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188 lines
52 KiB
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>07 June, 2022</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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<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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Situational shifts in habitual consumption: A longitudinal analysis of the effect of a COVID-19 lockdown on sugar-sweetened beverage consumption in England</strong> -
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Objectives A key challenge for behaviour change is by-passing the influence of habits. Habits are easily triggered by contextual cues; hence context changes have been suggested to facilitate behaviour change (i.e., habit discontinuity). We examined the impact of a COVID-19 lockdown in England on habitual consumption of sugar-sweetened beverages (SSBs). The lockdown created a naturalistic context change because it removed typical SSB consumption situations (e.g., going out). We hypothesised that SSB consumption would be reduced during lockdown compared to before and after lockdown, especially in typical SSB drinking situations. Design In two surveys among the same participants (N = 211, N = 160; consuming SSBs at least once/week) we assessed the frequency of SSBs and water consumption occasions before (Time 1), during (Time 2) and after lockdown (Time 3), across typical SSB and water drinking situations. We also assessed daily amount consumed in each period, and perceived habitualness of drinking SSBs and water. Results As predicted, participants reported fewer occasions of drinking SSBs during lockdown compared to before and after, especially in typical SSB drinking situations. However, the daily amount of SSBs consumed increased during lockdown, compared to before and after. Exploratory analyses suggest that during lockdown, participants increased their SSB consump¬-tion at home, especially if they had stronger perceived habitualness of SSB consumption. Conclusion These findings suggest that SSB consumption is easily transferred to other situations when the consumption context changes, especially for individuals with strong consumption habits. Habitual consumption may be hard to disrupt if the behaviour is rewarding.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/wdx5k/" target="_blank">Situational shifts in habitual consumption: A longitudinal analysis of the effect of a COVID-19 lockdown on sugar-sweetened beverage consumption in England</a>
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<li><strong>Transcriptomics Meta-Analysis Predicts Two Robust Human Biomarkers for Severe Infection with SARS-CoV-2</strong> -
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Defining the human factors associated with severe vs mild SARS-CoV-2 infection has become of increasing interest. Mining large numbers of public gene expression datasets is an effective way to identify genes that contribute to a given phenotype. Combining RNA-sequencing data with the associated clinical metadata describing disease severity can enable earlier identification of patients who are at higher risk of developing severe COVID-19 disease. We consequently identified 356 public RNA-seq human transcriptome samples from the Gene Expression Omnibus database that had disease severity metadata. We then subjected these samples to a robust RNA-seq data processing workflow to quantify gene expression in each patient. This process involved using Salmon to map the reads to the reference transcriptomes, edgeR to calculate significant differential expression levels, and gene ontology enrichment using Camera. We then applied a machine learning algorithm to the read counts data to identify features that best differentiated samples based on COVID-19 severity phenotype. Ultimately, we produced a ranked list of genes based on their Gini importance values that includes GIMAP7 and S1PR2, which are associated with immunity and inflammation (respectively). Our results show that these two genes can potentially predict people with severe COVID-19 at up to ~90% accuracy. We expect that our findings can help contribute to the development of improved prognostics for severe COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.06.22276040v1" target="_blank">Transcriptomics Meta-Analysis Predicts Two Robust Human Biomarkers for Severe Infection with SARS-CoV-2</a>
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<li><strong>Zooanthroponotic transmission of SARS-CoV-2 and host-specific viral mutations revealed by genome-wide phylogenetic analysis</strong> -
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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a generalist virus, infecting and evolving in numerous mammals, including captive and companion animals, free-ranging wildlife, and humans. Transmission among non-human species poses considerable risk for the establishment of SARS-CoV-2 reservoirs, makes eradication difficult, and provides the virus with opportunities for new evolutionary trajectories, including selection of adaptive mutations and emergence of new variant lineages. Here we use publicly available viral genome sequences and phylogenetic analysis to systematically investigate transmission of SARS-CoV-2 between mammalian species, both non-human and human, to identify mutations associated with each species. We found the highest frequency of animal-to-human transmission from mink, compared with negligible transmission from other sampled species (cat, dog, and deer). Although inferred transmission events could be limited by potential sampling biases, our results provide a useful baseline for further studies. Using genome-wide association studies, no single nucleotide variants (SNVs) were significantly associated with cats and dogs; however, three SNVs strongly associated with mink and 26 with deer. These SNVs are candidates for future experiments to identify their role in differential pathogenesis, immune escape and host response modulation. Together, our results are consistent with sustained deer-to-deer transmission and highlight the importance of studying animal-associated SARS-CoV-2 mutations to assess their potential impact on human and animal health.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.02.494559v1" target="_blank">Zooanthroponotic transmission of SARS-CoV-2 and host-specific viral mutations revealed by genome-wide phylogenetic analysis</a>
