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<title>17 September, 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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>SARS-CoV-2 and HSV-1 Induce Amyloid Aggregation in Human CSF</strong> -
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The corona virus (SARS-CoV-2) pandemic and the resulting long-term neurological complications in patients, known as long COVID, have renewed the interest in the correlation between viral infections and neurodegenerative brain disorders. While many viruses can reach the central nervous system (CNS) causing acute or chronic infections (such as herpes simplex virus 1, HSV-1), the lack of a clear mechanistic link between viruses and protein aggregation into amyloids, a characteristic of several neurodegenerative diseases, has rendered such a connection elusive. Recently, we showed that viruses can induce aggregation of purified amyloidogenic proteins via the direct physicochemical mechanism of heterogenous nucleation (HEN). In the current study, we show that the incubation of HSV-1 and SARS-CoV-2 with human cerebrospinal fluid (CSF) leads to the amyloid aggregation of several proteins known to be involved in neurodegenerative diseases, such as: APLP1 (amyloid beta precursor like protein 1), ApoE, clusterin, 2-macroglobulin, PGK-1 (phosphoglycerate kinase 1), ceruloplasmin, nucleolin, 14-3-3, transthyretin and vitronectin. Importantly, UV-inactivation of SARS-CoV-2 does not affect its ability to induce amyloid aggregation, as amyloid formation is dependent on viral surface catalysis via HEN and not its ability to replicate. Our results show that viruses can physically induce amyloid aggregation of proteins in human CSF, and thus providing a potential mechanism that may account for the association between persistent and latent/reactivating brain infections and neurodegenerative diseases.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.15.508120v1" target="_blank">SARS-CoV-2 and HSV-1 Induce Amyloid Aggregation in Human CSF</a>
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</div></li>
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<li><strong>Imprinted SARS-CoV-2 humoral immunity induces converging Omicron RBD evolution</strong> -
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Continuous evolution of Omicron has led to numerous subvariants that exhibits growth advantage over BA.5. Such rapid and simultaneous emergence of variants with enormous advantages is unprecedented. Despite their rapidly divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots, including R346, R356, K444, L452, N460K and F486. The driving force and destination of such convergent evolution and its impact on humoral immunity established by vaccination and infection remain unclear. Here we demonstrate that these convergent mutations can cause striking evasion of convalescent plasma, including those from BA.5 breakthrough infection, and existing antibody drugs, including Evusheld and Bebtelovimab. BA.2.75.2 is the most evasive strain tested, and only BQ.1.1 could compare. To clarify the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies (mAbs) isolated from convalescents of BA.2 and BA.5 breakthrough infection. Importantly, due to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection caused significant reductions of neutralizing antibody epitope diversity and increased proportion of non-neutralizing mAbs, which in turn concentrated humoral immune pressure and promoted the convergent RBD evolution. Additionally, the precise convergent RBD mutations and evolution trends of BA.2.75/BA.5 subvariants could be inferred by integrating the neutralization-weighted DMS profiles of mAbs from various immune histories (3051 mAbs in total). Moreover, we demonstrated that as few as five additional convergent mutations based on BA.5 or BA.2.75 could completely evade most plasma samples, including those from BA.5 breakthrough infections, while remaining sufficient hACE2-binding affinity. These results suggest herd immunity established by natural infection could hardly stop RBD evolution, and vaccine boosters using BA.5 may not provide sufficiently broad protection. Broad-spectrum SARS-CoV-2 vaccines and NAb drugs development should be in high priority and the constructed convergent mutants could serve to examine their effectiveness in advance.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.15.507787v1" target="_blank">Imprinted SARS-CoV-2 humoral immunity induces converging Omicron RBD evolution</a>
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</div></li>
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<li><strong>The role of multi-generational household clusters in COVID-19 in England</strong> -
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Background Household transmission has been demonstrated to be an important factor in the population-level growth of COVID-19. UK Health Security Agency (UKHSA) maintains data on positive tests for COVID-19 and the residential addresses of cases. We sought to use this information to characterise clusters of COVID-19 in multi-generational households in England. Methods Using cross-sectional design, cases of COVID-19 were assigned to clusters if they occurred in the same residential property in a 14-day rolling window. Patient demographic data were supplemented with reference to the ONS index of multiple deprivation and population density. Multi-generational households were defined as a cluster with at least three people, with one case in a person who was 0-16 years old and one case in a person who was ≥ 60 years old, with at least 16 years between two members of each age group. Results A total of 3,647,063 COVID-19 cases were reported between 01 April 2020 and 20 May 2021. Of these, 1,980,527 (54.3 %) occurred in residential clusters. Multi-generational households formed 1.5 % of clusters, with these more likely to occur in areas of higher population density and higher relative deprivation. Multi-generational clusters were more common among households of non-White ethnicity and formed larger clusters than non-multi-generational clusters (median cluster size 6, IQR 4-11 vs 3, IQR 3-4, respectively). Conclusion Multi-generational clusters were not highly prevalent in England during the study period, however were more common in certain populations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.11.22.21266540v2" target="_blank">The role of multi-generational household clusters in COVID-19 in England</a>
