Impact of the COVID-19 pandemic on the hospital attendance of patients with primary cervical cancer in Heilongjiang, China.

Information regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on cervical cancer in mainland China is lacking. We explored its impact on the hospital attendance of patients with primary cervical cancer. We included 1918 patients with primary cervical cancer who initially attended Harbin Medical University Cancer Hospital between January 23, 2019, and January 23, 2021. Attendance decreased by 31%, from 1135 in 2019 to 783 in 2020, mainly from January to June (𝜒2 = 73.362, P < .001). The percentage of patients detected by screening decreased from 12.1% in January-June 2019 to 5.8% in January-June 2020 (𝜒2 = 7.187, P = .007). Patients with stage I accounted for 28.4% in 2020 significantly lower than 36.6% in 2019 (𝜒2 = 14.085, P < .001), and patients with stage III accounted for 27.1% in 2020 significantly higher than 20.5% in 2019 (𝜒2 = 11.145, P < .001). Waiting time for treatment was extended from 8 days (median) in January-June and July-December 2019 to 16 days in January-June (𝜒2 = 74.674, P < .001) and 12 days in July-December 2020 (𝜒2 = 37.916, P < .001). Of the 179 patients who delayed treatment, 164 (91.6%) were for the reasons of the healthcare providers. Compared to 2019, the number of patients in Harbin or non-Harbin in Heilongjiang Province and outside the province decreased, and cross-regional medical treatment has been hindered. The COVID-19 pandemic has negatively impacted cervical cancer patient attendance at the initial phase. These results are solid evidence that a strategy and mechanism for the effective attendance of cervical cancer patients in response to public health emergencies is urgently needed.

Integrating local and neighboring area influences into vulnerability modeling of infectious diseases in Singapore

Infectious disease spreading is a spatial interaction process. Assessing community vulnerability to infectious diseases thus requires not only information on local demographic and built environmental conditions, but also insights into human activity interactions with neighboring areas that can lead to the transition of vulnerability from locations to locations. This study presented an analytical framework based on the Particle Swarm Optimization model to estimate the weights of the factors for vulnerability modeling, and a local proportional parameter for use in the integration of the local and neighboring area risks. A country model and five cross-region validation models were developed for the case study of Singapore to assess the vulnerability to COVID-19. The results showed that the identified weights for the factors were robust throughout the optimization process and across various models. The local proportional parameter could be set slightly higher in between 0.6 and 0.8 (out of 1), signifying that the local effect was higher than the neighboring effect. Computation of the weights from the optimal solutions for the integrated vulnerability index showed that the factors of human activity intensity and accessibility to amenities had much higher weights, at 0.5 and 0.3, respectively. Conversely, the weights of population density, elderly population, social economic status and land use diversity were much lower. These findings underscored the importance of considering non-equal weights for factors and incorporating spatial interactions between local and neighboring areas for vulnerability modeling, to provide to a more comprehensive assessment of vulnerability to infectious diseases.

Clinical efficacy of combination therapy of FuXi-Tiandi-Wuxing Decoction and anti-viral drugs in the treatment of novel coronavirus pneumonia: A prospective interventional study.

Introduction: The National Administration of Traditional Chinese Medicine of the People's Republic of China (NATCM) and the State Administration of Traditional Chinese medicine (TCM) advocated a combination therapy of TCM and anti-viral drugs for novel coronavirus pneumonia (NCP) to improve the efficacy of clinical treatment. Methods: Forty-six patients diagnosed with NCP were sequentially divided into intent-to-treat population: the experimental group (combination of FuXi-Tiandi-Wuxing Decoction and anti-viral drugs; n = 23) and the control group (anti-viral drugs only) (n = 23). The two groups were compared in terms of duration of fever, cough symptom score, fatigue, appetite, dyspnea, out-of-bed activities, chest computer tomography (CT) recovery, virological clearance, average length of hospital stay, and clinical effective rate of drug. After 6 days of observation, patients from the control group were divided into as-treated population: experimental subgroup (n = 14) to obtain clinical benefit and control subgroup (n = 9). Results: There was a significant improvement in the duration of fever (1.087 ± 0.288 vs 4.304 ± 2.490), cough (0.437 ± 0.589 vs 2.435 ± 0.662; P < 0.05), chest CT evaluation (82.6% vs 43.4%; P < 0.05), and virological clearance (60.8% vs 8.7%; P < 0.05) in patients of the experimental group compared with patients in the control group. Further observation in as-treated population reported that cough (0.742 ± 0.463 vs 1.862 ± 0.347; P < 0.05) and fatigue (78.5% vs 33.3%; P < 0.05) were significantly relieved after adding FuXi-Tiandi-Wuxing Decoction to the existing treatment. Conclusion: An early treatment with combination therapy of FuXi-Tiandi-Wuxing Decoction and anti-viral drugs significantly relieves the clinical symptoms of NCP, shows improvement in chest CT scan, improves virological clearance, shortens average length of hospital stay, and reduces the risk of severe illness. The effect of FuXi-Tiandi-Wuxing Decoction in NCP may be clinically important and require further consideration.