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<li><strong>Implications of Spike Protein Interactions with Zn-bound form of ACE2: A Computational Structural Study</strong> -
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The COVID-19 pandemic has generated a major interest in designing inhibitors to prevent SARS-CoV-2 binding on host cells to protect against infection. One promising approach to such research utilizes molecular dynamics (MD) to identify potential inhibitors that can prevent the interaction between spike (S) protein on the virus and angiotensin converting enzyme 2 (ACE2) receptor on the host cells. In these studies, many groups have chosen to exclude a zinc (Zn) ion bound to the ACE2 molecule which is critical for enzymatic activity. While the relatively distant location of Zn ion from the S protein binding site (S1 domain), combined with the difficulties in modeling this ion have motivated the decision of exclusion, Zn can potentially contribute to the structural stability of the entire protein, and thus, may have implications on spike protein interaction. In this study, we explored the effects of excluding Zn on the structural stability and binding free energy of the ACE2-S1 protein complex. We generated two versions of an experimentally-derived structure of the ACE2-S1 protein complex: one with Zn and one without. Examining the differences between these two complexes during MD simulation, we found that the Zn-bound complex exhibited greater instability at nearly all residues except for the interacting residues, which were more stable in the Zn-bound complex. Additionally, the Zn-bound complex had a stronger binding free energy at all internal dielectric constants greater than one. Since binding free energy is often used to score inhibitors’ performances, excluding Zn could potentially have implications on inhibitor selection and performance, both in the ACE2-S1 protein system and other protein complexes that include the Zn ion.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.05.494906v1" target="_blank">Implications of Spike Protein Interactions with Zn-bound form of ACE2: A Computational Structural Study</a>
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<li><strong>Modelling Lockdown Effects on Controlling the Spread of COVID-19</strong> -
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The COVID-19 variant omicron is spreading rapidly, infecting about 1.2 million people in 2 months in Hong Kong from early January 2022. Locking down the city at the beginning of outbreak for an adequate period is effective in mitigation and suppression of disease transmission. However, it is difficult to implement the locking down proposal without strong supporting argument because of the accompanied economic loss. An appropriate mathematical model to provide key predictive information on the local epidemic and evaluate the effects of lockdown is reported in this paper. The number of susceptible citizens, infection cases and recovery number under some assumption on isolating citizens are predicted by solving the ordinary differential equations analytically. Observed infected cases during the fifth wave of outbreak in Hong Kong is taken as an example to illustrate the concept. Three lockdown scenarios are proposed and assessed by the developed mathematical approach. Early lockdown is illustrated to keep infected cases low, therefore very effective in controlling the spread by isolating the citizens in their own units.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.04.22275993v1" target="_blank">Modelling Lockdown Effects on Controlling the Spread of COVID-19</a>
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<li><strong>Comparison of variant callers for wastewater-based epidemiology</strong> -
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Wastewater based epidemiology (WBE) has been extensively used during the COVID19 pandemic to detect and monitor the spread of the SARS CoV 2 virus and its variants. It has also proven to be an excellent tool to complement and support insights gained from reported clinical data. Globally, many groups have developed bioinformatics pipelines to analyse sequencing data from wastewater. Accurate calling of mutations from RNA extracted from wastewater samples is key in supporting clinical data to make informed decisions on the prevalence of variants, as well as in the use of WBE as a molecular surveillance tool. However, wastewater samples can be challenging to extract and sequence, and performance of variant calling algorithms in this context has, so far, not been investigated. Analysis of the data and assignment of circulating variants depends heavily on the accuracy of the variant caller, particularly given the degraded nature of the viral RNA and the heterogeneous nature of metagenomic samples. To address this, we compared the performance of six variant callers (VarScan, iVAR, GATK, FreeBayes, LoFreq and BCFtools), used widely in bioinformatics pipelines, on 19 synthetic samples with a known mix of three different SARS CoV 2 variant genomes (Alpha, Beta and Delta), as well as 13 wastewater samples collected in London between the 15th and 18th December 2021. Using the Quasimodo benchmarking tool to compare the six variant callers, we assessed the fundamental parameters of recall (sensitivity) and precision (specificity) in confirming the presence of a variant within the population. Our results show that BCFtools, FreeBayes and VarScan called the expected mutations with higher precision and recall than iVAR or GATK, although the latter identified more expected defining mutations. LoFreq gave the least reliable results due to the high number of false positive mutations detected, resulting in lower precision. Similar results were obtained for both the synthetic and wastewater samples.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.06.22275866v1" target="_blank">Comparison of variant callers for wastewater-based epidemiology</a>
