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HTML
180 lines
43 KiB
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<title>06 December, 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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<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>A social network analysis approach to studying whole system disruption related to COVID19 among people who use drugs in Scotland</strong> -
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<div>
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Background and aims: to assess the extent of disruption to service and social interactions among people with lived or living experience of substance use in Scotland, and explore potential reasons for variations in disruption Design: Cross sectional mixed methods interview, incorporating a social network ‘egonet interview’ approach asking about whether participants had interactions with a range of substance use, health, social care or third sector organisations, or informal social interactions. Setting: Five Alcohol and Drug Partnership Areas in Scotland. Participants: 57 (42% women) participants were involved in the study, on average 42 years old. Measurements: Five-point Likert scale reporting whether interactions with a range of services and people had gotten much better, better, no different (or no change), worse, or much worse since COVID19 and lockdown. Ratings were nested within participants (Individuals provided multiple ratings) and some ratings were also nested within treatment service (services received multiple ratings). The nested structure was accounted for using cross classified ordinal logistic multilevel models. Findings: While the overall average suggested only a slight negative change in interactions (mean rating 2.93), there were substantial variations according to type of interaction, and between individuals. Reported change was more often negative for mental health services (Adjusted OR = -0.80 95% CI -1.51, -0.07), and positive for pharmacies (1.29 95% CI 0.67, 1.93). The models found between-participant variation of around 10%, and negligible between-service variation of around 1% in ratings. Ratings didn’t vary by individual age or gender but there was variation between areas. Conclusions: Service adaptations due to COVID19 lockdown led to both positive and negative service user experiences. Social network methods provide an effective way to describe complex system-wide interaction patterns, and to measure variations at the individual, service, and area.
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🖺 Full Text HTML: <a href="https://osf.io/25scv/" target="_blank">A social network analysis approach to studying whole system disruption related to COVID19 among people who use drugs in Scotland</a>
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</div></li>
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<li><strong>Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: a cohort study using OpenSAFELY-TPP</strong> -
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Background Healthcare across all sectors, in the UK and globally, was negatively affected by the COVID-19 pandemic. We investigated the effect of the COVID-19 pandemic on the quantity of healthcare services delivered to people with pancreatic cancer. Methods With the approval of NHS England, and drawing from a nationally representative OpenSAFELY-TPP dataset of 24 million patients (over 40% of the English population), we undertook a cohort study of people diagnosed with pancreatic cancer. We queried electronic healthcare records for information on the provision of healthcare services across the pancreatic cancer pathway. To estimate the effect of the COVID-19 pandemic, we predicted the rates of healthcare services if the pandemic had not happened. We used generalised linear models (GLM) and the pre-pandemic data from January 2015 to February 2020 to predict rates in March 2020 to September 2022. The 95% confidence intervals of the predicted values were used to estimate the significance of the difference between the predicted and observed rates. Results The rate of pancreatic cancer and diabetes diagnoses in the cohort was not affected by the pandemic. There were 24,500 people diagnosed with pancreatic cancer from January 2015 to September 2022. The mean age at diagnosis was 72 (SD 11), 48% of people were female, 95% were of White ethnicity and 39% were diagnosed with diabetes. We found a reduction in surgical resections by nearly 25% during the pandemic. In addition, 20%, 10% and 5% fewer people received BMI, HbA1c and liver function tests respectively before they were diagnosed with pancreatic cancer. There was no impact of the pandemic on the number of people making contact with primary care, but the number of contacts increased on average by 1 to 2 per person amongst those who made contact. Abdominal scans decreased by 7% and reporting of jaundice decreased by 20%, but recovered within six months into the pandemic. Emergency department visits, hospital admissions and deaths were not affected. Conclusions The pandemic affected healthcare in England across the pancreatic cancer pathway. Positive lessons could be learnt from services that recovered quickly. The reductions in healthcare experienced by people with cancer have the potential to lead to worse outcomes. Current efforts should focus on addressing the unmet needs of people with cancer.
