A Newly Identified Spike Protein Targeted Linear B-Cell Epitope Based Dissolvable Microneedle Array Successfully Eliciting Neutralizing Activities against SARS-CoV-2 Wild-Type Strain in Mice.

Vaccination is a cost-effective medical intervention. Inactivated whole virusor large protein fragments-based severe acute respiratory syndrome coronavirus (SARS-CoV-2) vaccines have high unnecessary antigenic load to induce allergenicity and/orreactogenicity, which can be avoided by peptide vaccines of short peptide fragments that may induce highly targeted immune response. However, epitope identification and peptide delivery remain the major obstacles in developing peptide vaccines. Here, a multi-source data integrated linear B-cell epitope screening strategy is presented and a linear B-cell epitope enriched hotspot region is identified in Spike protein, from which a monomeric peptide vaccine (Epitope25) is developed and applied to subcutaneously immunize wildtype BALB/c mice. Indirect ELISA assay reveals specific and dose-dependent binding between Epitope25 and serum IgG antibodies from immunized mice. The neutralizing activity of sera from vaccinated mice is validated by pseudo and live SARS-CoV-2 wild-type strain neutralization assays. Then a dissolvable microneedle array (DMNA) is developed to pain-freely deliver Epitope25. Compared with intramuscular injection, DMNA and subcutaneous injection elicit neutralizing activities against SARS-CoV-2 wild-type strain as demonstrated by live SARS-CoV-2 virus neutralization assay. No obvious damages are found in major organs of immunized mice. This study may lay the foundation for developing linear B-cell epitope-based vaccines against SARS-CoV-2.

Effects of the COVID-19 Pandemic on Health Behaviors of Higher Education Students in Ghana: A Cross-Sectional Study.

Stressful events can significantly impact health behaviors of tertiary students in various ways. Many studies reported adverse alterations in health behaviors during the COVID-19 pandemic. However, there is limited knowledge about students from sub-Saharan African countries. Therefore, this study aimed to assess effects of the COVID-19 pandemic on the health behaviors of Ghanaian tertiary students, with an emphasis on the association between sleep and other health behaviors. A cross-sectional study with eligible tertiary students from the Kwame Nkrumah University of Science and Technology in Ghana (n = 129) was conducted. An online survey assessed quality and duration of sleep, financial stress, dietary risk, alcohol misuse, and physical exercise using validated tools. Health behaviors did not differ by gender. The COVID-19 pandemic negatively affected health behaviors for many students including dietary intake (20.2%), sleep quality (20.2%) and duration (81.4%), alcohol consumption (3.1%), exercise frequency (4.1%), and exercise intensity (38%). Shorter sleep duration was linked with greater alcohol misuse scores (p < 0.05). A majority of the students (56%) had increased financial stress during the pandemic. This study contributes important insights into the effects that stressful events such as a pandemic have on the health of higher education students in sub-Saharan Africa.

Gender Differences in the Relationships between Perceived Stress, Eating Behaviors, Sleep, Dietary Risk, and Body Mass Index.

BACKGROUND: Obesity is a growing epidemic among university students, and the high levels of stress reported by this population could contribute to this issue. Singular relationships between perceived stress; engagement in restrained, uncontrolled, and emotional eating; sleep; dietary risk; and body mass index (BMI) have been reported in the current body of literature; however, these constructs interact with each other, and the complex relationships among them are infrequently examined. Therefore, the aim of the present study was to explore the complex relationships between these constructs using mediation and moderation analyses stratified by gender. METHODS: A cross-sectional study, enrolling university students from the United States (U.S.), the Netherlands, South Korea, Malaysia, Ireland, Ghana, and China, was conducted between October 2020 and January 2021 during the COVID-19 pandemic. Perceived stress; maladaptive eating behaviors including restrained, uncontrolled, and emotional eating; sleep duration and quality; dietary risk; and BMI were assessed using validated questionnaires, which were distributed through an online platform. RESULTS: A total of 1392 students completed the online survey (379 male, 973 female, and 40 who self-identified as "other"). Uncontrolled and emotional eating mediated the relationship between perceived stress and dietary risk for both males and females; higher sleep quality weakened this relationship among female students but not males. Emotional eating mediated the relationship between perceived stress and BMI for both males and females, but higher sleep quality weakened this relationship only among females. CONCLUSIONS: Our findings suggest that students in higher education are likely to benefit from interventions to reduce uncontrolled and emotional eating. Programs that improve sleep quality, especially during highly stressful periods, may be helpful.

Relationships between Dairy and Calcium Intake and Mental Health Measures of Higher Education Students in the United States: Outcomes from Moderation Analyses.

