Search results
Found 8060 matches for
Longitudinal kinetics of the viral infection biomarker 3'-deoxy-3',4'-didehydro-cytidine in SARS-CoV-2, influenza A virus and RSV human challenge models.
3'-deoxy-3',4'-didehydro-cytidine (ddhC) is a recently discovered host biomarker for viral infections, though its temporal kinetics remain unclear. This study tests the hypothesis that ddhC is an acute phase reactant, rising shortly after viral infection and subsequently falling to baseline. We leveraged the precise monitoring facilitated by human challenge studies to investigate healthy participants inoculated with SARS-CoV-2, influenza A virus (H3N2), or respiratory syncytial virus (RSV). Using targeted liquid chromatography-tandem mass spectrometry, we quantified ddhC concentrations in serial plasma samples collected pre- and post-inoculation. In SARS-CoV-2 and H3N2 influenza A virus infection, but not RSV, ddhC levels peaked at 3-7 days post inoculation and declined to baseline by days 10-14. This pattern was also observed in asymptomatic or paucisymptomatic participants. A comparison of ddhC concentrations with matched timepoint whole blood gene expression revealed a correlation with interferon-related genes, including viperin and CMPK2-enzymes implicated in its upstream biosynthesis. Our results suggest that ddhC is a biomarker of the acute phase of viral infection, with potential to guide early interventions that reduce antimicrobial resistance and strengthen pandemic preparedness. Future work should explore ddhC dynamics in natural and experimental infections across varying severities and assess its utility in diverse populations and healthcare settings.
Mpox stigma in the UK and implications for future outbreak control: a cross-sectional mixed methods study.
BACKGROUND: Stigma emerged as a prominent public health challenge in the global mpox outbreak that began in 2022, impeding outbreak control efforts and the well-being of affected individuals. Addressing stigma is important for improving infection prevention and control. Despite frequent mention in public and policy discourse, robust assessment of mpox stigma is lacking. This study investigated the causes, manifestations, and impacts of mpox-related stigma in the UK, focusing on anticipated stigma among directly and indirectly affected communities. METHODS: We conducted an online, mixed-methods cross-sectional survey to assess mpox stigma. We developed and content validated a new tool, the Stigma Survey and Community-based Assessment for New and Re-emerging outbreaks (Stigma-SCANR) for this purpose. Through quota sampling, the survey targeted populations most affected by mpox at the time of data collection (March-July 2024), including gay, bisexual, and other men who have sex with men (GBMSM), and healthcare workers. The survey primarily explored anticipated stigma. Respondents with previous mpox diagnoses were asked about personal experiences of stigma. RESULTS: Of 479 respondents who initiated the survey, 437 (91%) were included in analyses. In modules related to drivers of stigma, pre-existing prejudices towards associated groups such as GBMSM and migrants were emphasised, alongside fear and misinformation. On average, respondents anticipated higher levels of negative judgement and unwarranted avoidance compared to other forms of social stigma, particularly from casual partners and the public. Among the 13 respondents who reported a previous mpox diagnosis, 11 (85%) had experienced mpox-related stigma. Nearly a quarter of respondents (24%) said they would not, or were unlikely to, tell a recent sexual partner about an mpox diagnosis. Feelings of shame were considered the most common barrier to care-seeking (299 respondents, 68%). CONCLUSIONS: This analysis of mpox stigma in the UK offers insights for international outbreak response, particularly in countries with similarly affected communities. Lessons learnt may also be transferable to other disease outbreaks. We propose practical recommendations for reducing stigma in future outbreaks, including peer support initiatives, distributing accessible information about safe timelines for returning to socialising and work or school, and co-designing public communications and contact tracing programmes with affected community members.
LISTEN: lived experiences of Long COVID: a social media analysis of mental health and supplement use
IntroductionLong COVID, or Post-Acute Sequelae of SARS-CoV-2 infection (PASC), is a complex condition characterized by a wide range of persistent symptoms that can significantly impact an individual's quality of life and mental health. This study explores public perspectives on the mental health impact of Long COVID and the use of dietary supplements for recovery, drawing on social media content. It uniquely addresses how individuals with Long COVID discuss supplement use in the absence of public health recommendations.MethodsThe study employs the LISTEN method (“Collaborative and Digital Analysis of Big Qual Data in Time Sensitive Contexts”), an interdisciplinary approach that combines human insight and digital analysis software. Social media data related to Long COVID, mental health, and supplement use were collected using the Pulsar Platform. Data were analyzed using the free-text discourse analysis tool Infranodus and collaborative qualitative analysis methods.ResultsThe findings reveal key themes, including the impact of Long COVID on mental health, occupational health, and the use of food supplements. Analysis of attitudes toward supplement use highlights the prevalence of negative emotions and experiences among Long COVID patients. The study also identifies the need for evidence-based recommendations and patient education regarding supplement use.DiscussionThe findings contribute to a better understanding of the complex nature of Long COVID and inform the development of comprehensive, patient-centered care strategies addressing both physical and mental health needs.