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<li><strong>The aerobiology of SARS-CoV-2 in UK hospitals and the impact of aerosol generating procedures</strong> -
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Background: SARS-CoV-2 nosocomial transmission to patients and healthcare workers (HCWs) has occurred throughout the COVID-19 pandemic. Aerosol generating procedures (AGPs) seemed particularly risky, and policies have restricted their use in all settings. We examined the prevalence of aerosolized SARS-CoV-2 in the rooms of COVID-19 patients requiring AGP or supplemental oxygen compared to those on room air. Methods: Samples were collected prospectively near to adults hospitalised with COVID-19 at two tertiary care hospitals in the UK from November 2020-October 2021. The Sartorius MD8 AirPort air sampler was used to collect air samples at a minimum distance of 1.5 meters from patients. RT-qPCR was used following overnight incubation of membranes in culture media and extraction. Results: We collected 219 samples from patients9 rooms: individuals on room air (n=67), receiving oxygen (n=65) or AGP (n=67). Of these, 54 (24.6%) samples were positive for SARS-CoV-2 viral RNA. The highest prevalence was identified in the air around patients receiving oxygen (32.3%, n=21, CI95% 22.2 to 44.3%) with AGP and room air recording prevalence of (20.7%, n=18, CI95% 14.1-33.7%) and (22.3%, n=15, CI95% 13.5-30.4%) respectively. We did not detect a significant difference in the observed frequency of viral RNA between interventions. Interpretation: SARS-CoV-2 viral RNA was detected in the air of hospital rooms of COVID-19 patients, and AGPs did not appear to impact the likelihood of viral RNA. Enhanced respiratory protection and appropriate infection prevention and control measures are required to be fully and carefully implemented for all COVID-19 patients to reduce risk of aerosol transmission.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.07.22279662v2" target="_blank">The aerobiology of SARS-CoV-2 in UK hospitals and the impact of aerosol generating procedures</a>
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</div></li>
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<li><strong>The impact of the COVID-19 pandemic on prescribing of pancreatic enzyme replacement therapy for people with unresectable pancreatic cancer in England. A cohort study using OpenSafely-TPP</strong> -
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Background: Cancer treatments were variably disrupted during the COVID-19 pandemic. Despite UK national guidelines recommending pancreatic enzyme replacement therapy to all people with unresectable pancreatic cancer, observational studies demonstrate under-prescribing. Aim: To investigate the impact of the COVID-19 pandemic on the prescribing of pancreatic enzyme replacement to people with unresectable pancreatic cancer. Methods: With the approval of NHS England, we conducted a cohort study using 24 million health records through the OpenSAFELY-TPP research platform. We modelled the effect of COVID-19 with multivariable linear regression. Results: We found no reduction in pancreatic enzyme replacement therapy during the COVID-19 pandemic. Overall, since 2015, the rates of prescribing increased steadily over time by 1% every year. The national rates ranged from 41% in 2015 to 48% in 2022. There was substantial regional variation. The highest rates of 50% to 60% were in the West Midlands and lowest (20% to 30%) in London. Conclusions: In contrast to many other treatments, prescribing of pancreatic enzyme replacement therapy was not affected during the COVID-19 pandemic. Although overall rates increased over time, substantial under-prescribing existed at the end of this study (March 2022). At just under 50% in 2022, the rates were still below the recommended 100% standard. Prior work evaluating quality of care in this area relied on manual audits which come at increased cost and reduced frequency of updates. With the methodological advantage of OpenSAFELY, we established an automated audit which allows for regular updates.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.08.22277317v4" target="_blank">The impact of the COVID-19 pandemic on prescribing of pancreatic enzyme replacement therapy for people with unresectable pancreatic cancer in England. A cohort study using OpenSafely-TPP</a>
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</div></li>
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<li><strong>Intolerance of aloneness as a prospective predictor of suicidal ideation during COVID-19</strong> -
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Background: Social distancing has been essential in mitigating the spread of the SARS-CoV-2 virus. Evidence regarding the impact of reduced social contact on mental health during the pandemic has been mixed, however, with studies suggesting that enduring personality traits and affect regulation impairments may together increase risk for suicidal distress during periods of lockdown. The present study utilized experience sampling and longitudinal follow-up methods to evaluate intolerance of aloneness (IA) as a predictor of suicidal ideation (SI) during the pandemic. Methods: A general adult sample (n=184) recruited online completed an 8-week experience sampling protocol via smartphone between April and September 2020. A subset of n=69 participants completed a follow-up assessment of SI six months after the initial study period. Results: IA was associated with suicidal ideation both at baseline and prospectively during the experience sampling period. Individuals with greater IA were more likely to report SI in the short-term context of reduced daily in-person social contact. Higher IA at baseline furthermore prospectively predicted the occurrence of SI during the 6-month follow-up period. Limitations: The sample was relatively homogenous in terms of demographic characteristics and excluded individuals with limited access to communication technology. While statistical models accounted for the impact of clinical status, other factors that were not assessed (such as adverse events) may have contributed to the development of SI. Conclusions: Findings enhance understanding of how personality-based factors may contribute to suicide risk during periods of social distancing, informing both clinical treatment, risk assessment, and public health intervention approaches.
