ML) analysis using 40 harmonic pulse indices (amplitude proportions, phase angles, and their variability indices) as features, and (2) a pulse-variability score analysis developed in the present study. Significant effects on the pulse harmonic indices were noted in Group V following vaccination. ML and pulse-variability score analyses provided acceptable AUCs (0.67 and 0.80, respectively) and hence can aid discriminations among subjects with cardiovascular side effects. When excluding ambiguous data points, the AUC of the score analysis further improved to 0.94 (with an adopted proportion of around 64.1%) for vascular side effects. The present findings may help to facilitate a time-saving and easy-to-use method for detecting changes in the vascular properties associated with the cardiovascular side effects following BNT162b2 vaccination.

Postoperative Recovery Time in Inguinal Herniotomy Under Ilioinguinal/Iliohypogastric Block and Sedation Versus General Anesthesia: A Retrospective Propensity-Score Matched Study.

Background Associated advantages of ilioinguinal/iliohypogastric block and sedation versus general anesthesia (GA) for inguinal hernia repair have not been reported. The use of regional anesthesia (RA) is advantageous during the COVID-19 pandemic as it eliminates the need for airway manipulation.This study aimed to determine the association between postoperative recovery time when ilioinguinal/iliohypogastric block and sedation were utilized for inguinal hernia versus GA. Method This single-center retrospective study used multivariable logistic regression to model the anesthetic modality as a function of age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status, major comorbidities to generate a propensity score for each patient for matching. Results After screening 295 patients, 80 patients each in the general and regional anesthesia groups were matched.RA was associated with a 35.6 minutes (95% CI: -46.6 to -25.0) shorter total postoperative recovery time when compared to GA without the increased preoperative time and adverse outcomes. Conclusions Inguinal hernia repair, when performed under ilioinguinal/iliohypogastric block and sedation, was associated with reduced postoperative recovery time. This can be advantageous during the time of the COVID-19 pandemic to reduce the risk of aerosol generation and shorten hospital stay. Future research can focus on establishing a causal relationship.

Statin Therapy and the Risk of Viral Infection: A Retrospective Population-Based Cohort Study.

Statins exert cholesterol-independent beneficial effects, including immunomodulatory effects. In this study, we attempted to investigate the association between statin therapy and the risk of viral infection. We conducted a retrospective cohort study using data from Taiwan's National Health Insurance Research Database. We identified patients with hyperlipidemia and divided them into two cohorts: statin users and statin nonusers. A 1:1 propensity score matching was conducted between the two cohorts, and a Cox proportional hazards model was used to evaluate the risk of viral infection. Overall, a total of 20,202 patients were included in each cohort. The median follow-up durations were 4.41 and 6.90 years for statin nonusers and users, respectively. The risk of viral infection was 0.40-fold (95% confidence interval = 0.38-0.41) in statin users than in statin nonusers after adjustment for potential confounders. Statin treatment was associated with a significantly lower risk of viral infection in all age groups older than 18 years in both men and women. Moreover, the risk of viral infection substantially reduced as the duration of statin treatment increased. Our findings suggest that statin therapy is associated with a significantly lower risk of viral infection in patients with hyperlipidemia.

Structural Basis for the Inhibition of Coronaviral Main Proteases by a Benzothiazole-Based Inhibitor.

The ongoing spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused hundreds of millions of cases and millions of victims worldwide with serious consequences to global health and economies. Although many vaccines protecting against SARS-CoV-2 are currently available, constantly emerging new variants necessitate the development of alternative strategies for prevention and treatment of COVID-19. Inhibitors that target the main protease (Mpro) of SARS-CoV-2, an essential enzyme that promotes viral maturation, represent a key class of antivirals. Here, we showed that a peptidomimetic compound with benzothiazolyl ketone as warhead, YH-53, is an effective inhibitor of SARS-CoV-2, SARS-CoV, and MERS-CoV Mpros. Crystal structures of Mpros from SARS-CoV-2, SARS-CoV, and MERS-CoV bound to the inhibitor YH-53 revealed a unique ligand-binding site, which provides new insights into the mechanism of inhibition of viral replication. A detailed analysis of these crystal structures defined the key molecular determinants required for inhibition and illustrate the binding mode of Mpros from other coronaviruses. In consideration of the important role of Mpro in developing antivirals against coronaviruses, insights derived from this study should add to the design of pan-coronaviral Mpro inhibitors that are safer and more effective.