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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/10.1101/2022.12.02.22283026v1" target="_blank">Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: a cohort study using OpenSAFELY-TPP</a>
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</div></li>
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<li><strong>Discovering Social Determinants of Health from Case Reports using Natural Language Processing: Algorithmic Development and Validation</strong> -
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Background: Social determinants of health are non-medical factors that influence health outcomes (SDOH). There is a wealth of SDOH information available via electronic health records, clinical reports, and social media, usually in free texts format, which poses a significant challenge and necessitates the use of natural language processing (NLP) techniques to extract key information. Objective: The objective of this research is to advance the automatic extraction of SDOH from clinical texts. Setting and Data: The case reports of COVID-19 patients from the published literature are curated to create a corpus. A portion of the data is annotated by experts to create gold labels, and active learning is used for corpus re-annotation. Methods: A named entity recognition (NER) framework is developed and tested to extract SDOH along with a few prominent clinical entities (diseases, treatments, diagnosis) from the free texts. The proposed model consists of three deep neural networks-A Transformer-based model, a BiLSTM model and a CRF module. Results: The proposed NER implementation achieves an accuracy (F1-score) of 92.98% on our test set and generalizes well on benchmark data. A careful analysis of case examples demonstrates the superiority of the proposed approach in correctly classifying the named entities. Conclusions: NLP can be used to extract key information, such as SDOH from free texts. A more accurate understanding of SDOH is needed to further improve healthcare outcomes.
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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/10.1101/2022.11.30.22282946v1" target="_blank">Discovering Social Determinants of Health from Case Reports using Natural Language Processing: Algorithmic Development and Validation</a>
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</div></li>
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<li><strong>Cyclic lipopeptides as membrane fusion inhibitors against SARS-CoV-2: new tricks for old dogs</strong> -
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<div>
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With the resurgence of the coronavirus pandemic, the repositioning of FDA-approved drugs against coronovirus and finding alternative strategies for antiviral therapy are both important. We previously identified the viral lipid envelope as a potential target for the prevention and treatment of SARS-CoV-2 infection with plant alkaloids. Here, we investigated the effects of eleven cyclic lipopeptides (CLPs), including well-known antifungal and antibacterial compounds, on the liposome fusion triggered by calcium, polyethylene glycol 8000, and a fragment of SARS-CoV-2 fusion peptide (816-827) by calcein release assays. Differential scanning microcalorimetry of the gel-to-liquid-crystalline and lamellar-to-inverted hexagonal phase transitions and confocal fluorescence microscopy demonstrated the relation of the fusion inhibitory effects of CLPs to alterations in lipid packing, membrane curvature stress and domain organization. The effects of the compounds were evaluated in an in vitro Vero-based cell model, and aculeacin A, anidulafugin, iturin A, and mycosubtilin attenuated the cytopathogenicity of SARS-CoV-2 without specific toxicity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.05.519140v1" target="_blank">Cyclic lipopeptides as membrane fusion inhibitors against SARS-CoV-2: new tricks for old dogs</a>
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</div></li>
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<li><strong>High resolution cryo-EM structures of two potently SARS-CoV-2 neutralizing monoclonal antibodies of same donor origin that vary in neutralizing Omicron variants</strong> -
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<div>
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While vaccines have by large been found to effective against the evolving SARS-CoV-2 variants, the profound and rapid effectivity of monoclonal antibodies (mAbs) in significantly reducing hospitalization to severe disease outcomes have also been demonstrated. In the present study, by high resolution cryo-electron microscopy (cryo-EM), we examined the structural insights of two trimeric spike (S) protein bound mAbs isolated from an Indian convalescent individual infected with ancestral SARS-CoV-2 which we recently reported to potently neutralize SARS-CoV-2 from its ancestral form through highly virulent Delta form however different in their ability to neutralize Omicron variants. Our findings showed binding and conformational heterogeneities of both the mAbs (THSC20.HVTR04 and THSC20.HVTR26) bound to S trimer in its apo and hACE-2 bound forms. Additionally, cryo-EM resolved structure assisted modeling highlighted key residues associated with the ability of these two mAbs to neutralize Omicron variants. Our findings highlighted key interacting features modulating antigen-antibody interacting that can further aid in structure guided antibody engineering to enhance their breadth and potency.