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<li><strong>Transplantation of solid organs recovered from deceased donors recently infected by SARS-CoV-2 in the United States</strong> -
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The COVID-19 pandemic has reduced access to solid organ transplantation, compounding organ shortages and waitlist mortality. A continued area of uncertainty is the safety of transplanting organs recovered from SARS-CoV-2 infected donors, as autopsies of patients who died with COVID-19 show that the virus can be found in extra-pulmonary organs1. Case reports and series on transplantation of these organs have been published 2 ,3, but population-level data is lacking. We queried a national transplant database for recipients of organs recovered from donors recently infected by SARS-CoV-2. In organs where there were over 50 cases, these were then propensity-score matched at a ratio of 1:10 to similar recipients of organs recovered from donors who tested negative for SARS-CoV-2 (controls). Data were extracted from the Scientific Registry of Transplant Recipients (SRTR - v2203 - updated March 2022), which collects detailed information on all solid organ transplants in the United States since 1985. Cases were defined as adult (≥ 18 years) recipients of organs recovered from deceased donors who tested positive for SARS-CoV-2 by nasopharyngeal or lower respiratory sample polymerase chain reaction or antigen assay within 7 days of organ transplantation. Multiple organ transplants were excluded. There were 775 kidney, 330 liver, 123 heart, 44 kidney-pancreas, 16 lung, 5 pancreas, and 3 small bowel transplants of organs recovered from 393 deceased donors recently infected by COVID-19. For kidney, liver, and heart transplants, Kaplan-Meier curves of both overall and graft survival at 90 days were similar between cases and controls. Our data shows that transplanting kidneys, livers, and hearts recovered from deceased donors recently infected by SARS-CoV-2 was not associated with increased recipient mortality or worse graft-survival. This should help transplant providers make decisions regarding acceptance of these organs, and counsel transplant candidates on the safety of receiving them. The limited number of kidney-pancreas, lung, pancreas, and intestinal cases precludes significant conclusions for these organs. Our data also strongly supports the notion that donors with recent COVID-19 infection should not be automatically excluded from the donor pool. receiving them. The limited number of kidney-pancreas, lung, pancreas, and intestinal cases precludes significant conclusions for these organs. Limitations include lack of data on donor infection timeline and estimates of viral load (PCR cycle thresholds), description of donor COVID-19 symptomatology at organ procurement, donor or recipient vaccination or prior COVID-19 infection status, which are not tracked in the database. We did not have information regarding transmission of COVID-19 to transplant recipients. Median follow up time was short, a reflection of how recent these transplants are (see Appendix). Future analysis of updated versions of the database should help address. Our data strongly support the notion that donors with recent COVID infection should not be automatically excluded from the donor pool. Prospective studies are needed to confirm our findings and provide insights on optimal post-transplant management of these recipients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.05.22276008v1" target="_blank">Transplantation of solid organs recovered from deceased donors recently infected by SARS-CoV-2 in the United States</a>
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<li><strong>Global emergence of resistance to fluconazole and voriconazole in Candida parapsilosis in tertiary hospitals in Spain during the COVID-19 pandemic</strong> -
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Background: Candida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins and is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole non-susceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last two years at the Spanish Mycology Reference Laboratory. Methods: Yeast were identified by molecular biology and antifungal susceptibility testing was performed using EUCAST protocol. ERG11 gene was sequenced to identify resistance mechanisms, and typification was carried out by microsatellite analysis. Results: We examined the susceptibility profile of the C. parapsilosis isolates available at our Reference Laboratory since 2000 (around 1,300 strains). During the last two years, the number of isolates with acquired resistance to fluconazole and voriconazole has increased in at least eight different Spanish hospitals. Typification of the isolates revealed that some prevalent clones had spread through several hospitals of the same geographical region. One of these clones was found in hospitals from the region of Catalonia, another in hospitals from Madrid and Burgos, and two other different genotypes from Santander. Conclusions: Our data suggests that the epidemiological situation caused by the COVID-19 pandemic might have induced a selection of fluconazole-resistant C. parapsilosis isolates that were already present at the hospitals. Further measures must be taken to avoid the establishment of clinical outbreaks that could threaten the life of infected patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.06.22275514v1" target="_blank">Global emergence of resistance to fluconazole and voriconazole in Candida parapsilosis in tertiary hospitals in Spain during the COVID-19 pandemic</a>