The lncRNAs involved in regulating the RIG-I signaling pathway

Understanding the targets and interactions of long non-coding RNAs (lncRNAs) related to the retinoic acid-inducible gene-I (RIG-I) signaling pathway is essential for developing interventions, which would enable directing the host inflammatory response regulation toward protective immunity. In the RIG-I signaling pathway, lncRNAs are involved in the important processes of ubiquitination, phosphorylation, and glycolysis, thus promoting the transport of the interferon regulatory factors 3 and 7 (IRF3 and IRF7) and the nuclear factor kappa B (NF-κB) into the nucleus, and activating recruitment of type I interferons (IFN-I) and inflammatory factors to the antiviral action site. In addition, the RIG-I signaling pathway has recently been reported to contain the targets of coronavirus disease-19 (COVID-19)-related lncRNAs. The molecules in the RIG-I signaling pathway are directly regulated by the lncRNA–microRNAs (miRNAs)–messenger RNA (mRNA) axis. Therefore, targeting this axis has become a novel strategy for the diagnosis and treatment of cancer. In this paper, the studies on the regulation of the RIG-I signaling pathway by lncRNAs during viral infections and cancer are comprehensively analyzed. The aim is to provide a solid foundation of information for conducting further detailed studies on lncRNAs and RIG-I in the future and also contribute to clinical drug development.

Primary and Booster Vaccination in Reducing Severe Clinical Outcomes Associated with Omicron Naïve Infection

Background Little is known about long-term effectiveness of COVID-19 vaccine in reducing severity and deaths associated with Omicron VOC not perturbed by prior infection and independent of oral anti-viral therapy and non-pharmaceutical (NPI). Methods A retrospective observational cohort study was applied to Taiwan community during the unprecedent large-scale outbreaks of Omicron BA.2 between April and August, 2022. Primary vaccination since March, 2021 and booster vaccination since January, 2022 were offered on population level. Oral Anti-viral therapy was also offered as of mid-May 2022. The population-based effectiveness of vaccination in reducing the risk of moderate and severe cases of and death from Omicron BA.2 with the consideration of NPI and oral anti-viral therapy were assessed by using Bayesian hierarchical models. Results The risks of three clinical outcomes associated with Omicron VOC infection were lowest for booster vaccination, followed by primary vaccination, and highest for incomplete vaccination with the consistent trends of being at increased risk for three outcomes from the young people aged 12 years or below until the elderly people aged 75 years or older with 7 age groups. Before the period using oral anti-viral therapy, complete primary vaccination with the duration more than 9 months before outbreaks conferred the statistically significant 47% (23-64%) reduction of death, 48% (30-61%) of severe disease, and 46% (95% CI: 37-54%) of moderate disease after adjusting for 10-20% independent effect of NPI. The benefits of booster vaccination within three months were further enhanced to 76% (95% CI: 67-86%), 74% (95% CI: 67-80%), and 61% (95% CI: 56-65%) for three corresponding outcomes. The additional effectiveness of oral anti-viral therapy in reducing moderate disease was 13% for the booster group and 5.8% for primary vaccination. Conclusions We corroborated population effectiveness of primary vaccination and its booster vaccination, independent of oral anti-viral therapy and NPI, in reducing severe clinical outcomes associated with Omicron BA.2 naïve infection population.

