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<title>24 July, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Protective role of N-acetylcysteine and Sulodexide on endothelial cells after SARS-CoV-2 infection</strong> -
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<div>
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Objective: Severe acute respiratory syndrome coronavirus-2 causes hyperinflammation and activation of coagulation cascade and in the result aggravates endothelial cell dysfunction. N-acetylcysteine and Sulodexide have been found to mitigate endothelial damage. Approach and Results: The influence on coronary artery endothelial cells of serum collected after 4+/-1 months from coronavirus infection was studied. The concentrations of serum samples of interleukin 6, von Willebrand Factor, tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 were studied. The cultures with serum of patients after coronavirus infection were incubated with N-acetylocysteine and Sulodexide to estimate their potential protective role. The blood inflammato-ry parameters were increased in the group of cultures incubated with serum from patients after coronavirus infection. Supplementation of the serum from patients after coronavirus infection with N-acetylcysteine or Sulodexide reduced the synthesis of interleukin 6, von Willebrand Fac-tor. No changes in the synthesis of tissue Plasminogen Activator were observed. N-acetylcysteine reduced the synthesis of Plasminogen Activator Inhibitor-1. N-acetylcysteine and Sulodexide increased the tPA/PAI-1 ratio. Conclusion: N-acetylcysteine may have a role in reducing the myocardial injury occurring in the post-COVID-19 syndrome. Sulodexide can also play a protective role in post-COVID-19 patients.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.19.549800v1" target="_blank">Protective role of N-acetylcysteine and Sulodexide on endothelial cells after SARS-CoV-2 infection</a>
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</div></li>
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<li><strong>Recombinant Ranpirnase enhances the expression of co-transfected mRNA by modulating cellular metabolic activity</strong> -
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<div>
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As the world's first approved prophylactic mRNA vaccine, the development of the Covid-19 mRNA vaccine marks a milestone in mRNA therapeutics. However, achieving efficient transgene expression in therapeutic applications such as protein replacement and cancer therapeutical vaccines remains challenging. This study explores the use of recombinant Ranpirnase, a small ribonuclease, as a novel expression-enhancing tool for mRNA-based therapeutics. In Balb/c mice, co-expression of Ranpirnase significantly increased transgene expression levels by 3- to 6-fold and prolonged expression duration by more than 85%, regardless of mRNA nucleoside modification status. Recombinant Ranpirnase induces a cytostatic state in host cells, stabilizing mRNA and protein transcripts, thereby enhancing transgene expression. Importantly, co-expression of Ranpirnase recombinants did not cause detectable cytotoxicity or alter the tissue distribution of transgene expression, ensuring safety and tolerability at higher translation levels. The compact size of the recombinant Ranpirnase gene allows for seamless fusion with the target gene or co-transfection with existing delivery technologies. Altogether, recombinant Ranpirnase shows promise as an expression-enhancing element in mRNA-based therapeutics, including veterinary applications.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.22.550185v1" target="_blank">Recombinant Ranpirnase enhances the expression of co-transfected mRNA by modulating cellular metabolic activity</a>
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</div></li>
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<li><strong>High seroprevalence after the second wave of SARS-COV2 respiratory infection in a small settlement in the northern coastal of Peru.</strong> -
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Background. Due to more infections from variations that could escape vaccination and immunity by asymptomatic to uninfected transmission, COVID-199s second wave had higher seroprevalence globally. Public health constraints and herd immunity may not work against these novel variations9 infectivity. This population-based study in Peru9s Tumbes Region during the second wave of COVID-19 seeks to determine seroprevalence and demographic changes from the first wave. Methodology/Principal findings. In Dec 2021-Jan 2022, a study in Tumbes9 informal settlement sampled individuals over 2 years old from one in every four households. Finger-prick blood samples and symptom surveys were collected. On the second wave, there was a substantial rise in adjusted seroprevalence (50.15%, 95% CI [45.92 – 54.40]) compared with the first wave (24.82 %, 95%CI [22.49 – 27.25]), with females maintaining a higher seroprevalence (53.89; 95% CI [48.48-59.23]) vs. 45.49; 95% CI [38.98-52.12], p=0.042) compare to males. Those under 18 years of age had the highest IgG seropositivity: the 12–17 age group during the second wave (85.14%) and the 2–11 age group (25.25%) during the first wave. Nasal congestion and cough were symptoms associated with seropositivity, unlike the first wave. Conclusions/Significance. In Tumbes, the seroprevalence of COVID-19 increased by twofold compared to the initial wave. Inadequate infrastructure and limitations in human resources and supplies in healthcare facilities made the Peruvian health system collapse. We must include in epidemiological surveillance mHealth tools that enable real-time reporting of new cases. Working alongside the community is the only way to improve any new intervention strategy to prevent or control a new pandemic.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.19.23292491v1" target="_blank">High seroprevalence after the second wave of SARS-COV2 respiratory infection in a small settlement in the northern coastal of Peru.</a>
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</div></li>
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<li><strong>Mucosal and Systemic Immune Correlates of Viral Control following SARS-CoV-2 Infection Challenge in Seronegative Adults</strong> -
