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188 lines
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<title>06 April, 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>Covid-19 effects on medical industry</strong> -
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<div>
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The COVID-19 pandemic has had a significant influence on the medical system and pharmaceutical sector in practically every nation on the planet. Communication with patients in their homes away from clinics was a typical practice in order to give safety actions to the healthcare team; however, health services have been interrupted on many levels throughout the world. The financial success of hospitals and health insurers was impacted by these measures. Another difficulty in this circumstance was the inability of medication manufacturers to get active medicinal components from Chinese companies. The considerable disruption of international trade and travel has had a negative effect on the actual economy. Different procedures based on currently available drugs were used to treat coronavirus infections.
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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://osf.io/ntmb6/" target="_blank">Covid-19 effects on medical industry</a>
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</div></li>
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<li><strong>Preprints as a medium for public debate on the COVID-19 pandemic: Observations on the blurring of internal and external scientific communication</strong> -
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<div>
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The growing popularity of preprint servers, notably during the Covid-19 pandemic, prompts a reevaluation of their role in science communication. This study delves into discussions and commentators on preprint servers, applying systems theory and boundary objects to scholarly and science communication. The approach is to analyze a sample of COVID-19-related pre-prints of bioRxiv and medRxiv and examine their comments and associated Twitter posts. Using mostly quantitative methods, the data was split in two groups: comments by biomedical peers and non-peers inside and outside academia. The results show that almost half of the comments can be attributed to peers, who also discussed different topics than the rest of the sample. On Twitter, the proportion of comments from peers was significantly lower, and the social network of academic and non-academic communities is intertwined. In summary, pre-prints can be seen as boundary objects that stabilize rather than blur the distinction between science and non-science. In this way, they promote the dissemination of knowledge and inter-disciplinary discourse. However, communication between scientists and the public remains ambivalent due to high barriers to entry. Challenges remain for integrating discussions into the peer review process without diluting standards and encouraging engagement from experts and laypersons.
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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://osf.io/preprints/socarxiv/75gs6/" target="_blank">Preprints as a medium for public debate on the COVID-19 pandemic: Observations on the blurring of internal and external scientific communication</a>
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</div></li>
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<li><strong>AI-Guided Discovery of Novel SARS-CoV-2 PLpro Inhibitors: Accelerating Antiviral Drug Development in the Fight Against COVID-19</strong> -
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<div>
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The global pandemic caused by SARS-CoV-2 has highlighted the urgent need for effective antiviral drugs. The papain-like protease (PLpro) is a key viral enzyme involved in the replication and immune evasion of SARS-CoV-2, making it a promising target for antiviral drug development. In this study, we employed an artificial intelligence (AI)-driven drug discovery platform, LIME, to generate novel inhibitors of the SARS-CoV-2 PLpro. LIME is based on generative language models that can generate diverse, valid, and synthetically accessible compounds. The LIME software was used to identify potential inhibitors with strong binding affinity and specificity to the target protein. The top 13 hit compounds were tested in vitro, and the top 5 inhibitors with strong binding affinity and specificity were selected for further analysis. A top candidate molecule, CSEMRS-1376, exhibited similar binding energies and structural similarities to the known SARS-CoV-2 PLpro inhibitor, XR8-89. Computational analysis of the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles of the hit compounds and XR8-89 showed that both CSEMRS-1376 and XR8-89 demonstrated favorable ADMET profiles. Overall, the LIME software successfully identified several novel molecules, including CSEMRS-1376, with strong potential as a therapeutic agent against SARS-CoV-2. The study highlights the potential of AI-driven drug discovery platforms, such as LIME, to accelerate the drug development process and pave the way for more efficient and effective therapeutics.