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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/10.1101/2022.12.03.518949v1" target="_blank">High resolution cryo-EM structures of two potently SARS-CoV-2 neutralizing monoclonal antibodies of same donor origin that vary in neutralizing Omicron variants</a>
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</div></li>
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<li><strong>Covidscope: An atlas-scale COVID-19 resource for single-cell meta analysis at sample and cell levels</strong> -
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<div>
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Recent advancements in the use of single-cell technologies in large cohort studies enable the investigation of cellular response and mechanisms associated with disease outcome, including COVID-19. Several efforts have been made using single-cell RNA-sequencing to better understand the immune response to COVID-19 virus infection. Nonetheless, it is often difficult to compare or integrate data from multiple data sets due to challenges in data normalisation, metadata harmonisation, and having a common interface to quickly query and access this vast amount of data. Here we present Covidscope (http://covidsc.d24h.hk/), a well-curated open web resource that currently contains single-cell gene expression data and associated metadata of almost 5 million blood and immune cells extracted from almost 1,000 COVID-19 patients across 20 studies around the world. Our collection contains the integrated data with harmonised metadata and multi-level cell type annotations. By combining NoSQL and optimised index, our Covidscope achieves rapid subsetting of high-dimensional gene expression data based on both data set level, donor-level (e.g., age and sex of patients) and cell-level (e.g., expression of specific gene markers) metadata, enabling multiple efficient downstream single-cell meta-analysis.
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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/10.1101/2022.12.03.518997v1" target="_blank">Covidscope: An atlas-scale COVID-19 resource for single-cell meta analysis at sample and cell levels</a>
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<li><strong>Cryo-EM structure of SARS-CoV-2 postfusion spike in membrane</strong> -
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Entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells depends on refolding of the virus-encoded spike protein from a prefusion conformation, metastable after cleavage, to a lower energy, stable postfusion conformation. This transition overcomes kinetic barriers for fusion of viral and target cell membranes. We report here a cryo-EM structure of the intact postfusion spike in a lipid bilayer that represents single-membrane product of the fusion reaction. The structure provides structural definition of the functionally critical membrane-interacting segments, including the fusion peptide and transmembrane anchor. The internal fusion peptide forms a hairpin-like wedge that spans almost the entire lipid bilayer and the transmembrane segment wraps around the fusion peptide at the last stage of membrane fusion. These results advance our understanding of the spike protein in a membrane environment and may guide development of intervention strategies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.05.519151v1" target="_blank">Cryo-EM structure of SARS-CoV-2 postfusion spike in membrane</a>
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<li><strong>How is the COVID-19 pandemic affecting cooperation?</strong> -
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Do crises bring people together or pull them apart? Here we examine how people’s willingness to help others and their perceived interdependence with others changed during the COVID-19 pandemic, and assess what factors are associated with any change. We collected data at 4 time points from the same cohort of 497 paid participants, starting on March 6th, before the pandemic was declared, through April 2. We found that perceived interdependence with neighbors and with humanity increased over time on multiple measures. However, regarding cooperation, agreement with the statement that helping someone in need “is the right thing to do” decreased over time (towards both a neighbor and a citizen of another country). Although the changes per time period were small for some of these effects, cumulatively they were non-trivial (ranging from a .33 to a .75 change on a 7 point likert scale). There was no change over time in participants’ reported willingness to help somebody in their neighborhood (cooperation) or their feelings that when “All of humanity succeeds” they feel good (interdependence). We found reliable associations of change in cooperation and interdependence with sex, age, and pre-existing medical condition. We are collecting data on an ongoing basis which will allow us to investigate how these variables continue to change or not as the pandemic unfolds.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/pk6jy/" target="_blank">How is the COVID-19 pandemic affecting cooperation?</a>
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<li><strong>Deep mutational scanning to predict antibody escape in SARS-CoV-2 Omicron subvariants</strong> -
