LAPIS is a fast web API for massive open virus sequencing data.

BACKGROUND: Recent epidemic outbreaks such as the SARS-CoV-2 pandemic and the mpox outbreak in 2022 have demonstrated the value of genomic sequencing data for tracking the origin and spread of pathogens. Laboratories around the globe generated new sequences at unprecedented speed and volume and bioinformaticians developed new tools and dashboards to analyze this wealth of data. However, a major challenge that remains is the lack of simple and efficient approaches for accessing and processing sequencing data. RESULTS: The Lightweight API for Sequences (LAPIS) facilitates rapid retrieval and analysis of genomic sequencing data through a REST API. It supports complex mutation- and metadata-based queries and can perform aggregation operations on massive datasets. LAPIS is optimized for typical questions relevant to genomic epidemiology. Using a newly-developed in-memory database engine, it has a high speed and throughput: between 25 January and 4 February 2023, the SARS-CoV-2 instance of LAPIS, which contains 14.5 million sequences, processed over 20 million requests with a mean response time of 411 ms and a median response time of 1 ms. LAPIS is the core engine behind our dashboards on genspectrum.org and we currently maintain public LAPIS instances for SARS-CoV-2 and mpox. CONCLUSIONS: Powered by an optimized database engine and available through a web API, LAPIS enhances the accessibility of genomic sequencing data. It is designed to serve as a common backend for dashboards and analyses with the potential to be integrated into common database platforms such as GenBank.

The effects of lipoic acid on respiratory diseases

Respiratory diseases, including lung cancer, pulmonary fibrosis, asthma, and the recently emerging fatal coronavirus disease-19 (COVID-19), are the leading causes of illness and death worldwide. The increasing incidence and mortality rates have attracted much attention to the prevention and treatment of these conditions. Lipoic acid (LA), a naturally occurring organosulfur compound, is not only essential for mitochondrial aerobic metabolism but also shows therapeutic potential via certain pharmacological effects (e.g., antioxidative and anti-inflammatory effects). In recent years, accumulating evidence (animal experiments and in vitro studies) has suggested a role of LA in ameliorating many respiratory diseases (e.g., lung cancer, fibrosis, asthma, acute lung injury and smoking-induced lung injury). Therefore, this review will provide an overview of the present investigational evidence on the therapeutic effect of LA against respiratory diseases in vitro and in vivo. We also summarize the corresponding mechanisms of action to inspire further basic studies and clinical trials to confirm the health benefits of LA in the context of respiratory diseases.

CoV-Spectrum: Analysis of Globally Shared SARS-CoV-2 Data to Identify and Characterize New Variants.

SUMMARY: The CoV-Spectrum website supports the identification of new SARS-CoV-2 variants of concern and the tracking of known variants. Its flexible amino acid and nucleotide mutation search allows querying of variants before they are designated by a lineage nomenclature system. The platform brings together SARS-CoV-2 data from different sources and applies analyses. Results include the proportion of different variants over time, their demographic and geographic distributions, common mutations, hospitalization and mortality probabilities, estimates for transmission fitness advantage and insights obtained from wastewater samples. AVAILABILITY AND IMPLEMENTATION: CoV-Spectrum is available at https://cov-spectrum.ethz.ch. The code is released under the GPL-3.0 license at https://github.com/cevo-public/cov-spectrum-website.

Swiss public health measures associated with reduced SARS-CoV-2 transmission using genome data.

Genome sequences from evolving infectious pathogens allow quantification of case introductions and local transmission dynamics. We sequenced 11,357 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Switzerland in 2020 - the sixth largest effort globally. Using a representative subset of these data, we estimated viral introductions to Switzerland and their persistence over the course of 2020. We contrasted these estimates with simple null models representing the absence of certain public health measures. We show that Switzerland's border closures de-coupled case introductions from incidence in neighboring countries. Under a simple model, we estimate an 86-98% reduction in introductions during Switzerland's strictest border closures. Furthermore, the Swiss 2020 partial lockdown roughly halved the time for sampled introductions to die out. Last, we quantified local transmission dynamics once introductions into Switzerland occurred, using a phylodynamic model. We found that transmission slowed 35-63% upon outbreak detection in summer 2020, but not in fall. This finding may indicate successful contact tracing over summer before overburdening in fall. The study highlights the added value of genome sequencing data for understanding transmission dynamics.

Early detection and surveillance of SARS-CoV-2 genomic variants in wastewater using COJAC.