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🖺 Full Text HTML: <a href="https://osf.io/5kfp8/" target="_blank">Intolerance of aloneness as a prospective predictor of suicidal ideation during COVID-19</a>
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<li><strong>Quantifying aerosol and droplet generation during upper and lower gastrointestinal endoscopy: whole procedure and event-based analysis</strong> -
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Objective Aerosol generating procedures have become an important healthcare issue due to the COVID-19 pandemic, as the SARS-CoV-2 virus can be transmitted via aerosols. We aimed to characterise aerosol and droplet generation in gastrointestinal endoscopy, where there is little evidence. Design This prospective observational study included patients undergoing routine per-oral gastroscopy (POG, n=36), trans-nasal endoscopy (TNE, n=11) and lower gastrointestinal (LGI) endoscopy (n=48). Particle counters took measurements near the appropriate orifice (two models used, diameter ranges 0.3um-25um and 20um-3000um). Quantitative analysis was performed by recording specific events and subtracting the background particles. Results POG produced 2.06x the level of background particles (p<0.001), and 2.13x the number of particles compared to TNE. LGI procedures produce significant particle counts (p<0.001), with a rate of 8.8x106/min/m3 compared to 13.0x106/min/m3 for POG. Events significant relative to the noise floor of background particles were: POG- throat spray (112.3x, p<0.01), oesophageal extubation (36.7x, p<0.001), coughing/gagging (30.7x, p<0.01); TNE- nasal spray (32.8x, p<0.01), nasal extubation (25.6x, p<0.01), coughing/gagging (23.3x, p<0.01); LGI- rectal intubation (3.5x, p<0.05), rectal extubation (11.8x, p<0.01), application of abdominal pressure (4.9x, p<0.05). These all produced particle counts larger than or comparable to volitional cough. Conclusions Gastrointestinal endoscopy performed via the mouth, nose or rectum all generates significant quantities of aerosols and droplets. As the infectivity of procedures is not established, we therefore suggest adequate PPE is used for all GI endoscopy where there is a high population prevalence of COVID-19. Avoiding throat and nasal spray would significantly reduce particles generated from UGI procedures.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.04.15.21255544v2" target="_blank">Quantifying aerosol and droplet generation during upper and lower gastrointestinal endoscopy: whole procedure and event-based analysis</a>
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<li><strong>A general theory for infectious disease dynamics.</strong> -
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We present a general theory of infection spreading, which directly follows from conservation laws and takes as inputs the probability density functions of latent times. The derivation of the theory substantially differs from Kermack and McKendrick (1927) argument, which instead was based on the concept of removal rates. We demonstrate the formal equivalence of the two approaches, but our theory provides a clear interpretation of the kernels of the integro-differential governing the infection spreading in terms of survival function of the latent times distributions. This aspect was never captured before. Real distributions of latent times can be, then, employed, thus overcoming the limitations of standard SIR, SEIR and other similar models, which implicitly make use of exponential or exponential-related distributions. SIR and SEIR-type models are, in fact, a subclass of the theory here presented. We show that beside the infection rate ν, the joint probability density function p_{EI}(τ,τ₁) of latent times in the exposed and infectious compartments governs the infection spreading. Assuming that the number of infected individuals is negligibile compare to the entire population, we were able to study the stability of the dynamical system and provide the general solution of equations in terms characteristic functions of the probability distribution of latent times. We present asymptotic solutions for the case R₀=1 and demostrate that the moments of the latent times distribution govern the rate of disease spreading in this case. The present theory is employed to simulate the diffusion of COVID-19 infection in Italy during the first 120 days. The estimated value of the basic reproduction number is R₀≈3.5, in very good agreement with existing data.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.12.22278744v2" target="_blank">A general theory for infectious disease dynamics.</a>
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<li><strong>Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine</strong> -
