Epidemiology of hand, foot, and mouth disease and the genetic characteristics of Coxsackievirus A16 in Taiyuan, Shanxi, China from 2010 to 2021.

Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by human enteroviruses (EV). This study aimed to describe the epidemiological features of HFMD and the genetic characteristics of Coxsackievirus A16 (CVA16) in Taiyuan, Shanxi, China, from 2010 to 2021. Descriptive epidemiological methods were used to analyze the time and population distribution of HFMD and the genetic characteristics of CVA16. Except being affected by the COVID-19 epidemic in 2020, HFMD epidemics were sporadic from January to March each year, and began to increase in April, with a major epidemic peak from May to August, which declined in September, followed by a secondary peak from October to December. The prevalence of EV infection was the highest in children aged one to five years (84.42%), whereas its incidence was very low in children under one year of age (5.48%). Enterovirus nucleic acid was detected by real-time reverse transcription polymerase chain reaction in 6641 clinical specimens collected from patients with HFMD from 2010 to 2021, and 4236 EV-positive specimens were detected, including 988 enterovirus A71 (EV-A71), 1488 CVA16, and 1760 other enteroviruses. CVA16 remains prevalent and has co-circulated with other EVs in Taiyuan from 2010 to 2021. A phylogenetic tree constructed based on the VP1 region showed that all CVA16 strains belonged to two different clades of the B1 genotype, B1a and B1b. They showed a nucleotide similarity of 86.5-100%, and an amino acid similarity of 96.9-100%. Overall, these findings add to the global genetic resources of CVA16, demonstrate the epidemiological characteristics of HFMD as well as the genetic features of CVA16 in Taiyuan City during 2010-2021, and provide supporting evidence for the prevention and control of HFMD.

Environmental and Mobility Strategies During Early COVID-19: Insights From an Empirical Study Focusing on Park Visitations in El Paso, TX.

OBJECTIVES: We explored the importance of environmental and mobility strategies during early COVID-19 by age and ethnicity and investigated predictors of park visitations considering the COVID-19 impacts. BACKGROUND: Parks are safe and accessible venues to stay active and reduce social isolation, which is especially important considering COVID-19 and the associated lockdowns. METHODS: We analyzed online survey data from 683 residents (collected July 2020) of El Paso, TX, and objective measures of neighborhood park characteristics. Chi-square tests and mixed-effects logistic regression analyses were performed to examine the environmental/mobility strategies, personal and environmental factors, and park visitations, considering the COVID-19 impacts. RESULTS: The percentage of those who visited (1+ times/week) parks or trails/paths in the neighborhood dropped from 41.7% to 19.5% since the start of COVID-19 (OR = 0.015, p < .001). Before COVID-19, middle-aged and older adults were less likely to visit parks than younger adults, while this difference became insignificant during early COVID-19. Hispanic adults were more likely to visit parks than non-Hispanics both before and during early COVID-19. Positive environmental predictors of park visitations included park availability in the neighborhood, proximity to the closest park, seeing people being physically active in the neighborhood, and neighborhood aesthetics. CONCLUSIONS: Proximately located parks, trails, and paths well integrated into residential communities, and high aesthetic quality of the neighborhood are the potential features of pandemic-resilient communities and should be considered an important national priority to maintain and promote the health and well-being of the population, especially during pandemics like COVID-19.

COVID-19 and campus users: A longitudinal and place-based study of university mobilities in Texas.

The COVID-19 pandemic has disrupted people's daily routines, including travel behaviors, social interactions, and work-related activities. However, the potential impacts of COVID-19 on the use of campus locations in higher education such as libraries, food courts, sports facilities, and other destinations are still unknown. Focusing on three largest universities in Texas (Texas A&M university, the University of Texas at Austin, and Texas Tech University), this study compares changes in campus destination visitations between pre and post COVID-19 outbreak (2019 Fall and 2021 Fall semesters, respectively) using the mobility data from SafeGraph. It also examines the potential moderation effects of walkable distance (i.e. 1 km) and greenery (i.e. NDVI value). The results presented the significant effects of COVID-19 on decreasing visitations to various campus places. The visitation decreased more significantly for people living within 1 km (defined as a walkable distance) of campus and for the food, eating, and drinking places and the sports, recreation, and sightseeing places. This finding suggests that those living near campus (mostly students) decreased their reliance on campus destinations, especially for eating/drinking and recreation purposes. The level of greeneries at/around campus destinations did not moderate campus visitations after COVID-19. Policy implications on campus health and urban planning were discussed.