The continuing emergence of SARS-CoV-2 variants of concern and variants of interest emphasizes the need for early detection and epidemiological surveillance of novel variants. We used genomic sequencing of 122 wastewater samples from three locations in Switzerland to monitor the local spread of B.1.1.7 (Alpha), B.1.351 (Beta) and P.1 (Gamma) variants of SARS-CoV-2 at a population level. We devised a bioinformatics method named COJAC (Co-Occurrence adJusted Analysis and Calling) that uses read pairs carrying multiple variant-specific signature mutations as a robust indicator of low-frequency variants. Application of COJAC revealed that a local outbreak of the Alpha variant in two Swiss cities was observable in wastewater up to 13 d before being first reported in clinical samples. We further confirmed the ability of COJAC to detect emerging variants early for the Delta variant by analysing an additional 1,339 wastewater samples. While sequencing data of single wastewater samples provide limited precision for the quantification of relative prevalence of a variant, we show that replicate and close-meshed longitudinal sequencing allow for robust estimation not only of the local prevalence but also of the transmission fitness advantage of any variant. We conclude that genomic sequencing and our computational analysis can provide population-level estimates of prevalence and fitness of emerging variants from wastewater samples earlier and on the basis of substantially fewer samples than from clinical samples. Our framework is being routinely used in large national projects in Switzerland and the UK.

Advancing genomic epidemiology by addressing the bioinformatics bottleneck: Challenges, design principles, and a Swiss example.

The SARS-CoV-2 pandemic led to a huge increase in global pathogen genome sequencing efforts, and the resulting data are becoming increasingly important to detect variants of concern, monitor outbreaks, and quantify transmission dynamics. However, this rapid up-scaling in data generation brought with it many IT infrastructure challenges. In this paper, we report about developing an improved system for genomic epidemiology. We (i) highlight key challenges that were exacerbated by the pandemic situation, (ii) provide data infrastructure design principles to address them, and (iii) give an implementation example developed by the Swiss SARS-CoV-2 Sequencing Consortium (S3C) in response to the COVID-19 pandemic. Finally, we discuss remaining challenges to data infrastructure for genomic epidemiology. Improving these infrastructures will help better detect, monitor, and respond to future public health threats.

Effect of remote mindfulness-based interventions on symptoms of anxiety and depression in patients with chronic obstructive pulmonary disease: a protocol for systematic review and meta-analysis.

BACKGROUND: The incidence of chronic obstructive pulmonary disease (COPD) is high worldwide, and patients with COPD commonly suffer from mood disorders, such as symptoms of anxiety and depression. However, it is difficult to communicate with patients face to face to solve these psychological problems in the case of the fluctuations in symptoms of COPD and COVID-19 prevalence, which may lead to the fact that patients with COPD are more likely to suffer exacerbations, frequent readmissions and worse survival. Mindfulness-based interventions are a stress-reducing therapy with mindfulness at its core. Remote mindfulness-based interventions combine the advantages of high availability, accessibility, low cost and anonymity and can solve the barriers to access that many patients face when attending face-to-face programmes. Therefore, remote mindfulness-based interventions may be an effective way to improve the mental health of patients with COPD. METHODS AND ANALYSIS: We will search PubMed, Embase, Cochrane Library, CNKI, PsycNET, MEDLINE, Psychology & Behavioral Sciences Collection and Web of Science to select eligible studies that were published. The eligible studies will be screened, extracted and then the methodological quality will be evaluated independently by two reviewers. Review manager software V.5.3 software and Stata V.14.0 software will be used for meta-analysis. ETHICS AND DISSEMINATION: Ethical approval is not required for a systematic review protocol. Findings of the proposed systematic review will be disseminated through conference presentations and publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021265286.

Quantification of the spread of SARS-CoV-2 variant B.1.1.7 in Switzerland.

BACKGROUND: In December 2020, the United Kingdom (UK) reported a SARS-CoV-2 Variant of Concern (VoC) which is now named B.1.1.7. Based on initial data from the UK and later data from other countries, this variant was estimated to have a transmission fitness advantage of around 40-80 % (Volz et al., 2021; Leung et al., 2021; Davies et al., 2021). AIM: This study aims to estimate the transmission fitness advantage and the effective reproductive number of B.1.1.7 through time based on data from Switzerland. METHODS: We generated whole genome sequences from 11.8 % of all confirmed SARS-CoV-2 cases in Switzerland between 14 December 2020 and 11 March 2021. Based on these data, we determine the daily frequency of the B.1.1.7 variant and quantify the variant's transmission fitness advantage on a national and a regional scale. RESULTS: We estimate B.1.1.7 had a transmission fitness advantage of 43-52 % compared to the other variants circulating in Switzerland during the study period. Further, we estimate B.1.1.7 had a reproductive number above 1 from 01 January 2021 until the end of the study period, compared to below 1 for the other variants. Specifically, we estimate the reproductive number for B.1.1.7 was 1.24 [1.07-1.41] from 01 January until 17 January 2021 and 1.18 [1.06-1.30] from 18 January until 01 March 2021 based on the whole genome sequencing data. From 10 March to 16 March 2021, once B.1.1.7 was dominant, we estimate the reproductive number was 1.14 [1.00-1.26] based on all confirmed cases. For reference, Switzerland applied more non-pharmaceutical interventions to combat SARS-CoV-2 on 18 January 2021 and lifted some measures again on 01 March 2021. CONCLUSION: The observed increase in B.1.1.7 frequency in Switzerland during the study period is as expected based on observations in the UK. In absolute numbers, B.1.1.7 increased exponentially with an estimated doubling time of around 2-3.5 weeks. To monitor the ongoing spread of B.1.1.7, our plots are available online.