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Human infection challenge permits characterisation of the associated immune response in unparalleled depth, enabling evaluation of early pre-symptomatic immune changes and the dynamic immune factors important for viral clearance. Here, 34 healthy young adult volunteers, seronegative to SARS-CoV-2, were inoculated with a D614G-containing pre-Alpha SARS-CoV-2 strain. Nasal and systemic soluble mediator and antibody responses, and peripheral blood T cell and B cell responses were measured by MesoScale Discovery and flow cytometry just before and up to 1 year after intra-nasal inoculation. In the 18 (53%) participants who became infected, both nasal and systemic mediator responses were dominated by interferons (IFN) but with divergent kinetics. T cell activation and proliferation in blood peaked at day 10 in CD4+ T cells and day 14 in CD8+ T cells, returning to baseline by day 28. Following infection, antigen-specific T cells were largely CD38+Ki67+ and displayed central and effector memory phenotypes. T cells contracted after viral clearance with expanded antigen-specific memory T cell populations persisting past day 28. Both mucosal and systemic antibodies became detectable around day 10 but nasal antibodies plateaued after day 14 while circulating antibodies continued to rise. Using piecewise linear regression modelling, viral load related closely to the induction of type I IFN responses, moreover, CD8+ T cell responses and early IgA responses were strongly associated with viral clearance. Detailed analysis of innate and adaptive immune responses to primary SARS-CoV-2 infection following human challenge thus revealed the relationship between immune kinetics and viral load as factors associated with resolution of infection.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.21.23292994v1" target="_blank">Mucosal and Systemic Immune Correlates of Viral Control following SARS-CoV-2 Infection Challenge in Seronegative Adults</a>
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<li><strong>Social Cohesion and Covid-19: an integrative review</strong> -
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Background Nations of considerable wealth and sophisticated healthcare infrastructures have seen high rates of illness and death from Covid-19. Others with limited economic means and less developed healthcare infrastructures have achieved much lower burdens. In order to build a full understanding, an appraisal of the contribution of social relationships is necessary. Social cohesion represents a promising conceptual tool. Objective The aim was to examine scholarship on social cohesion during the Covid-19 pandemic: specifically – the constructions of social cohesion deployed, how it was measured, and the effects of and on social cohesion reported. Methods The Pubmed, Scopus and JSTOR databases were searched for relevant journal articles and grey literature. 66 studies met the inclusion criteria. Data were extracted and analysed from these using spreadsheet software. Results Several constructions of social cohesion were found. These concerned interpersonal relationships; sameness and difference; collective action; perceptions/emotions of group members; structures and institutions of governance; local or cultural specificity; and hybrid/multidimensional models. Social cohesion was reported as influential on health outcomes, health behaviours, and resilience and emotional wellbeing; but also that there was some potential for it to drive undesirable outcomes. Scholarship reported increases or decreases in quantitative measures of social cohesion, a temporary ‘rally round the flag’ effect early in the pandemic, the variable impacts of policy on cohesion, and changing interpersonal relationships due to pandemic conditions. There are numerous issues with the literature that reflect the well-documented limitations of popular versions of the social cohesion concept. Conclusions Social cohesion has been used to express a range of different aspects of relationships during the pandemic. It is said to promote better health outcomes, more engagement with positive health behaviours, and greater resilience and emotional wellbeing. The literature presents a range of ways in which it has been altered by the pandemic conditions.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.19.23292904v1" target="_blank">Social Cohesion and Covid-19: an integrative review</a>
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<li><strong>Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment</strong> -
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As the heterogeneity of symptoms is increasingly recognized among long-COVID patients, it appears highly relevant to study potential pathophysiological differences along the different subtypes. Preliminary evidence suggests distinct alterations in brain structure and systemic inflammatory patterns in specific groups of long-COVID patients. To this end, we analyzed differences in cortical thickness and peripheral immune signature between clinical subgroups based on 3T-MRI scans and signature inflammatory markers in n=120 participants comprising healthy never-infected controls, healthy COVID-19 survivors, and subgroups of long-COVID patients with and without cognitive impairment according to screening with Montreal Cognitive Assessment. Whole-brain comparison of cortical thickness between the 4 groups was conducted by surface-based morphometry. We identified distinct cortical areas showing a progressive increase in cortical thickness across different groups, starting from healthy individuals who had never been infected with COVID-19, followed by healthy COVID-19 survivors, long-COVID patients without cognitive deficits (MoCA ≥ 26), and finally, long-COVID patients exhibiting significant cognitive deficits (MoCA < 26). These findings highlight the continuum of cortical thickness alterations associated with COVID-19, with more pronounced changes observed in individuals experiencing cognitive impairment (p<0.05, FWE-corrected). Affected cortical regions covered prefrontal and temporal gyri, insula, posterior cingulate, parahippocampal gyrus, and parietal areas. Additionally, we discovered a distinct immunophenotype, with elevated levels of IL-10, IFNg, and sTREM2 in long-COVID patients, especially in the group suffering from cognitive impairment. We demonstrate lingering cortical and immunological alterations in healthy and impaired subgroups of COVID-19 survivors. This implies a complex underlying pathomechanism in long-COVID and emphasizes the necessity to investigate the whole spectrum of post-COVID biology to determine targeted treatment strategies targeting specific sub-groups.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.21.23292988v1" target="_blank">Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment</a>