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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/10.1101/2023.04.05.535700v1" target="_blank">AI-Guided Discovery of Novel SARS-CoV-2 PLpro Inhibitors: Accelerating Antiviral Drug Development in the Fight Against COVID-19</a>
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</div></li>
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<li><strong>SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19</strong> -
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<div>
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Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and brain tissue loss, raising concerns about the virus’s acute and potential chronic impact on the central nervous system. In this study, we utilized mouse models and human post-mortem tissues to investigate the presence and distribution of the SARS-CoV-2 spike protein in the skull-meninges-brain axis. Our results revealed the accumulation of the spike protein in the skull marrow, brain meninges, and brain parenchyma. The injection of the spike protein alone caused cell death in the brain, highlighting a direct effect on brain tissue. Furthermore, we observed the presence of spike protein in the skull of deceased long after their COVID-19 infection, suggesting that the spike’s persistence may contribute to long-term neurological symptoms. The spike protein was associated with neutrophil-related pathways and dysregulation of the proteins involved in the PI3K-AKT as well as complement and coagulation pathway. Overall, our findings suggest that SARS-CoV-2 spike protein trafficking from CNS borders into the brain parenchyma and identified differentially regulated pathways may present insights into mechanisms underlying immediate and long-term consequences of SARS-CoV-2 and present diagnostic and therapeutic opportunities.
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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/10.1101/2023.04.04.535604v1" target="_blank">SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19</a>
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</div></li>
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<li><strong>The purinergic receptor P2X7 and the NLRP3 inflammasome are druggable host factors required for SARS-CoV-2 infection</strong> -
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<div>
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Purinergic receptors and NOD-like receptor protein 3 (NLRP3) inflammasome regulate inflammation and viral infection, but their effects on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain poorly understood. Here, we report that the purinergic receptor P2X7 and NLRP3 inflammasome are cellular host factors required for SARS-CoV-2 infection. Lung autopsies from patients with severe coronavirus disease 2019 (COVID-19) reveal that NLRP3 expression is increased in host cellular targets of SARS-CoV-2 including alveolar macrophages, type II pneumocytes and syncytia arising from the fusion of infected macrophages, thus suggesting a potential role of NLRP3 and associated signaling pathways to both inflammation and viral replication. In vitro studies demonstrate that NLRP3-dependent inflammasome activation is detected upon macrophage abortive infection. More importantly, a weak activation of NLRP3 inflammasome is also detected during the early steps of SARS-CoV-2 infection of epithelial cells and promotes the viral replication in these cells. Interestingly, the purinergic receptor P2X7, which is known to control NLRP3 inflammasome activation, also favors the replication of D614G and alpha SARS-CoV-2 variants. Altogether, our results reveal an unexpected relationship between the purinergic receptor P2X7, the NLRP3 inflammasome and the permissiveness to SARS-CoV-2 infection that offers novel opportunities for COVID-19 treatment.
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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/10.1101/2023.04.05.531513v1" target="_blank">The purinergic receptor P2X7 and the NLRP3 inflammasome are druggable host factors required for SARS-CoV-2 infection</a>
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</div></li>
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<li><strong>Lower prevalence of Post-Covid-19 Condition following Omicron SARS-CoV-2 infection.</strong> -
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<div>
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Background: Different SARS-CoV-2 variants can differentially affect the prevalence of Post Covid-19 Condition (PCC). This prospective study assesses prevalence and severity of symptoms three months after an Omicron infection, compared to Delta, test-negative and population controls. This study also assesses symptomology after reinfection and breakthrough infections . Methods: After a positive SARS-CoV-2 test, cases were classified as Omicron or Delta based on ≥ 85% surveillance prevalence. Population controls were representatively invited and symptomatic test-negative controls enrolled after a negative SARS-CoV-2 test. Three months after enrolment, participants indicated point prevalence for 41 symptoms and severity of four symptoms. Permutation tests identified significantly elevated symptoms in cases compared to controls. PCC prevalence was estimated as the difference in prevalence of at least one elevated symptom in cases compared to population controls. Findings: At three months follow-up, five symptoms and severe dyspnea were significantly elevated in Omicron cases (n = 4138) compared to test-negative (n= 1672) and population controls (n= 2762). PCC prevalence was 10.4% for Omicron cases and 17.7% for Delta cases (n = 6855). Prevalence of severe fatigue and dyspnea were higher in reinfected compared to primary infected Omicron cases, while severity of symptoms did not significantly differ between Omicron cases with a booster or primary vaccination course. Interpretation: Three months after Omicron, prevalence of PCC is 41% lower than after Delta. Reinfection seems associated with more prevalent severe long-term symptoms compared to a first infection. A booster prior to infection does not seem to improve the outcome of long-term symptoms. Funding: The study is executed by the National Institute for Public Health and the Environment by order of the Ministry of Health, Welfare and Sport.