Immunogenicity and Safety of ChAdOx1 nCoV-19 (AZD1222) as a Homologous Fourth-Dose Booster: A Substudy of the Phase 3 COV003 Trial in Brazil
Objective: To address that, despite widespread use of ChAdOx1 nCoV-19 (AZD1222) as a COVID-2019 booster, fourth-dose clinical outcomes data are limited. We report immunogenicity and safety for ChAdOx1 nCoV-19 as a homologous fourth-dose booster. Participants and Methods: Participants (aged ≥18 years) who had received 2 doses of ChAdOx1 nCoV-19 in phase 3 COV003 trial in Brazil were offered a third dose after a planned dose interval from 11 to 13 months and a fourth dose after a planned interval from 6 to 15 months (both 5 × 1010 viral particles). All fourth doses were administered to substudy participants between August 18 and October 28, 2022. The data cutoff was December 9, 2022. The primary immunogenicity outcome was noninferiority of ancestral severe acute respiratory syndrome coronavirus (SARS-CoV)-2–neutralizing antibody responses 28 days after dose 4 versus dose 3. Solicited and unsolicited adverse events were recorded 7 and 28 days postdose 4, respectively. Results: 172 participants received a fourth dose (median interval postthird dose, 10.7 months). Ancestral SARS-CoV-2–neutralizing antibody titers postdose 4 were noninferior to those postdose 3; geometric mean fold rise was 1.9 (95% CI, 1.6-2.4; n=112). Immunogenicity results were consistent across all variants analyzed. Local and systemic solicited adverse events were reported in 60.3% (n=35/58) and 43.1% (n=25/58) of participants, respectively. Conclusion: Immune responses after a fourth dose of ChAdOx1 nCoV-19 were noninferior to those after a third dose across SARS-CoV-2 variants. The fourth dose was well tolerated with no emergent safety concerns, supporting the continued development of the ChAdOx1 platform in preparation for future pandemics. Trial Registration: clinicaltrials.gov Identifier: NCT04536051
SPIKELLM: SCALING UP SPIKING NEURAL NETWORK TO LARGE LANGUAGE MODELS VIA SALIENCY-BASED SPIKING
Recent advancements in large language models (LLMs) with billions of parameters have improved performance in various applications, but their inference processes demand significant energy and computational resources. In contrast, the human brain, with approximately 86 billion neurons, is much more energy-efficient than LLMs with similar parameters. Inspired by this, we redesign 7∼70 billion parameter LLMs using bio-plausible spiking mechanisms, emulating the efficient behavior of the human brain. We propose the first spiking large language model, SpikeLLM. Coupled with the proposed model, two essential approaches are proposed to improve spike training efficiency: Generalized Integrate-and-Fire (GIF) neurons to compress spike length from T to TL log2 L bits, and an Optimal Brain Spiking framework to divide outlier channels and allocate different T for GIF neurons, which further compresses spike length to approximate log2T bits. The necessity of spike-driven LLM is proved by comparison with quantized LLMs with similar operations. In the OmniQuant pipeline, SpikeLLM reduces 11.01% WikiText2 perplexity and improves 2.55% accuracy of common scene reasoning on a LLAMA-7B W4A4 model. In the GPTQ pipeline, SpikeLLM achieves direct additive in linear layers, significantly exceeding PB-LLMs. Our code is publicly available at https://github.com/Xingrun-Xing2/SpikeLLM.
How COVID-19 affected academic publishing: a 3-year study of 17 million research papers.
BackgroundThe COVID-19 pandemic induced an unprecedented response from the scientific research community. Previous studies have described disruption of the norms of academic publishing during this time. This study uses an epidemiological statistical toolkit alongside machine-learning methods to investigate the functioning of the scientific information-generation and -consumption ecosystem throughout the pandemic.MethodsA dataset of 17 million scientific research papers that were published between January 2019 and December 2022 was analysed. Data on citations and Altmetrics were harvested, and topic modelling was applied to abstracts. COVID-19-related articles were identified from title text. We investigated publication dynamics, correlations between citation metrics and Altmetrics, rates of publication in preprints, and temporal trends in topics, and compared these metrics in COVID-19 papers vs non-COVID-19 papers.ResultsThroughout 2020-2, 3.7% of English-language research output was on the topic of COVID-19. Journal articles on COVID-19 were published at a consistent rate during this period, while preprints peaked in early 2020 and decreased thereafter. COVID-19 preprints had lower publication rates in the peer-reviewed literature than other preprints, particularly those that were preprinted during early 2020. COVID-19 research received significantly more media and social media attention than non-COVID-19 research, and preprints received more attention, on average, than journal articles, with attention peaking during the initial wave and subsequent peaks corresponding to the emergence of novel variants. COVID-19 articles exhibited a higher correlation between Altmetrics and citation metrics compared with non-COVID-19 publications, suggesting a strong alignment between scientific and public attention.ConclusionThis study provides a comprehensive description of the rapid expansion of COVID-19 research, revealing evolving research areas and waxing and waning public interest across different topics. Preprints played an important role in disseminating scientific findings, but the level of coverage of preprinted findings emphasizes the need for guidelines in handling preprint research in media, particularly during a pandemic.