ApoE4 causes severe COVID-19 outcomes via downregulation of ACE2 (preprint)

Background Recent numerous epidemiology and clinical association studies reported that ApoE polymorphism may associate with the risk and severity of coronavirus disease 2019 (COVID-19), and yielded inconsistent results. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptor expressed on host cell membranes.Methods A meta-analysis was conducted to clarify the association between ApoE polymorphism and the risk and severity of COVID-19. Multiple protein interaction assays were utilized to investigate the potential molecular link between ApoE and spike protein and between ApoE and also the SARS-CoV-2 primary receptor ACE2. Immunoblotting and immunofluorescence staining methods were used to access the regulatory effect of different ApoE isoform on ACE2 protein expression.Results ApoE gene polymorphism (ε4 carries genotypes VS non-ε4 carries genotypes) is associated with the increased risk (P = 0.0003, OR = 1.44, 95% CI: 1.18–1.76) and progression (P < 0.00001, OR = 1.85, 95% CI: 1.50–2.28) of COVID-19. ApoE interacts with both the spike protein and ACE2 but did not show isoform-dependent binding effects. ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1–7.Conclusions ApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Instead, ApoE4 downregulates ACE2 protein expression and subsequently the dysregulation of renin–angiotensin system (RAS) may provide explanation by which ApoE4 exacerbates COVID-19 disease.

Dissection of the Active Ingredients and Potential Mechanism of Han-Shi-Yu-Fei-Decoction in Treating COVID-19 Based on In Vivo Substances Profiling and Clinical Symptom-Guided Network Pharmacology

This work was aimed to elucidate the mechanism of action of Han-Shi-Yu-Fei-decoction (HSYFD) for treating patients with mild coronavirus disease 2019 (COVID-19) based on clinical symptom-guided network pharmacology. Experimentally, an ultra-high performance liquid chromatography technique coupled with quadrupole time-of-flight mass spectrometry method was used to profile the chemical components and the absorbed prototype constituents in rat serum after its oral administration, and 11 out of 108 compounds were identified. Calculatingly, the disease targets of Han-Shi-Yu-Fei symptoms of COVID-19 were constructed through the TCMIP V2.0 database. The subsequent network pharmacology and molecular docking analysis explored the molecular mechanism of the absorbed prototype constituents in the treatment of COVID-19. A total of 42 HSYFD targets oriented by COVID-19 clinical symptom were obtained, with EGFR, TP53, TNF, JAK2, NR3C1, TH, COMT, and DRD2 as the core targets. Enriched pathway analysis yielded multiple COVID-19-related signaling pathways, such as the PI3K/AKT signaling pathway and JAK-STAT pathway. Molecular docking showed that the key compounds, such as 6-gingerol, 10-gingerol, and scopoletin, had high binding activity to the core targets like COMT, JAK2, and NR3C1. Our work also verified the feasibility of clinical symptom-guided network pharmacology analysis of chemical compounds, and provided a possible agreement between the points of views of traditional Chinese medicine and western medicine on the disease.

Intranasal delivery of NS1-deleted influenza virus vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response (preprint)

The emergence of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) variants and "anatomical escape" characteristics threaten the effectiveness of current coronavirus disease (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. In this study, we investigated immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants. Intranasal delivery of dNS1-RBD induced innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrained the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (IL-6, IL-1B, and IFN-{gamma}) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden.

University students' perspectives on emergency online GIS learning amid the Covid‐19 pandemic

This study investigated GIS students' perspectives on emergency online learning (EOL) during the Covid‐19 pandemic through a case study at National University of Singapore. Questionnaire surveys administered to three GIS courses were conducted, the result of which suggests that the GIS teaching could be completed effectively online during the crisis. In addition, the positive and negative influences of this learning mode have been discussed in connection to relevant student perspectives on social media and relevant findings in the literature. Relatively, senior and independent learners adapted better to the EOL, while beginners and less self‐disciplined learners may need more face‐to‐face guidance, interactions, and direct supervision. It is worth pointing out that despite some students seeing the demand for a higher level of self‐discipline as being negative, others saw this property contributed to them being better independent learners with self‐motivation, suggesting the need for a nuanced interpretation of the results that consider perspectives. Based on the pros and cons of the EOL investigated, this article further stresses the need to cultivate a post‐pandemic blended GIS learning pedagogy for enhancing higher GIS education's quality and resilience in times of crisis. [ FROM AUTHOR] Copyright of Transactions in GIS is the property of Wiley-Blackwell 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.)