Implementing caregiver management measures in general hospitals to prevent the COVID-19 pandemic.

AIM: To summarize the whole process management measures for caregivers of inpatients in a non-new coronavirus pneumonia designated hospital in China during the novel coronavirus pneumonia epidemic. The implementation of these measures is mainly to prevent the virus pandemic caused by crowd gathering. DESIGN: A quasi-experimental study. METHODS: Novel coronavirus pneumonia prevention and control measures were implemented in the 'pre-hospital link, hospitalization link and discharge link' for the whole process of the hospitalized patients' caregivers. To evaluate the effects by time point inspection, the results were fed back using information technology for quality improvement. RESULTS: The results of three time point inspections indicated that the management quality of many projects improved continuously (p < 0.05). From January to June of 2021, 20 departments implemented a facial recognition information management system. The ratio of patients/caregivers admitted was 1:0.528~1:0.965; It was found that it is effective to implement the whole process management measures. The facial recognition system plays a key role in the comprehensive management of the caregivers.

Financial impact of cost of capital on tourism-based SMEs in COVID-19: implications for tourism disruption mitigation.

Opportunities for funding Tourism SMEs are emerging globally due to the expansion of tourism sector. However, it is still being determined how these financial arrangements will be controlled at more significant sizes equitably. In the contemporary period, E7 economy is deficient in producing the financial resources to ensure the availability of funds for the acquisition of funds for tourism-based SMEs. However, this research tested the empirical position of cost of debt in E-7 economies during COVID-19 crises. Study findings have shown significant outcomes between the constructs. The variation of conditions, structural uncertainty, transection systems, and variation in support by the financial institution for tourism-based SMEs are the main reasons that lessen borrowing and lending system of funds, from banks to SMEs. However, theorists must revisit the transaction system of debt financing for SMEs. Policymakers are suggested to develop viable and SME system-friendly policies to finance through debt capital from the banks in the time of structural imposed crises, like COVID-19.

A Synthetic SARS-CoV-2-Derived T-Cell and B-Cell Peptide Cocktail Elicits Full Protection against Lethal Omicron BA.1 Infection in H11-K18-hACE2 Mice.

Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developing the capacity for immune evasion and resistance to existing vaccines and drugs. To address this, development of vaccines against coronavirus disease 2019 (COVID-19) has focused on universality, strong T cell immunity, and rapid production. Synthetic peptide vaccines, which are inexpensive and quick to produce, show low toxicity, and can be selected from the conserved SARS-CoV-2 proteome, are promising candidates. In this study, we evaluated the effectiveness of a synthetic peptide cocktail containing three murine CD4+ T-cell epitopes from the SARS-CoV-2 nonspike proteome and one B-cell epitope from the Omicron BA.1 receptor-binding domain (RBD), along with aluminum phosphate (Al) adjuvant and 5' cytosine-phosphate-guanine 3' oligodeoxynucleotide (CpG-ODN) adjuvant in mice. The peptide cocktail induced good Th1-biased T-cell responses and effective neutralizing-antibody titers against the Omicron BA.1 variant. Additionally, H11-K18-hACE2 transgenic mice were fully protected against lethal challenge with the BA.1 strain, with a 100% survival rate and reduced pulmonary viral load and pathological lesions. Subcutaneous administration was found to be the superior route for synthetic peptide vaccine delivery. Our findings demonstrate the effectiveness of the peptide cocktail in mice, suggesting the feasibility of synthetic peptide vaccines for humans. IMPORTANCE Current vaccines based on production of neutralizing antibodies fail to prevent the infection and transmission of SARS-CoV-2 Omicron and its subvariants. Understanding the critical factors and avoiding the disadvantages of vaccine strategies are essential for developing a safe and effective COVID-19 vaccine, which would include a more effective and durable cellular response, minimal effects of viral mutations, rapid production against emerging variants, and good safety. Peptide-based vaccines are an excellent alternative because they are inexpensive, quick to produce, and very safe. In addition, human leukocyte antigen T-cell epitopes could be targeted at robust T-cell immunity and selected in the conserved region of the SARS-CoV-2 variants. Our study showed that a synthetic SARS-CoV-2-derived peptide cocktail induced full protection against lethal infection with Omicron BA.1 in H11-K18-hACE2 mice for the first time. This could have implications for the development of effective COVID-19 peptide vaccines for humans.

