关键词： COVID-19   Prekallikrein   Antisense therapy  

摘要： Purpose: To assess the effect of antisense therapy to block kallikrein-kinin pathway in COVID-19 patients. Material and methods: Randomized, placebo-controlled, double blind, controlled trial enrolling hospitalized COVID-19 patients that required supplementary oxygen to sustain peripheral oxygen saturation. Key exclusion criteria included use of mechanical ventilation or vasopressors, and patients with more than 10 days since symptom onset or more than 48 h of oxygen use. Patients were randomized to either one subcutaneous dose of ISIS721744, an antisense that blocks prekallikrein, or placebo. The primary outcome was the number of days alive and free of oxygen support up to 15 days (DAFOR15). Secondary endpoints included organ failure score, need and duration of mechanical ventilation up to 15 days, and all-cause mortality at 30 days. Exploratory endpoints included physiological parameters, biomarkers, and quality of life. Results: From October 10, 2020, to December 09, 2020, 111 patients were randomized at thirteen sites in Brazil (56 to treatment and 55 to control group). Average age was 57.5 years, and most patients were male (68.5%). There were no significant differences in DAFOR15 between groups (5.9 +/- 5.2 days for the intervention arm and 7.7 +/- 5.1 for the control group; mean difference- 0.65, 95% confidence intervals from-2.95 to 1.36, p = 0.520). Conclusion: Antisense therapy designed to block the kallikrein-kinin pathway did not demonstrate clinical benefits in increasing days-alive without respiratory support at 15 days in patients with COVID-19 during the first wave in 2020. *** Identifier: NCT04549922

关键词： COVID-19 attitudes and knowledge   Infectious disease prevention   Antiviral treatment   Health disparities   Health communication   PREDICTORS   CITIES   ACCESS  

摘要： Objectives: Knowledge, access, and use of testing and antiviral treatments is critical to managing and mitigating the continuing burden of the novel Corona Virus (COVID-19) in the United States. This study measured knowledge, attitude, behaviors, and self -reported barriers towards COVID-19 testing and outpatient anti -viral medications (OPA) treatments among Black and older individuals who face greater hospitalization and mortality from the disease. Study design: Cross-sectional structured survey. Methods: Respondents were randomly selected from an opt -in national panel in December 2022. Equal numbers of Black and White US adults over the age of 40 (n = 1037) completed the 42 item online survey. The main measures were key sociodemographic variables of respondents, race, age, political affiliation and COVID-19 attitudes, beliefs, testing behaviors, and knowledge and barriers to OPA access. Results: Overall , awareness and knowledge of COVID-19 outpatient treatments was low. Black respondents were more likely to test for COVID-19 than White respondents but less likely to know about OPA treatments. Insurance coverage was a significant factor in use of home tests. Knowledge of OPA treatments was low across groups. White respondents were more likely than Black respondents to be aware of OPA treatments (1.75, 95 % CI [1.31 -2.33]) as were higher income respondents (1.13, 95 % CI [1.08 -1.17]) and self -identified Liberals (1.79, 95 % CI [1.29 -2.49]). Conclusions: Clinicians should know large numbers of patients may not be testing for COVID-19, nor are they aware of outpatient treatment options and may hold inaccurate beliefs about them. Developing culturally specific patient education materials are warranted to increase testing, utilization of vaccinations and OPAs.

关键词： COVID-19   SARS-CoV-2   Post-acute sequelae   Selective serotonin reuptake inhibitors   PLASMA-LEVELS   CYTOKINES   INFLAMMATION   FLUOXETINE   ANTIDEPRESSANTS   DEPRESSION   SERTRALINE  

摘要： Background: Post-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties although clinical trial data are lacking. Materials and Methods: This retrospective study was conducted leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C) to evaluate whether SSRIs with agonist activity at the sigma-1 receptor (S1R) lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. Additionally, determine whether the potential benefit could be traced to S1R agonism. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code. Results: Of the 17,908 patients identified, 1521 were exposed at baseline to a S1R agonist SSRI, 1803 to a nonS1R agonist SSRI, and 14,584 to neither. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed. A 29% reduction in the RR of PASC (0.704 [95% CI, 0.58-0.85]; P = 4 x10-4) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 21% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.79 [95% CI, 0.67 - 0.93]; P = 0.005). Thus, SSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC.