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The major concern of COVID-19 therapeutic monoclonal antibodies is the loss of efficacy to continuously emerging SARS-CoV-2 variants. To predict the antibodies efficacy to the future Omicron subvariants, we conducted deep mutational scanning (DMS) encompassing all single mutations in the receptor binding domain of BA.2 strain. In case of bebtelovimab that preserves neutralization activity against BA.2 and BA.5, broad range of amino acid substitutions at K444, V445 and G446 and some substitutions at P499 and T500 were indicated to achieve the antibody escape. Among currently increasing subvariants, BA2.75 carrying G446S partly and XBB with V445P and BQ.1 with K444T completely evade the neutralization of bebtelovimab, consistent with the DMS results. DMS can comprehensively characterize the antibody escape for efficient and effective management of future variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.02.518937v1" target="_blank">Deep mutational scanning to predict antibody escape in SARS-CoV-2 Omicron subvariants</a>
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<li><strong>Enhanced Protection from SARS-CoV-2 Variants by MVA-Based Vaccines Expressing Matched or Mismatched S Proteins Administered Intranasally to hACE2 Mice</strong> -
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The continuous evolution of SARS-CoV-2 strains is contributing to the prolongation of the global pandemic. We previously reported the prevention or more rapid clearance of SARS-CoV-2 from the nasal turbinates and lungs of susceptible K18-hACE2 mice that had been vaccinated intranasally (IN) rather than intramuscularly (IM) with a recombinant MVA (rMVA) expressing a modified S protein of the ancestor SARS-CoV-2 strain. Here, we constructed additional rMVAs and pseudoviruses expressing modified S protein of SARS-CoV-2 variants and compared the ability of vaccines with S proteins that were matched or mismatched to neutralize variants, bind to S proteins and protect K18-hACE2 mice against SARS-CoV-2 challenge. Although vaccines with matched S proteins induced higher neutralizing antibodies, vaccines with mismatched S proteins still protected against severe disease and reduced virus and mRNAs in the lungs and nasal turbinates, though not as well as vaccines with matched S proteins. In mice earlier primed and boosted with rMVA expressing ancestral S, antibodies to the latter increased after one immunization with rMVA expressing Omicron S, but neutralizing antibody to Omicron required a second immunization. Passive transfer of Wuhan immune serum with Omicron S binding but undetectable neutralizing activities reduced infection of the lungs by the variant. Notably, the reduction in infection of the nasal turbinates and lungs was significantly greater when the rMVAs were administered IN rather than IM and this held true for vaccines that were matched or mismatched to the challenge SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.03.518963v1" target="_blank">Enhanced Protection from SARS-CoV-2 Variants by MVA-Based Vaccines Expressing Matched or Mismatched S Proteins Administered Intranasally to hACE2 Mice</a>
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<li><strong>Convergent evolution in SARS-CoV-2 Spike creates a variant soup that causes new COVID-19 waves.</strong> -
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The first 2 years of the COVID-19 pandemic were mainly characterized by convergent evolution of mutations of SARS-CoV-2 Spike protein at residues K417, L452, E484, N501 and P681 across different variants of concern (Alpha, Beta, Gamma, and Delta). Since Spring 2022 and the third year of the pandemic, with the advent of Omicron and its sublineages, convergent evolution has led to the observation of different lineages acquiring an additional group of mutations at different amino acid residues, namely R346, K444, N450, N460, F486, F490, Q493, and S494. Mutations at these residues have become increasingly prevalent during Summer and Autumn 2022, with combinations showing increased fitness. The most likely reason for this convergence is the selective pressure exerted by previous infection- or vaccine-elicited immunity. Such accelerated evolution has caused failure of all anti-Spike monoclonal antibodies, including bebtelovimab and cilgavimab. While we are learning how fast coronaviruses can mutate and recombine, we should reconsider opportunities for economically sustainable escape-proof combination therapies, and reevaluate the potential for polyclonal therapies (such as COVID19 convalescent plasma) in immunocompromised patients.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.05.518843v1" target="_blank">Convergent evolution in SARS-CoV-2 Spike creates a variant soup that causes new COVID-19 waves.</a>
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<li><strong>Convergent evolution of the SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant</strong> -
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In late 2022, although the SARS-CoV-2 Omicron subvariants have highly diversified, some lineages have convergently acquired amino acid substitutions at five critical residues in the spike protein. Here, we illuminated the evolutionary rules underlying the convergent evolution of Omicron subvariants and the properties of one of the latest lineages of concern, BQ.1.1. Our phylogenetic and epidemic dynamics analyses suggest that Omicron subvariants independently increased their viral fitness by acquiring the convergent substitutions. Particularly, BQ.1.1, which harbors all five convergent substitutions, shows the highest fitness among the viruses investigated. Neutralization assays show that BQ.1.1 is more resistant to breakthrough BA.2/5 infection sera than BA.5. The BQ.1.1 spike exhibits enhanced binding affinity to human ACE2 receptor and greater fusogenicity than the BA.5 spike. However, the pathogenicity of BQ.1.1 in hamsters is comparable to or even lower than that of BA.5. Our multiscale investigations provide insights into the evolutionary trajectory of Omicron subvariants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.05.519085v1" target="_blank">Convergent evolution of the SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant</a>