Emergence and antibody evasion of BQ, BA.2.75 and SARS-CoV-2 recombinant sub-lineages in the face of maturing antibody breadth at the population level.

BACKGROUND: The Omicron era of the COVID-19 pandemic commenced at the beginning of 2022 and whilst it started with primarily BA.1, it was latter dominated by BA.2 and the related sub-lineage BA.5. Following resolution of the global BA.5 wave, a diverse grouping of Omicron sub-lineages emerged derived from BA.2, BA.5 and recombinants thereof. Whilst emerging from distinct lineages, all shared similar changes in the Spike glycoprotein affording them an outgrowth advantage through evasion of neutralising antibodies. METHODS: Over the course of 2022, we monitored the potency and breadth of antibody neutralization responses to many emerging variants in the Australian community at three levels: (i) we tracked over 420,000 U.S. plasma donors over time through various vaccine booster roll outs and Omicron waves using sequentially collected IgG pools; (ii) we mapped the antibody response in individuals using blood from stringently curated vaccine and convalescent cohorts. (iii) finally we determine the in vitro efficacy of clinically approved therapies Evusheld and Sotrovimab. FINDINGS: In pooled IgG samples, we observed the maturation of neutralization breadth to Omicron variants over time through continuing vaccine and infection waves. Importantly, in many cases, we observed increased antibody breadth to variants that were yet to be in circulation. Determination of viral neutralization at the cohort level supported equivalent coverage across prior and emerging variants with isolates BQ.1.1, XBB.1, BR.2.1 and XBF the most evasive. Further, these emerging variants were resistant to Evusheld, whilst increasing neutralization resistance to Sotrovimab was restricted to BQ.1.1 and XBF. We conclude at this current point in time that dominant variants can evade antibodies at levels equivalent to their most evasive lineage counterparts but sustain an entry phenotype that continues to promote an additional outgrowth advantage. In Australia, BR.2.1 and XBF share this phenotype and, in contrast to global variants, are uniquely dominant in this region in the later months of 2022. INTERPRETATION: Whilst the appearance of a diverse range of omicron lineages has led to primary or partial resistance to clinically approved monoclonal antibodies, the maturation of the antibody response across both cohorts and a large donor pools importantly observes increasing breadth in the antibody neutralisation responses over time with a trajectory that covers both current and known emerging variants. FUNDING: This work was primarily supported by Australian Medical Foundation research grants MRF2005760 (SGT, GM & WDR), Medical Research Future Fund Antiviral Development Call grant (WDR), the New South Wales Health COVID-19 Research Grants Round 2 (SGT & FB) and the NSW Vaccine Infection and Immunology Collaborative (VIIM) (ALC). Variant modeling was supported by funding from SciLifeLab's Pandemic Laboratory Preparedness program to B.M. (VC-2022-0028) and by the European Union's Horizon 2020 research and innovation programme under grant agreement no. 101003653 (CoroNAb) to B.M.

A Beta Strain-Based Spike Glycoprotein Vaccine Candidate Induces Broad Neutralization and Protection against SARS-CoV-2 Variants of Concern.