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The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines. Here, we report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein, dimerised with an immunoglobulin IgG1 Fc domain. These were tested in conjunction with three different adjuvants: a TLR2 agonist R4-Pam2Cys, an NKT cell agonist glycolipid alpha-Galactosylceramide, or MF59 squalene oil-in-water adjuvant. Each formulation drove strong neutralising antibody (nAb) responses and provided durable and highly protective immunity against lower and upper airway infection in mouse models of COVID-19. We have also developed an RBD-human IgG1 Fc vaccine with an RBD sequence of the highly immunoevasive beta variant (N501Y, E484K, K417N). This beta variant RBD vaccine, combined with MF59 adjuvant, induced strong protection in mice against the beta strain as well as the ancestral strain. Furthermore, when used as a third dose booster vaccine following priming with whole spike vaccine, anti-sera from beta-RBD-Fc immunised mice increased titres of nAb against other variants including alpha, delta, delta+, gamma, lambda, mu, and omicron BA.1 and BA.2. These results demonstrated that an RBD-Fc protein subunit/MF59 adjuvanted vaccine can induce high levels of broad nAbs, including when used as a booster following prior immunisation of mice with whole ancestral-strain Spike vaccines. This vaccine platform offers a potential approach to augment some of the currently approved vaccines in the face of emerging variants of concern, and it has now entered a phase I clinical trial.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.05.22278425v2" target="_blank">Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine</a>
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<li><strong>Strategies for using antigen rapid diagnostic tests to reduce transmission of SARS-CoV-2 in low- and middle-income countries: a mathematical modelling study applied to Zambia</strong> -
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Background Increasing the availability of antigen rapid diagnostic tests (Ag-RDTs) in low- and middle-income countries (LMICs) is key to alleviating global SARS-CoV-2 testing inequity (median testing rate in December 2021-March 2022 when the Omicron variant was spreading in multiple countries; high-income countries=600 tests/100,000 people/day; LMICs=14 tests/ 100,000 people/day). However, target testing levels and effectiveness of asymptomatic community screening to impact SARS-CoV-2 transmission in LMICs are unclear. Methods We used PATAT, an LMIC-focused agent-based model to simulate COVID-19 epidemics, varying the amount of Ag-RDTs available for symptomatic testing at healthcare facilities and asymptomatic community testing in different social settings. We assumed that testing was a function of access to healthcare facilities and availability of Ag-RDTs. We explicitly modelled symptomatic testing demand from non-SARS-CoV-2 infected individuals and measured impact based on the number of infections averted due to test-and-isolate. Results Testing symptomatic individuals yields greater benefits than any asymptomatic community testing strategy until most symptomatic individuals who sought testing have been tested. Meeting symptomatic testing demand likely requires at least 200-400 tests/100,000 people/day on average as symptomatic testing demand is highly influenced by non-SARS-CoV-2 infected individuals. After symptomatic testing demand is satisfied, excess tests to proactively screen for asymptomatic infections among household members yields the largest additional infections averted. Conclusions Testing strategies aimed at reducing transmission should prioritize symptomatic testing and incentivizing test-positive individuals to adhere to isolation to maximize effectiveness.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.16.22276516v2" target="_blank">Strategies for using antigen rapid diagnostic tests to reduce transmission of SARS-CoV-2 in low- and middle-income countries: a mathematical modelling study applied to Zambia</a>
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<li><strong>SARS-CoV-2 diagnostic testing rates determine the sensitivity of genomic surveillance programs</strong> -
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The first step in SARS-CoV-2 genomic surveillance is testing to identify infected people. However, global testing rates are falling as we emerge from the acute health emergency and remain low in many low- and middle-income countries (LMICs) (mean = 27 tests/100,000 people/day). We simulated COVID-19 epidemics in a prototypical LMIC to investigate how testing rates, sampling strategies, and sequencing proportions jointly impact surveillance outcomes and showed that low testing rates and spatiotemporal biases delay time-to-detection of new variants by weeks-to-months and can lead to unreliable estimates of variant prevalence even when the proportion of samples sequenced is increased. Accordingly, investments in wider access to diagnostics to support testing rates of ~100 tests/100,000 people/day could enable more timely detection of new variants and reliable estimates of variant prevalence. The performance of global SARS-CoV-2 genomic surveillance programs is fundamentally limited by access to diagnostic testing.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.20.22275319v2" target="_blank">SARS-CoV-2 diagnostic testing rates determine the sensitivity of genomic surveillance programs</a>
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<li><strong>SARS-CoV-2 infection of human neurons requires endosomal cell entry and can be blocked by inhibitors of host phosphoinositol-5 kinase</strong> -