关键词： Fertility   Birth decline   COVID-19   Economic uncertainty   Vaccination   Oxford Stringency Index   Fertility plans  

摘要： Following the onset of the COVID-19 pandemic, many countries faced short-term fertility declines in 2020-2021, a development which did not materialize in the majority of German-speaking and Nordic countries. However, more recent birth statistics show a steep fertility decline in 2022. We aim to provide empirical evidence on the unexpected birth decline in 2022 in Germany and Sweden. We rely on monthly birth statistics and present seasonally adjusted monthly Total Fertility Rates (TFR) for Germany and Sweden. We relate the nine-month lagged fertility rates to contextual developments regarding COVID-19. The seasonally adjusted monthly TFR of Germany dropped from 1.5-1.6 in 2021 to 1.4 in early 2022 and again in autumn 2022, a decline of about 10% in several months. In Sweden, the corresponding TFR dropped from about 1.7 in 2021 to 1.5-1.6 in 2022, a decline of almost 10%. There is no association of the fertility trends with changes in unemployment, infection rates, or COVID-19 deaths, but a strong association with the onset of vaccination programmes and the weakening of pandemic-related restrictions. The fertility decline in 2022 in Germany and Sweden is remarkable. Common explanations of fertility change during the pandemic do not apply. The association between the onset of mass vaccinations and subsequent fertility decline indicates that women adjusted their behaviour to get vaccinated before becoming pregnant. Fertility decreased as societies were opening up with more normalized life conditions. We provide novel information on fertility declines and the COVID-19-fertility nexus during and in the immediate aftermath of the pandemic.

关键词： Loneliness   Age   Life course   Longitudinal   COVID-19   Pandemic   EMOTIONAL LONELINESS   OLDER-ADULTS   PREDICTORS   SCALE   LIFE   MULTIMORBIDITY   PREVALENCE   GENDER   WOMEN   RISK  

摘要： The COVID-19 pandemic entailed restrictions that hampered face-to-face interactions and social gatherings. In this paper, we examine whether loneliness increased to different extents among age groups due to these restrictions, and if these differences were mediated by specific life course conditions. Based on longitudinal data from the Swiss Household Panel, our results show that loneliness increased disproportionately among younger individuals during the pandemic. This finding aligns with the social convoy model and the socioemotional selectivity theory, which postulate a decline of social network size over the life course. It also corresponds to findings indicating a decrease in contact frequency with increasing age. Individuals aged 30 years and above experienced a lower increase in loneliness when they lived in shared households; however, this protective effect was not observed for younger individuals. Living together with a partner, being male, and not anticipating health complications in case of a COVID-19 infection moderated the increases of loneliness, but they were independent of age.

关键词： Occupational safety and health   Worker health   COVID-19   Heat   Seasonality   OCCUPATIONAL INJURY   TIME-SERIES   US  

摘要： Introduction: Millions of workers are injured on the job each year. Updated injury reporting regulations from the Occupational Safety and Health Administration (OSHA) in 2014 have resulted in publicly available data on reported severe injuries. Methods: OSHA severe injury reports (SIRs) were analyzed from 2015 to 2022. Severe injury rates were calculated using total employment estimates by industry and state to characterize the distribution of SIRs. Secondary analyses examined how SIRs differed seasonally, as well as before and after the start of the COVID-19 pandemic. Results: There were 83,338 severe workplace injuries reported across the 29 states that are under federal OSHA coverage. Manufacturing (375.98 per 100,000 workers) and Utilities (277.21 per 100,000 workers) had the highest rates of severe injuries. Despite summertime peaks in SIRs, there were not significant differences between seasons when examining SIRs by industry (p = 0.9763) or various injury factors. 1,846 of the SIRs were heat-related, and Utilities had the highest rate of heat-related severe injuries (13.34 per 100,000 workers). There was a statistically significant difference in the average injury rate when comparing preand post-COVID-19 periods (p < 0.001), which was statistically similar across all industries (p = 0.8143). Conclusions: Although several prior studies have examined the OSHA SIR data, this is the first known analysis of SIRs in relation to state- and industry-specific employment data. Despite the lack of a significant seasonality in SIRs, many industries seem to be impacted by heat-related injuries across all states. The number and rate of SIRs declined during COVID-19 similarly across all industries, with some industries maintaining low injury reporting rates through 2022. Practical Application: Findings of which industries and states may be experiencing a disproportionate burden of SIRs, including heat-related injuries, can inform injury prevention efforts. Additional work i

关键词： Cultural heritage   Air pollution   Corrosion risk   India   Risk management   DOSE-RESPONSE FUNCTIONS   LONG-TERM TRENDS   CULTURAL-HERITAGE   SULFUR-DIOXIDE   POLLUTION   URBAN   CORROSION   MONUMENTS   DETERIORATION   ENVIRONMENT  