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<li><strong>Pathogen-Host Adhesion between SARS-CoV-2 S Proteins from Different Variants and Human ACE2 Probed at Single-Molecule and Single-Cell Levels</strong> -
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Pathogen-Host adhesion is considered the first step of infection for many pathogens such as bacteria and virus. The binding of the receptor binding domain (RBD) of SARS-CoV-2 Spike protein (S protein) onto human angiotensin-converting enzyme 2 (ACE2) is considered as the first step for the SARS-CoV-2 to adhere onto the host cells during the infection. Within three years, a number of variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been found all around the world. Here, we investigated the adhesion of S Proteins from different variants and ACE2 using atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) and single-cell force spectroscopy (SCFS). We found that the unbinding force and binding probability of the S protein from Delta variant to the ACE2 was the highest among the variants tested in our study at both single-molecule and single-cell levels. Molecular dynamics simulation showed that ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations, when compared with Delta variant. In addition, a neutralizing antibody, produced by immunization with wild type RBD of S protein, could effectively inhibit the binding of S proteins from wild type, Delta and Omicron variants onto ACE2. Our results provide new insight for the molecular mechanism of the adhesive interactions between S protein and ACE2 and suggest effective monoclonal antibody can be prepared using wild type S protein against the Delta and Omicron variants by inhibit the pathogen-host adhesion.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.05.493249v1" target="_blank">Pathogen-Host Adhesion between SARS-CoV-2 S Proteins from Different Variants and Human ACE2 Probed at Single-Molecule and Single-Cell Levels</a>
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<li><strong>A uniquely stable trimeric model of SARS-CoV-2 spike transmembrane domain</strong> -
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The spike (S) protein of SARS-CoV-2 effectuates membrane fusion and virus entry into target cells. Its transmembrane domain (TMD) represents a homotrimer of -helices anchoring the spike in the viral envelope. Although S-protein models available to date include the TMD, its precise configuration was given brief consideration. Understanding viral fusion entails realistic TMD models, while no reliable approaches towards predicting the 3D structure of transmembrane (TM) trimers exist. Here, we propose a comprehensive computational framework to model the spike TMD (S-TMD) based solely on its primary structure. First, we performed amino acid sequence pattern matching and compared molecular hydrophobicity potential (MHP) distribution on the helix surface against TM homotrimers with known 3D structures and thus selected the TMD of the tumour necrosis factor receptor 1 (TNFR-1) for subsequent template-based modelling. We then iteratively built an all-atom homotrimer model of S-TMD based on “dynamic MHP portraits” and residue variability motifs. In this model each helix possessed two overlapping interfaces interacting with either of the remaining helices, which include conservative residues I1216, F1220, I1227, M1229, and M1233. Finally, the stability of this and several alternative models (including a recent NMR structure) and a set of mutant forms was tested in all-atom molecular dynamics (MD) simulations in a POPC bilayer mimicking the viral envelope membrane. Unlike other configurations, our model trimer remained extraordinarily tightly packed over a microsecond-range MD and retained its stability when palmitoylated in accordance with experimental data. Palmitoylation had no significant impact on the TMD conformation nor the way in which the lipid bilayer was perturbed in the presence of the trimer. Overall, the resulting model of S-TMD conforms to known basic principles of TM helix packing and will be further used to explore the complex machinery of membrane fusion from a broader perspective beyond the TMD.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.05.494856v1" target="_blank">A uniquely stable trimeric model of SARS-CoV-2 spike transmembrane domain</a>
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<li><strong>Discovery of Chlorofluoroacetamide-Based Covalent Inhibitors for SARS-CoV-2 3CL Protease</strong> -
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The pandemic of coronavirus disease 2019 (COVID-19) has urgently necessitated the development of antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). The 3C-like protease (3CLpro) is a promising target for COVID-19 treatment. Here, we report the new class of covalent inhibitors for 3CLpro possessing chlorofluoroacetamide (CFA) as a cysteine reactive warhead. Based on the aza-peptide scaffold, we synthesized the series of CFA derivatives in enantiopure form and evaluated their biochemical efficiencies. The data revealed that 8a (YH-6) with R configuration at the CFA unit strongly blocks the SARS-CoV-2 replication in the infected cells and this potency is comparable to that of nirmatrelvir. The X-ray structural analysis shows that 8a (YH-6) forms a covalent bond with Cys145 at the catalytic center of 3CLpro. The strong antiviral activity and sufficient pharmacokinetics property of 8a (YH-6) suggest its potential as a lead compound for treatment of COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.05.494897v1" target="_blank">Discovery of Chlorofluoroacetamide-Based Covalent Inhibitors for SARS-CoV-2 3CL Protease</a>