The coronavirus disease 2019 (COVID-19) pandemic is still ongoing. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) are circulating worldwide, making it resistant to existing vaccines and antiviral drugs. Therefore, the evaluation of variant-based expanded spectrum vaccines to optimize the immune response and provide broad protectiveness is very important. In this study, we expressed spike trimer protein (S-TM) based on the Beta variant in a GMP-grade workshop using CHO cells. Mice were immunized twice with S-TM protein combined with aluminum hydroxide (Al) and CpG Oligonucleotides (CpG) adjuvant to evaluate its safety and efficacy. BALB/c immunized with S-TM + Al + CpG induced high neutralizing antibody titers against the Wuhan-Hu-1 strain (wild-type, WT), the Beta and Delta variants, and even the Omicron variant. In addition, compared with the S-TM + Al group, the S-TM + Al + CpG group effectively induced a stronger Th1-biased cell immune response in mice. Furthermore, after the second immunization, H11-K18 hACE2 mice were well protected from challenge with the SARS-CoV-2 Beta strain, with a 100% survival rate. The virus load and pathological lesions in the lungs were significantly reduced, and no virus was detected in mouse brain tissue. Our vaccine candidate is practical and effective for current SARS-CoV-2 VOCs, which will support its further clinical development for potential sequential immune and primary immunization. IMPORTANCE Continuous emergence of adaptive mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the use and development of existing vaccines and drugs. The value of variant-based vaccines that are capable of inducing a higher and broader protection immune response against SARS-CoV-2 variants is currently being evaluated. This article shows that a recombinant prefusion spike protein based on a Beta variant was highly immunogenic and could induced a stronger Th1-biased cell immune response in mice and was effectively protective against challenge with the SARS-CoV-2 Beta variant. Importantly, this Beta-based SARS-CoV-2 vaccine could also offer a robust humoral immune response with effectively broad neutralization ability against the wild type and different variants of concern (VOCs): the Beta, Delta, and Omicron BA.1 variants. To date, the vaccine described here has been produced in a pilot scale (200L), and the development, filling process, and toxicological safety evaluation have also been completed, which provides a timely response to the emerging SARS-CoV-2 variants and vaccine development.

Lead change of a HIF-2α antagonist guided by multiparameter optimization and utilization of an Olp → π*Ar interaction (preprint)

Pharmacokinetic properties of our first-generation HIF-2α antagonist PT2385, including modest solubility, resulted in a high recommended phase 2 dose (RP2D) of 800 mg BID and motivated the pursuit of novel scaffolds which could improve solubility and formulation parameters with the goal of improved pharmacokinetics. Herein we disclose our successful efforts to identify such HIF-2α antagonists through an optimization strategy characterized by: (1) increasing the fraction of sp3 hybridized carbons (Fsp3), (2) replacing the aromatic portion of the indane core with pyridine heterocycles, and (3) improving a putative Olp → π*Ar interaction, an underutilized electrostatic contact in medicinal chemistry. These efforts emphasize the importance of employing multiple strategies in parameter optimization. In isolation, modifications to areas (1) and (2) improved solubility, but with the compromise of reduced potency. In area (3), understanding the importance of an Olp → π*Ar interaction, as documented through a wealth of crystal structures and retrospective calculations, proved essential in guiding SAR and identifying the trifluoromethyl group as a suitable replacement of the sulfone. Only by combining these three strategies could inhibitors with substantially improved solubility and comparable potency be discovered. Finally, the overall improvement in pharmacokinetic properties of the newly identified inhibitors is highlighted through a battery of ADME and in vivo data, including use of pharmacodynamic biomarkers indicative of HIF-2α antagonism.

Engineered LwaCas13a with enhanced collateral activity for nucleic acid detection.

Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 13 (Cas13) has been rapidly developed for nucleic-acid-based diagnostics by using its characteristic collateral activity. Despite the recent progress in optimizing the Cas13 system for the detection of nucleic acids, engineering Cas13 protein with enhanced collateral activity has been challenging, mostly because of its complex structural dynamics. Here we successfully employed a novel strategy to engineer the Leptotrichia wadei (Lwa)Cas13a by inserting different RNA-binding domains into a unique active-site-proximal loop within its higher eukaryotes and prokaryotes nucleotide-binding domain. Two LwaCas13a variants showed enhanced collateral activity and improved sensitivity over the wild type in various buffer conditions. By combining with an electrochemical method, our variants detected the SARS-CoV-2 genome at attomolar concentrations from both inactive viral and unextracted clinical samples, without target preamplification. Our engineered LwaCas13a enzymes with enhanced collateral activity are ready to be integrated into other Cas13a-based platforms for ultrasensitive detection of nucleic acids.