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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/10.1101/2023.04.05.23288157v1" target="_blank">Lower prevalence of Post-Covid-19 Condition following Omicron SARS-CoV-2 infection.</a>
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</div></li>
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<li><strong>Superior antibody and membrane protein-specific T cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Strategies to improve the immunogenicity of COVID-19 vaccines are necessary to optimise their protection against disease. Fractional dosing by intradermal administration (ID) has been shown to be equally immunogenic as intramuscular (IM) for several vaccines, but the immunogenicity of ID inactivated whole-virus SARS-CoV-2 at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T cell responses of full-dose CoronaVac by ID over IM in adolescents. Participants aged 11-17 years received 2 doses IM or ID, followed by the 3rd dose 13-42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively. S IgG, S-RBD IgG, S IgG FcγRIIIa-binding, SNM-specific IL-2+CD4+, SNM-specific IL-2+CD8+, S-specific IL-2+CD8+, N-specific IL-2+CD4+, N-specific IL-2+CD8+ and M-specific IL-2+CD4+ responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test (sVNT), 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2+CD4+, interferon-γ+CD8+ and IL-2+CD8+ responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. More in the ID groups reported local, mild adverse reactions. This is the first study to demonstrate superior antibody and M-specific T cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve immunogenicity of inactivated vaccines.
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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/10.1101/2023.04.05.23288005v1" target="_blank">Superior antibody and membrane protein-specific T cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents</a>
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</div></li>
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<li><strong>Structural epitope profiling identifies antibodies associated with critical COVID-19 and long COVID</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Antibodies can have beneficial, neutral, or harmful effects so resolving an antibody repertoire to its target epitopes may explain heterogeneity in susceptibility to infectious disease. However, the three-dimensional nature of antibody-epitope interactions limits discovery of important targets. We describe and experimentally validated a novel computational method and synthetic biology pipeline for identifying epitopes that are structurally stable and functionally important and apply it to the SARS-CoV-2 proteome. We show patterns of epitope-binding antibodies associated with immunopathology, including a non-isotype switching IgM response to a Membrane protein epitope which is amongst the strongest immunological features associated with severe COVID-19 to date (adjusted OR 72.14, 95% CI: 9.71 - 1300.15). Consistent with a hypothesis that the mechanism driving the non-switching response was T independent B cell activation, we find that B cells secrete IgM and proliferate on exposure to virus-like particles lacking Spike. We also identified persistence (> 1 year) of this response in individuals with longCOVID particularly affected by fatigue and depression. These findings point to a previously unrecognized coronavirus host-pathogen interaction. We demonstrate that the Membrane epitope is a promising vaccine and monoclonal antibody target, which may complement spike-directed vaccination broadening immunological protection.
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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/10.1101/2022.07.11.22277368v3" target="_blank">Structural epitope profiling identifies antibodies associated with critical COVID-19 and long COVID</a>
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</div></li>
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<li><strong>How to survey citizens’ compliance with COVID-19 public health measures? Evidence from three survey experiments</strong> -
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<div>
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The extent to which citizens comply with newly-enacted public health measures such as social distancing or lockdowns strongly affects the propagation of the virus and the number of deaths from COVID-19. It is however very difficult to identify non-compliance through survey research because claiming to follow the rules is socially desirable. Using three survey experiments, we examine the efficacy of different “face-saving” questions that aim to reduce social desirability in the measurement of compliance with public health measures. Our treatments soften the social norm of compliance by way of a short preamble in combination with a guilty-free answer choice making it easier for respondents to admit non-compliance. We find that self-reported non-compliance increases by up to 11 percentage points when making use of a face-saving question. Considering the current context and the importance of measuring non-compliance, we argue that researchers around the world should adopt our most efficient face-saving question.
