Non-neutralizing antibodies to SARS-Cov-2-related linear epitopes induce psychotic-like behavior in mice.

Objective: An increasing number of studies have reported that numerous patients with coronavirus disease 2019 (COVID-19) and vaccinated individuals have developed central nervous system (CNS) symptoms, and that most of the antibodies in their sera have no virus-neutralizing ability. We tested the hypothesis that non-neutralizing anti-S1-111 IgG induced by the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could negatively affect the CNS. Methods: After 14-day acclimation, the grouped ApoE-/- mice were immunized four times (day 0, day 7, day 14, day 28) with different spike-protein-derived peptides (coupled with KLH) or KLH via subcutaneous injection. Antibody level, state of glial cells, gene expression, prepulse inhibition, locomotor activity, and spatial working memory were assessed from day 21. Results: An increased level of anti-S1-111 IgG was measured in their sera and brain homogenate after the immunization. Crucially, anti-S1-111 IgG increased the density of microglia, activated microglia, and astrocytes in the hippocampus, and we observed a psychomotor-like behavioral phenotype with defective sensorimotor gating and impaired spontaneity among S1-111-immunized mice. Transcriptome profiling showed that up-regulated genes in S1-111-immunized mice were mainly associated with synaptic plasticity and mental disorders. Discussion: Our results show that the non-neutralizing antibody anti-S1-111 IgG induced by the spike protein caused a series of psychotic-like changes in model mice by activating glial cells and modulating synaptic plasticity. Preventing the production of anti-S1-111 IgG (or other non-neutralizing antibodies) may be a potential strategy to reduce CNS manifestations in COVID-19 patients and vaccinated individuals.

The Effectiveness of a Blended Learning-Based Life Design Course: Implications of Instruction and Application of Technology

Purpose Due to the outbreak of the COVID-19 pandemic in 2021 in Taiwan, we have adapted the face-to-face Life Design course to a blended learning approach with educational technology to cope with the problem of cross-generational confusion and anxiety towards later life from learners. The objectives of this study are to. evaluate learners' reactions after attending the Life Design course including their level of satisfaction, engagement (Level 1), and the applicability of courses in their life. evaluate their learning outcomes after attending the Life Design course, such as their acquisition of knowledge, skills, attitudes, confidence, commitment (Level 2), and behavioral changes (Level 3). explore the factors that enable and prevent students from transferring their learning in this course to the action taking and making behavioral changes. explore how the application of educational technology can enhance the teaching and learning in the Life Design course. Methods This study used an action research method to solve two main problems we identified in practice: students' confusion about their future life and the shortcomings of traditional teaching methods, which cannot meet the learning needs of this type of course due to the requirement of intensive personal reflection and self-disclosure. Participants were 36 master's students who completed the Life Design course. Based on this course's design, implementation, and evaluation, we used the new Kirkpatrick Learning Assessment Model (Kirkpatrick J, Kirkpatrick WK. An introduction to the new world Kirkpatrick Model. Kirkpatrick Partners, 2021) to analyze the learning effectiveness on the Reaction, Learning, and Behavioral levels. Results To facilitate learners to overcome the cross-generational confusion of their life design and solve the shortage of face-to-face teaching methods, we took biographical learning as the core theme for this Life Design course and designed online and offline learning activities. The blended learning approach with educational technology allowed us to go beyond time and location constraints and provide a holistic and inseparable learning experience in both formats. The result of the evaluation shows that students who took the Life Design course were highly satisfied with the overall course design, topics, and the suitability of a blended learning approach, which motivated them to extend their learning outside the classroom and helped them benefit from a more trusted, personal and hybrid interaction with teachers and their peers both online and offline. On the learning level, students not only learned the correct knowledge of age perspectives, changed their views of career and personal development, and acquired skills for life design, but were also confident and committed to applying what they have learned in their future life. After the course, many students applied and integrated the learning into behavioral changes in their life. In terms of the difficulties and hindrances encountered in action taking, many students mentioned the lack of peers' support and constraints from their busy daily life. Many suggested providing extra support after the course with regular impulse, follow-ups, and individual feedback from teachers and peers in an online learning community. This indicates how educational technology can better support these elements in continuous learning and the transfer of learning. Conclusion Based on these results, we affirm that implementing this Life Design course with a blended learning approach is indeed better than a fully physical course. However, the focus of a blended learning approach should be on learners from a pedagogical perspective rather than technology.

The SARS-CoV-2 envelope protein disrupts barrier function in an in vitro human blood-brain barrier model.

