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tANCHOR cell-based ELISA approach as a surrogate for antigen-coated plates to monitor specific IgG directed to the SARS-CoV-2 receptor-binding domain
Get PDFEnzyme-linked immunosorbent assay (ELISA) systems use plates coated with peptides or expressed and purified proteins to monitor immunoglobulins derived from patient serum. However, there is currently no easy, flexible, and fast adaptive ELISA-based system for testing antibodies directed against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. In this study, we utilized the tANCHOR protein display system that provides a cell surface decorated with the receptor-binding domain (RBD) to monitor specific antibodies derived from SARS-CoV-2 convalescent and vaccinated individuals directed against it. To test sera from vaccinees or convalescent individuals, only the RBD coding sequence needs to be cloned in the tANCHOR vector system and transfected into HeLa cells. Time-consuming protein expression, isolation, and purification followed by coating assay plates are not necessary. With this technique, the immune evasion of new SARS-CoV-2 variants from current vaccination regimes can be examined quickly and reliably.Peer Reviewe
Guidelines for managing and using the digital phenotypes of pluripotent stem cell lines
Get PDFEach pluripotent stem cell line has a physical entity as well as a digital phenotype, but linking the two unambiguously is confounded by poor naming practices and assumed knowledge. Registration gives each line a unique and persistent identifier that links to phenotypic data generated over the lifetime of that line. Registration is a key recommendation of the 2023 ISSCR Standards for the use of human stem cells in research. Here we consider how community adoption of stem cell line registration could facilitate the establishment of integrated digital phenotypes of specific human pluripotent stem cell (hPSC) lines.Peer Reviewe
Electron microscopy images and morphometric data of SARS-CoV-2 variants in ultrathin plastic sections
Get PDFConventional thin section electron microscopy of viral pathogens, such as the pandemic SARS-CoV-2, can provide structural information on the virus particle phenotype and its evolution. We recorded about 900 transmission electron microscopy images of different SARS-CoV-2 variants, including Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron BA.2 (B.1.1.529) and determined various morphometric parameters, such as maximal diameter and spike number, using a previously published measurement method. The datasets of the evolved virus variants were supplemented with images and measurements of the early SARS-CoV-2 isolates Munich929 and Italy-INMI1 to allow direct comparison. Infected Vero cell cultures were cultivated under comparable conditions to produce the viruses for imaging and morphometric analysis. The images and measurements can be used as a basis to analyse the morphometric changes of further evolving viruses at the particle level or for developing automated image processing workflows and analysis.Peer Reviewe
End-to-end simulation of nanopore sequencing signals with feed-forward transformers
Get PDFMotivation:
Nanopore sequencing represents a significant advancement in genomics, enabling direct long-read DNA sequencing at the single-molecule level. Accurate simulation of nanopore sequencing signals from nucleotide sequences is crucial for method development and for complementing experimental data. Most existing approaches rely on predefined statistical models, which may not adequately capture the properties of experimental signal data. Furthermore, these simulators were developed for earlier versions of nanopore chemistry, which limits their applicability and adaptability to the latest flow cell data.
Results:
To enhance the quality of artificial signals, we introduce seq2squiggle, a novel transformer-based, non-autoregressive model designed to generate nanopore sequencing signals from nucleotide sequences. Unlike existing simulators that rely on static k-mer models, our approach learns sequential contextual information from segmented signal data. We benchmark seq2squiggle against state-of-the-art simulators on real experimental R9.4.1 and R10.4.1 data, evaluating signal similarity, basecalling accuracy, and variant detection rates. Seq2squiggle consistently outperforms existing tools across multiple datasets, demonstrating superior similarity to real data and offering a robust solution for simulating nanopore sequencing signals with the latest flow cell generation.
Availability and implementation:
seq2squiggle is freely available on GitHub at: github.com/ZKI-PH-ImageAnalysis/seq2squiggle.Peer Reviewe
How far are we? Assessing progress in hepatitis C response towards the WHO 2030 elimination goals by the civil society monitoring in 25 European countries, period 2020 to 2023
No full textBackground:
With the advent of direct acting antivirals (DAAs) the World Health Organisation (WHO) adopted global strategy to eliminate hepatitis C virus (HCV) infection by 2030. In Europe, people who inject drugs (PWID) account for the majority of new cases, however testing and treatment remain suboptimal. The aim was to monitor progress in HCV policy and cascade-of-care for PWID, led by the civil society organisations (CSO) that provide harm reduction services for PWID across Europe.
Methods:
In period 2020–2023, CSOs representing focal points of Correlation-European Harm Reduction Network were annually invited to complete online questionnaire on use/impact of HCV test-and-treat guidelines for PWID, availability/functioning of continuum-of-care, and role/limitations of harm reduction services for PWID. A retrospective longitudinal analysis of responses to questions answered each year by the same respondents was performed, and a comparison among the studied years was made.
