Progress in the research of COVID-19 effects on Alzheimer's disease

Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More than one-third of patients with COVID-19 experience neurological symptoms, including confusion, headaches, and decreased/disordered taste. Alzheimer's disease (AD) is a slowly progressive neurodegenerative disease and the most common type of dementia. Alzheimer's disease patients are at high risk and susceptible to infection with COVID-19, which may cause severe illness and even death. There appears to be an interaction between AD and COVID-19, and on the one hand, patients with COVID-19 seem to be more likely to develop AD. AD patients, on the other hand, may be more susceptible to severe COVID-19. Therefore, understanding the common link between COVID-19 and AD may help to develop treatment strategies. Risk factors common to AD and COVID-19 are aging, ApoE T4 allele, beta-amyloid (Abeta) deposition, angiotensin-converting enzyme (ACE), neuroinflammation, oxidative stress. Here, this article focuses on the relationship between COVID-19 and AD, explores common risk factors and potential pathogenesis, and provides help for early prevention, treatment and recovery.

Psychological support and demand for death education among Chinese college students during the COVID-19 pandemic: The mediating role of neutral death attitude.

AIM: This study aimed to explore the mediating role of neutral death attitude between psychological support and demand for death education among college students during COVID-19. DESIGN: A cross-sectional survey was conducted with 1800 college students selected by convenience and snowball sampling from 20 provinces and municipalities. METHODS: A questionnaire survey (The Psychological Support Scale, Demand for Death Education Scale and Neutral Death Attitude Scale) was distributed to 1800 college students. RESULTS: Psychological support had a significant positive predictive effect on demand for death education and neutral death attitude, with neutral death attitude partially regulating the demand for death education of college students after receiving psychological support.

Role of the extracellular matrix in COVID-19.

An outbreak of coronavirus disease 2019 (COVID-19) has spread globally, with over 500 million cases and 6 million deaths to date. COVID-19 is associated with a systemic inflammatory response and abnormalities of the extracellular matrix (ECM), which is also involved in inflammatory storms. Upon viral infection, ECM proteins are involved in the recruitment of inflammatory cells and interference with target organ metabolism, including in the lungs. Additionally, serum biomarkers of ECM turnover are associated with the severity of COVID-19 and may serve as potential targets. Consequently, understanding the expression and function of ECM, particularly of the lung, during severe acute respiratory syndrome of the coronavirus 2 infection would provide valuable insights into the mechanisms of COVID-19 progression. In this review, we summarize the current findings on ECM, such as hyaluronic acid, matrix metalloproteinases, and collagen, which are linked to the severity and inflammation of COVID-19. Some drugs targeting the extracellular surface have been effective. In the future, these ECM findings could provide novel perspectives on the pathogenesis and treatment of COVID-19.

College students' exercise experience and aggression during COVID-19: A chain mediating model.

Aim: This study aimed to explore to how exercise experience affects the aggression of college students and the mediating effects of mood and exercise attitude in COVID-19. Methods: A questionnaire survey [The Subjective Exercise Experience Scale (SEES); Profile of Mood State (POMS); Exercise Attitude Scale; and Aggression Questionnaire (AQ)] was conducted among 1,006 college students. Results: Exercise experience had a significant effect on aggression. The direct effect of exercise well-being was not significant, but indirectly affected the aggression through independent mediation and chain mediation of mood and exercise attitude. The direct effect of exercise distress was not significant, but indirectly affected the aggression through independent mediation and chain mediation of mood and exercise attitude. Conclusion: Mood and exercise attitude are powerful factors to alleviate the impact of exercise experience on aggression during the pandemic. Actively adjusting the mood and exercise attitude from a cognitive perspective may be an effective way to promote college students' physical exercise and reduce aggression.

Changes in Couples' Relationships and Their Differences in Type during the COVID-19 Pandemic in China.