ApoE4 causes severe COVID-19 outcomes via downregulation of ACE2 (preprint)

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); host cell entry by this virus relies on the interaction between the receptor-binding domain (RBD) of its spike glycoprotein and the angiotensin-converting enzyme 2 (ACE2) receptor on cell membranes. In addition to serving as a receptor for SARS-CoV-2, ACE2 was originally discovered as a protective factor in the renin-angiotensin system (RAS) that catalyses the degradation of angiotensin II (Ang II) to Ang 1-7, which is involved in multiple organ pathology. Recent genetic and clinical studies reported that ApoE4 expression is associated with increased susceptibility to SARS-CoV-2 infection and the development of severe COVID-19, but the underlying mechanism is currently unclear. In the present study, by using immunofluorescence staining, molecular dynamics simulations, proximity ligation assay (PLA) and coimmunoprecipitation (Co-IP) combined with a biolayer interferometry (BLI) assay, we found that ApoE interacts with both the spike protein and ACE2 but does not show obvious isoform-dependent binding effects. These data suggest that ApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Importantly, further immunoblotting and immunofluorescence staining results showed that ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1-7, which could worsen tissue lesions; these findings provide a possible explain by which ApoE4 exacerbates COVID-19 disease.

Negative perfectionism and sleep quality in Chinese international students under COVID-19 epidemic: A moderated mediation

Objective This study used a moderated mediation model to test the mediating effect of anxiety on the relationship between negative perfectionism and sleep quality and the moderating effect of COVID-19 epidemic risk perception during the COVID-19 pandemic in Chinese international students. Materials and methods A sample of 239 Chinese international students from the south of China, was surveyed with the Negative and Positive Perfectionism Scale, the Pittsburgh Sleep Quality Index, the General Anxiety Disorder Scale, and the COVID-19 Epidemic Risk Perception Inventory. Version 23.0 of SPSS and version 3.4 of PROCESS were used to perform the correlation analyses, mediation analysis, and moderated mediation analysis. Results (1) Negative perfectionism was significantly correlated with anxiety (r = 0.371, p < 0.01) and poor sleep quality (r = 0.291, p < 0.01). Anxiety was significantly correlated with poor sleep quality (r = 0.594, p < 0.01). (2) The mediating effect test showed that anxiety had a mediating effect between negative perfectionism and poor sleep quality (β = 0.157, p < 0.01). (3) Epidemic risk perception moderated the mediating effect of anxiety between negative perfectionism and poor sleep quality (β = 0.070, p < 0.01). Conclusion Negative perfectionism affected sleep quality indirectly through anxiety. In particular, COVID-19 epidemic risk perception moderated the relationship between anxiety and sleep quality, such that the association was stronger when the COVID-19 epidemic risk perception was high. These results provide a more comprehensive understanding of the negative link between negative perfectionism and poor sleep quality.

Evaluation of a Functional Single Nucleotide Polymorphism of the SARS-CoV-2 Receptor ACE2 That Is Potentially Involved in Long COVID

Since the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, SARS-CoV-2 has led to a global coronavirus disease 2019 (COVID-19) pandemic. A better understanding of the SARS-CoV-2 receptor ACE2 at the genetic level would help combat COVID-19, particularly for long COVID. We performed a genetic analysis of ACE2 and searched for its common potential single nucleotide polymorphisms (SNPs) with minor allele frequency >0.05 in both European and Chinese populations that would contribute to ACE2 gene expression variation. We thought that the variation of the ACE2 expression would be an important biological feature that would strongly affect COVID-19 symptoms, such as “brain fog”, which is highlighted by the fact that ACE2 acts as a major cellular receptor for SARS-CoV-2 attachment and is highly expressed in brain tissues. Based on the human GTEx gene expression database, we found rs2106809 exhibited a significant correlation with the ACE2 expression among multiple brain and artery tissues. This expression correlation was replicated in an independent European brain eQTL database, Braineac. rs2106809*G also displays significantly higher frequency in Asian populations than in Europeans and displays a protective effect (p = 0.047) against COVID-19 hospitalization when comparing hospitalized COVID-19 cases with non-hospitalized COVID-19 or SARS-CoV-2 test-negative samples with European ancestry from the UK Biobank. Furthermore, we experimentally demonstrated that rs2106809*G could upregulate the transcriptional activity of ACE2. Therefore, integrative analysis and functional experiment strongly support that ACE2 SNP rs2106809 is a functional brain eQTL and its potential involvement in long COVID, which warrants further investigation.