Epidemiology of hand, foot, and mouth disease and the genetic characteristics of Coxsackievirus A16 in Taiyuan, Shanxi, China from 2010 to 2021

Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by human enteroviruses (EV). This study aimed to describe the epidemiological features of HFMD and the genetic characteristics of Coxsackievirus A16 (CVA16) in Taiyuan, Shanxi, China, from 2010 to 2021. Descriptive epidemiological methods were used to analyze the time and population distribution of HFMD and the genetic characteristics of CVA16. Except being affected by the COVID-19 epidemic in 2020, HFMD epidemics were sporadic from January to March each year, and began to increase in April, with a major epidemic peak from May to August, which declined in September, followed by a secondary peak from October to December. The prevalence of EV infection was the highest in children aged one to five years (84.42%), whereas its incidence was very low in children under one year of age (5.48%). Enterovirus nucleic acid was detected by real-time reverse transcription polymerase chain reaction in 6641 clinical specimens collected from patients with HFMD from 2010 to 2021, and 4236 EV-positive specimens were detected, including 988 enterovirus A71 (EV-A71), 1488 CVA16, and 1760 other enteroviruses. CVA16 remains prevalent and has co-circulated with other EVs in Taiyuan from 2010 to 2021. A phylogenetic tree constructed based on the VP1 region showed that all CVA16 strains belonged to two different clades of the B1 genotype, B1a and B1b. They showed a nucleotide similarity of 86.5–100%, and an amino acid similarity of 96.9–100%. Overall, these findings add to the global genetic resources of CVA16, demonstrate the epidemiological characteristics of HFMD as well as the genetic features of CVA16 in Taiyuan City during 2010–2021, and provide supporting evidence for the prevention and control of HFMD.

Highly diverse ribonucleic acid viruses in the viromes of eukaryotic host species in Yunnan province, China.

Background: The diversity in currently documented viruses and their morphological characteristics indicates the need for understanding the evolutionary characteristics of viruses. Notably, further studies are needed to obtain a comprehensive landscape of virome, the virome of host species in Yunnan province, China. Materials and methods: We implemented the metagenomic next-generation sequencing strategy to investigate the viral diversity, which involved in 465 specimens collected from bats, pangolins, monkeys, and other species. The diverse RNA viruses were analyzed, especially focusing on the genome organization, genetic divergence and phylogenetic relationships. Results: In this study, we investigated the viral composition of eight libraries from bats, pangolins, monkeys, and other species, and found several diverse RNA viruses, including the Alphacoronavirus from bat specimens. By characterizing the genome organization, genetic divergence, and phylogenetic relationships, we identified five Alphacoronavirus strains, which shared phylogenetic association with Bat-CoV-HKU8-related strains. The pestivirus-like virus related to recently identified Dongyang pangolin virus (DYPV) strains from dead pangolin specimens, suggesting that these viruses are evolving. Some genomes showed higher divergence from known species (e.g., calicivirus CS9-Cali-YN-CHN-2020), and many showed evidence of recombination events with unknown or known strains (e.g., mamastroviruses BF2-astro-YN-CHN-2020 and EV-A122 AKM5-YN-CHN-2020). The newly identified viruses showed extensive changes and could be assigned as new species, or even genus (e.g., calicivirus CS9-Cali-YN-CHN-2020 and iflavirus Ifla-YN-CHN-2020). Moreover, we identified several highly divergent RNA viruses and estimated their evolutionary characteristics among different hosts, providing data for further examination of their evolutionary dynamics. Conclusion: Overall, our study emphasizes the close association between emerging viruses and infectious diseases, and the need for more comprehensive surveys.

Cardiac Rehabilitation and the COVID-19 Pandemic: Persistent Declines in CR Participation and Access Among US Medicare Beneficiaries.