Impact of Daycare Service Interruption during COVID-19 Pandemic on Physical and Mental Functions and Nutrition in Older People with Dementia.

This study evaluated changes of cognitive, physical, and nutritional status before and after the interruption and resumption of daycare services during the COVID-19 pandemic in older dementia people in a daycare center. Comprehensive geriatric assessment data were analyzed before and after the lockdown of daycare center services, including mini-mental state examination, activities of daily living (ADL) scores, mini-nutritional assessment-short forms (MNA-SF), and timed up-and-go (TUG) tests. Among 19 dementia people participating in daycare services, 17 participants were enrolled in the study with, finally, two excluded because of incomplete follow-ups. They had a median age of 81 years; their MNA-SF scores and TUG values deteriorated significantly after a 3-month closure of daycare services (p < 0.05), and after resumption of daycare services the MNA-SF scores and TUG values recovered to near the pre-lockdown levels (p < 0.05). Besides, baseline ADL scores predicted a decline and recovery of TUG and MNA-SF values. Our findings suggest that planning continuous support for older dementia adults is important for daycare facilities during COVID-19 pandemic confinement.

An overview of gastrointestinal diseases in patients with COVID-19: A narrative review.

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has emerged as a global health concern. This study aimed to review the epidemiology and pathophysiology of COVID-19 and provide evidence for the implementation of control measures. We utilized several online databases, including MEDLINE (National Library of Medicine, Bethesda, Maryland, USA), PubMed, EMBASE, Web of Science, and Google Scholar, to collect relevant published papers using a combination of the following keywords: "COVID-19," "SARS-CoV-2," "novel coronavirus," "epidemiology," and "pathophysiology." The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used in this study. Globally, approximately 3-46% of patients with SARS-CoV-2 infection experience gastrointestinal symptoms. The clinical spectrum of COVID-19 is wide, ranging from mild to severe, and even fatal. COVID-19 was initially reported as a respiratory tract disease; however, gastrointestinal symptoms have only recently been reported. COVID-19 Patients with gastrointestinal symptoms may have more severe clinical manifestations and poor prognosis. This study highlights the need to better understand the mechanisms involved in the development of gastrointestinal symptoms in patients with COVID-19 to prevent the further spread of this pathogen.

Conference Attendance Tracking and Evaluation in the Era of Virtual Conferences.

RATIONALE AND OBJECTIVES: The coronavirus pandemic upended in-person radiology education and led to a transition to virtual platforms. We needed a new method to monitor lecture attendance, previously relying on a physical badge system. Our goal was to develop and implement a virtual conference attendance system that is user-friendly, automated, useable in any virtual conference environment, and accurate. MATERIALS AND METHODS: We developed a web-based platform to serve as a virtual conference attendance tracking and evaluation platform. Daily, the application synchronizes with our lecture calendar to identify scheduled conferences and generates a unique attendance link for each event. The link is automatically posted in the conference chat and attendees must be logged in by the time it is posted to click the link, prompting single sign-on authentication. We integrated the system with resident schedules to excuse residents when appropriate. Real-time attendance reports are accessible in a user-friendly dashboard with a 5-star lecture review and comment system. We surveyed residents on satisfaction with the application after 1-year of use. RESULTS: Over the 2020-2021 academic year, we registered 376 conferences with 5,040 virtual swipes from 65 users. Once set up, virtual swipes take seconds to perform with minimal disruption to the conference. Average satisfaction for the platform was rated as 4.69 on a scale of 1 to 5. All respondents agreed or strongly agreed that use of the platform should be continued for future years, with 85% strongly agreeing. CONCLUSION: We developed an online platform for radiology conference attendance logging and evaluation, designed for virtual conferences.