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<li><strong>Cross-Cultural Adaptation and Validation of the 5C Scale to Identify Factors Associated With COVID-19 and Influenza Vaccine Hesitancy Among Healthcare Workers in Cape Town, South Africa – A Protocol</strong> -
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Background: Healthcare workers are at an increased risk of acquiring vaccine-preventable diseases and are known to be reliable source of information for the patients and their relatives. Knowledge and attitudes of Healthcare workers about vaccines are thus important determinants of their own vaccination uptake and their intention to recommend vaccinations to their patients. However, culturally adapted tools and studies to address vaccine uptake and hesitancy as well as related behaviours among Healthcare workers in the Global South are limited. Methods: We propose a mixed methods project to understand the extent and determinants of vaccination hesitancy among Healthcare workers and construct a validated scale to measure this complex and context-specific phenomenon in Cape Town. We will summarise responses as counts and percentages for categorical variables and means with standard deviations (or median with inter quartile ranges) for continuous variables. We will run the Shapiro-Wilks test to assess the normality. Analysis of the variance, chi-square tests, and equivalents will be conducted as appropriate for group comparisons. Logistic regression models will also be performed to assess association between variables. We will focus on the seasonal influenza and COVID-19 vaccine. We will use an existing tool developed and validated in Germany and the United States of America to measure five psychological determinants of vaccination (referred to as the 5C scale), as the basis to develop and validate a scale to measure the scope and determinants of vaccine hesitancy and acceptance among Healthcare workers in Cape Town. Discussion and conclusion: Through this study, we hope to expand the scientific evidence based on vaccination acceptance and demand among Healthcare workers in South Africa and build resources to enable better understanding of, detection, and response to vaccination hesitancy in Cape Town.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.06.22276038v1" target="_blank">Cross-Cultural Adaptation and Validation of the 5C Scale to Identify Factors Associated With COVID-19 and Influenza Vaccine Hesitancy Among Healthcare Workers in Cape Town, South Africa – A Protocol</a>
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<li><strong>Correlates of protection, thresholds of protection, and immunobridging in SARS-CoV-2 infection</strong> -
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Several studies show neutralizing antibody levels are an important correlate of immune protection from COVID-19 and have estimated the relationship between neutralizing antibodies and protection. However, a number of these studies appear to yield quite different estimates of the level of neutralizing antibodies required for protection. Here we show that after normalization of antibody titers current studies converge on a consistent relationship between antibody levels and protection from COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.05.22275943v1" target="_blank">Correlates of protection, thresholds of protection, and immunobridging in SARS-CoV-2 infection</a>
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<li><strong>Does place connectivity moderate the association between concentrated disadvantage and COVID-19 fatality in the United States?</strong> -
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Concentrated disadvantaged areas have been disproportionately affected by COVID-19 outbreak in the United States (US). Meanwhile, highly connected areas may contribute to higher human movement, leading to higher COVID-19 cases and deaths. This study examined whether place connectivity moderated the association between concentrated disadvantage and COVID-19 fatality. Using COVID-19 fatality over four time periods, we performed mixed-effect negative binomial regressions to examine the association between concentrated disadvantage, Twitter-based place connectivity, and county-level COVID-19 fatality, considering potential state-level variations. Results revealed that concentrated disadvantage was significantly associated with an increased COVID-19 fatality. More importantly, moderation analysis suggested that place connectivity significantly exacerbated the harmful effect of concentrated disadvantage on COVID-19 fatality, and this significant moderation effect increased over time. In response to COVID-19 and other future infectious disease outbreaks, policymakers are encouraged to focus on the disadvantaged areas that are highly connected to provide additional pharmacological and non-pharmacological intervention policies.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.06.22276053v1" target="_blank">Does place connectivity moderate the association between concentrated disadvantage and COVID-19 fatality in the United States?</a>
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<li><strong>Population-weighted greenspace exposure tied to lower COVID-19 mortality rates: A nationwide dose-response study in the United States</strong> -