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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://osf.io/preprints/socarxiv/gursd/" target="_blank">How to survey citizens’ compliance with COVID-19 public health measures? Evidence from three survey experiments</a>
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</div></li>
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<li><strong>GRAPHENE FIELD EFFECT BIOSENSOR FOR CONCURRENT AND SPECIFIC DETECTION OF SARS-COV-2 AND INFLUENZA</strong> -
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The SARS-CoV-2 pandemic has highlighted the need for devices capable of carrying out rapid differential detection of viruses that may manifest similar physiological symptoms yet demand tailored treatment plans. Seasonal influenza may be exacerbated by COVID-19 infections, increasing the burden on healthcare systems. In this work, we demonstrate a technology, based on liquid-gated graphene field-effect transistors, for rapid and ultraprecise detection and differentiation of influenza and SARS-CoV-2 surface protein. Most distinctively, our device consists of 4 onboard graphene field-effect electrolyte-gated transistors arranged in a quadruple architecture, where each quarter is functionalized individually (with either antibodies or chemically passivated control) but measured collectively. Our sensor platform was tested against a range of concentrations of viral surface proteins from both viruses with the lowest tested and detected concentration at ~50 ag/mL, or 88 zM for COVID-19 and 227 zM for Flu, which is 5-fold lower than the values reported previously on a similar platform. Unlike the classic Real-Time Polymerase Chain Reaction (RT-PCR) test, which has a turnaround time of a few hours, our technology presents an ultrafast response time of ~10 seconds even in complex media such as saliva. Thus, we have developed a multi-analyte, highly sensitive, and fault-tolerant technology for rapid diagnostic of contemporary, emerging, and future pandemics.
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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/10.1101/2022.10.04.22280705v2" target="_blank">GRAPHENE FIELD EFFECT BIOSENSOR FOR CONCURRENT AND SPECIFIC DETECTION OF SARS-COV-2 AND INFLUENZA</a>
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</div></li>
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<li><strong>How Interactions During Viral-Viral Coinfection Can Shape Infection Kinetics</strong> -
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<div>
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Respiratory virus infections are a leading cause of disease worldwide with multiple viruses detected in 20-30% of cases and several viruses simultaneously circulating. Some infections with viral copathogens have been shown to result in reduced pathogenicity while other virus pairings can worsen disease. The mechanisms driving these dichotomous outcomes are likely variable and have only begun to be examined in the laboratory and clinic. To better understand viral-viral coinfections and predict potential mechanisms that result in distinct disease outcomes, we first systematically fit mathematical models to viral load data from ferrets infected with respiratory syncytial virus (RSV) followed by influenza A virus (IAV) after 3 days. The results suggested that IAV reduced the rate of RSV production while RSV reduced the rate of IAV infected cell clearance. We then explored the realm of possible dynamics for scenarios not examined experimentally, including different infection order, coinfection timing, interaction mechanisms, and viral pairings. IAV coinfection with rhinovirus (RV) or SARS-CoV-2 (CoV2) was examined by using human viral load data from single infections together with murine weight loss data from IAV-RV, RV-IAV, and IAV-CoV2 coinfections to guide the interpretation of the model results. Similar to the results with RSV-IAV coinfection, this analysis showed that the increased disease severity observed during murine IAV-RV or IAV-CoV2 coinfection was likely due to slower clearance of IAV infected cells by the other viruses. On the contrary, the improved outcome when IAV followed RV could be replicated when the rate of RV infected cell clearance was reduced by IAV. Simulating viral-viral coinfections in this way provides new insights about how viral-viral interactions can regulate disease severity during coinfection and yields testable hypotheses ripe for experimental evaluation.