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<li><strong>Covid-19 related cognitive, structural and functional brain changes among Italian adolescents and young adults: a multimodal longitudinal case-control study</strong> -
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Coronavirus disease 2019 (COVID-19) has been associated with brain functional, structural, and cognitive changes that persist months after infection. Most studies of the neurologic outcomes related to COVID-19 focus on severe infection and aging populations. Here, we investigated the neural activities underlying COVID-19 related outcomes in a case-control study of mildly infected youth enrolled in a longitudinal study in Lombardy, Italy, a global hotspot of COVID-19. All participants (13 cases, 27 controls, mean age 24 years) completed resting state functional (fMRI), structural MRI, cognitive assessments (CANTAB spatial working memory) at baseline (pre-COVID) and follow-up (post-COVID). Using graph theory eigenvector centrality (EC) and data-driven statistical methods, we examined differences in ECdelta (i.e., the difference in EC values pre- and post-COVID-19) and volumetricdelta (i.e., the difference in cortical volume of cortical and subcortical areas pre- and post-COVID) between COVID-19 cases and controls. We found that ECdeltasignificantly between COVID-19 and healthy participants in five brain regions; right intracalcarine cortex, right lingual gyrus, left hippocampus, left amygdala, left frontal orbital cortex. The left hippocampus showed a significant decrease in volumetricdelta between groups (p=0.041). The reduced ECdelta in the right amygdala associated with COVID-19 status mediated the association between COVID-19 and disrupted spatial working memory. Our results show persistent structural, functional and cognitive brain changes in key brain areas associated with olfaction and cognition. These results may guide treatment efforts to assess the longevity, reversibility and impact of the observed brain and cognitive changes following COVID-19.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.19.23292909v1" target="_blank">Covid-19 related cognitive, structural and functional brain changes among Italian adolescents and young adults: a multimodal longitudinal case-control study</a>
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<li><strong>COVID-19 mitigation behaviors and policies limited SARS-CoV-2 transmission in the United States from September 2020 through November 2021</strong> -
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United States jurisdictions implemented varied policies to slow SARS-CoV-2 transmission. Understanding patterns of these policies alongside individuals behaviors can inform effective outbreak response. To do so, we estimated the time-varying reproduction number (Rt), a weekly measure of real-time transmission using US COVID-19 cases from September 2020-November 2021. We then assessed the association between Rt and policies, personal COVID-19 mitigation behaviors, variants, immunity, and social vulnerability indicators using two multi-level regression models. First, we fit a model with state-level policy stringency according to the Oxford Stringency Index, a composite indicator reflecting the strictness of COVID-19 policies and strength of pandemic-related communication. Our second model included a subset of specific policies. We found that personal mitigation behaviors and vaccination were more strongly associated with decreased transmission than policies. Importantly, transmission was reduced not by a single measure, but by various layered measures. These results underscore the need for policy, behavior change, and risk communication integration to reduce virus transmission during epidemics.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.19.23292882v1" target="_blank">COVID-19 mitigation behaviors and policies limited SARS-CoV-2 transmission in the United States from September 2020 through November 2021</a>
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<li><strong>Can computer simulation support strategic service planning? Modelling a large integrated mental health system on recovery from COVID-19</strong> -
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Background COVID-19 has had a significant impact on people9s mental health and mental health services. During the first year of the pandemic, existing demand was not fully met while new demand was generated, resulting in large numbers of people requiring support. To support mental health services to recover without being overwhelmed, it was important to know where services will experience increased pressure, and what strategies could be implemented to mitigate this. Methods We implemented a computer simulation model of patient flow through an integrated mental health service in Southwest England covering General Practice (GP), community-based - talking therapies - (IAPT), acute hospital care, and specialist care settings. The model was calibrated on data from 1 April 2019 to 1 April 2021. Model parameters included patient demand, service-level length of stay, and probabilities of transitioning to other care settings. We used the model to compare - do nothing - (baseline) scenarios to - what if -(mitigation) scenarios, including increasing capacity and reducing length of stay, for two future demand trajectories from 1 April 2021 onwards. Results The results from the simulation model suggest that, without mitigation, the impact of COVID-19 will be an increase in pressure on GP and specialist community based services by 50% and 50-100% respectively. Simulating the impact of possible mitigation strategies, results show that increasing capacity in lower-acuity services, such as GP, results in demand being shifted to other parts of the mental health system while decreasing length of stay in higher acuity services is insufficient to mitigate the impact of increased demand. Conclusion In capturing the interrelation of patient flow related dynamics between various mental health care settings, we demonstrate the value of computer simulation for assessing the impact of interventions on system flow.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.19.23292289v1" target="_blank">Can computer simulation support strategic service planning? Modelling a large integrated mental health system on recovery from COVID-19</a>