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The COVID-19 outbreak has caused enormous deaths and profound social and economic disruption globally. Accumulating evidence suggests exposure to greenspace may reduce the risk of COVID-19 mortality. Greenspace exposure enhances immune functioning, reduces inflammation, and replenishes gut microbiota may protect against the risk of mortality among those with COVID-19. However, previous studies often fail to distinguish the health effect of different types of greenspace, explore the dose-response association and optimal buffer distance, and consider the spatial dynamics of population distribution and geographic locations of greenspace. This study examined the associations among ratio of different types of greenspaces, population-weighted exposure to different types of greenspaces, and COVID-19 mortality rates using a negative binomial generalized linear mixed effects model across 3,025 counties in the United States, adjusted for socioeconomic, demographic, pre-existing chronic disease, policy and regulation, behavioral, and environmental factors. The population-weighted measure gave proportionally greater weight to greenspace near areas of higher population density. Exposure to forest and pasture was negatively associated with COVID-19 mortality rates, while developed open space has insignificant or positive associations with mortality rates. Forest outside park has the largest effect size across all buffer distances, followed by forest inside park. The optimal exposure buffer distance is 1km for forest outside park, with 1 unit of increase in exposure associated with a 9.9% decrease in mortality rates (95% confidence interval: 6.9% -12.8%). The optimal exposure buffer distance of forest inside park is 400m, with 1 unit of increase in exposure, associated with a 4.7% decrease in mortality rates (95% confidence interval: 2.4% - 6.9%). Greenspaces, especially nearby forest, may be effective at lowering the mortality risk of COVID-19 patients. Our findings suggest that policymakers and planners should prioritize forestry within walking distance of residential clusters to mitigate mortality rates during current and future respiratory pandemics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.24.22275549v2" target="_blank">Population-weighted greenspace exposure tied to lower COVID-19 mortality rates: A nationwide dose-response study in the United States</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>A Study to Assess the Safety and Immunogenicity of a COVID-19 Vaccine Booster in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Prime-2-CoV_Beta<br/><b>Sponsors</b>: University Hospital Tuebingen; FGK Clinical Research GmbH; VisMederi srl; Staburo GmbH; Viedoc Technologies AB<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>Eucalyptus Oil as Adjuvant Therapy for Coronavirus Disease 19 (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Eucalyptus Oil; Drug: Standard COVID medication<br/><b>Sponsors</b>: Hasanuddin University; Ministry of Agriculture, Republic of Indonesia<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>Study of Oral High/Low-dose Cepharanthine Compared With Placebo in Non Hospitalized Adults With COVID-19</strong> - <b>Condition</b>: Asymptomatic COVID-19<br/><b>Interventions</b>: Drug: Cepharanthine; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Jiao Tong University School of Medicine; YUNNAN BAIYAO GROUP 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>Evaluation of COVID-19 Vaccines Given as a Booster in Healthy Adults in Indonesia (MIACoV Indonesia)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Pfizer-BioNTech Standard dose; Biological: AstraZeneca Standard dose; Biological: Pfizer-BioNTech Fractional dose; Biological: AstraZeneca Fractional dose; Biological: Moderna Standard dose; Biological: Moderna Fractional dose<br/><b>Sponsors</b>: Murdoch Childrens Research Institute; Universitas Padjadjaran (UNPAD); Universitas Indonesia (UI); Health Development Policy Agency, Ministry of Health Republic of Indonesia; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity<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>α-synuclein Seeding Activity in the Olfactory Mucosa in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Real-time Quaking-Induced Conversion (RT-QuIC)<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>Randomized, Single-blinded, Multicenter Trial Comparing the Immune Response to a 2nd Booster Dose of COVID-19 mRNA Vaccine (Pfizer-BioNTech) or Sanofi /GSK B.1.351 Adjuvanted Vaccine in Adults</strong> - <b>Condition</b>: COVID-19 Vaccines<br/><b>Interventions</b>: Biological: 2nd booster with Comirnaty® (Pfizer-BioNTech); Biological: CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK<br/><b>Sponsors</b>: Assistance Publique - Hôpitaux de Paris; IREIVAC/COVIREIVAC Network<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>Immunogenicity and Safety of a Third Dose of COVID-19 Vaccine(Vero Cell), Inactivated in the Elderly</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: COVID-19 Vaccine (Vero cell), Inactivated<br/><b>Sponsor</b>: Sinovac Research and Development Co., Ltd.