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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/10.1101/2023.04.05.535744v1" target="_blank">How Interactions During Viral-Viral Coinfection Can Shape Infection Kinetics</a>
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</div></li>
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<li><strong>Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses</strong> -
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<div>
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We measured brain injury markers, inflammatory mediators, and autoantibodies in 203 participants with COVID-19; 111 provided acute sera (1-11 days post admission) and 56 with COVID-19-associated neurological diagnoses provided subacute/convalescent sera (6-76 weeks post-admission). Compared to 60 controls, brain injury biomarkers (Tau, GFAP, NfL, UCH-L1) were increased in acute sera, significantly more so for NfL and UCH-L1, in patients with altered consciousness. Tau and NfL remained elevated in convalescent sera, particularly following cerebrovascular and neuroinflammatory disorders. Acutely, inflammatory mediators (including IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) were higher in participants with altered consciousness, and correlated with brain injury biomarker levels. Inflammatory mediators were lower than acute levels in convalescent sera, but levels of CCL2, CCL7, IL-1RA, IL-2Rα, M-CSF, SCF, IL-16 and IL-18 in individual participants correlated with Tau levels even at this late time point. When compared to acute COVID-19 patients with a normal GCS, network analysis showed significantly altered immune responses in patients with acute alteration of consciousness, and in convalescent patients who had suffered an acute neurological complication. The frequency and range of autoantibodies did not associate with neurological disorders. However, autoantibodies against specific antigens were more frequent in patients with altered consciousness in the acute phase (including MYL7, UCH-L1, GRIN3B, and DDR2), and in patients with neurological complications in the convalescent phase (including MYL7, GNRHR, and HLA antigens). In a novel low-inoculum mouse model of SARS-CoV-2, while viral replication was only consistently seen in mouse lungs, inflammatory responses were seen in both brain and lungs, with significant increases in CCL4, IFNγ, IL-17A, and microglial reactivity in the brain. Neurological injury is common in the acute phase and persists late after COVID-19, and may be driven by a para-infectious process involving a dysregulated host response.
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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/10.1101/2023.04.03.23287902v1" target="_blank">Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses</a>
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</div></li>
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<li><strong>A second update on mapping the human genetic architecture of COVID-19</strong> -
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<div>
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Investigating the role of host genetic factors in COVID-19 severity and susceptibility can inform our understanding of the underlying biological mechanisms that influence adverse outcomes and drug development. Here we present a second updated genome-wide association study (GWAS) on COVID-19 severity and infection susceptibility to SARS-CoV-2 from the COVID-19 Host Genetic Initiative (data release 7). We performed a meta-analysis of up to 219,692 cases and over 3 million controls, identifying 51 distinct genome-wide significant loci—adding 28 loci from the previous data release. The increased number of candidate genes at the identified loci helped to map three major biological pathways involved in susceptibility and severity: viral entry, airway defense in mucus, and type I interferon.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.24.22283874v2" target="_blank">A second update on mapping the human genetic architecture of COVID-19</a>
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</div></li>
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<li><strong>SARS-CoV-2 infection and post-acute risk of non-Covid-19 infectious disease hospitalizations: a nationwide cohort study of Danish adults aged ≥50 years</strong> -
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Reports suggest that the potential long-lasting health consequences of SARS-CoV-2 infection may involve persistent dysregulation of some immune populations, but the potential clinical implications are unknown. In a nationwide cohort of 2,430,694 50+-year-olds, we compared the rates of non-Covid-19 infectious disease inpatient hospitalizations (of ≥5 hours) following the acute phase of SARS-CoV-2 infection in 930,071 individuals with rates among SARS-CoV-2 uninfected from 1 January 2021 to 10 December 2022. The post-acute phase of SARS-CoV-2 infection was associated with an incidence rate ratio of 0.90 (95% confidence interval 0.88-0.92) for any infectious disease hospitalization. Findings were similar for upper- (1.08, 0.97-1.20), lower respiratory tract (0.90, 0.87-0.93), influenza (1.04, 0.94-1.15), gastrointestinal (1.28, 0.78-2.09), skin (0.98, 0.93-1.03), urinary tract (1.01, 0.96-1.08), certain invasive bacterial (0.96, 0.91-0.1.01), and other (0.96, 0.92-1.00) infectious disease hospitalizations and in subgroups. Our study does not support an increased susceptibility to non-Covid-19 infectious disease hospitalization following SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.03.23288102v1" target="_blank">SARS-CoV-2 infection and post-acute risk of non-Covid-19 infectious disease hospitalizations: a nationwide cohort study of Danish adults aged ≥50 years</a>