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</div></li>
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<li><strong>Serum VEGF Levels on Admission in COVID-19 Patients Correlate with SP-D and Neutrophils, Reflecting Disease Severity: A Prospective Study</strong> -
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Background and objective: The COVID-19 pandemic caused by SARS-CoV-2 has resulted in significant global morbidity and mortality. This study aimed to investigate the clinical significance of serum vascular endothelial growth factor (VEGF) in COVID-19 patients and its association with disease severity and pulmonary injury. Methods: We prospectively collected data from 71 hospitalized COVID-19 patients between June 2020 and January 2021. Patients were classified as either mild or severe based on their oxygen requirements during hospitalization. Serum VEGF levels were measured using an ELISA kit. Results: In comparison to mild cases, significantly elevated serum VEGF levels were observed in severe COVID-19 patients. Furthermore, VEGF levels exhibited a positive correlation with white blood cell count, neutrophil count, and lymphocyte count. Notably, serum surfactant protein-D (SP-D), an indicator of alveolar epithelial cell damage, was significantly higher in patients with elevated VEGF levels. Conclusion: These results suggest that elevated serum VEGF could levels serve as a prognostic biomarker for COVID-19 as it is indicative of alveolar epithelial cell injury caused by SARS-CoV-2 infection. Additionally, we observed a correlation between VEGF and neutrophil activation, which plays a role in the immune response during endothelial cell injury, indicating a potential involvement of angiogenesis in disease progression. Further research is needed to elucidate the underlying mechanisms of VEGF in COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.17.23292653v1" target="_blank">Serum VEGF Levels on Admission in COVID-19 Patients Correlate with SP-D and Neutrophils, Reflecting Disease Severity: A Prospective Study</a>
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<li><strong>Risk of SARS-CoV-2 infection and hospitalization in individuals with natural, vaccine-induced and hybrid immunity: a retrospective population-based cohort study from Estonia</strong> -
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A large proportion of the worlds population has some form of immunity against SARS-CoV-2, through either infection (natural), vaccination or both (hybrid). This retrospective cohort study used data on SARS-CoV-2, vaccination, and hospitalization from national health system from February 2020 to June 2022 and Cox regression modelling to compare those with natural immunity to those with no (Cohort1, n=92917), hybrid (Cohort2, n=46813), and vaccine (Cohort3, n=252414) immunity. In Cohort 1, those with natural immunity were at lower risk for infection during the Delta (aHR 0.17, 95%CI 0.15-0.18) and higher risk (aHR 1.24, 95%CI 1.18-1.32) during the Omicron period than those with no immunity. Natural immunity conferred substantial protection against COVID-19-hospitalization. Cohort 2 - in comparison to natural immunity hybrid immunity offered strong protection during the Delta (aHR 0.61, 95%CI 0.46-0.80) but not the Omicron (aHR 1.05, 95%CI 0.93-1.1) period. COVID-19-hospitalization was extremely rare among individuals with hybrid immunity. In Cohort 3, individuals with vaccine-induced immunity were at higher risk than those with natural immunity for infection (Delta aHR 4.90, 95%CI 4.48-5.36; Omicron 1.13, 95%CI 1.06-1.21) and hospitalization (Delta aHR 7.19, 95%CI 4.02-12.84). These results show that risk of infection and severe COVID-19 are driven by personal immunity history and the variant of SARS-CoV-2 causing infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.18.23292858v1" target="_blank">Risk of SARS-CoV-2 infection and hospitalization in individuals with natural, vaccine-induced and hybrid immunity: a retrospective population-based cohort study from Estonia</a>
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<li><strong>Exploring COVID-19 vaccine uptake among healthcare workers in Zimbabwe: A mixed methods study</strong> -
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With COVID-19 no longer categorized as a public health emergency of international concern, vaccination strategies and priority groups for vaccination have evolved. Africa Centers for Diseases Prevention and Control proposed the ‘100-100-70%’ strategy which aims to vaccinate all healthcare workers, all vulnerable groups, and 70% of the general population. Understanding whether healthcare workers were reached during previous vaccination campaigns and what can be done to address concerns, anxieties, and other influences on vaccine uptake, will be important to optimally plan how to achieve these ambitious targets. In this mixed-methods study, between June 2021 and July 2022 a quantitative survey was conducted with healthcare workers accessing a comprehensive health check in Zimbabwe to determine whether and, if so, when they had received a COVID-19 vaccine. Healthcare workers were categorized as those who had received the vaccine ‘early’ (before 30.06.2021) and those who had received it ‘late’ (after 30.06.2021). In addition, 17 in-depth interviews were conducted to understand perceptions and beliefs about COVID-19 vaccines. Of the 2905 healthcare workers employed at 37 facilities who participated in the study, 2818 (97%, 95% CI [92%-102%]) reported that they had received at least one vaccine dose. Geographical location, older age, higher educational attainment and having a chronic condition was associated with receiving the vaccine early. Qualitatively, (mis)information, infection risk perception, quasi-mandatory vaccination requirements, and legitimate concerns such as safety and efficacy influenced vaccine uptake. Meeting the proposed 100-100-70 target entails continued emphasis on strong communication while engaging meaningfully with healthcare workers’ concerns. Mandatory vaccination may undermine trust and should not be a substitute for sustained engagement.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.17.23292791v1" target="_blank">Exploring COVID-19 vaccine uptake among healthcare workers in Zimbabwe: A mixed methods study</a>