Investigation of the mechanism of fangfeng tongsheng pills in the treatment COVID-19 by network pharmacology and molecular docking

Objective: To explore the active components and potential mechanism of Fangfeng Tongsheng Pills by using network pharmacology and molecular docking in the treatment of coronavirus disease 19(COVID-19). Methods The main chemical constituents and action targets of various medicines in Fangfeng Tongsheng Pills were collected via traditional Chinese medicine system pharmacology database and online analysis platform(TCMSP). The related targets of COVID-19 were collected by using GeneCards database, and the repeating parts with Fangfeng Tongsheng Pills were taken as the research targets. Cytoscape software was used to create a drug-target-disease network. The common target was imported into STRING database, and the protein-protein interaction network diagram was constructed by Cytoscape software. The GO(gene ontology) function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed by DAVID to predict their mechanism. The core components of Fangfeng Tongsheng Pills were docked with the therapeutic target of COVID-19 by AutoDock software. Results A total of 224 active compounds and 696 active targets were screened from Fangfeng Tongsheng Pills, including 79 targets coincided with COVID-19, and 10 active compounds, i.e. quercetin, luteolin, kaempferol,beta-sitosterol, naringenin, etc., 23 effective targets, i.e. PTGS2, PTGS1, NOS2, F10, DPP4, etc. A total of 65 GO function enrichment analysis results and 101 KEGG pathway enrichment results were obtained, including inflammatory response, tumor necrosis factor(TNF) signaling pathway, hypoxia inducible factor-1(HIF-1) signaling pathway, vascular endothelial growth factors(VEGF) signaling pathway, toll-like receptors(TLRs) signaling pathway, phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt) signaling pathway, and mitogen-activated protein kinase(MAPK) signaling pathway. Conclusion The active components in Fangfeng Tongsheng Pills, such as beta-sitosterol, quercetin, luteolin, kaempferol and naringenin, can combine with SARS-Co V2-3CL hydrolase and ACE2, act on the key target [TNF, Caspase-3, mitogen-activated protein kinase(MAPK1), interleukin-6(IL-6), prostaglandin-endoperoxide synthase 2(PGTS2)] of TNF, HIF-1, VEGF, MAPK and toll-like receptor signaling pathway, and play the roles of anti-inflammation, immune regulation, anti-hypoxic stress and anti-virus infection, thus play a role in the treatment of COVID-19.

Application of Visitor Eye Movement Information to Museum Exhibit Analysis

The motivation of this study is that after the COVID-19 epidemic, museum exhibition visits have also been significantly affected. The purpose of this research is to better understand the visual cognition of visitors, so as to improve the application of physical field or online exhibitions. Currently, no research is available on the differences in the visitor's viewing and cognitive process with eye movements sequence analysis that stem from the exhibition planning and design of different museums. This study tracks and analyzes the eye movement trajectories of visitors and studies its relation to learning and cognition and finds the key to influencing cognition through behavioral sequence analysis of displayed content. The results show that those interested in the displayed content have better cognitive performance, are immersed in reading text, and have a substantial shift in eye movement. Contrarily, those not interested in the displayed content are distracted and often turn their attention back to the title of the content. In this study, eye movement and fixation are indicators that can be used as a reference for the future design of displays to improve the effectiveness of presenting information to a visitor. Furthermore, this research can also provide future applications in integrating the virtual world and cognitive information, in the application of AR, VR, or metaverse environment, to provide people's cognition of rapid information in the virtual environment.

The Relationship of Breathing and COVID-19 Anxiety When Using Smart Watches for Guided Respiration Practice: A Cross-Sectional Study