Background: The impact of the COVID-19 pandemic on participation in and availability of cardiac rehabilitation (CR) is unknown. Methods: Among eligible Medicare fee-for-service beneficiaries, we evaluated, by month, the number of CR sessions attended per 100,000 beneficiaries, individuals eligible to initiate CR, and centers offering in-person CR between January 2019 and December 2021. We compared these outcomes between two periods: December 1, 2019 through February 28, 2020 (period 1, prior to declaration of the pandemic-related national emergency) and October 1, 2021 through December 31, 2021 (period 2, the latest period for which data are currently available). Results: In period 1, Medicare beneficiaries participated in (mean ± SD) 895 ± 84 CR sessions per 100,000 beneficiaries each month. After the national emergency was declared, CR participation sharply declined to 56 CR sessions per 100,000 beneficiaries in April 2020. CR participation recovered gradually through December 2021, but remained lower than pre-pandemic levels (Period 2: 698 ± 29 CR sessions per month per 100,000 beneficiaries, p=.02). Declines in CR participation were most marked among dual Medicare and Medicaid enrollees, and patients residing in rural areas or socially vulnerable communities. There was no statistically significant change in CR eligibility between the two periods. Compared with 2,618 ± 5 CR centers in period 1, there were 2,464 ± 7 in period 2 (p<0.01). Compared with CR centers that survived the pandemic, 220 CR centers that closed were more likely to be affiliated with public hospitals, located in rural areas, and serve the most socially vulnerable communities. Conclusions: The COVID-19 pandemic was associated with a persistent decline in CR participation and the closure of CR centers, which disproportionately affected rural and low-income patients and the most socially vulnerable communities. Innovation in CR financing and delivery is urgently needed to equitably enhance CR participation among Medicare beneficiaries.

A local COVID - 19 outbreak in Dalian caused by imported cold - chain products contaminated by SARS-CoV-2

On December 15, 2020, four dock workers tested positive for severe acute respiratory syndrome-coronavirus 2 (SARS-COV-2) nucleic acids and were reported by Dalian. Up until then, Dalian City had not reported local cases for 136 consecutive days. In this coronavirus disease 2019 (COVID-19) outbreak (referred to as the "Dalian COVID-19 outbreak"), samples from all infected persons (83) and part from the ship cargoes in contact With them during December 15, 2020 to January 8, 2021 were collected. Confirmed cases accounted for 61.45% (51/83) and asymptomatic infections accounted for 38.55% (32/83). Through high-throughput sequencing, 76 SARS-CoV-2 whole-genome sequences were obtained, of which 72 (86.75%) were from clinical samples, and 4 from cold-chain food packaging surface samples on cargo ship A of country R. Refer to Wuhan reference strain (NC_045512), genome analysis revealed 12-16 nucleotide mutations in 76 whole genomes sharing 12 nucleotide mutations and belong to the SARS-CoV-2 branch of B.1.1. Viral genomics and field epidemiological investigations showed that the Dalian COVID-19 outbreak was a local epidemic caused by dock workers infected with imported cold - chain products contaminated with SARS - CoV - 2. During transmission, 3 Virus generations and three relatively independent transmission chains were formed.

Research on Ecological Landscape Design and Healing Effect Based on 3D Roaming Technology.

Impacted by the COVID-19 epidemic, the human sub-health in national high-tech zones (hereinafter referred to as high-tech zones) has become more prominent. It is critical for the mental sub-health group in the high-tech zone to relieve the anxiety and tension caused by the pressure of life and work. This paper uses SketchUp virtual engine (Unity 2019) software, and 3D roaming technology to carry out the ecological landscape transformation design of the Baotzixi ecological corridor in the East Lake High-tech Zone, to construct a 3D roaming landscape scene and measure its therapeutic effect by inviting subjects to participate in an interactive experience experiment on the ErgoLAB platform. The results illustrate that: (1) the thermogram trend shows that the more attractive the 3D roaming landscape scene is, the stronger the subjects' interest is; (2) the participants have a positive emotional arousal state in the immersive experience of the 3D roaming landscape scene after the modification design; and (3) the mean skin conductance (SC) fluctuation variance of the subjects is 5.819%, indicating that the healing effect is significant in the state of positive emotional arousal. The research results show that there is a connection between the subjects and the 3D roaming landscape scene after the transformation design of "high interest, emotional arousal and significant healing".

Guidelines for the prevention and management of children and adolescents with COVID-19.

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. CONCLUSION: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged. WHAT IS KNOWN: • Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence. WHAT IS NEW: • The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.