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<li><strong>Examining the Evolution and Drivers of COVID-19 Transmission Waves in Ghana, 2020 - 2022</strong> -
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Background: Ghana reported the first COVID-19 cases on 12 March 2020. Response actions were rolled out along seven thematic pillars to limit the importation, detect and contain the virus, effectively manage cases, ensure effective coordination and maintain essential services. A whole-of-government and whole-of-society approach was adopted for the response. The government instituted restriction measures at various stages of the response to contain the pandemic or limit the impact of the pandemic on the health, social and economic wellbeing of the citizens. Four distinct transmission waves were recorded within the first 2 years of the pandemic. The study examined the key drivers of the major waves. Methods: A descriptive analysis of the pandemic from March 2020 to March 2022 was conducted using data reported through the country’s COVID-19 surveillance platforms. All RT-PCR confirmed cases reported from the 16 administrative regions over the two-year period were analysed. The effective reproduction number was computed using a model developed by Cori and colleagues. Results: A total of 160,761 cases with 99.1% (159,227) recoveries or discharges were reported as of 12 March 2022. The Greater Accra Region reported 56.3% of the confirmed cases. Within the period, 1,445 deaths (CFR= 0.9%) were reported. Approximately 2.3 million tests (76,774 per million population) tests were conducted with a cumulative test positivity rate of 6.8%. COVID-19 vaccination was enrolled a year after the first cases were reported and 21.3% of the target population was fully vaccinated as of 12 March 2022. Ghana recorded four major COVID-19 transmission waves characterized mainly by variants of concern and sub-optimal adherence to the public health and social measures. Conclusion: Scaling up and enhancing community acceptance of COVID-19 vaccination as well optimising the current surveillance and response systems are essential is sustaining the current gains and limiting the emergence of new variants of concern.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.17.23292790v1" target="_blank">Examining the Evolution and Drivers of COVID-19 Transmission Waves in Ghana, 2020 - 2022</a>
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<li><strong>Worldwide trends in COVID-19 related attacks against healthcare</strong> -
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Background: During the COVID-19 pandemic, violence targeting healthcare reportedly increased. Attacks against healthcare have the potential to impair the public health response and threaten the availability of healthcare services. However, there is little systematic understanding of the extent and characteristics of healthcare attacks in the setting of a pandemic. This study aimed to investigate global trends regarding COVID-19 related attacks against healthcare from January 2020 until January 2023. Methodology: COVID-19 related incidents that occurred between January 2020 and January 2023 were extracted from the Safeguarding Health in Conflict Coalition database and screened for eligibility. Data collected per incident included temporal factors; country; setting; attack and weapon type; perpetrator; motive; number of healthcare workers (HCWs) and patients killed, injured or kidnapped; and whether the incident caused damage to a health facility. Results: This study identified 255 COVID-19 related attacks against healthcare. The attacks occurred globally and throughout the course of the pandemic. Incidents were heterogeneous with regards to motives, attack types and outcomes. At least 18 HCWs were killed, 147 HCWs were injured and 86 facilities were damaged or destroyed. There were two periods with a peak incidence of reports. The first peak occurred during the beginning of the pandemic, and predominantly concerned stigma-related attacks against healthcare. The second peak, in 2021, was mainly composed of conflict-related attacks in Myanmar, and attacks targeting the global vaccination campaign. Conclusion: COVID-19 related attacks against healthcare occurred globally and in a variety of settings throughout the course of the pandemic. The findings of this study can be used to prevent and mitigate healthcare attacks during the ongoing and future pandemics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.18.23292819v1" target="_blank">Worldwide trends in COVID-19 related attacks against healthcare</a>
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<li><strong>The Sustainable Factors of the East Priangan Micro and Small Entrepreneurs during the COVID-19 Pandemic</strong> -
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In Indonesia, the number of micro and small businesses is dominant; therefore, their economic defense against uncertainty becomes vital, especially during the Covid-19 pandemic. By utilizing the explorative approach, this study wants to know the effect of this pandemic on the ability of micro and small businesses in East Priangan to sustain and detect their internal and external sustainability factors during this pandemic. Furthermore, to accomplish these purposes, this study uses interviews to get the data based on the viewpoint of the eight businesspersons in one city: Tasikmalaya, and two regencies: Pangandaran and Ciamis. Based on the result, this study concludes that a heavily damaging effect exists in the business related to tourist attractions (a restaurant in Pangandaran), supplier of materials to restaurants (a tempeh producer in Ciamis), and crowding creation (the seller of various snacks and a wedding organizer in Ciamis). Meanwhile, the middle-damaging impact happens in the coffee shop in Tasikmalaya, the hawker of round-shaped snacks with a chewy texture, and the food staller of hollow tofu with a sauce made of salt, onion, and brown sugar in Ciamis but a street vegetable hawker in Ciamis experiences low-damaging influence. After being asked about internal and external sustainable factors fronting this pandemic, they declare that having money left and using Instagram and WhatsApp to receive consumer orders become their internal sustainable factors. Meanwhile, receiving government aid is an external factor for business survival during the pandemic.