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</div></li>
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<li><strong>Spatial Variation in Excess Mortality Across Europe: A Cross-sectional Study of 561 Regions in 21 Countries</strong> -
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Objective: To measure the burden of the COVID-19 pandemic in 2020 at the subnational level by estimating excess mortality, defined as the increase in all-cause mortality relative to an expected baseline mortality level. Design: Statistical and demographic analyses of regional all-cause mortality data. Setting: The vital statistics systems of 21 European countries. Participants: The entire population of 561 spatial units in 21 European countries. Main Outcome Measures: Losses of life expectancy at ages 0 and 60 for males and females. Results: Evidence was found of a loss in life expectancy in 391 regions, while only three regions exhibit notable gains in life expectancy in 2020. For 12 regions, losses of life expectancy amounted to more than 2 years, and three regions showed losses greater than 3 years. Geographic clusters of high mortality were found in Northern Italia, Spain and Poland, while clusters of low mortality were found in Western France, Germany/Denmark and Norway/Sweden. Conclusions: Regional differences of loss of life expectancy are impressive, ranging from a loss of more than 4 years to a gain of 8 months. These findings provide a strong rationale for regional analysis, as national estimates hide significant regional disparities.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.04.04.23284990v1" target="_blank">Spatial Variation in Excess Mortality Across Europe: A Cross-sectional Study of 561 Regions in 21 Countries</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>Evaluation of Safety & Efficacy of MIR 19 ® Inhalation Solution in Patients With Mild COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: MIR 19 ®; Combination Product: Standard therapy<br/><b>Sponsor</b>: National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia<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>LACTYFERRIN™ Forte and ZINC Defense™ and Standard of Care (SOC) vs SOC in the Treatment of Non-hospitalized Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Sesderma LACTYFERRIN™ Forte and Sesderma ZINC Defense™; Drug: Placebo<br/><b>Sponsors</b>: Jose David Suarez, MD; Sesderma S.L.; Westchester General Hospital Inc. DBA Keralty Hospital Miami; MGM Technology Corp<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 Nasal Treatment for COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Optate; Drug: Placebo<br/><b>Sponsor</b>: Indiana University<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>Effect of a Health Pathway for People With Persistent Symptoms Covid-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: usual care and follow-up by a nurse; Other: Personalized Multifactorial Intervention (IMP)<br/><b>Sponsor</b>: Centre Hospitalier Universitaire de Saint Etienne<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>RCT for Yinqiaosan-Maxingganshitang in the Treatment of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Chinese Herb; Diagnostic Test: Placebo<br/><b>Sponsor</b>: Chinese University of Hong Kong<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 Understand the Effect and Safety of the Study Medicine PF-07817883 in Adults Who Have Symptoms of COVID-19 But Are Not Hospitalized.</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: PF-07817883; Drug: Placebo<br/><b>Sponsor</b>: Pfizer<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>Traditional Chinese Medicine or Low-dose Dexamethasone in COVID-19 Pneumonia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Other: conventional western medicine treatment; Drug: Dexamethasone oral tablet; Other: Traditional Chinese medicine decoction<br/><b>Sponsor</b>: China-Japan Friendship 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>A Clinical Study on Safety and Effectiveness of Mesenchymal Stem Cell Exosomes for the Treatment of COVID-19.</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Biological: Extracellular Vesicles from Mesenchymal Stem Cells<br/><b>Sponsor</b>: First Affiliated Hospital of Wenzhou Medical University<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>Inpatient COVID-19 Lollipop Study</strong> - <b>Conditions</b>: COVID-19; Diagnostic Test<br/><b>Intervention</b>: Device: Lollipop<br/><b>Sponsor</b>: University of Wisconsin, Madison<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>Study of the Safety, Tolerability and Efficacy of NP-101 in Treating High Risk Participants Who Are Covid-19 Positive.