COVID-19 mortality rates are increasing worldwide, which has led to many highly restrictive precautionary measures and a strong sense of anxiety about the outbreak for many people around the world. There is thus an increasing concern about COVID-19 anxiety, resulting in recommending approaches for effective self-care. From a positive psychology perspective, it is also important for people to have positive affect when dealing with this pandemic. According to previous literature, respiration is considered to be an effective way to enhance people’s mental health. Among all the wearable devices, Apple Watch has the largest market share, so this study recruited Chinese users that use respiration exercise function on Apple Watch;a total of 316 valid data were retrieved. Meanwhile, to understand one approach related to using Apple Watch to practice respiration to reduce COVID-19 anxiety about being infected during the COVID-19 outbreak, this study used a web-based cross-sectional survey to examine anxiety about being infected by COVID-19 among Chinese people who had been using the Apple Watch to practice respiration during the period of the COVID-19 outbreak. The study was based on the Health Theoretical Model, and the model was developed with four dimensions and was validated with structural equation modeling. The results of this study showed that practicing few minutes had a positive relationship on positive attitude, and positive attitude had a negative relationship on pandemic anxiety and a positive relationship on continuance use intention. Anxiety about the pandemic had a negative relationship on the intention to continue using the function. This showed that respiration practice can help to suppress the increase in anxiety levels regarding this pandemic.

Research and Challenges of Reinforcement Learning in Cyber Defense Decision-Making for Intranet Security

In recent years, cyber attacks have shown diversified, purposeful, and organized characteristics, which pose significant challenges to cyber defense decision-making on internal networks. Due to the continuous confrontation between attackers and defenders, only using data-based statistical or supervised learning methods cannot cope with increasingly severe security threats. It is urgent to rethink network defense from the perspective of decision-making, and prepare for every possible situation. Reinforcement learning has made great breakthroughs in addressing complicated decision-making problems. We propose a framework that defines four modules based on the life cycle of threats: pentest, design, response, recovery. Our aims are to clarify the problem boundary of network defense decision-making problems, to study the problem characteristics in different contexts, to compare the strengths and weaknesses of existing research, and to identify promising challenges for future work. Our work provides a systematic view for understanding and solving decision-making problems in the application of reinforcement learning to cyber defense.

Evaluation on potential detriments from lockdown-related isolation to mental health among school-aged youth in central China (preprint)

Background: Home isolation is a generally effective strategy for coronavirus disease control during lockdown periods. This study is to determine the potential adverse consequences of home isolation to mental health among school-aged youth after lifting of major lockdown measures in central China. Methods: This cohort study assessed the mental health of school-aged children and adolescents enrolled in Wuhan city and nearby areas in Hubei province, China, from July 1 to August 31, 2020. Post-lockdown responses to anxiety, depression, sleep disturbances and post-traumatic stress symptoms were assessed in online questionnaire-based surveys. Participants’ scores for the Zung self-rated anxiety scale, the Patient Health Questionnaire-9, the self-rating scale of sleep and the post-traumatic stress disorder self-rating scale (PTSS) were analyzed. Results: Questionnaire responses of 730 school children were collected. Among the participants, 6.25% of them had scores above thresholds for PTSS, 5.81% had anxiety, and 48.84% had depression. All subjects reported that they experienced sleep disturbances. Subjects who had anxiety might have a high risk for developing depression [OR: 16.07, p =0.008, 95%CI (2.08-123.94)] and PTSS [OR: 12.97, p <0.001, 95%CI (5.41-31.11)]. Both depression [OR: 17.35, p =0.006, 95%CI (2.28-131.87)] and PTSS [OR: 14.18, p <0.001, 95%CI (6.00-33.47)] were risk factors for developing anxiety among participants. Interestingly, higher educational levels of primary caregivers were a risk factor for developing depression [OR: 1.62, p =0.005, 95%CI (1.16-2.28)] in the participants, but a protective factor against PTSS [OR: 0.47, p =0.048, 95%CI (0.23-0.99)].Conclusions: The local youth had less than expected degree of increases in their self-reported PTSS and anxiety, after exiting lockdown-related isolation. As a result of a combination of compensatory mechanisms including internet-based home-schooling and increased intra-familial interactions, home isolation did not affect the mental health of local school-aged youth to an extent as great as expected.Trial registration: The Registration number of this trial is ChiCTR2000033054.