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<li><strong>New insights into the structure of Comirnaty Covid-19 vaccine: A theory on soft nanoparticles with mRNA-lipid supercoils stabilized by hydrogen bonds</strong> -
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Despite the worldwide success of mRNA-LNP Covid-19 vaccines, the nanoscale structure of these formulations is still poorly understood. To fill this gap, we used a combination of atomic force microscopy (AFM), dynamic light scattering (DLS), transmission electron microscopy (TEM), cryogenic transmission electron microscopy (cryo-TEM) and the determination of LNP pH gradient to analyze the nanoparticles (NPs) in BNT162b2 (Comirnaty), comparing it with the well characterized pegylated liposomal doxorubicin (Doxil). Comirnaty NPs had similar size to Doxil, however, unlike Doxil liposomes, wherein the stable ammonium and pH gradient enables accumulation of 14C-methylamine in the intraliposomal aqueous phase, Comirnaty LNPs lack such pH gradient in spite of the fact that the pH 4, at which LNPs are prepared, is raised to pH 7.2 after loading of the mRNA. Mechanical manipulation of Comirnaty NPs with AFM revealed soft, compliant structures. The sawtooth-like force transitions seen during cantilever retraction implies that molecular strands, corresponding to mRNA, can be pulled out of NPs, and the process is accompanied by stepwise rupture of mRNA-lipid bonds. Unlike Doxil, cryo-TEM of Comirnaty NPs revealed a granular, solid core enclosed by mono- and bilayers. Negative staining TEM shows 2-5 nm electron-dense spots in the liposom’s interior that are aligned into strings, semicircles, or labyrinth-like networks, which may imply crosslink-stabilized supercoils. The neutral intra-LNP core questions the dominance of ionic interactions holding together this scaffold, raising the alternative possibility of hydrogen bonding between the mRNA and the lipids. Such interaction, described previously for another mRNA/lipid complex, is consistent with the steric structure of ionizable lipid in Comirnaty, ALC-0315, displaying free =O and -OH groups. It is hypothesized that the latter groups can get into steric positions that enable hydrogen bonding with the nitrogenous bases in the mRNA. These newly recognized structural features of mRNA-LNP may be important for the vaccine’s efficacy.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.02.518611v1" target="_blank">New insights into the structure of Comirnaty Covid-19 vaccine: A theory on soft nanoparticles with mRNA-lipid supercoils stabilized by hydrogen bonds</a>
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<li><strong>Comparative effectiveness of sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients on kidney replacement therapy: observational cohort study using the OpenSAFELY-UKRR linked platform and SRR database</strong> -
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Background Patients on kidney replacement therapy (KRT; dialysis and kidney transplantation) are at the highest risk of severe outcomes from COVID-19. Due to limited inclusion of patients on KRT in clinical trials, information is limited on the effectiveness of sotrovimab (a neutralising monoclonal antibody). We sought to address this by comparing its effectiveness against molnupiravir (an antiviral) in preventing severe COVID-19 outcomes in non-hospitalised adults with symptomatic COVID-19. Methods With the approval of NHS England we used routine clinical data from 24 million patients in England linked to the UK Renal Registry (UKRR) to identify patients on KRT, and data on antiviral treatments, COVID-19 test results, hospitalisation events and death from the OpenSAFELY-TPP data resource. Cox proportional hazards models (stratified for region) were used to estimate hazard ratios of sotrovimab vs. molnupiravir with regards to COVID-19 related hospitalisation or deaths in the subsequent 28 days (as the primary outcome). Further analyses were conducted using propensity score weighting (adjusted for region) and to investigate robustness of results with regards to different time periods, missing data, and adjustment variables. We also conducted a complementary analysis using data from patients in the Scottish Renal Registry (SRR) treated with sotrovimab or molnupiravir, following similar analytical approaches. Results Among the 2367 renal patients treated with sotrovimab (n=1852) or molnupiravir (n=515) between December 16, 2021 and August 1, 2022 in England, 38 cases (1.6%) of COVID-19 related hospitalisations/deaths were observed during the 28 days of follow-up after treatment initiation, with 21 (1.1%) in the sotrovimab group and 17 (3.3%) in the molnupiravir group. In multiple-adjusted analysis sotrovimab was associated with substantially lower risk of 28-day COVID-19 related hospitalisation/death than treatment with molnupiravir (hazard ratio, HR=0.35, 95% CI: 0.17 to 0.71; P=0.004), with results remaining robust in sensitivity analyses. In the SRR cohort, there were 19 cases (1.9%) of COVID-19 related hospitalisations/deaths during the 28 days of follow-up after treatment initiation of sotrovimab (n=723) or molnupiravir (n=270). In multiple-adjusted analysis, sotrovimab showed a trend toward lower risk of 28-day COVID-19 related hospitalisation/death than treatment with molnupiravir (HR=0.39, 95% CI: 0.13 to 1.21; P=0.106). In both datasets, sotrovimab had no evidence of association with other hospitalisation/death compared with molnupiravir (HRs ranging from 0.73-1.29; P>0.05). Conclusions In routine care of non-hospitalised patients with COVID-19 on kidney replacement therapy, those who received sotrovimab had substantially lower risk of severe COVID-19 outcomes than those receiving molnupiravir.