BACKGROUND: The prevalence of mental health concerns among university students in the United States (U.S.) continues to increase, while current treatments, including medication and counseling, present shortcomings. Higher dairy and calcium intakes are associated with protective effects on mental health; however, previous studies have focused on investigating singular relationships between dairy and calcium intakes and mental health measures. A more complex exploration of these relationships is warranted to better examine whether increasing dairy and calcium intakes could serve as an intervention to improve mental health. The present study sought to further characterize the relationships between dairy and calcium intake, perceived stress, and a variety of mental health measures using linear regression and moderation analyses. METHODS: The present cross-sectional study involved students studying at three large U.S. universities, and data collection occurred from April to May 2020 when students were learning remotely due to the COVID-19 pandemic. An online survey comprising validated tools was distributed among students to assess dairy and calcium intake, perceived stress, anxiety, negative and positive moods, rumination, and resilience, sleep quality and duration, dietary risk, and physical activity. RESULTS: A total of 1233 students completed the study. Higher dairy and calcium intake was coincident with lower perceived stress and higher positive mood scores, while higher calcium intake was also coincident with lower anxiety, rumination, and higher resilience scores. Additionally, as calcium intake increased, the relationship between perceived stress and anxiety and the relationship between perceived stress and negative mood weakened. Dairy intake did not have this effect. CONCLUSIONS: Based on the results, and considering that calcium is a shortfall nutrient, universities should consider initiating programs and public health campaigns to promote dairy and calcium intake among this population.

Limited negative effects of the COVID-19 pandemic on mental health measures of Ghanaian university students.

BACKGROUND: Stress and mental health outcomes are negatively correlated among university students throughout the world. Reports of differences in stress perception by gender exist, but there is limited data on students from sub-Saharan African countries. This study describes the burden of perceived and financial stress; characterizes mood and degree of anxiety symptoms; examines stress coping mechanisms, including resilience and repetitive negative thinking (RNT); and explores how students at a Ghanaian university believed the COVID-19 pandemic affected these measures. METHODS: Students (n = 129) were recruited from the Kwame Nkrumah University of Science and Technology, Kumasi, Ghana from October 2020 - January 2021. Validated surveys were used. Participants were asked "Are your answers to the questions affected by the COVID-19 pandemic?" RESULTS: No differences in mean scores were observed between genders. For female students, financial stress was positively associated with RNT (p = 0.009), negative mood (p = 0.002), and anxiety (p < 0.001). Males were more likely to report decreased stress during the pandemic (p = 0.002), but there was no difference in mental health outcomes by perceived stress (PS) change category among males. Effects of the pandemic on mental health outcomes were mixed, but substantial proportions of students reported improvements or no change in financial stress, mood, anxiety, and RNT. LIMITATIONS: Students from one university particiapted in this cross-sectional survey. CONCLUSIONS: This study adds to the understanding of how higher education students are experiencing stress and are coping with the uncertainties of the COVID-19 pandemic in Ghana.

Comparing mental health and well-being of US undergraduate and graduate students during the early stages of the COVID-19 pandemic.

Objective: This study explored how COVID-related mental health and well-being varied between undergraduate and graduate students. Relationships with physical health behaviors were also examined. Participants: Undergraduate (n = 897) and graduate (n = 314) students were recruited from three US universities between mid-April and late-May 2020. Methods: Participants in this cross-sectional survey self-reported perceived stress, financial stress, resilience, repetitive negative thinking, mood, anxiety, diet, sleep, and physical activity using validated instruments. Results: Undergraduate students reported more perceived stress, more repetitive negative thinking, less positive mood, and less support from professors than graduate students. Perceived stress, repetitive negative thinking, negative mood, and anxiety increased among all students (p < .05 for all). Correlations between mental health outcomes and physical health behaviors were weak to moderate (r = .08 to .49). Conclusions: College students, particularly undergraduates, perceived negative mental health impacts during COVID. Creative approaches for meeting student needs are necessary.

Insufficient Sleep and Poor Sleep Quality Completely Mediate the Relationship between Financial Stress and Dietary Risk among Higher Education Students.

The coronavirus disease 2019 (COVID-19) pandemic worsened financial stress for higher education students in the U.S. Financial stress is associated with poor dietary behaviors; however, factors that might influence this relationship are not well characterized. The present cross-sectional study investigated the associations between financial stress and dietary intake and dietary risk scores among higher education students (undergraduate and graduate students) in the U.S. and examined whether poor sleep quality and short sleep duration mediated the relationship between financial stress and dietary risk score. Validated tools were used to assess financial stress, sleep quality, sleep duration, dietary intake, and dietary risk. A total of 1280 students from three large U.S. universities completed the study. Results indicated that higher financial stress was associated with lower vegetable, fruit, fiber, and calcium intake, higher added sugar intake from sugar sweetened beverages, and higher dietary risk score. Further, the positive relationship between financial stress and dietary risk score was completely mediated by poor sleep quality among students who reported poor sleep quality and by short sleep duration among students who slept less than 7 h per night. These findings suggest that students might benefit from both financial management training and sleep education services to reduce undesirable dietary behaviors.