PURPOSE: This study explores changes in couples' relationships during the COVID-19 pandemic, and analyzes the differences in the changes across three types: positive communication, criticism/defense, and demand/withdrawal. METHOD: A total of 600 (567 valid) Chinese respondents participated in this study, and a questionnaire was utilized to determine changes in their overall relationship, verbal and nonverbal communication, emotion, and activities with their spouses. RESULTS: The average score of items related to positive communication is higher, compared with that of negative communication. Compared with the other two types of relationships, respondents with positive communication scored highest on all items related to positive communication and lowest on all items related to negative communication. Significant differences were noted between the positive communication types and the others. CONCLUSIONS: Results show that the relationships of couples included in this study have improved during the current pandemic. Therefore, improved consistency in the type of intimacy can lead to improved quality of couples' relationships during the COVID-19 pandemic.

Cancer Clinical Trials Beyond Pandemic: Report of an American Statistical Association Biopharmaceutical Section Open Forum Discussion

This article provides a summary of discussions from the American Statistical Association (ASA) Biopharmaceutical (BIOP) Section Open Forum organized by the ASA BIOP Statistical Methods in Oncology Scientific Working Group in coordination with the US FDA Oncology Center of Excellence and LUNGevity Foundation on January 14, 2021, and February 8, 2021. Diverse stakeholders including oncologists, patient advocates, experts from international regulatory agencies, academicians, and representatives of the pharmaceutical industry engaged in a discussion on how best to incorporate lessons learned during the COVID-19 pandemic into the design of future oncology trials. While recognizing that decentralized or hybrid cancer trials may increase variability associated with measurement error and potentially increase bias in treatment effect estimation, panel discussions highlighted the importance of flexibility for decreasing patient burden, which has the potential to increase access to and retention in cancer clinical trials and may broaden the representation of real-world patients in the trial setting. [ FROM AUTHOR] Copyright of Statistics in Biopharmaceutical Research is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

A follow-up study depressive and anxiety symptoms of children in Wuhan City, Hubei Province

Objective: To investigate the progression of depressive and anxiety symptoms of children, especially whose parents were frontline workers in the combat of the coronavirus disease 2019(COVID-19), and to provide evidence for children's mental health promotion.

Effects of learning and lifestyle behaviors during home confinement on depressive and anxiety symptoms among primary school students

Objective: To examine the changes of depressive and anxiety symptoms in school-aged children during home confinement and to identify possible influence of learning and lifestyle behaviors on mental health changes.

Research progress on mental health of school-age children under major public health emergencies

Children were vulnerable groups in major public health emergencies. In 2020, the coronavirus disease 2019 (COVID-19) pandemic was widespread in the world. The mental health of school-age children has become a worldwide concern. Herein, we conducted this review to evaluate the impact of COVID-19 on the mental health of general children and special children with a high risk of psychological problems, focusing on the prevalence of anxiety, depression, and post-traumatic stress disorder among school-age children in different countries and regions during the COVID-19 epidemic. Considering the susceptibility between individuals and the accessibility of social resources, we further explored the child, family, and social related factors affecting the mental health of school-age children. Finally, some suggestions on the construction of children's mental health service system in major public health emergencies were put forward at the national, school-family-community, and individual levels. Building a safe and reliable child mental health protection network required the joint efforts of all sectors of society.

Psychological Symptom Progression in School-Aged Children After COVID-19 Home Confinement: A Longitudinal Study.