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.02.22283049v2" target="_blank">Comparative effectiveness of sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients on kidney replacement therapy: observational cohort study using the OpenSAFELY-UKRR linked platform and SRR database</a>
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<li><strong>Brain Alterations in COVID Recovered Revealed by Susceptibility-Weighted Magnetic Resonance Imaging.</strong> -
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The increasing number of reports of mild to severe psychological, behavioral, and cognitive sequelae in COVID-19 survivors motivates a need for a thorough assessment of the neurological effects of the disease. In this regard, we have conducted a neuroimaging study to understand the neurotropic behavior of the coronavirus. We hypothesize that the COVID-recovered subjects have developed alterations in the brain which can be measured through susceptibility differences in various regions of the brain when compared to healthy controls (HCs). Hence, we performed our investigations on susceptibility-weighted imaging (SWI) volumes. Fatigue, being of the most common symptoms of Long COVID, has also been studied in this work. SWI volumes of 46 COVID and 30 HCs were included in this study. The COVID patients were imaged within six months of their recovery. We performed an unpaired two-sample t-test over the pre-processed SWI volumes of both groups and multiple linear regression was performed to observe group differences and correlation of fatigue with SWI values. The group analysis showed that COVID recovered subjects had significantly higher susceptibility imaging values in regions of the frontal lobe and the brain stem. The clusters obtained in the frontal lobe primarily show differences in the white matter regions. The COVID group also demonstrated significantly higher fatigue levels than the HC group. The regression analysis on the COVID group yielded clusters in the anterior cingulate gyrus and midbrain, which exhibited negative correlations with fatigue scores. This study suggests an association of Long COVID with prolonged effects on the brain and also indicates the viability of the SWI modality for analysis of post-COVID symptoms.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.21.22282600v2" target="_blank">Brain Alterations in COVID Recovered Revealed by Susceptibility-Weighted Magnetic Resonance Imaging.</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>Pilot Clinical Trial to Explore Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Pyramax<br/><b>Sponsor</b>: Shin Poong Pharmaceutical Co. Ltd.<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>Animation Supported COVID-19 Education</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Other: Animation-Supported Education<br/><b>Sponsor</b>: Siirt University<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>CareSuperb COVID-19 Antigen Test Usability</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: CareSuperb COVID-19 Antigen Home Test Kit<br/><b>Sponsor</b>: AccessBio, 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>Feasibility and Usability of COVID-19 Antigen RDTs in Uganda</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Diagnostic Test: PMC Sure Status COVID-19 Antigen Test; Diagnostic Test: Acon Flowflex COVID-19 Antigen Home Test<br/><b>Sponsor</b>: PATH<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>The Roles of Vitamin D and Microbiome in Children With Post-acute COVID-19 Syndromes (PACS) and Long COVID</strong> - <b>Condition</b>: Post-acute COVID-19 Syndromes<br/><b>Interventions</b>: Other: Vitamin D; Other: Placebo<br/><b>Sponsor</b>: China Medical University 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 Study to Learn About Bivalent COVID-19 RNA Vaccine Candidate(s) in Healthy Infants and Children</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 3 microgram dose; Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 6 microgram dose; Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 10 microgram dose; Biological: Bivalent BNT162b2 (original/Omicron BA.4/BA.5) 1 microgram dose<br/><b>Sponsors</b>: BioNTech SE; 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>SUNRISE-3: Efficacy and Safety of Bemnifosbuvir in High-Risk Outpatients With COVID-19</strong> - <b>Conditions</b>: SARS CoV 2 Infection; COVID-19<br/><b>Interventions</b>: Drug: Bemnifosbuvir (BEM); Drug: Placebo<br/><b>Sponsor</b>: Atea Pharmaceuticals, 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>Evaluation of an Integrative Medicine Outpatient Clinical Setting for Post-COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Fatigue<br/><b>Interventions</b>: Behavioral: outpatient clinic with multimodal integrative medicine and naturopathy for post-COVID-19 patients; Other: waiting group<br/><b>Sponsor</b>: Universität Duisburg-Essen<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 Study to Evaluate the Efficacy, Safety, and Immunogenicity of SARS-CoV-2 Variant (BA.4 /5) mRNA Vaccine.