Results:
Twenty-five CSOs from cities in 25 European countries were included and responded to 25 questions. Between 2020 and 2023, there was positive trend in number of HCV treatment guidelines, separate guidelines for PWID, and their positive impact on acess to testing/treatment (24/25, 5/25, and 16/25 in 2023, respectively). DAAs were available in all countries, predominantly prescribed by specialist physicians only (slight increase at primary care), with restrictions including active drug use, stage of liver fibrosis or/and reimbursement policies (2/25, 4/25, and 3/25 in 2023, respectively). A decrease in HCV testing sites was noted. Treatment was consistently most common at clinical settings, however an increase outside the specialist settings was detected, particularly in prisons (12/25 and 15/25 in 2020–2021, respectively). Comparing 2022–2023, number of HCV-testing services increased in many cities with positive dynamic in nearly all the settings; increase in treatment at harm reduction services/community centres was noted (6/25 to 8/25, respectively). Between 2020 and 2023 the frequency of various limitations to CSOs addressing HCV was oscillating, presenting an increase between 2022 and 2023 (9/25 to 14/25, respectively).
Conclusion:
The overall progress towards WHO HCV elimination goals across Europe remains insufficient, most probably also due to the influence of Covid-19 pandemic. Further improvements are needed, also by including CSOs for PWID in continuum-of-care services, and in monitoring progress.Peer Reviewe
Discrimination based on gender identity and decision-making regarding HIV/STI-protected sex, a cross-sectional study among trans and non-binary people in Germany
No full textBackground:
Trans and non-binary people are often discriminated against. Discrimination has a negative impact on health and may affect sexual health and behavior. We explored the relationship between discrimination based on gender identity and the perceived ability to make decisions about their sex life to feel as protected as desired from HIV and sexually transmitted infections (STI) among trans and non-binary people in Germany. Secondarily, we assessed whether feeling unable of making HIV/STI-protected sex decisions was associated with behaviors related to increased HIV/STI risk.
Methods:
We conducted a cross-sectional study using data from the Sexual Health and HIV/STI in Trans and Non-Binary Communities (TASG) survey conducted online between March-July 2022 among trans and/or non-binary people aged 18 years and older living in Germany. We described the prevalence of frequent discrimination based on gender identity. We calculated prevalence ratios (PR) with 95% confidence intervals (95% CI) for the associations between frequent experienced discrimination based on gender identity and feeling unable of making HIV/STI-protected sex decisions, and between feeling unable of making HIV/STI-protected sex decisions and behaviors related to increased HIV/STI risk.
Results:
Among 3077 participants, 22% reported frequent discrimination based on gender identity. Participants experiencing such discrimination reported 1.4 times more often to feel unable to make HIV/STI-protected sex decisions (PR 1.4, 95% CI 1.1–1.8). This perceived inability was associated with increased prevalence of sex under drug influence (PR 2.9, 95% CI 2.3–3.7) and condomless penetrative sex with multiple partners without PrEP (PR 2.0, 95% CI 1.4–2.9).
Conclusion:
Feeling unable to make decisions to feel protected from HIV/STI among trans and non-binary people was associated with both frequent discrimination and behaviors that increase the HIV/STI risk. Strategies for empowering trans and non-binary people to assert their sexual decision-making needs should be explored.Peer Reviewe
General hospital patients’ attitude towards systematic health risk behavior screening and intervention
Get PDFBackground:
Systematic counseling on behavioral health risk factors (HRFs) may be suitable to promote health among general hospital patients. This study aimed to investigate the openness of patients towards systematic screening and intervention of HRFs, its relation to actual participation in a multi-behavioral intervention, and whether socio-economic characteristics, HRFs and health indicators are related to approval.
Methods:
All 18- to 64-year-old patients hospitalized in five medical departments at the University Medicine Hospital Greifswald in Germany were asked between May and July 2022 to participate in a survey and in a subsequent pre-post intervention study. Among all eligible patients, 225 (78.9%) participated in the survey. Patients’ approval of systematic screening and intervention of HRFs was assessed using five statements with a total sum score of 0–20 (i.e., scores of 0–6, 7–13, 14–20 referring to low, medium and high approval). Associations with intervention participation, socio-economic, behavioral and health-related patient characteristics were analyzed using logistic and multivariable linear regression analyses.
Results:
The mean total approval of screening and intervention was 13.8 (SD = 4.8). Of the 125/ 73/ 16 patients with high/ medium/ low approval, 88.0%/ 78.1%/ 50.0% participated in the subsequent intervention, respectively. Approval was independent of socio-demographic and -economic characteristics and self-rated general health. Current tobacco smoking was the only HRF negatively (p = 0.02) and diabetes mellitus was the only disease positively (p = 0.01) associated with approval.
Conclusion:
High approval of HRF screening, which was rather independent of socio-economic characteristics and worse self-rated general health, speaks in favor of proactively approaching and motivating all general hospital patients to participate in health behavior change intervention. Tobacco smokers might need higher efforts to motivate participation than non-smokers.