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🖺 Full Text HTML: <a href="https://osf.io/hgw8u/" target="_blank">The Sustainable Factors of the East Priangan Micro and Small Entrepreneurs during the COVID-19 Pandemic</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Smell in COVID-19 and Efficacy of Nasal Theophylline (SCENT 3)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: theophylline; Drug: Placebo<br/><b>Sponsor</b>: Washington University School of Medicine<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Lymph Node Aspiration to Decipher the Immune Response of Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Lymph node aspiration / Blood sampling<br/><b>Sponsor</b>: Assistance Publique - Hôpitaux de Paris<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Trial of the Candidate Vaccine MVA-SARS-2-S in Adults</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: MVA-SARS-2-S; Other: Placebo<br/><b>Sponsors</b>: Universitätsklinikum Hamburg-Eppendorf; German Center for Infection Research; Philipps University Marburg Medical Center; Ludwig-Maximilians - University of Munich; University Hospital Tuebingen; CTC-NORTH<br/><b>Withdrawn</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Treatment of Long COVID (TLC) Feasibility Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Low-dose Naltrexone (LDN); Drug: Cetirizine; Drug: Famotidine; Drug: LDN Placebo; Drug: Cetirizine Placebo; Drug: Famotidine Placebo<br/><b>Sponsors</b>: Emory University; CURE Drug Repurposing Collaboratory (CDRC)<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficiency and Safety of Paxlovid for COVID-19 Patients With Severe Chronic Kidney Disease</strong> - <b>Conditions</b>: COVID-19; Renal Insufficiency, Chronic<br/><b>Intervention</b>: Drug: Nirmatrelvir/ritonavir<br/><b>Sponsor</b>: Chinese PLA General Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety, Efficacy, and Dosing of VIX001 in Patients With Neurological Symptoms of Post Acute COVID-19 Syndrome (PACS).</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome; Cognitive Impairment; Neurological Complication<br/><b>Intervention</b>: Drug: VIX001<br/><b>Sponsor</b>: Neobiosis, LLC<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19</strong> - <b>Condition</b>: SARS-CoV-2<br/><b>Interventions</b>: Drug: Upamostat; Drug: Placebo (PO)<br/><b>Sponsors</b>: Henry M. Jackson Foundation for the Advancement of Military Medicine; Joint Program Executive Office Chemical, Biological, Radiological, and Nuclear Defense Enabling Biotechnologies; FHI Clinical, Inc.; RedHill Biopharma Limited<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Evaluation of the Safety and Efficacy of Randomized Placebo Versus the 8-aminoquinoline Tafenoquine for Early Symptom Resolution in Patients With Mild to Moderate COVID 19 Disease and Low Risk of Disease Progression</strong> - <b>Conditions</b>: COVID 19 Disease; Mild to Moderate COVID 19 Disease; SARS-CoV-2; Infectious Disease; Severe Acute Respiratory Syndrome Coronavirus 2<br/><b>Interventions</b>: Drug: Tafenoquine Oral Tablet; Drug: Placebo<br/><b>Sponsor</b>: 60P Australia Pty Ltd<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Efficacy, Safety, Tolerability and PK of SNS812 in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>: Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (Disorder)<br/><b>Interventions</b>: Drug: MBS-COV; Drug: Placebo<br/><b>Sponsor</b>: Oneness Biotech Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of the Therapy With BRAINMAX® Using fMRI for the Treatment of Patients With Asthenia After COVID-19</strong> - <b>Conditions</b>: Asthenia; COVID-19; Functional MRI; Cognitive Impairment<br/><b>Interventions</b>: Other: Structural and functional MRI; Drug: Ethyl methyl hydroxypyridine succinate + Meldonium; Drug: Placebo<br/><b>Sponsor</b>: Promomed, LLC<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>NDV-HXP-S Vaccine Clinical Trial (COVIVAC)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: COVIVAC vaccine<br/><b>Sponsors</b>: Institute of Vaccines and Medical Biologicals, Vietnam; National Institute of Hygiene and Epidemiology (NIHE), Vietnam; Center for Disease Control of Thai Binh Province, Vietnam<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunoadsorption vs. Sham Treatment in Post COVID Patients With Chronic Fatigue Syndrome</strong> - <b>Conditions</b>: Fatigue; Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Procedure: Immunoadsorption vs. sham immunoadsorption<br/><b>Sponsor</b>: Hannover Medical School<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MR-spectroscopy in Post-covid Condition Prior to and Following a Yoga Breathing Intervention</strong> - <b>Conditions</b>: Post COVID-19 Condition; Somatic Symptom Disorder<br/><b>Interventions</b>: Behavioral: yoga; Behavioral: social contact<br/><b>Sponsor</b>: Medical University Innsbruck<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Evaluation of SARS-COV-2 (COVID-19), Influenza and RSV 8-Well MT-PCR Panel for In Vitro Diagnostics</strong> - <b>Condition</b>: Respiratory Viral Infection<br/><b>Interventions</b>: Diagnostic Test: SARS-COV-2, Influenza and RSV 8-Well MT-PCR