<br/><b>Active, not 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, Safety and Immunogenicity Study of the Recombinant Two-component COVID-19 Vaccine (CHO Cell)(Recov)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant two-component COVID-19 vaccine (CHO cell); Biological: Placebo<br/><b>Sponsor</b>: Jiangsu Rec-Biotechnology 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>A Phase 1a Trial to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 mRNA Chimera Vaccine Against COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: RQ3013; Biological: Comirnaty<br/><b>Sponsors</b>: Walvax Biotechnology Co., Ltd.; Shanghai RNACure Biopharma 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>A Phase 1b Trial to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 mRNA Chimera Vaccine Against COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: RQ3013; Biological: Comirnaty<br/><b>Sponsors</b>: Walvax Biotechnology Co., Ltd.; Shanghai RNACure Biopharma 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>Treatment of COVID-19 Post-acute Cognitive Impairment Sequelae With tDCS</strong> - <b>Conditions</b>: Cognitive Impairment; Post-Acute Sequelae of SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Procedure: Active tDCS and cognitive training; Procedure: Sham tDCS and cognitive training<br/><b>Sponsors</b>: University of Sao Paulo; Fundação de Amparo à Pesquisa do Estado de São Paulo<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 and Effectiveness of EV-Pure + WJ-Pure Treatment on Pulmonary Fibrosis Secondary to Covid-19</strong> - <b>Conditions</b>: Pulmonary Fibrosis; COVID-19 Respiratory Infection<br/><b>Interventions</b>: Drug: EV-Pure™ and WJ-Pure™ plus standard care; Drug: Placebo<br/><b>Sponsor</b>: Vitti Labs, LLC<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>Long Haul COVID Rehabilitation & Recovery Research Program</strong> - <b>Condition</b>: Long Haul COVID or Post Acute Sequella of COVID - PASC (U09.9)<br/><b>Intervention</b>: Other: Virtual vs On Site Pulmonary Rehabilitation<br/><b>Sponsor</b>: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center<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 and Effectiveness of Placental Derived Exosomes and Umbilical Cord Mesenchymal Stem Cells in Moderate to Severe Acute Respiratory Distress Syndrome (ARDS) Associated With the Novel Corona Virus Infection (COVID-19)</strong> - <b>Conditions</b>: COVID-19 Acute Respiratory Distress Syndrome; Respiratory Distress Syndrome<br/><b>Interventions</b>: Drug: EV-Pure™ and WJ-Pure™; Drug: Placebo<br/><b>Sponsor</b>: Vitti Labs, LLC<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>Glucoside- and Rutinoside-rich Crude Material for Relieving Side Effects of COVID-19 Vaccines</strong> - <b>Conditions</b>: Vaccine Adverse Reaction; Side-Effect<br/><b>Intervention</b>: Dietary Supplement: Mulberry juice<br/><b>Sponsor</b>: Taipei Medical University<br/><b>Not yet recruiting</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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Novel cleavage sites identified in SARS-CoV-2 spike protein reveal mechanism for cathepsin L-facilitated viral infection and treatment strategies</strong> - The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important target for vaccine and drug development. However, the rapid emergence of variant strains with mutated S proteins has rendered many treatments ineffective. Cleavage of the S protein by host proteases is essential for viral infection. Here, we discovered that the S protein contains two previously unidentified Cathepsin L (CTSL) cleavage sites (CS-1 and CS-2). Both sites are highly conserved among…</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>Performance analysis among multiple fully automated anti-SARS-CoV-2 antibody measurement reagents: A potential indicator for the correlation of protection in the antibody titer</strong> - CONCLUSIONS: The performance observed for each anti-SARS-CoV-2 antibody detection reagent was sufficient. The reference values based on the inhibition rate of sVNT have potential as indicators of the correlation of protection and are expected to be leveraged in automated antibody tests.</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>Review of Anti-inflammatory and Antiviral Therapeutics for Hospitalized Patients Infected with Severe Acute Respiratory Syndrome Coronavirus 2</strong> - Severe acute respiratory syndrome coronavirus 2 infection leads to dysregulation of immune pathways. Therapies focusing on suppressing cytokine activity have some success. Current evidence supports the use of dexamethasone in hospitalized patients requiring oxygen to decrease mortality. Interleukin-6 inhibitors, like tocilizumab and sarilumab, are also beneficial in hypoxemic patients, if used early. Janus kinase inhibition in combination with glucocorticoids is emerging as a potential…</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>Epitope Mapping of an Anti-Chinese/Golden Hamster Podoplanin Monoclonal Antibody</strong> - Chinese hamster (Cricetulus griseus) and golden hamster (Mesocricetus auratus) are important animal models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, which affect several organs, including respiratory tract, lung, and kidney. Podoplanin (PDPN) is a marker of lung type I alveolar cells, kidney podocytes, and lymphatic endothelial cells. The development of anti-PDPN monoclonal antibodies (mAbs) for these animals is essential to evaluate the pathogenesis by…</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>Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells</strong> - COVID-19 is a disease of dysfunctional immune responses, but the mechanisms triggering immunopathogenesis are not established. The functional plasticity of macrophages allows this cell type to promote pathogen elimination and inflammation or suppress inflammation and promote tissue remodeling and injury repair. During an infection, the clearance of dead and dying cells, a process named efferocytosis, can modulate the interplay between these contrasting functions. Here, we show that engulfment 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>Melatonin and multiple sclerosis: antioxidant, anti-inflammatory and immunomodulator mechanism of action</strong> - CONCLUSION: Melatonin could exert a beneficial effect in people suffering from MS, running as a promising candidate for the treatment of this disease. However, more research in human is needed to help understand the possible interaction between melatonin and certain sex hormones, such as estrogens, to know the potential therapeutic efficacy in both men and women.