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: NP-101; Other: Placebo<br/><b>Sponsor</b>: Novatek Pharmaceuticals<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>Effectiveness of Testofen Compared to Placebo on Long COVID Symptoms</strong> - <b>Condition</b>: Long Covid19<br/><b>Interventions</b>: Drug: Testofen; Drug: Microcrystalline cellulose<br/><b>Sponsor</b>: RDC Clinical 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>Care for Veterans Post-COVID</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Interventions</b>: Behavioral: Concordant Care Training; Behavioral: Education Packet Training<br/><b>Sponsor</b>: VA Office of Research and Development<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>Complementary Self-help Strategies for Patients With Post-COVID Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Behavioral: Complementary self-help strategies in addition to treatment as usual; Other: Treatment as usual<br/><b>Sponsor</b>: Universität Duisburg-Essen<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>Safety & Immunogenicity of RVM-V001/RVM-V002 or RVMV001+RVMV002 (Co Administered as Separate Injections) in Healthy Individuals</strong> - <b>Conditions</b>: Infectious Disease; COVID-19<br/><b>Interventions</b>: Biological: RVM-V001 30 µg; Biological: RVM-V002 30 µg; Biological: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration<br/><b>Sponsor</b>: RVAC Medicines (US), Inc.<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>HH-120 Nasal Spray for Post-exposure Prevention of SARS-CoV-2</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: HH-120 Nasal Spray; Drug: Placebo<br/><b>Sponsor</b>: Huahui Health<br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</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>Chemical Composition of Honeysuckle (<em>Lonicerae japonicae</em>) Extracts and Their Potential in Inhibiting the SARS-CoV-2 Spike Protein and ACE2 Binding, Suppressing ACE2, and Scavenging Radicals</strong> - Honeysuckle (Lonicerae japonicae) has been used in functional tea products. The chemical compositions of the water and ethanol extracts of honeysuckle were examined in the present study, along with their potential in inhibiting SARS-CoV-2 spike protein binding to ACE2, suppressing ACE2 activity, and scavenging reactive free radicals. Thirty-six compounds were tentatively identified from the honeysuckle extracts using HPLC-MS/MS, with ten reported for the first time in honeysuckle. Both…</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>Surfactin-like lipopeptides from <em>Bacillus clausii</em> efficiently bind to spike glycoprotein of SARS-CoV-2</strong> - The coronavirus disease 2019 (COVID-19) rapidly spread across the globe, infecting millions and causing hundreds of deaths. It has been now around three years but still, it remained a serious threat worldwide, even after the availability of some vaccines. Bio-surfactants are known to have antiviral activities and might be a potential alternative for the treatment of SARS-CoV-2 infection. In the present study, we have isolated and purified, a surfactin-like lipopeptide produced by a probiotic…</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>Repurposing immune boosting and anti-viral efficacy of <em>Parkia</em> bioactive entities as multi-target directed therapeutic approach for SARS-CoV-2: exploration of lead drugs by drug likeness, molecular docking and molecular dynamics simulation methods</strong> - The COVID-19 pandemic has caused adverse health (severe respiratory, enteric and systemic infections) and environmental impacts that have threatened public health and the economy worldwide. Drug repurposing and small molecule multi-target directed herbal medicine therapeutic approaches are the most appropriate exploration strategies for SARS-CoV-2 drug discovery. This study identified potential multi-target-directed Parkia bioactive entities against SARS-CoV-2 receptors (S-protein, ACE2,…</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>Attitudes and concerns regarding booster dose of COVID-19 vaccine among Egyptian patients with autoimmune and rheumatic diseases: a cross-sectional survey study</strong> - CONCLUSIONS: There is a low acceptability rate of booster dose of COVID-19 vaccine among Egyptian patients with ARD diseases. Public health workers and policymakers need to make sure that all ARD patients get clear messages about accepting the COVID-19 booster dose.</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>Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?</strong> - Despite the need for novel, effective therapeutics for the COVID-19 pandemic, no curative regimen is yet available, therefore patients are forced to rely on supportive and nonspecific therapies. Some SARS-CoV-2 proteins, like the 3 C-like protease (3CLpro) or the major protease (Mpro), have been identified as promising targets for antiviral drugs. The Mpro has major a role in protein processing as well as pathogenesis of the virus, and could be a useful therapeutic target. The antiviral drug…</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 pentasodium diethylenetriamine pentaacetate in ameliorating anosmia post COVID-19</strong> - CONCLUSION: This study confirmed the efficacy of DTPA in treating post-COVID-19 anosmia.