COVID-19 impacts on non-work travel patterns: A place-based investigation using smartphone mobility data

The COVID-19 pandemic has brought unprecedented changes to our mobility. It has not only changed our work-related travel patterns but also impacted leisure and other utilitarian activities. Non–work-related trips tend to be more seriously affected by the neighborhood/contextual factors such as socioeconomic status (SES), and destination accessibility, and COVID-19 impact on non-work trips may not be equal across different neighborhood SES. This study compares non–work-related travel patterns between the pre- and during COVID-19 pandemic in the City of El Paso, Texas. By utilizing smartphone mobility data, we captured the visitation data for major non-work destinations such as restaurants, supermarkets, drinking places, religious organizations, and parks. We used Census block groups (n = 424) within the city and divided them into low- and high-income neighborhoods based on the citywide median. Overall, the total frequency of visitations and the distances traveled to visit these non-work destinations were influenced by the COVID-19 pandemic. However, significant variations existed in their visitation patterns by the type of non-work destinations. While the overall COVID-19 effects on non-work activities were evident, its effects on the travel patterns to each destination were not equal by neighborhood SES. We also found that COVID-19 had differently influenced non-work activities between high- and low-income block groups. Our findings suggest that the COVID-19 pandemic may exacerbate neighborhood-level inequalities in non-work trips. Thus, safe and affordable transportation options together with compact and walkable community development appear imperative to support daily travel needs for various utilitarian and leisure purposes, especially in low-income neighborhoods.

Back Cover: Amplification‐Free Detection of SARS‐CoV‐2 and Respiratory Syncytial Virus Using CRISPR Cas13a and Graphene Field‐Effect Transistors (Angew. Chem. Int. Ed. 32/2022)

Nucleic acid detection plays a critical role in medical diagnostics, environmental monitoring, and food safety. In their Research Article (e202203826), Xue Gao, Yi Zhang and co‐workers developed a new biosensor for amplification‐free nucleic acid detection via harnessing the trans‐cleavage mechanism of Cas13a and ultrasensitive graphene field‐effect transistors (gFETs). The illustration shows the Cas13a‐mediated RNA trans‐cleavage on a gFET surface for sensor signal transduction.

Risk assessment of public health emergencies concerned in the mainland of China, June 2021

Objective: To assess the risk of public health emergencies, both the indigenous ones and the imported ones, which might occur in the mainland of China in June 2021. Methods: An internet based expert counsel was conducted to analyze the surveillance data of public health emergencies and priority communicable diseases in China reported through different channels, and the experts in all provincial centers for disease control and prevention attended this video conference. Results: Generally speaking, it is predicted that the incidence of public health emergencies would be similar in June with May. The risk of imported cases and secondary infections of COVID-19 would continue to exist, but would be controllable. It is the high incidence season of severe fever with thrombocytopenia syndrome and most cases would be sporadic, however, the risk of cluster exits especially in previous epidemic areas. The incidences of food poisoning caused by toxic animal or plant or poisonous mushroom would increase significantly, and the incidences of food poisoning caused by microbe would be high. The earthquake-stricken areas such as Yunnan and Qinghai should further strengthen post-disaster public health responses. The potential flood-stricken areas predicted by the meteorological department need to pay attention to the risks of water-borne, food-borne and vector-borne diseases that may increase after the disaster. Conclusion: Special attention should be paid to COVID-19, and general attention should be paid to severe fever with thrombocytopenia syndrome, food poisoning and natural disaster.

Diagnostic accuracy of CRISPR technology for detecting SARS-CoV-2: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of CRISPR-Cas technology for SARS-CoV-2. METHODS: RT-qPCR is defined as the reference standard. Data was collected and assessed by Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. A bivariate model for pooling was employed and subgroups analysis was used to explore heterogeneity. RESULTS: 2264 samples from 28 articles were extracted for evaluating the accuracy of CRISPR technology for diagnosing SARS-CoV-2. The pooled sensitivity and specificity of CRISPR technology were 0.98 (95% CI: 0.95-0.99) and 1.0 (95% CI: 0.98-1.00), respectively. High risks in patient selection bias and unclear risk of index test bias may affect accuracy. Subgroup analysis showed that CRISPR-Cas12 is applicable for molecular diagnostics for its active editing characteristics. RT-LAMP and RT-RPA are usually used for pre-amplification and fluorescence detection to output results quantitatively. Nasopharyngeal swabs and dual-genes perform greatly in our study. CONCLUSION: The results concluded from all studies showed that CRISPR technology is a promising molecular method for detecting SARS-CoV-2. Standard methods including comparable sample material, patient selection, operating procedure and operators should be established.