摘要： India, one of the most dynamic ancient civilizations, possesses a multitude of historical artifacts, with 37 of its notable architectural structures recognized as UNESCO World Heritage Sites. Yet, the ever-changing climate, especially air pollution, expedites the natural deterioration of historic sites and diminishes their aesthetic appeal, causing socio-economic damage. With this in mind, the current study aims to offer a logical scientific foundation for the implications of air pollution, seasonal shifts, and COVID-19 on 14 significant historical places in India during the year 2019-20. Delhi, among the cities most severely affected by atmospheric pollution, recorded an alarming air quality index (AQI) of 102-141, which can intensify the risk of cultural sites to corrode and deteriorate. Analysis reveals that the winter season had elevated levels of NO2 and particle pollution (PM2.5, PM10), whereas summer had the higher levels of O3. Throughout the 5-month lockdown period, ozone levels exhibited an elevation, contrasting with the reduction observed in other air parameters. Notably, there was a substantial 70% decrease in particulate matter concentration, which had previously remained stable over the course of the year. Variations in geographic locales and anthropogenic influences contribute significantly to the dose-response statistics, revealing an unprecedented elevation in corrosion risks to historical limestone and sandstone structures across target sites. Moreover, the research addresses available Governmental initiatives, and effective strategies designed to safeguard heritage sites against the corrosion and material degradation, offering a comprehensive exploration of protective measures. Thereby, the current research is centred on establishing a foundational understanding of the impact of air pollution on cultural heritage, utilizing a comparison to the year with the lowest air pollution levels, which can aid policymakers in enhancing risk management and i

关键词： Complement   MAC   SARS-CoV-2   Respiratory syncytial virus   Influenza   Animal models   ACTIVATED PROTEIN-KINASE   REGULATOR CD59 PROTECTS   MANNOSE-BINDING LECTIN   ACUTE LUNG INJURY   FUNCTIONAL-CHARACTERIZATION   INTRACELLULAR COMPLEMENT   CHROMOSOMAL LOCALIZATION   TISSUE DISTRIBUTION   TARGETED DELETION   MOLECULAR-CLONING  

摘要： The complement system, a key component of innate immunity, provides the first line of defense against bacterial infection; however, the COVID-19 pandemic has revealed that it may also engender severe complications in the context of viral respiratory disease. Here, we review the mechanisms of complement activation and regulation and explore their roles in both protecting against infection and exacerbating disease. We discuss emerging evidence related to complement-targeted therapeutics in COVID-19 and compare the role of the complement in other respiratory viral diseases like influenza and respiratory syncytial virus. We review recent mechanistic studies and animal models that can be used for further investigation. Novel knockout studies are proposed to better understand the nuances of the activation of the complement system in respiratory viral diseases.

关键词： COVID-19  

摘要： A crucial step in the battle against the coronavirus disease 2019 (Covid-19) pandemic is efficient screening of the Covid affected patients. Deep learning models are used to improve the manual judgements made by healthcare professionals in classifying Chest X-Ray (CXR) images into Covid pneumonia, other viral/bacterial pneumonia, and normal images. This work uses two open source CXR image dataset having a total of 15,153 (dataset 1), and 4575 (dataset 2) images respectively. We trained three neural network models with a balanced subset of dataset 1 (1345 images per class), balanced dataset 2 (1525 images per class), and an unbalanced full dataset 1. The models used are VGG16 and Inception Resnet (IR) using transfer learning and a tailor made Convolutional Neural Network (CNN). The first model, VGG16 gives an accuracy, sensitivity, specificity, and F1 score of 96%, 97.8%, 95.92%, 97% respectively. The second model, IR gives an accuracy, sensitivity, specificity and F1 score of 97%, 98.51%, 97.28%, 99% respectively. The third and best proposed model, CNN gives an accuracy, sensitivity, specificity, and F1 score of 97%, 98.21%, 96.62%, 98% respectively. These performance metrics were obtained for the balanced dataset 1 and all models used 80:10:10 cross validation technique. The highest accuracy using CNN for all the three datasets are 97%, 96%, and 93% respectively. Gradient-weighted Class Activation Mapping (Grad-CAM) is used to ensure that the model uses genuine pathology markers to generalize. © The Author(s) 2024.

关键词： COVID-19   Coronavirus   Quarantine   Travel   Imported case   SARS-COV-2  

摘要： Background: Hong Kong enforced stringent travel restrictions during the COVID-19 pandemic. Understanding the characteristics of imported COVID-19 cases is important for establishing evidence-based control measures. Methods: Retrospective cohort study summarising the characteristics of imported cases detected in Hong Kong between 13 November 2020 and 31 January 2022, when compulsory quarantine was implemented. Findings: A total of 2269 imported COVID-19 cases aged 0 -85 years were identified, of which 48.6 % detected on arrival. A shorter median delay from arrival to isolation was observed in Delta and Omicron cases (3 days) than in ancestral strain and other variants cases (12 days; p < 0.001). Lower Ct values at isolation were observed in Omicron cases than in ancestral strain or other variants cases. No Omicron cases were detected beyond 14 days after arrival. Cases detected after 14 days of quarantine (n =58, 2.6 %) were more likely asymptomatic at isolation and had higher Ct value during isolation, some of them indicating re-positivity or post-arrival infections. Conclusions: Testing inbound travellers at arrival and during quarantine can detect imported cases early, but may not prevent all COVID-19 introductions into the community. Public health measures should be adapted in response to the emergence of SARS-CoV-2 variants based on evidence from ongoing surveillance.