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COVID-19 is a disease caused by coronavirus SARS-CoV-2. In addition to respiratory illness, COVID-19 patients exhibit neurological symptoms that can last from weeks to months (long COVID). It is unclear whether these neurological manifestations are due to infection of brain cells. We found that a small fraction of cortical neurons, but not astrocytes, were naturally susceptible to SARS-CoV-2. Based on the inhibitory effect of blocking antibodies, the infection seemed to depend on the receptor angiotensin-converting enzyme 2 (ACE2), which was expressed at very low levels. Although only a limited number of neurons was infectable, the infection was productive, as demonstrated by the presence of double-stranded RNA in the cytoplasm (the hallmark of viral replication), abundant synthesis of viral late genes localized throughout the neuronal cell, and an increase in viral RNA in the culture medium within the first 48 h of infection (viral release). The productive entry of SARS-CoV-2 requires the fusion of the viral and cellular membranes, which results in the delivery of viral genome into the cytoplasm of the target cell. The fusion is triggered by proteolytic cleavage of the viral surface protein spike, which can occur at the plasma membrane or from endo/lysosomes. Using specific combinations of small-molecule inhibitors, we found that SARS-CoV-2 infection of human neurons was insensitive to nafamostat and camostat, which inhibit cellular serine proteases found on the cell surface, including TMPRSS2. In contrast, the infection was blocked by apilimod, an inhibitor of phosphatidyl-inositol 5 kinase (PIK5K) that regulates endosomal maturation.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.14.508057v1" target="_blank">SARS-CoV-2 infection of human neurons requires endosomal cell entry and can be blocked by inhibitors of host phosphoinositol-5 kinase</a>
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<li><strong>The impact of access to financial services on mitigating COVID-19 mortality globally</strong> -
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The COVID-19 pandemic has disproportionately affected different social and demographic groups, deepening the negative health implications of social and economic inequalities and highlighting the importance of social determinants of health. Despite a deep literature on pandemic-related disparities, specifically regarding social determinants and health outcomes, the influence of the accessibility of financial services on health outcomes during COVID-19 remains largely unexplored. Modeling (pre-omicron) COVID-19 mortality across 142 nations, we assess the impact of national-level usage and access to formal financial services. Two financial access indexes constructed through principal component analysis capture (1) usage of and access to formal financial tools and (2) reliance on alternative and informal financial tools. On average, nations with higher pre-pandemic use of and access to formal financial services had substantially lower population mortality risk from COVID-19, controlling for key population health, demographic, and socioeconomic covariates. The scale of effect is similar in magnitude—but opposite in direction—to major risk factors identified in previous literature, such as lung cancer, hypertension, and income inequality. Findings suggest that financial services deserve greater attention both in the public health literature related to COVID-19 and more broadly in policy discussions about fostering better public health overall.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.12.22279872v1" target="_blank">The impact of access to financial services on mitigating COVID-19 mortality globally</a>
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<li><strong>BRAin-wide Neuron quantification Tool reveals strong sexual dimorphism in the evolution of fear memory</strong> -
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The neuronal and molecular mechanisms underlying behavioral responses triggered by fear have received wide interest now, especially with the surge of fear-related disorders associated with the recent Covid-19 pandemic. Fear responses are functionally adaptive behaviors that are strengthened as memories. Indeed, knowing fear circuitry could be the turning point for the comprehension of this emotion and its pathological states, even addressing potential treatments. Understanding memory dynamics presents fundamental technological challenges and calls for the development of new tools and methods able to analyze the entire brain with single-neuron resolution. In this context, we developed the BRAin-wide Neuron quantification Tool (BRANT) for mapping neuronal activation at micron resolution, combining tissue clearing protocol, high-resolution light-sheet microscopy, and automated 3D image analysis. This method allowed us to quantify the evolution of neuronal activation patterns across multiple phases of memory. This approach highlighted a strong sexual dimorphism in the circuits recruited during memory recall, which had no counterpart in the behaviour. The methodology presented here paves the way for a comprehensive functional characterization of the evolution of fear memory.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.12.507637v1" target="_blank">BRAin-wide Neuron quantification Tool reveals strong sexual dimorphism in the evolution of fear memory</a>