Patients with coronavirus disease 2019 (COVID-19) have been frequently reported to exhibit neurological manifestations and disruption of the blood-brain barrier (BBB). Among the risk factors for BBB breakdown, the loss of endothelial cells and pericytes has caused widespread concern. Recent studies have revealed that severe acute respiratory syndrome coronavirus 2 envelope (S2E) protein caused cell death. We tested the hypothesis that the S2E protein alone could induce BBB dysfunction. The S2E protein bound to human BBB-related cells and inhibited cell viability in a dose- and time-dependent manner. Importantly, the S2E protein disrupted barrier function in an in vitro BBB model composed of HCMEC/D3 (brain endothelial cell line), HBVP (brain vascular pericyte), and U87MG (astrocyte cell line) cells and suppressed the expression of major genes involved in maintaining endothelial permeability and function. In addition, the S2E protein crossed the HCMEC/D3 monolayer. The S2E protein triggered inflammatory responses in HCMEC/D3 and U87MG cells. Taken together, these results show for the first time that the S2E protein has a negative impact on the BBB. Therapies targeting the S2E protein could protect against and treat central nervous system manifestations in COVID-19 patients.

Clinical characteristics of 14 COVID-19 deaths in Tianmen, China: a single-center retrospective study.

BACKGROUND: The treatment of critically ill patients with COVID-19 who were hospitalized in Wuhan has been reported. However, the clinical characteristics of patients who died of COVID-19 in regions with relatively scarce healthcare resources remain unknown. METHODS: In this retrospective study, a total of 14 patients who were admitted from January 18 to February 11, 2020 and died of COVID-19 were evaluated. The epidemiological, symptomatic, laboratory, radiological and treatment records were reviewed and analyzed. RESULTS: The mean age of the 14 patients was 56.7 (SD 15.3) years, and 8 (57.1%) were older than 50 years. Eight (57.1%) were men, and 11 (78.6%) had one or more high risk factors. The most common chronic diseases among these patients were cardiovascular disease (7, 50.0%), hypertension (6, 42.9%), and chronic kidney disease (5, 35.7%). General symptoms included cough (12, 85.7%), fever (11, 78.6%), and dyspnea (10, 71.4%). The median duration from the onset of symptoms to death was 11 (IQR 6.5-19.5) days, and the median duration from admission to death was 4.5 (1.0-11.8) days. Patients who died within 4.5 days had more severe pulmonary lesions, significantly reduced lymphocytes and elevated C-reactive protein (CRP). Most patients had organ dysfunction, including 13 (92.9%) with acute respiratory distress syndrome (ARDS), 4 (28.6%) with cardiac injury, 3 (21.4%) with acute kidney injury, and 3 (21.4%) with liver dysfunction. CONCLUSIONS: Elderly SARS-CoV-2-infected patients with comorbidities, especially those with ARDS and severe chest CT findings on admission, are at increased risk of death and deserve special attention and quality medical treatment.

The psychological impact of COVID-19 on the families of first-line rescuers.

Under the COVID-19 epidemic, the families of front-line rescue workers are under unusual pressure. We aim to understand the extent of their psychological distress in this epidemic and whether they have received sufficient support. Thus targeted to provide support for them and indirectly reduce the concerns of the rescue workers. From February 27 to March 1, 2020, we used the scales of Perceived Stress Scale, 10-items Connor-Davidson Resilience Scale, Generalized Anxiety Disorder-7, Patient Health Questionnaire-2, and primary care-posttraumatic stress disorder (PTSD) to evaluate the mental health level of the family members of front-line rescue workers online. Six hundred and seventy one family members voluntarily filled out the questionnaire after reading the purpose of the study. A total of 671 family members of front-line rescue workers participated in the survey, including 194 husbands/wives, 52 parents, 49 children, 76 brothers and sisters, and 300 other relationships. Among them, 55% of the family members reported sleep problems, 49.0% of the family members had mild, and above anxiety symptoms, 12.2% of the family members reported clinically significant depression symptoms, and 10.4% of the family members may have PTSD, 8.3% of family members had thoughts of self-injury or suicide. The feeling of stress was positively correlated with anxiety and depression, but there was no significant correlation between psychological elasticity and various symptoms. Family members who are more worried about the safety, physical condition and living security of front-line rescue workers are more likely to report symptoms such as sleep disorders, anxiety, and depression. Family members' first-line rescue has a significant impact on their daily life, raising children and supporting the elderly, which is also related to the occurrence of mental and psychological symptoms. During the period of front-line support, they received support from the units or organizations of the first-line workers, mainly including telephone greetings and daily necessities. The top three concerns about the information of the epidemic were the time of the end of the epidemic, the time of the return of the family and the progress of COVID-19's treatment. After the end of the epidemic, what they most want to do is to pay more attention to and accompany their families, family gatherings, and do more exercise. The psychological impact of this epidemic on the families of front-line rescue workers is mainly sleep problems and anxiety. The psychological intervention of family members should mainly start from the relief of stress and increase of material and spiritual support.