Peimine inhibits variants of SARS-CoV-2 cell entry via blocking the interaction between viral spike protein and ACE2.

Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several vaccines against SARS-CoV-2 have been approved; however, variants of concern (VOCs) can evade vaccine protection. Therefore, developing small compound drugs that directly block the interaction between the viral spike glycoprotein and ACE2 is urgently needed to provide a complementary or alternative treatment for COVID-19 patients. We developed a viral infection assay to screen a library of approximately 126 small molecules and showed that peimine inhibits VOCs viral infections. In addition, a fluorescence resonance energy transfer (FRET) assay showed that peimine suppresses the interaction of spike and ACE2. Molecular docking analysis revealed that peimine exhibits a higher binding affinity for variant spike proteins and is able to form hydrogen bonds with N501Y in the spike protein. These results suggest that peimine, a compound isolated from Fritillaria, may be a potent inhibitor of SARS-CoV-2 variant infection. PRACTICAL APPLICATIONS: In this study, we identified a naturally derived compound of peimine, a major bioactive alkaloid extracted from Fritillaria, that could inhibit SARS-CoV-2 variants of concern (VOCs) viral infection in 293T/ACE2 and Calu-3 lung cells. In addition, peimine blocks viral entry through interruption of spike and ACE2 interaction. Moreover, molecular docking analysis demonstrates that peimine has a higher binding affinity on N501Y in the spike protein. Furthermore, we found that Fritillaria significantly inhibits SARS-CoV-2 viral infection. These results suggested that peimine and Fritillaria could be a potential functional drug and food for COVID-19 patients.

COVID-19-related fear, stress and depression in school principals: impacts of symptoms like COVID-19, information confusion, health-related activity limitations, working hours, sense of coherence and health literacy.

BACKGROUND: School principals have been reported to have a higher prevalence of burnout and psychological problems than their colleagues. During the pandemic, extra workload and pressure from unprecedented situations potentially cause fear, stress and depression. Therefore, we aimed to explore associated factors of stress, fear of COVID-19 (F-CoV-19S) and depressive symptoms among school principals. METHODS: A cross-sectional online survey was conducted in Taiwan from 23 June to 16 July 2021. Data of 413 school principals were collected, including socio-demographic factors, COVID-19-related factors, work-related information, health status, sense of coherence (SoC), health literacy (HL), F-CoV-19S, stress and depression. Multiple linear and logistic regression models were utilized to explore associations. RESULTS: School principals with symptoms like COVID-19 (S-COVID-19-S), or with health-related activity limitations had a higher score of stress (B = 0.92; p = .039) (B = 1.52; p < .001) and a higher depression likelihood (OR = 3.38; p < .001) (OR = 3.06; p < .001), whereas those with a better SoC had a lower stress score (B = -1.39; p < .001) and a lower depression likelihood (OR = 0.76; p = .020). School principals confusing about COVID-19-related information had a higher score of stress (B = 2.47; p < .001) and fear (B = 3.77; p < .001). The longer working time was associated with a higher fear score (B = 1.69; p = .006). Additionally, school principals with a higher HL score had a lower stress score (B = -1.76; p < .001), a lower fear score (B = -1.85; p < .001) and a lower depression likelihood (OR = 0.53; p = .043). CONCLUSIONS: Health-related activity limitations, S-COVID-19-S, COVID-19-related information confusion and longer working hours were positively associated with at least one mental health problem (e.g. stress, fear and depression), whereas better SoC and HL showed the benefits to mitigate fear, stress and depressive symptoms in school principals. Our study provides evidence for appropriate strategies to improve principals' mental health during the pandemic.Key messages:School principals with health-related activity limitations or with symptoms like COVID-19 were more likely to be stressed and depressed.Higher levels of stress and fear were observed in school principals who confused about COVID-19-related information, and who had longer working time than before the pandemic.Better sense of coherence and higher health literacy could potentially mitigate the fear, stress and depressive symptoms in school principals.