Panel; Diagnostic Test: BioFire Respiratory Panel 2.1<br/><b>Sponsor</b>: AusDiagnostics Pty Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Expressive Interviewing Agents to Support Health-Related Behavior Change</strong> - <b>Condition</b>: Mental Stress<br/><b>Intervention</b>: Other: Expressive Interviewing<br/><b>Sponsors</b>: University of Michigan; University of Texas at Austin<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Regulation of autophagy by SARS-CoV-2: The multifunctional contributions of ORF3a</strong> - Severe acute respiratory syndrome-coronavirus-1 (SARS-CoV-2) regulates autophagic flux by blocking the fusion of autophagosomes with lysosomes, causing the accumulation of membranous vesicles for replication. Multiple SARS-CoV-2 proteins regulate autophagy with significant roles attributed to ORF3a. Mechanistically, open reading frame 3a (ORF3a) forms a complex with UV radiation resistance associated, regulating the functions of the PIK3C3-1 and PIK3C3-2 lipid kinase complexes, thereby…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Fangchinoline inhibits the PEDV replication in intestinal epithelial cells via autophagic flux suppression</strong> - Animal and human health are severely threatened by coronaviruses. The enteropathogenic coronavirus, porcine epidemic diarrhea virus (PEDV), is highly contagious, leading to porcine epidemic diarrhea (PED), which causes large economic losses in the world’s swine industry. Piglets are not protected from emerging PEDV variants; therefore, new antiviral measures for PED control are urgently required. Herein, the anti-PEDV effects and potential mechanisms of fangchinoline (Fan) were investigated. Fan…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Silver N-heterocyclic carbene complexes are potent uncompetitive inhibitors of the papain-like protease with antiviral activity against SARS-CoV-2</strong> - The ongoing SARS-CoV-2 pandemic has caused a high demand for novel innovative antiviral drug candidates. Despite promising results, metal complexes have been relatively unexplored as antiviral agents in general and in particular against SARS-CoV-2. Here we report on silver NHC complexes with chloride or iodide counter ligands that are potent inhibitors of the SARS-CoV-2 papain-like protease (PL^(pro)) but inactive against 3C-like protease (3CL^(pro)) as another SARS-CoV-2 protease. Mechanistic…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Nanoparticle approaches for the renin-angiotensin system</strong> - The renin-angiotensin system (RAS) is a hormonal cascade that contributes to several disorders: systemic hypertension, heart failure, kidney disease, and neurodegenerative disease. Activation of the RAS can promote inflammation and fibrosis. Drugs that target the RAS can be classified into 3 categories, AT1 angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and renin inhibitors. The therapeutic efficacy of current RAS-inhibiting drugs is limited by poor…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Natural fucoidans inhibit coronaviruses by targeting viral spike protein and host cell furin</strong> - Fucoidans are a class of long chain sulfated polysaccharides and have multiple biological functions. Herein, four natural fucoidans extracted from Fucus vesiculosus, F. serratus, Laminaria japonica and Undaria pinnatifida, were tested for their HCoV-OC43 inhibition and found to demonstrate EC(50) values ranging from 0.15 to 0.61 µg/mL. That from U. pinnatifida exhibited the most potent anti-HCoV-OC43 activity with an EC(50) value of 0.15 ± 0.02 µg/mL, a potency largely independent of its sulfate…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>One master and two servants: One Zr(Ⅳ) with two ligands of TCPP and NH<sub>2</sub>-BDC form the MOF as the electrochemiluminescence emitter for the biosensing application</strong> - Here we put forward an innovative “one master and two servants” strategy for enhancing the ECL performance. A novel ECL luminophore named Zr-TCPP/NH(2)-BDC (TCPP@UiO-66-NH(2)) was synthesized by self-assembly of meso-tetra(4-carboxyphenyl)porphine (TCPP) and 4-aminobenzoic acid (NH(2)-BDC) with Zr clusters. TCPP@UiO-66-NH(2) has a porous structure and a highly ordered structure, which allows the molecular motion of TCPP to be effectively confined, thereby inhibiting nonradiative energy transfer….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Understanding structure activity relationships of Good HEPES lipids for lipid nanoparticle mRNA vaccine applications</strong> - Lipid nanoparticles (LNPs) have shown great promise as delivery vehicles to transport messenger ribonucleic acid (mRNA) into cells and act as vaccines for infectious diseases including COVID-19 and influenza. The ionizable lipid incorporated within the LNP is known to be one of the main driving factors for potency and tolerability. Herein, we describe a novel family of ionizable lipids synthesized with a piperazine core derived from the HEPES Good buffer. These ionizable lipids have unique…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification and validation of fusidic acid and flufenamic acid as inhibitors of SARS-CoV-2 replication