Background: The long-term mental health effects of coronavirus disease 2019 (COVID-19) in children are rarely reported. We aimed to investigate the progression of depressive and anxiety symptoms among a cohort of children in the initial epicenter of COVID-19 in China. Methods: Two waves of surveys were conducted in the same two primary schools in Wuhan and Huangshi, Hubei province: Wave 1 from 28 February to 5 March, 2020 (children had been confined to home for 30-40 days) and Wave 2 from 27 November to 9 December, 2020 (schools had reopened for nearly 3 months). Depressive and anxiety symptoms were estimated using the Children's Depression Inventory - Short Form (CDI-S) and the Screen for Child Anxiety Related Emotional Disorders (SCARED), respectively. ΔCDI-S and ΔSCARED scores between Wave 2 and Wave 1 were calculated and further categorized into tertiles. Multivariable linear regression and multinomial logistic regression models were then applied. Results: A total of 1,224 children completed both surveys. The prevalence of mental health outcomes at Wave 2 increased significantly compared to Wave 1, specifically depressive symptoms (age-standardized prevalence rates: 37.5 vs. 21.8%) and anxiety symptoms (age-standardized prevalence rates: 24.0 vs. 19.6%). Higher ΔSCARED scores were observed in females and children in Wuhan, and children with experience of neglect had higher ΔCDI-S (ß = 1.12; 95% CI = 0.67-1.58) and ΔSCARED (ß = 6.46; 95% CI = 4.73-8.19) scores compared with those without experience of neglect. When the Δ scores were further categorized into tertiles, similar results were found. Conclusions: The prevalence of depressive and anxiety symptoms after schools resumed was increased compared with that during the home quarantine period, even though the COVID-19 pandemic was under control. Females and children in Wuhan, and also children with experience of neglect were at increased risk of mental health disorders.

Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial.

BACKGROUND: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). METHODS: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18-59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 µg, 10 µg, 15 µg, 20 µg, and 25 µg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). FINDINGS: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 µg group, 13 [65%] of 20 in the 10 µg group, 17 [85%] of 20 in the 15 µg group, 19 [95%] of 20 in the 20 µg group, 16 [100%] of 16 in the 25 µg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 µg group, three (15%) of 20 in the 10 µg group, six (30%) of 20 in the 15 µg group, seven (35%) of 20 in the 20 µg group, five (31%) of 16 in the 25 µg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 µg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19. INTERPRETATION: ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale. FUNDING: National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences.

Case Report: Genomic Characteristics of the First Known Case of SARS-CoV-2 Imported From Spain to Sichuan, China.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been basically under control in China since March 2020, but the import of domestic SARS-CoV-2 has begun to increase. This study reported the first case of asymptomatic SARS-CoV-2 infection imported from Spain into Sichuan Province, China, on March 11, 2020. The infected male had a body temperature of 37.5°C, normal blood oxygen saturation levels, and a computed tomography (CT) examination showed that his lungs had no shadows. However, a throat swab from the subject tested positive for SARS-CoV-2 using qPCR assay. In this study, we conducted transcriptome sequencing on respiratory throat swabs from the subject and found that the dominant SARS-CoV-2 sequence (Gene Bank ID: MW301121) was a spike protein D614G mutant strain, which is currently popular throughout world. We downloaded and analyzed SARS-CoV-2 sequences collected from cases in China and Spain for comparison and tracing purposes. After March 11, 2020, the Chinese domestic clade was naturally divided into the imported SARS-CoV-2 D614G mutant strain and evolutionarily-related similar sequences and that of sequences collected in the original Wuhan area. The sequence reported in this study was located on a small branch, far from the evolution of Wuhan sequences. As expected, the identified sequence was closely related to the evolution of the SARS-CoV-2 D614G mutant strain circulating in Spain.

Sensing of cytoplasmic chromatin by cGAS activates innate immune response in SARS-CoV-2 infection.

The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved. Here, we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection induces the cellular level of 2'3'-cGAMP associated with STING activation. cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection. We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion. Furthermore, cytoplasmic chromatin-cGAS-STING pathway, but not MAVS-mediated viral RNA sensing pathway, contributes to interferon and pro-inflammatory gene expression upon cell fusion. Finally, we show that cGAS is required for host antiviral responses against SARS-CoV-2, and a STING-activating compound potently inhibits viral replication. Together, our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection, mediated by cytoplasmic chromatin from the infected cells. Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19. In addition, these findings extend our knowledge in host defense against viral infection by showing that host cells' self-nucleic acids can be employed as a "danger signal" to alarm the immune system.