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: ABO1020; Biological: Placebo<br/><b>Sponsor</b>: Suzhou Abogen Biosciences 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>Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Rapid Panel Professional Use Product Using Mid-Turbinate Nasal Swabs</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza Type B<br/><b>Intervention</b>: Diagnostic Test: Panbio™<br/><b>Sponsor</b>: Abbott Rapid Dx<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of a Physical and Respiratory Rehabilitation Program for Patients With Persistent COVID-19 (SARS-CoV-2).</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19 Recurrent; Cognitive Dysfunction; Fatigue<br/><b>Intervention</b>: Other: COPERIA-REHAB<br/><b>Sponsors</b>: Fundacin Biomedica Galicia Sur; University of Vigo; Galician South Health Research Institute<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>Randomised Clinical Trial to Evaluate the Efficacy of an Online Cognitive Rehabilitation Programme (COPERIA-COG) for Patients With Persistent COVID-19</strong> - <b>Conditions</b>: COVID-19; Neuro-Degenerative Disease; Psychological; SARS CoV 2 Infection<br/><b>Intervention</b>: Other: Sessions of cognitive stimulation<br/><b>Sponsors</b>: Fundacin Biomedica Galicia Sur; Centro de Investigación Biomédica en Red de Salud Mental; Galician South Health Research Institute<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>Evaluate the Efficacy and Safety of Azvudine in Preventing SARS-Cov-2 Infection in Household Contacts of Covid-19</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Drug: Azvudine; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Henlius Biotech; Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.; HeNan Sincere Biotech Co., Ltd<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>VNS for Long-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Postural Tachycardia Syndrome; Dysautonomia<br/><b>Interventions</b>: Device: Non-invasive vagus nerve stimulation; Device: Sham Intervention<br/><b>Sponsor</b>: Icahn School of Medicine at Mount Sinai<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>Effects of an Immersive Virtual Reality Intervention</strong> - <b>Conditions</b>: Nurse’s Role; COVID-19 Pandemic; Mental Stress<br/><b>Interventions</b>: Behavioral: Mindfulness-based Stress Reduction by Therapeutic VR; Behavioral: Mindfulness-based Stress Reduction<br/><b>Sponsor</b>: Nanjing University of Traditional Chinese Medicine<br/><b>Active, not 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>Mechanistic investigation of SARS-CoV-2 main protease to accelerate design of covalent inhibitors</strong> - No abstract</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>FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2</strong> - No abstract</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 impact of sphinogosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination</strong> - No abstract</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>Correction: A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines</strong> - No abstract</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 and Safety of Pacritinib vs Placebo for Patients With Severe COVID-19: A Phase 2 Randomized Clinical Trial</strong> - No abstract</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>Sertraline Is an Effective SARS-CoV-2 Entry Inhibitor Targeting the Spike Protein</strong> - No abstract</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>Real-time monitoring of enzyme-catalyzed phosphoribosylation of anti-influenza prodrug favipiravir by time-lapse NMR spectroscopy</strong> - No abstract</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 live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections</strong> - No abstract</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>Establishment of Quality Evaluation Method for Yinqiao Powder: A Herbal Formula against COVID-19 in China</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of FDA-approved drugs against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) through computational virtual screening</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of highly effective inhibitors against SARS-CoV-2 main protease: From virtual screening to in vitro study</strong> - No abstract</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>Xuebijing injection inhibited neutrophil extracellular traps to reverse lung injury in sepsis mice <em>via</em> reducing Gasdermin D</strong> - No abstract</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>Increased IL-26 associates with markers of hyperinflammation and tissue damage in patients with acute COVID-19</strong> - No abstract</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 of drugs for combined treatment of COVID-19 cytokine storm using machine learning</strong> - No abstract</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 evolution of the global COVID-19 epidemic in Morocco and understanding the different therapeutic approaches of chitosan in the control of the pandemic</strong> - No abstract</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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