</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>Propolis effects in periodontal disease seem to affect coronavirus disease: a meta-analysis</strong> - This meta-analysis aimed to investigate the effects of propolis on the severity of coronavirus disease symptoms by reducing periodontal disease. PubMed, EMBASE, SciELO, Web of Science, and SCOPUS databases were systematically searched. Studies have been conducted analyzing propolis’s effects on COVID-19 and periodontitis. The study was conducted according to the PRISMA statement and registered in PROSPERO. Risk of Bias (RoB) assessment and meta-analysis of clinical studies were performed (Review…</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>Reduced serological response to COVID-19 booster vaccine is associated with reduced B cell memory in patients with Inflammatory Bowel Disease; VARIATION (VAriability in Response in IBD AgainsT SARS-COV-2 ImmunisatiON)</strong> - CONCLUSIONS: Patients with IBD have an attenuated response to three doses of SARS-CoV-2 vaccine. Physicians should consider patients with higher anti-TNF drug levels and/or zinc deficiency as potentially at higher risk of attenuated response to vaccination.</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>Comprehensive structural analysis reveals broad-spectrum neutralizing antibodies against SARS-CoV-2 Omicron variants</strong> - The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread around the world. Mutant strains of SARS-CoV-2 are constantly emerging. At present, Omicron variants have become mainstream. In this work, we carried out a systematic and comprehensive analysis of the reported spike protein antibodies, counting the epitopes and genotypes of these antibodies. We further comprehensively analyzed the impact of Omicron mutations on antibody epitopes and classified these antibodies according to their…</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>Phosphatidylglycerol-specific phospholipase C from Amycolatopsis sp. NT115 strain: purification, characterization, and gene cloning</strong> - Recently, phosphatidylglycerol (PG) focused on its important role in chloroplast photosynthesis, mitochondrial function of the sperm, an inhibitory effect on SARS-CoV-2 ability to infect naïve cells and reducing lung inflammation caused by COVID-19. To develop an enzymatic PG determination method as the high-throughput analysis of PG, a PG-specific phospholipase C (PG-PLC) was found in the culture supernatant of Amycolatopsis sp. NT115. PG-PLC (54 kDa by SDS-PAGE) achieved the maximal activity…</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>Antiviral Activity of Cell Membrane-Bound Amphiphilic Polymers</strong> - We demonstrate that cholesterol-modified polyethylene glycol has antiviral activity, exerted by anchoring to plasma membranes and sterically inhibiting viruses from entering cells. These polymers distribute sparsely on cell membranes even at binding saturation. However, the polymers have sufficient elastic repulsion energy to repel various kinds of viruses with sizes larger than the mean distances between anchored polymers, including SARS-CoV-2 pseudoparticles. Our strategy can be applied to…</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 Omicron Infection and Changes in Serum Antibody Response to Wild-Type, Delta, and Omicron After a Booster Dose With BNT163b2 Vaccine in Korean Healthcare Workers</strong> - CONCLUSION: Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination. Further studies are needed to understand the characteristics of immunogenicity in these populations.</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>Cyanometabolites: molecules with immense antiviral potential</strong> - Cyanometabolites are active compounds derived from cyanobacteria that include small low molecular weight peptides, oligosaccharides, lectins, phenols, fatty acids, and alkaloids. Some of these compounds may pose a threat to human and environment. However, majority of them are known to have various health benefits with antiviral properties against pathogenic viruses including Human immunodeficiency virus (HIV), Ebola virus (EBOV), Herpes simplex virus (HSV), Influenza A virus (IAV) etc….</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>Heat shock protein 90 facilitates SARS-CoV-2 structural protein-mediated virion assembly and promotes virus-induced pyroptosis</strong> - Inhibition of heat shock protein 90 (Hsp90), a prominent molecular chaperone, effectively limits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but little is known about any interaction between Hsp90 and SARS-CoV-2 proteins. Here, we systematically analyzed the effects of the chaperone isoforms Hsp90α and Hsp90β on individual SARS-CoV-2 viral proteins. Five SARS-CoV-2 proteins, namely nucleocapsid (N), membrane (M), and accessory proteins Orf3, Orf7a, and Orf7b 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>CCL12 induces trabecular bone loss by stimulating RANKL production in BMSCs during acute lung injury</strong> - In the last three years, the capacity of health care systems and the public health policies of governments worldwide were challenged by the spread of SARS-CoV-2. Mortality due to SARS-CoV-2 mainly resulted from the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Moreover, millions of people who survived ALI/ARDS in SARS-CoV-2 infection suffer from multiple lung inflammation-induced complications that lead to disability and even death. The lung-bone axis refers…</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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