Direct or Collateral Liver Damage in SARS-CoV-2-Infected Patients.

Liver injury can result from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with more than one-third of COVID-19 patients exhibiting elevated liver enzymes. Microvesicular steatosis, inflammation, vascular congestion, and thrombosis in the liver have been described in autopsy samples from COVID-19 patients. Several factors, including direct cytopathic effect of the virus, immune-mediated collateral damage, or an exacerbation of preexisting liver disease may contribute to liver pathology in COVID-19. Due to its immunological functions, the liver is an organ likely to participate in the viral response against SARS-CoV-2 and this may predispose it to injury. A better understanding of the mechanism contributing to liver injury is needed to develop and implement early measures to prevent serious liver damage in patients suffering from COVID-19. This review summarizes current reports of SARS-CoV-2 with an emphasis on how direct infection and subsequent severe inflammatory response may contribute to liver injury in patients with and without preexisting liver disease.

Psychometric property study of the posttraumatic stress disorder checklist for DSM-5 (PCL-5) in Chinese healthcare workers during the outbreak of corona virus disease 2019.

BACKGROUND: Previous studies about the reliability and validity of the updated PCL version for the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders (PCL-5) have only been evaluated in certain samples of the population, which lacks in the sample of Healthcare Workers. Our study focused on the factor structure, reliability and validity of the PCL-5 among Chinese Healthcare Workers during the Outbreak of Corona Virus Disease 2019. METHODS: We conducted an online survey of frontline healthcare workers using the PCL-5 for PTSD. Total of 212 frontline healthcare providers were included in this study. RESULTS: The findings showed that PCL-5 is a reliable instrument in our sample. The total and subscale scores showed good internal consistency. The convergent and discriminant validity of the PCL-5 were also well demonstrated. Our result showed a better fit with the seven-factor hybrid model compared with other models and supported that the PCL-5 Chinese version can be used as a reliable screening tool to conduct psychological screening for Chinese healthcare workers. LIMITATION: We could not examine other aspects of reliability and validity like test-retest reliability or criterion validity. We didn't use the gold-standard structured interview for PTSD in our study. Besides, most of our samples were young people who had access to the internet. Not all professional levels and seniorities were presented because our sample had a lower mean income and educational level. CONCLUSION: Our study shows that the Chinese PCL-5 has good validity and reliability in frontline healthcare workers during the outbreak.

Early Epidemiological Features and Trends of the COVID-19 Outbreak in Southeast Asia: a Population-Level Observational Study (preprint)

Background: The global outbreak of coronavirus disease 2019 (COVID-19) has been ongoing in Southeast Asia since 13 January 2020. We conducted an observational study to investigate underlying disease patterns of COVID-19 in Southeast Asia, and consequently to guide intervention strategies against the pandemic.Methods: In this population-level observational study set in Southeast Asia, we compiled a list of patients with COVID-19 (n = 925) and daily country-level case counts (n = 1346) from 13 January 2020 through 16 March 2020. All epidemiological data were extracted from official websites of the WHO and health authorities of each Southeast Asian country. Relevant spatiotemporal distributions, demographic characteristics, and short-term trends were assessed.Results: A total of 1,346 confirmed cases of COVID-19, with 217 (16.1%) recoveries and 18 (1.3%) deaths, were reported in Southeast Asia as of 16 March 2020. Early transmission dynamics were examined with an exponential regression model: y=0.30e0.13x (p<0·01, adjusted R2 = 0.96).  Using this model, we predicted that the cumulative number of reported COVID-19 cases in Southeast Asia would exceed 10,000 by early April 2020. A total of 74 cities across eight countries in Southeast Asia were affected by COVID-19. Most of the confirmed cases were located in five international metropolitan areas. Demographic analyses of the 925 confirmed cases indicated a median age of 44 years and a sex ratio of 1.25. The median age of the local patient population was significantly higher than that of the corresponding country’s general population (p<0·01), whereas the sex ratio did not significantly differ.Conclusions: The COVID-19 situation in Southeast Asia is unevenly geographically distributed and pessimistic in the short term. Age may play a significant role in both the susceptibility to and outcome of infection. Real-time active surveillance and targeted intervention strategies are urgently needed to contain the pandemic.