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<li><strong>Semantic and population analysis of the genetic targets related to COVID-19 and its association with genes and diseases</strong> -
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SARS-CoV-2 is a coronavirus responsible for one of the most serious, modern worldwide pandemics, with lasting and multi-faceted effects. By late 2021, SARS-CoV-2 has infected more than 180 million people and has killed more than 3 million. The virus gains entrance to human cells through binding to ACE2 via its surface spike protein and causes a complex disease of the respiratory system, termed COVID-19. Vaccination efforts are being made to hinder the viral spread and therapeutics are currently under development. Towards this goal, scientific attention is shifting towards variants and SNPs that affect factors of the disease such as susceptibility and severity. This genomic grammar, tightly related to the dark part of our genome, can be explored through the use of modern methods such as natural language processing. We present a semantic analysis of SARS-CoV-2 related publications, which yielded a repertoire of SNPs, genes and disease ontologies. Population data from the 100Genomes Project were subsequently integrated into the pipeline. Data mining approaches of this scale have the potential to elucidate the complex interaction between COVID-19 pathogenesis and host genetic variation; the resulting knowledge can facilitate the management of high-risk groups and aid the efforts towards precision medicine.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.16.508278v1" target="_blank">Semantic and population analysis of the genetic targets related to COVID-19 and its association with genes and diseases</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>Association Between Smell Training and Quality of Life in Patients With Impaired Sense of Smell Following COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Olfactory training with essential oils; Other: Olfactory training with fragrance-free oils<br/><b>Sponsor</b>: Ditte Gertz Mogensen<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Fourth Dose Study in Australia</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Tozinameran; Biological: Elasomeran; Biological: Bivalent Pfizer-BioNTech; Biological: Bivalent Moderna<br/><b>Sponsors</b>: Murdoch Childrens Research Institute; 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>Safety and Effects of an Investigational COVID-19 Vaccine as a Booster in Healthy People</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Biological: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg; Biological: BNT162b4 5 µg; Biological: BNT162b4 10 µg; Biological: BNT162b4 15 µg<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>Trial of 2nd Booster Dose of COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Invitation to get a 2nd booster dose of COVID-19 vaccine<br/><b>Sponsor</b>: Norwegian Institute of Public Health<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>SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Text Message Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)<br/><b>Sponsors</b>: University of Utah; Utah Department of Health; Association for Utah Community Health; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)<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>SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Conversational Agent Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Text-Messaging (TM); Behavioral: Conversational Agent (CA); Behavioral: Patient Navigation (PN)<br/><b>Sponsors</b>: University of Utah; Utah Department of Health; Association for Utah Community Health; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)<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>PBI-0451 Phase 2 Study in Nonhospitalized Symptomatic Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: PBI-0451; Drug: Placebo<br/><b>Sponsor</b>: Pardes Biosciences, 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>Evaluating the Safety and Efficacy of AD17002 Intranasal Spray in Treating Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AD17002 + Formulation buffer; Biological: Placebo<br/><b>Sponsors</b>: Advagene Biopharma Co. Ltd.; Gadjah Mada University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Community-Based Health Education Programs for the Early Detection of, and Vaccination Against, COVID-19 and the Adoption of Self-Protective Measures of Hong Kong Residents</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Community-based Health Education based on core intervention package; Behavioral: Health Information Sharing Group<br/><b>Sponsors</b>: The Hong Kong Polytechnic University; Food and Health Bureau, Hong Kong<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>Multidisciplinary Day-hospital Versus Waiting List Management of Post-COVID-19 Persistent Symptoms (ECHAP-COVID)</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Intervention</b>: Behavioral: Personalized multidisciplinary day-hospital intervention<br/><b>Sponsor</b>: Assistance Publique - Hôpitaux de Paris<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>Simvastatin Nasal Rinses for the Treatment of COVID-19 Mediated Dysomsia</strong> - <b>Conditions</b>: Olfactory Disorder; COVID-19<br/><b>Intervention</b>: Drug: Simvastatin<br/><b>Sponsors</b>: Washington University School of Medicine; Duke University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety Evaluation of Paxlovid for COVID-19: a Real-world Case-control Study</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: standard-of-care plus Paxlovid; Drug: standard-of-care<br/><b>Sponsor</b>: Ruijin 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>Booster Study of PTX-COVID19-B in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: PTX-COVID19-B; Biological: Comirnaty®<br/><b>Sponsor</b>: Everest Medicines (Singapore) Pte. 