</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>Interleukin-6 Elevation Is a Key Pathogenic Factor Underlying COVID-19-Associated Heart Rate-Corrected QT Interval Prolongation</strong> - CONCLUSION: For the first time, we demonstrated that in severe COVID-19, systemic inflammatory activation can per se promote QTc prolongation via IL-6 elevation, leading to ventricular electric remodeling. Despite being transitory, such modifications may significantly contribute to arrhythmic events and associated poor outcomes in COVID-19. These findings provide a further rationale for current anti-inflammatory treatments for COVID-19, including IL-6-targeted therapies.</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>Severe acute respiratory syndrome coronavirus 2 infection: Role of interleukin-6 and the inflammatory cascade</strong> - Since December 2019, a novel coronavirus that represents a serious threat to human lives has emerged. There is still no definite treatment for severe cases of the disease caused by this virus, named coronavirus disease 2019 (COVID-19). One of the most considered treatment strategies targets the exaggerated immune regulator, and interleukin (IL)-6 is a crucial pro-inflammatory mediator. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases show an elevated level of IL-6 related 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>Omicron BA.1 and BA.2 Neutralizing Activity Following Pre-Exposure Prophylaxis with Tixagevimab plus Cilgavimab in Vaccinated Solid Organ Transplant Recipients</strong> - Neutralizing antibody responses are attenuated in many solid organ transplant recipients (SOTRs) despite SARS-CoV-2 vaccination. Pre-exposure prophylaxis (PrEP) with the monoclonal antibody combination Tixagevimab and Cilgavimab (T+C) might augment immunoprotection, yet activity against Omicron sublineages in vaccinated SOTRs is unknown. Vaccinated SOTRs who received 300+300mg T+C (either single dose or two 150+150mg doses) within a prospective observational cohort submitted pre- and…</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>The DNA glycosylase NEIL2 plays a vital role in combating SARS-CoV-2 infection</strong> - Compromised DNA repair capacity of individuals could play a critical role in the severity of SARS-CoV-2 infection-induced COVID-19. We therefore analyzed the expression of DNA repair genes in publicly available transcriptomic datasets of COVID-19 patients and found that the level of NEIL2, an oxidized base specific mammalian DNA glycosylase, is particularly low in the lungs of COVID-19 patients displaying severe symptoms. Downregulation of pulmonary NEIL2 in CoV-2-permissive animals and…</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>Inhibition of major histocompatibility complex-I antigen presentation by sarbecovirus ORF7a proteins</strong> - Viruses employ a variety of strategies to escape or counteract immune responses, including depletion of cell surface major histocompatibility complex class I (MHC-I), that would ordinarily present viral peptides to CD8+ cytotoxic T cells. As part of a screen to elucidate biological activities associated with individual SARS-CoV-2 viral proteins, we found that ORF7a reduced cell surface MHC-I levels by approximately 5-fold. Nevertheless, in cells infected with SARS-CoV-2, surface MHC-I levels…</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 dual role for CRTH2 in acute lung injury</strong> - Acute respiratory distress syndrome (ARDS) is a life-threatening clinical condition defined by rapid onset respiratory failure following acute lung injury (ALI). Its increased incidence due to COVID-19 and high mortality rate (∼40%) make the study of ARDS pathogenesis a crucial research priority. CRTH2 is a G protein-coupled receptor with established roles in type 2 immunity and well-characterized inhibitors. Prior studies have shown it also promotes neutrophilic inflammation, indicating that…</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>Impact of a blood-stage vaccine on <em>Plasmodium vivax</em> malaria</strong> - CONCLUSIONS: Vaccination of malaria-naïve adults with a delayed booster regimen of PvDBPII/ Matrix-M™ significantly reduces the growth of blood-stage P. vivax . Funded by the European Commission and Wellcome Trust; VAC069, VAC071 and VAC079 ClinicalTrials.gov numbers NCT03797989 , NCT04009096 and NCT04201431 .</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 a Rapid Immuno-Based Screening Assay for the Detection of Adenovirus in Eye Infections</strong> - Despite progress in fighting infectious diseases, human pathogenesis and death caused by infectious diseases remain relatively high worldwide exceeding that of cancer and cardiovascular diseases. Human adenovirus (HAdV) infects cells of the upper respiratory tract causing flu-like symptoms that are accompanied by pain and inflammation. Diagnosis of HAdV is commonly achieved by conventional methods such as viral cultures, immunoassays, and polymerase chain reaction (PCR) techniques. However,…</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 Potent Neutralizing Nanobody Targeting the Spike Receptor-Binding Domain of SARS-CoV-2 and the Structural Basis of Its Intimate Binding</strong> - The continuous spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has raised unprecedented challenges to the human society. Antibodies and nanobodies possessing neutralization activity represent promising drug candidates. In this study, we report the identification and characterization of a potent SARS-CoV-2 neutralizing nanobody that targets the viral spike receptor-binding domain (S-RBD). The nanobody, termed as Nb-007, engages SARS-CoV-2 S-RBD with the…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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