Willingness and influential factors of parents of 3-6-year-old children to vaccinate their children with the COVID-19 vaccine in China.

The impact of Coronavirus disease 2019 (COVID-19) on children aged 3-6 can be severe. Vaccination for COVID-19 is one of the most important primary preventative measures to reduce disease transmission. Parents are hesitant to vaccinate their children against COVID-19 because it was reported in the news that some adults have had adverse reactions to the vaccine. This study aims to investigate the willingness of Chinese parents of 3-6 year old children to vaccinate them with the COVID-19 vaccine and identify what factors influence their decisions. A survey was conducted using a two-stage stratified random sampling method from December 2020 to February 2021. We used univariate analysis and multivariate binary logistic analysis to explore potential factors that may determine the acceptance of the COVID-19 vaccine. Of the 468 parents who participated, 86.75% were willing to vaccinate their children with the COVID-19 vaccine. Parents who were female (OR = 2.591; 95% CI: 0.432-4.689), recognized their children in the high-risk category (OR = 2.494; 95% CI:1.244-5.002), often followed-up with COVID-19 vaccine-related information (OR = 9.065; 95% CI: 3.220-28.654), believed in the safety of the COVID-19 vaccine (OR = 3.068; 95% CI: 1.313-7.168), or thought the COVID-19 vaccine could prevent COVID-19 (OR = 13.750; 95% CI: 2.516-75.140) were more willing to vaccinate their children. To ease parents' hesitation about vaccines, the authority organization should release updated information on the safety and reliability of vaccines, target gender-specific health education for parents, and ask the media to report scientifically support information.

The effect of remote peer support on stigma in patients after breast cancer surgery during the COVID-19 pandemic: A protocol for systematic review and meta-analysis.

BACKGROUND: Patients after breast cancer surgery have a high sense of stigma due to the formation of surgical scars, loss of breast shape or other reasons, leading to anxiety, depression, and other adverse mental health problems, thus reducing their quality of life. Remote peer support intervention based on telephone, internet or email is low-cost and easy to spread, and protects patients' privacy, solves the barriers to access that many patients face when attending face-to-face programs. Therefore, remote peer support may be an effective way to reduce stigma and improve mental health in patients after breast cancer surgery during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Eight databases (PubMed, Embase, Cochrane Library, CNKI, PsycNET, MEDLINE, Psychology & Behavioral Sciences Collection and Web of Science) will be used to select eligible studies that were published from inception to May, 2021. The eligible studies will be screened, extracted and then the methodological quality will be evaluated independently by 2 reviewers. Review manager software version 5.3 software and Stata version 14.0 software will be used for meta-analysis. RESULTS: The results of this study will show the effect of remote peer support on stigma, depression and anxiety in patients after breast cancer surgery during the COVID-19 pandemic and will be submitted to a peer-reviewed journal for publication. CONCLUSION: The results of this study will provide evidence for the effectiveness of remote peer support in patients after breast cancer surgery during the COVID-19 pandemic. PROSPERO REGISTRATION NUMBER: CRD42021255971.

SARS-CoV-2 N501Y Introductions and Transmissions in Switzerland from Beginning of October 2020 to February 2021-Implementation of Swiss-Wide Diagnostic Screening and Whole Genome Sequencing.

The rapid spread of the SARS-CoV-2 lineages B.1.1.7 (N501Y.V1) throughout the UK, B.1.351 (N501Y.V2) in South Africa, and P.1 (B.1.1.28.1; N501Y.V3) in Brazil has led to the definition of variants of concern (VoCs) and recommendations for lineage specific surveillance. In Switzerland, during the last weeks of December 2020, we established a nationwide screening protocol across multiple laboratories, focusing first on epidemiological and microbiological definitions. In January 2021, we validated and implemented an N501Y-specific PCR to rapidly screen for VoCs, which are then confirmed using amplicon sequencing or whole genome sequencing (WGS). A total of 13,387 VoCs have been identified since the detection of the first Swiss case in October 2020, with 4194 being B.1.1.7, 172 B.1.351, and 7 P.1. The remaining 9014 cases of VoCs have been described without further lineage specification. Overall, all diagnostic centers reported a rapid increase of the percentage of detected VOCs, with a range of 6 to 46% between 25 to 31 of January 2021 increasing towards 41 to 82% between 22 to 28 of February. A total of 739 N501Y positive genomes were analysed and show a broad range of introduction events to Switzerland. In this paper, we describe the nationwide coordination and implementation process across laboratories, public health institutions, and researchers, the first results of our N501Y-specific variant screening, and the phylogenetic analysis of all available WGS data in Switzerland, that together identified the early introduction events and subsequent community spreading of the VoCs.