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>Booster Superiority Study of PTX-COVID19-B Compared to Vaxzevria® in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: PTX-COVID19-B; Biological: Vaxzevria®<br/><b>Sponsor</b>: Everest Medicines (Singapore) Pte. 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>Engaging Church Health Ministries to Decrease Coronavirus Disease-19 Vaccine Hesitancy in Underserved Populations</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Active Intervention Group<br/><b>Sponsor</b>: Pennington Biomedical Research Center<br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Differential proinflammatory activities of Spike proteins of SARS-CoV-2 variants of concern</strong> - The coronavirus disease 2019 (COVID-19) pandemic turned the whole world upside down in a short time. One of the main challenges faced has been to understand COVID-19-associated life-threatening hyperinflammation, the so-called cytokine storm syndrome (CSS). We report here the proinflammatory role of Spike (S) proteins from different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern in zebrafish. We found that wild-type/Wuhan variant S1 (S1WT) promoted neutrophil…</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>Molecular insights on bioactive compounds againstCovid-19: A Network pharmacological and computational study</strong> - CONCLUSION: This work illustrates probable strategy for identification of phytochemical based cocktails and off-targets which are effective against SARS_CoV 2.</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>Carbohydrate-binding protein from stinging nettle as fusion inhibitor for SARS-CoV-2 variants of concern</strong> - Urtica dioica agglutinin (UDA) is a carbohydrate-binding small monomeric protein isolated from stinging nettle rhizomes. It inhibits replication of a broad range of viruses, including coronaviruses, in multiple cell types, with appealing selectivity. In this work, we investigated the potential of UDA as a broad-spectrum antiviral agent against SARS-CoV-2. UDA potently blocks transduction of pseudotyped SARS-CoV-2 in A549.ACE2^(+)-TMPRSS2 cells, with IC(50) values ranging from 0.32 to 1.22 µM….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 and the potential of Janus family kinase (JAK) pathway inhibition: A novel treatment strategy</strong> - Recent evidence proposed that the severity of the coronavirus disease 2019 (COVID-19) in patients is a consequence of cytokine storm, characterized by increased IL-1β, IL-6, IL-18, TNF-α, and IFN-γ. Hence, managing the cytokine storm by drugs has been suggested for the treatment of patients with severe COVID-19. Several of the proinflammatory cytokines involved in the pathogenesis of COVID-19 infection recruit a distinct intracellular signaling pathway mediated by JAKs. Consequently, JAK…</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><em>In vitro</em> Screening of Herbal Medicinal Products for Their Supportive Curing Potential in the Context of SARS-CoV-2</strong> - COVID-19 herbal medicinal products may have the potential for symptom relief in nonsevere or moderate disease cases. In this in vitro study we screened the five herbal medicinal products Sinupret extract (SINx), Bronchipret thyme-ivy (BRO-TE), Bronchipret thyme-primula (BRO TP), Imupret (IMU), and Tonsipret (TOP) with regard to their potential to (i) interfere with the binding of the human angiotensin-converting enzyme 2 (ACE2) receptor with the SARS-CoV-2 spike S1 protein, (ii) modulate the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A potent synthetic nanobody with broad-spectrum activity neutralizes SARS-CoV-2 virus and the Omicron variant BA.1 through a unique binding mode</strong> - The major challenge to controlling the COVID pandemic is the rapid mutation rate of the SARS-CoV-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is essential to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-CoV-2 variants. Here, we report a synthetic nanobody (named C5G2) obtained by phage display and subsequent antibody engineering. C5G2 has a single-digit nanomolar binding affinity 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>Complement C5a inhibition: a new form of COVID-19 treatment for mechanically ventilated patients?