Trial registration:
ClinicalTrials.gov Identifier NCT05365269 on May 9, 2022.Peer Reviewe
Vaccine effectiveness against influenza hospitalisation in adults during the 2022/2023 mixed season of influenza A(H1N1)pdm09, A(H3N2) and B circulation, Europe: VEBIS SARI VE hospital network
Get PDFWe conducted a multicentre hospital-based test-negative case–control study to measure vaccine effectiveness (VE) against PCR-confirmed influenza in adult patients with severe acute respiratory infection (SARI) during the 2022/2023 influenza season in Europe. Among 5547 SARI patients ≥18 years, 2963 (53%) were vaccinated against influenza. Overall VE against influenza A(H1N1)pdm09 was 11% (95% CI: −23–36); 20% (95% CI: −4–39) against A(H3N2) and 56% (95% CI: 22–75) against B. During the 2022/2023 season, while VE against hospitalisation with influenza B was >55%, it was ≤20% for influenza A subtypes. While influenza vaccination should be a priority for future seasons, improved vaccines against influenza are needed.Peer Reviewe
Post-viral symptoms and conditions are more frequent in COVID-19 than influenza, but not more persistent
Get PDFBackground:
Post-viral symptoms have long been known in the medical community but have received more public attention during the COVID-19 pandemic. Many post-viral symptoms were reported as particularly frequent after SARS-CoV-2 infection. However, there is still a lack of evidence regarding the specificity, frequency and persistence of these symptoms in comparison to other viral infectious diseases such as influenza.
Methods:
We investigated a large population-based cohort based on German routine healthcare data. We matched 573,791 individuals with a PCR-test confirmed SARS-CoV-2 infection from the year 2020 to contemporary controls without SARS-CoV-2 infection and controls from the last influenza outbreak in 2018 and followed them up to 18 months.
Results:
We found that post-viral symptoms as defined for COVID-19 by the WHO as well as tissue damage were more frequent among the COVID-19 cohort than the influenza or contemporary control cohort. The persistence of post-viral symptoms was similar between COVID-19 and influenza.
Conclusion:
Post-viral symptoms following SARS-CoV-2 infection constitute a substantial disease burden as they are frequent and often persist for many months. As COVID-19 is becoming endemic, the disease must not be trivialized. Research should focus on the development of effective treatments for post-viral symptoms.Peer Reviewe
Effects of Face Mask Mandates on COVID-19 Transmission in 51 Countries: Retrospective Event Study
Get PDFBackground: The question of the utility of face masks in preventing acute respiratory infections has received renewed attention during the COVID-19 pandemic. However, given the inconclusive evidence from existing randomized controlled trials, evidence based on real-world data with high external validity is missing.
Objective: To add real-world evidence, this study aims to examine whether mask mandates in 51 countries and mask recommendations in 10 countries increased self-reported face mask use and reduced SARS-CoV-2 reproduction numbers and COVID-19 case growth rates.
Methods: We applied an event study approach to data pooled from four sources: (1) country-level information on self-reported mask use was obtained from the COVID-19 Trends and Impact Survey, (2) data from the Oxford COVID-19 Government Response Tracker provided information on face mask mandates and recommendations and any other nonpharmacological interventions implemented, (3) mobility indicators from Google’s Community Mobility Reports were also included, and (4) SARS-CoV-2 reproduction numbers and COVID-19 case growth rates were retrieved from the Our World in Data—COVID-19 data set.
Results: Mandates increased mask use by 8.81 percentage points (P=.006) on average, and SARS-CoV-2 reproduction numbers declined on average by −0.31 units (P=.008). Although no significant average effect of mask mandates was observed for growth rates of COVID-19 cases (−0.98 percentage points; P=.56), the results indicate incremental effects on days 26 (−1.76 percentage points; P=.04), 27 (−1.89 percentage points; P=.05), 29 (−1.78 percentage points; P=.04), and 30 (−2.14 percentage points; P=.02) after mandate implementation. For self-reported face mask use and reproduction numbers, incremental effects are seen 6 and 13 days after mandate implementation. Both incremental effects persist for >30 days. Furthermore, mask recommendations increased self-reported mask use on average (5.84 percentage points; P<.001). However, there were no effects of recommendations on SARS-CoV-2 reproduction numbers or COVID-19 case growth rates (−0.06 units; P=.70 and −2.45 percentage points; P=.59). Single incremental effects on self-reported mask use were observed on days 11 (3.96 percentage points; P=.04), 13 (3.77 percentage points; P=.04) and 25 to 27 (4.20 percentage points; P=.048 and 5.91 percentage points; P=.01) after recommendation. Recommendations also affected reproduction numbers on days 0 (−0.07 units; P=.03) and 1 (−0.07 units; P=.03) and between days 21 (−0.09 units; P=.04) and 28 (−0.11 units; P=.05) and case growth rates between days 1 and 4 (−1.60 percentage points; P=.03 and −2.19 percentage points; P=.03) and on day 23 (−2.83 percentage points; P=.05) after publication.
Conclusions: Contrary to recommendations, mask mandates can be used as an effective measure to reduce SARS-CoV-2 reproduction numbers. However, mandates alone are not sufficient to reduce growth rates of COVID-19 cases. Our study adds external validity to the existing randomized controlled trials on the effectiveness of face masks to reduce the spread of SARS-CoV-2.Peer Reviewe