Omicron-specific mRNA vaccine induced potent neutralizing antibody against Omicron but not other SARS-CoV-2 variants (preprint)

The emerging SARS-CoV-2 variants of concern (VOC) harbor mutations associated with increasing transmission and immune escape, hence undermine the effectiveness of current COVID-19 vaccines. In late November of 2021, the Omicron (B.1.1.529) variant was identified in South Africa and rapidly spread across the globe. It was shown to exhibit significant resistance to neutralization by serum not only from convalescent patients, but also from individuals recieving currently used COVID-19 vaccines with multiple booster shots. Therefore, there is an urgent need to develop next generation vaccines against VOCs like Omicron. In this study, we develop a panel of mRNA-LNP-based vaccines using the receptor binding domain (RBD) of Omicron and Delta variants, which are dominant in the current wave of COVID-19. In addition to the Omicron- and Delta-specific vaccines, the panel also includes a Hybrid vaccine that uses the RBD containing all 16 point-mutations shown in Omicron and Delta RBD, as well as a bivalent vaccine composed of both Omicron and Delta RBD-LNP in half dose. Interestingly, both Omicron-specific and Hybrid RBD-LNP elicited extremely high titer of neutralizing antibody against Omicron itself, but few to none neutralizing antibody against other SARS-CoV-2 variants. The bivalent RBD-LNP, on the other hand, generated antibody with broadly neutralizing activity against the wild-type virus and all variants. Surprisingly, similar cross-protection was also shown by the Delta-specifc RBD-LNP. Taken together, our data demonstrated that Omicron-specific mRNA vaccine can induce potent neutralizing antibody response against Omicron, but the inclusion of epitopes from other variants may be required for eliciting cross-protection. This study would lay a foundation for rational development of the next generation vaccines against SARS-CoV-2 VOCs.

Food for thought: Eating before saliva collection and interference with SARS-CoV-2 detection (preprint)

Background: Saliva is an optimal specimen for detection of viruses that cause upper respiratory infections including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to its cost-effectiveness and non-invasive collection. However, together with intrinsic enzymes and oral microbiota, children's unique dietary habits may introduce substances that interfere with diagnostic testing. Methods: To determine whether children's dietary choices impact SARS-CoV-2 detection in saliva, we performed a diagnostic study that simulates testing of real-life specimens provided from healthy children (n=5) who self-collected saliva at home before and at 0, 20, and 60 minutes after eating from 20 foods they selected. Each of seventy-two specimens was split into two volumes and spiked with SARS-CoV-2-negative or -positive standards prior to side-by-side testing by reverse-transcription polymerase chain reaction matrix-assisted laser desorption ionization time-of-flight (RT-PCR/MALDI-TOF) assay. Results: Detection of internal extraction control and SARS-CoV-2 nucleic acids was reduced in replicates of saliva collected at 0 minutes after eating 11 of 20 foods. Interference resolved at 20 and 60 minutes after eating all foods except hot dog in one participant. This represented a significant improvement in detection of nucleic acids compared to saliva collected at 0 minutes after eating (P=0.0005). Conclusions: We demonstrate successful detection of viral nucleic acids in saliva self-collected by children before and after eating a variety of foods. Fasting is not required before saliva collection for SARS-CoV-2 testing by RT-PCR/MALDI-TOF, but waiting 20 minutes after eating is sufficient for accurate testing. These findings should be considered for SARS-CoV-2 testing and broader viral diagnostics in saliva specimens.

RT-PCR/MALDI-TOF diagnostic target performance reflects circulating SARS-CoV-2 variant diversity in New York City (preprint)

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate, multiple variants of concern (VOC) have emerged. New variants pose challenges for diagnostic platforms since sequence diversity can alter primer/probe binding sites (PBS), causing false-negative results. The Agena MassARRAY(R) SARS-CoV-2 Panel utilizes reverse-transcription polymerase chain reaction and mass-spectrometry to detect five multiplex targets across N and ORF1ab genes. Herein, we utilize a dataset of 256 SARS-CoV-2-positive specimens collected between April 11, 2021-August 28, 2021 to evaluate target performance with paired sequencing data. During this timeframe, two targets in the N gene (N2, N3) were subject to the greatest sequence diversity. In specimens with N3 dropout, 69% harbored the Alpha-specific A28095U polymorphism that introduces a 3-mismatch to the N3 forward PBS and increases risk of target dropout relative to specimens with 28095A (relative risk (RR): 20.02; p<0.0001; 95% Confidence Interval (CI): 11.36-35.72). Furthermore, among specimens with N2 dropout, 90% harbored the Delta-specific G28916U polymorphism that creates a 3-mismatch to the N2 probe PBS and increases target dropout risk (RR: 11.92; p<0.0001; 95% CI: 8.17-14.06). These findings highlight the robust capability of Agena MassARRAY(R) SARS-CoV-2 Panel target results to reveal circulating virus diversity and underscore the power of multi-target design to capture VOC.