</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>Discovery and Crystallographic Studies of Trisubstituted Piperazine Derivatives as Non-Covalent SARS-CoV-2 Main Protease Inhibitors with High Target Specificity and Low Toxicity</strong> - The continuous spread of SARS-CoV-2 calls for more direct-acting antiviral agents to combat the highly infectious variants. The main protease (M^(pro)) is an promising target for anti-SARS-CoV-2 drug design. Here, we report the discovery of potent non-covalent non-peptide M^(pro) inhibitors featuring a 1,2,4-trisubstituted piperazine scaffold. We systematically modified the non-covalent hit MCULE-5948770040 by structure-based rational design combined with multi-site binding and privileged…</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 refractory warm autoimmune haemolytic anaemia after the SARS-CoV-2 Pfizer-BioNTech vaccine (BNT162b2 mRNA) managed with emergency splenectomy and complement inhibition with eculizumab</strong> - A male in his teens with a history of liver transplant for biliary atresia (aged 2 years) and autoimmune haemolytic anaemia (AIHA, aged 6 years) presented with jaundice, dark urine, fatigue and chest discomfort that began 48 hours after the first dose of SARS-CoV-2 Pfizer-BioNTech vaccine (BNT162b2 mRNA). Investigations revealed a warm AIHA picture. Over 4 weeks the patient developed life-threatening anaemia culminating in haemoglobin of 35 g/L (after transfusion), lactate dehydrogenase of 1293…</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>Therapeutic properties and molecular docking study of some phenolic compounds as anti-human lung cancer potential: A biochemical approach</strong> - Chloroxine (5,7-dichloro-8-hydroxyquinoline) is a molecule utilized in some shampoos for the therapy of seborrheic dermatitis of the scalp and dandruff. In this study, we investigated the inhibition effects of 5,7-dichloro-8-hydroxyquinoline and methyl 3,4,5-trihydroxybenzoate compounds on the 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA Reductase) and urease enzymes. We have obtained results for the HMG-CoA Reductase and urease enzymes at the micromolar level. In our study, inhibition result…</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><em>In silico</em> studies of M<sup>pro</sup> and PL<sup>pro</sup> from SARS-CoV-2 and a new class of cephalosporin drugs containing 1,2,4-thiadiazole</strong> - The SARS-CoV-2 proteases M^(pro) and PL^(pro) are important targets for the development of antivirals against COVID-19. The functional group 1,2,4-thiadiazole has been indicated to inhibit cysteinyl proteases, such as papain and cathepsins. Of note, the 1,2,4-thiadiazole moiety is found in a new class of cephalosporin FDA-approved antibiotics: ceftaroline fosamil, ceftobiprole, and ceftobiprole medocaril. Here we investigated the interaction of these new antibiotics and their main metabolites…</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>Remdesivir analog as SARS-CoV-2 polymerase inhibitor: virtual screening of a database generated by scaffold replacement</strong> - By the end of 2019, a novel strain of the corona viral family named SARS-CoV-2 emerged in Wuhan, China and started to spread worldwide causing one of the most dangerous lethal pandemics. Researchers utilized various reported inhibitors and drug databases for virtual screening analysis against this novel strain. Later on, they succeeded to fish and repurpose remdesivir, an antiviral nucleotide analogue that inhibits RNA polymerase of the Ebola virus, as a promising candidate against SARS-CoV-2….</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 CHARTER-Ireland trial: can nebulised heparin reduce acute lung injury in patients with SARS-CoV-2 requiring advanced respiratory support in Ireland: a study protocol and statistical analysis plan for a randomised control trial</strong> - BACKGROUND: COVID-19 pneumonia is associated with the development of acute respiratory distress syndrome (ARDS) displaying some typical histological features. These include diffuse alveolar damage with extensive pulmonary coagulation activation. This results in fibrin deposition in the microvasculature, leading to the formation of hyaline membranes in the air sacs. Well-conducted clinical trials have found that nebulised heparin limits pulmonary fibrin deposition, attenuates progression of ARDS,…</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>Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture</strong> - Hydroxychloroquine (HCQ), a drug used to treat lupus and malaria, was proposed as a treatment for SARS-coronavirus-2 (SARS-CoV-2) infection, albeit with controversy. In vitro, HCQ effectively inhibits viral entry, but its use in the clinic has been hampered by conflicting results. A better understanding of HCQ’s mechanism of actions in vitro is needed. Recently, anesthetics were shown to disrupt ordered clusters of monosialotetrahexosylganglioside1 (GM1) lipid. These same lipid clusters recruit…</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>Exploring experiences with telehealth-delivered allied healthcare services for people with permanent and significant disabilities funded through a national insurance scheme: a qualitative study examining challenges and suggestions to improve services</strong> - CONCLUSIONS: Some people with permanent and significant disabilities who accessed allied healthcare via telehealth during the pandemic experienced challenges, particularly children. These unique barriers to telehealth need customised solutions so that people with disabilities are not left behind when telehealth services become more mainstream. Increasing experience with telehealth, setting expectations before consultations, supplying resources for therapy and assessing the suitability of clients…</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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