The Effects of Sleep Quality and Resilience on Perceived Stress, Dietary Behaviors, and Alcohol Misuse: A Mediation-Moderation Analysis of Higher Education Students from Asia, Europe, and North America during the COVID-19 Pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has increased the already high levels of stress that higher education students experience. Stress influences health behaviors, including those related to dietary behaviors, alcohol, and sleep; yet the effects of stress can be mitigated by resilience. To date, past research studying the connections between dietary behaviors, alcohol misuse, sleep, and resilience commonly investigated singular relationships between two of the constructs. The aim of the current study was to explore the relationships between these constructs in a more holistic manner using mediation and moderation analyses. METHODS: Higher education students from China, Ireland, Malaysia, South Korea, Taiwan, the Netherlands, and the United States were enrolled in a cross-sectional study from April to May 2020, which was during the beginning of the COVID-19 pandemic for most participants. An online survey, using validated tools, was distributed to assess perceived stress, dietary behaviors, alcohol misuse, sleep quality and duration, and resilience. RESULTS: 2254 students completed the study. Results indicated that sleep quality mediated the relationship between perceived stress and dietary behaviors as well as the relationship between perceived stress and alcohol misuse. Further, increased resilience reduced the strength of the relationship between perceived stress and dietary behaviors but not alcohol misuse. CONCLUSION: Based on these results, higher education students are likely to benefit from sleep education and resilience training, especially during stressful events.

Health Behaviors of Higher Education Students from 7 Countries: Poorer Sleep Quality during the COVID-19 Pandemic Predicts Higher Dietary Risk.

Health behaviors of higher education students can be negatively influenced by stressful events. The global COVID-19 pandemic presents a unique opportunity to characterize and compare health behaviors across multiple countries and to examine how these behaviors are shaped by the pandemic experience. Undergraduate and graduate students enrolled in universities in China, Ireland, Malaysia, South Korea, Taiwan, the Netherlands and the United States (USA) were recruited into this cross-sectional study. Eligible students filled out an online survey comprised of validated tools for assessing sleep quality and duration, dietary risk, alcohol misuse and physical activity between late April and the end of May 2020. Health behaviors were fairly consistent across countries, and all countries reported poor sleep quality. However, during the survey period, the COVID-19 pandemic influenced the health behaviors of students in European countries and the USA more negatively than Asian countries, which could be attributed to the differences in pandemic time course and caseloads. Students who experienced a decline in sleep quality during the COVID-19 pandemic had higher dietary risk scores than students who did not experience a change in sleep quality (p = 0.001). Improved sleep quality was associated with less sitting time (p = 0.010). Addressing sleep issues among higher education students is a pressing concern, especially during stressful events. These results support the importance of making education and behavior-based sleep programming available for higher education students in order to benefit students' overall health.

Effect of COVID-19 on Epidemiological Characteristics of Road Traffic Injuries in Suzhou:A Retrospective Study (preprint)

Background: To present the new trends in epidemiology of road traffic injuries (RTIs) in Suzhou under the impact of Coronavirus disease 2019 (COVID-19) and control measures.Methods: Pre-hospital care records of RTIs in January-May 2020 and January-May 2019 were collected from the database of Suzhou emergency center, Jiangsu, China， and relevant clinical data were extracted for a retrospective study. RTIs in 2020 and 2019 were defined as observation group and control group respectively.Results: There were 7288 RTIs in the observation group, accounting for 82.17% of the control group. The number of RTIs per month from January to May in the observation group were 79.72%, 47.69%, 79.30%, 85.72% and 99.39% of the control group, respectively. Subgroup analysis showed that the number and composition ratio of electric bicycle related RTIs in the observation group were significantly higher than those in the control group (2641, 36.24% vs 2380, 26.84%, P<0.001). We observed a statistically significant increase in proportion of RTIs with consciousness disorder in the observation group compared to the control group (7.22% vs 6.13%, P = 0.006).Conclusions: Under the impact of COVID-19, the total number of RTIs in Suzhou from January to May 2020 decreased obviously. Nevertheless, there was an obvious rise in electric bicycle related RTIs, and the proportion of RTIs with consciousness disorder also increased. It is necessary for electric bicycle riders to wear helmets.

Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies (preprint)

SARS-CoV-2 unprecedentedly threatens the public health at worldwide level. There is an urgent need to develop an effective vaccine within a highly accelerated time. Here, we present the most comprehensive S-protein-based linear B-cell epitope candidate list by combining epitopes predicted by eight widely-used immune-informatics methods with the epitopes curated from literature published between Feb 6, 2020 and July 10, 2020. We find four top prioritized linear B-cell epitopes in the hotspot regions of S protein can specifically bind with serum antibodies from horse, mouse, and monkey inoculated with different SARS-CoV-2 vaccine candidates or a patient recovering from COVID-19. The four linear B-cell epitopes can induce neutralizing antibodies against both pseudo and live SARS-CoV-2 virus in immunized wild-type BALB/c mice. This study suggests that the four linear B-cell epitopes are potentially important candidates for serological assay or vaccine development.

The MERS-CoV receptor gene is among COVID-19 risk factors inherited from Neandertals (preprint)

In the current SARS-CoV-2 pandemic, two genetic regions derived from Neandertals have been shown to increase and decrease, respectively, the risk of falling severely ill upon infection. Here, we show that 2-8% of people in Eurasia carry a variant promoter region of the DPP4 gene inherited from Neandertals. This gene encodes an enzyme that serves as a receptor for the coronavirus MERS-CoV and is currently not believed to be a receptor for SARS-CoV-2. However, the Neandertal DPP4 variant doubles the risk to become critically ill in COVID-19.

Millisecond-scale molecular dynamics simulation of spike RBD structure reveals evolutionary adaption of SARS-CoV-2 to stably bind ACE2 (preprint)

The Receptor Binding Domain (RBD) of the SARS-CoV-2 surface spike (S) protein interacts with host angiotensin converting enzyme 2 (ACE2) to gain entry to host cells and initiate infection1-3. Detailed, accurate understanding of key interactions between S RBD and ACE2 provides critical information that may be leveraged in the development of strategies for the prevention and treatment of COVID-19. Utilizing the published sequences and cryo-EM structures of both the viral S RBD and ACE24,5, we performed in silico molecular dynamics (MD) simulations of free S RBD and of its interaction with ACE2 over the exceptionally long durations of 2.9 and 2 milliseconds, respectively, to elucidate the nature and relative affinity of S RBD surface residues for the ACE2 binding region. Our findings reveal that free S RBD has assumed an optimized ACE2 binding-ready conformation, incurring little entropic penalty for binding, an evolutionary adaptation that contributes to its high affinity for the receptor6. We further identified high probability molecular binding interactions that inform both vaccine design and therapeutic development, which may include recombinant ACE2-based spike decoys7 and/or allosteric S RBD-ACE2 binding inhibitors8,9 to prevent or arrest infection and thus disease.

Increased Resilience Weakens the Relationship between Perceived Stress and Anxiety on Sleep Quality: A Moderated Mediation Analysis of Higher Education Students from 7 Countries.

High levels of perceived stress and anxiety among university students are a global concern and are known to negatively influence sleep. However, few studies have explored how stress response styles, like psychological resilience and rumination, might alter these relationships. Using validated tools, perceived stress, anxiety, stress response styles, and sleep behaviors of undergraduate and graduate students from seven countries during the height of the COVID-19 pandemic were characterized in order to examine the relationships between these factors using mediation and moderation analyses. Students enrolled in universities in China, Ireland, Malaysia, Taiwan, South Korea, the Netherlands, and the United States were recruited in May 2020. A total of 2254 students completed this cross-sectional study. Perceived stress and anxiety were negatively associated with sleep quality through the mediation of rumination. Increased psychological resilience weakened the relationships between perceived stress and anxiety on sleep quality. The majority of students reported that COVID-19 negatively influenced their mental health and sleep quality but not sleep duration. Based on these results, university students would likely benefit from sleep education and mental health promotion programs that include trainings to increase psychological resilience and reduce rumination, particularly during times of increased stress.

Endoscopy works during the pandemic of coronavirus COVID-19: recommendations by the Chinese Society of Digestive Endoscopy.

Since December 2019, a novel coronavirus disease, COVID-19, has occurred in China and has spread around the world rapidly. As an acute respiratory infectious disease, COVID-19 has been included in type B infectious diseases and managed according to the standard of type A infectious disease in China. Given the high risk of COVID-19 infection during endoscopic procedures via an airborne route, the Chinese Society of Digestive Endoscopy issued a series of recommendations to guide the endoscopy works in China during the pandemic. To the best of our knowledge, no new infectious case of COVID-19 resulting from endoscopic procedures has been reported in China to date. Here, these recommendations are integrated to provide guidance about the prevention of COVID-19 for endoscopists. The recommendations include advice about postponing non-urgent endoscopies, excluding the possibility of COVID-19 in patients undergoing endoscopy, protection of medical staff from coronavirus infection, and cleaning of endoscopy centres.