Epidemiological profiles and outcomes of healthcare workers hospitalized for COVID-19 in five Sub-Saharan African countries: a cohort study.
BackgroundThe COVID-19 pandemic placed immense strain on global health systems and healthcare workers (HCWs). This study aimed to analyze the epidemiological profiles and outcomes of HCWs hospitalized for COVID-19 across five sub-Saharan African countries.MethodsThis was a cohort study using secondary data collected between January 30, 2020, and December 31, 2022, as part of the International Severe Acute Respiratory and emerging Infection Consortium study. The study population consisted of HCWs who were hospitalized due to clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Demographic and clinical characteristics and case management were summarized using proportions or medians and interquartile ranges. Factors associated with risk of mortality among HCWs were assessed using a Cox proportional hazards model, adjusted for age and sex.ResultsFindings showed that South Africa recorded a lower percentage (2.4%) of patients who were HCWs compared to Gambia, Ghana, Guinea, and Malawi. Overall, many HCWs were aged ≥50 years and the majority were females (66.8%). In three of the five countries, however, the majority of the HCWs were <39 years old and were males. Antibiotics were the most commonly used medical treatments across three countries (Ghana, 67.8%; Guinea, 97.3%; Malawi, 80%), while antimalarials were commonly used in Guinea (87.8%) and Ghana (30.4%). Guinea and South Africa reported deaths with case-fatality rates varying from 22% in March 2020 to 1.4% in February 2022. Risk factors for mortality included age over 50 years, hypertension, diabetes mellitus, and chronic kidney disease.ConclusionsOur study underscores the critical need for continuous protection and enhanced readiness for HCWs, particularly during epidemics and pandemics. Strengthening infection prevention and control measures and focusing on vulnerable groups such as older and female HCWs are essential for mitigating the impact of future health crises. Further research is required to fully comprehend the implications of these findings.
Association of cancer and outcomes of patients hospitalized for COVID-19 between 2020 and 2023.
BackgroundThe coronavirus disease 2019 (COVID-19) has caused substantial morbidity and mortality on a global scale. A strong correlation has been found between COVID-19 treatment outcomes and noncommunicable diseases such as cancers. However, there is limited information on the outcomes of cancer patients who were hospitalised for COVID-19.MethodsWe conducted an analysis on data collected in a large prospective cohort study set-up by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). All patients with laboratory-confirmed or clinically-diagnosed SARS-CoV-2 infection were included. Cancer was defined as having a current solid organ or haematological malignancy. The following outcomes were assessed; 30-day in-hospital mortality, intensive care unit (ICU) admission, length of hospitalization and receipt of higher-level care.ResultsOf the 560,547 hospitalised individuals who were analysed, 27,243 (4.9%) had cancer. Overall, cancer patients were older and had more comorbidities than non-cancer patients. Patients with cancer had higher 30-day in-hospital mortality than non-cancer patients (29.1.3% vs 18.0%) and longer hospital stays (median of 12 days vs 8 days). However, patients with cancer were admitted less often to intensive care units than non-cancer patients (12.6% vs 17.1%) and received less invasive mechanical ventilation than non-cancer patients (4.5% vs 7.6%). The hazard ratio of dying from cancer, adjusted for age, sex and country income level was 1.18 (95%CI: 1.15-1.2).ConclusionsThis study's findings underscore the heightened vulnerability of hospitalized COVID-19 patients with cancer, revealing a higher mortality rate, longer hospital stays, and an unstructured pattern of care that reflects the complexity of managing severely ill patients during a public health crisis like the COVID-19 pandemic.
Research prioritisation in preparedness for and response to outbreaks of high-consequence pathogens: a scoping review
Abstract Background Priority setting for research on epidemic/pandemic-prone pathogens is essential for the allocation of limited resources to optimise impact. It involves the identification of gaps in knowledge crucial to effective preparedness and response to outbreaks. This review maps priority-setting exercises, reviews their approaches to research prioritisation and describes associated monitoring and evaluation processes for research priorities on high-consequence pathogens. Methods Using search terms associated with high-consequence pathogens, as defined by the WHO (2020), EMERGE (2019), European CDC (2022) and the Association of Southeast Asian Nations (2021), and research prioritisation, we searched WHO Global Index Medicus; Ovid Medline; Ovid Embase; Ovid Global Health; and Scopus. Grey literature sources were Google Scholar and the WHO websites, complemented by recommendations from stakeholder consultation. Two independent reviewers screened abstracts and full-texts including documents describing research prioritisation activities. Results were analysed using descriptive statistics and narrative synthesis. Results We identified 125 publications presenting priority setting activities on 17 high-consequence pathogens published between 1975 and 2022. Most (62%) were related to SARS-CoV-2, 5.6% to Ebola virus and 5% to Zika virus. Three different broad approaches to setting priorities were identified, most (53%) involved external consultations with experts. Few (6%) indicated plans to monitor progress against set priorities. Conclusions Our results highlight the diversity in research prioritisation practice in the context of high-consequence pathogens and a limited application of the existing standards in health research prioritisation. An increased uptake of these standards and harmonisation of practice may improve quality and confidence and ultimately improve alignment of funded research with the resulting priorities.