using DrugSolver CavitomiX</strong> - In this work, we present DrugSolver CavitomiX, a novel computational pipeline for drug repurposing and identifying ligands and inhibitors of target enzymes. The pipeline is based on cavity point clouds representing physico-chemical properties of the cavity induced solely by the protein. To test the pipeline’s ability to identify inhibitors, we chose enzymes essential for SARS-CoV-2 replication as a test system. The active-site cavities of the viral enzymes main protease (M^(pro)) and papain-like…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antibody Fc-binding profiles and ACE2 affinity to SARS-CoV-2 RBD variants</strong> - Emerging SARS-CoV-2 variants, notably Omicron, continue to remain a formidable challenge to worldwide public health. The SARS-CoV-2 receptor-binding domain (RBD) is a hotspot for mutations, reflecting its critical role at the ACE2 interface during viral entry. Here, we comprehensively investigated the impact of RBD mutations, including 5 variants of concern (VOC) or interest-including Omicron (BA.2)-and 33 common point mutations, both on IgG recognition and ACE2-binding inhibition, as well as…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A quantum chemical study on the anti-SARS-CoV-2 activity of TMPRSS2 inhibitors</strong> - Nafamostat and camostat are known to inhibit the spike protein-mediated fusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by forming a covalent bond with the human transmembrane serine protease 2 (TMPRSS2) enzyme. Previous experiments revealed that the TMPRSS2 inhibitory activity of nafamostat surpasses that of camostat, despite their structural similarities; however, the molecular mechanism of TMPRSS2 inhibition remains elusive. Herein, we report the energy profiles of the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Sulforaphane on SARS‑CoV‑2 infection and NF‑κB dependent expression of genes involved in the COVID‑19 ‘cytokine storm’</strong> - Since its spread at the beginning of 2020, the coronavirus disease 2019 (COVID‑19) pandemic represents one of the major health problems. Despite the approval, testing, and worldwide distribution of anti‑severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) vaccines, the development of specific antiviral agents targeting the SARS‑CoV‑2 life cycle with high efficiency, and/or interfering with the associated ‘cytokine storm’, is highly required. A recent study, conducted by the authors’…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>New Viral Diseases and New Possible Remedies by Means of the Pharmacology of the Renin-Angiotensin System</strong> - All strains of SARS-CoV-2, as well as previously described SARS-CoV and MERS-CoV, bind to ACE2, the cell membrane receptor of β-coronaviruses. Monocarboxypeptidase ACE2 activity stops upon viral entry into cells, leading to inadequate tissue production of angiotensin 1-7 (Ang1-7). Acute lung injury due to the human respiratory syncytial virus (hRSV) or avian influenza A H7N9 and H5N1 viruses is also characterized by significant downregulation of lung ACE2 and increased systemic levels of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of nanozymes for promising alleviation of COVID-19-associated arthritis</strong> - The COVID-19 pandemic caused by SARS-CoV-2 has been identified as a culprit in the development of a variety of disorders, including arthritis. Although the emergence of arthritis following SARS-CoV-2 infection may not be immediately discernible, its underlying pathogenesis is likely to involve a complex interplay of infections, oxidative stress, immune responses, abnormal production of inflammatory factors, cellular destruction, etc. Fortunately, recent advancements in nanozymes with enzyme-like…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Toxic effects of aging mask microplastics on E. coli and dynamic changes in extracellular polymeric matter</strong> - Contamination of disposable medical masks has become a growing problem globally in the wake of Covid-19 due to their widespread use and improper disposal. Three different mask layers, namely the outer layer, the meltblown (MB) filler layer and the inner layers release three different types of microplastics, whose physical and chemical properties change after prolonged environmental weathering. In this study, physical and chemical changes of mask microplastics before and after aging were…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>New cyclic arylguanidine scaffolds as a platform for development of antimicrobial and antiviral agents</strong> - According to WHO, infectious diseases are still a significant threat to public health. The combine effects of antibiotic resistance, immunopressure, and mutations within the bacterial and viral genomes necessitates the search for new molecules exhibiting antimicrobial and antiviral activities. Such molecules often contain cyclic guanidine moiety. As part of this work, we investigated the selected antimicrobial and antiviral activity of compounds from the cyclic arylguanidine group. Molecules…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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