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188 lines
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>25 February, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<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>Machine learning on large scale perturbation screens for SARS-CoV-2 host factors identifies β-catenin/CBP inhibitor PRI-724 as a potent antiviral</strong> -
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<div>
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Expanding antiviral treatment options against SARS-CoV-2 remains crucial as the virus evolves rapidly and drug resistant strains have emerged. Broad spectrum host-directed antivirals (HDA) are promising therapeutic options, however the robust identification of relevant host factors by CRISPR/Cas9 or RNA interference screens remains challenging due to low consistency in the resulting hits. To address this issue, we employed machine learning based on experimental data from knockout screens and a drug screen. As gold standard, we assembled perturbed genes reducing virus replication or protecting the host cells. The machines based their predictions on features describing cellular localization, protein domains, annotated gene sets from Gene Ontology, gene and protein sequences, and experimental data from proteomics, phospho-proteomics, protein interaction and transcriptomic profiles of SARS-CoV-2 infected cells. The models reached a remarkable performance with a balanced accuracy of 0.82 (knockout based classifier) and 0.71 (drugs screen based classifier), suggesting patterns of intrinsic data consistency. The predicted host dependency factors were enriched in sets of genes particularly coding for development, morphogenesis, and neural related processes. Focusing on development and morphogenesis-associated gene sets, we found {beta}-catenin to be central and selected PRI-724, a canonical {beta}-catenin/CBP disruptor, as a potential HDA. PRI-724 limited infection with SARS-CoV-2 variants, SARS-CoV-1, MERS-CoV and IAV in different cell line models. We detected a concentration-dependent reduction in CPE development, viral RNA replication, and infectious virus production in SARS-CoV-2 and SARS-CoV-1-infected cells. Independent of virus infection, PRI-724 treatment caused cell cycle deregulation which substantiates its potential as a broad spectrum antiviral. Our proposed machine learning concept may support focusing and accelerating the discovery of host dependency factors and the design of antiviral therapies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.23.529833v1" target="_blank">Machine learning on large scale perturbation screens for SARS-CoV-2 host factors identifies β-catenin/CBP inhibitor PRI-724 as a potent antiviral</a>
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</div></li>
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<li><strong>Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution</strong> -
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<div>
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During the COVID-19 pandemic, human behavior change as a result of nonpharmaceutical interventions such as isolation may have induced directional selection for viral evolution. By combining previously published empirical clinical data analysis and multi-level mathematical modeling, we found that the SARS-CoV-2 variants selected for as the virus evolved from the pre-Alpha to the Delta variant had earlier and higher infectious periods but a shorter duration of infection. Selection for increased transmissibility shapes the viral load dynamics, and the isolation measure is likely to be a driver of these evolutionary transitions. In addition, we showed that a decreased incubation period and an increased proportion of asymptomatic infection were also positively selected for as SARS-CoV-2 mutated to the extent that people did not isolate. We demonstrated that the Omicron variants evolved in these ways to adapt to human behavior. The quantitative information and predictions we present here can guide future responses in the potential arms race between pandemic interventions and viral evolution.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.23.529742v1" target="_blank">Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution</a>
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</div></li>
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<li><strong>Multiviral Quartet Nanocages Elicit Broad Anti-Coronavirus Responses for Proactive Vaccinology</strong> -
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<div>
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Defending against future pandemics may require vaccine platforms that protect across a range of related pathogens. The presentation of multiple receptor-binding domains (RBDs) from evolutionarily-related viruses on a nanoparticle scaffold elicits a strong antibody response to conserved regions. Here we produce quartets of tandemly-linked RBDs from SARS-like betacoronaviruses coupled to the mi3 nanocage through a SpyTag/SpyCatcher spontaneous reaction. These Quartet Nanocages induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented on the vaccine. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increased the strength and breadth of an otherwise narrow immune response. Quartet Nanocages are a strategy with potential to confer heterotypic protection against emergent zoonotic coronavirus pathogens and facilitate proactive pandemic protection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.24.529520v1" target="_blank">Multiviral Quartet Nanocages Elicit Broad Anti-Coronavirus Responses for Proactive Vaccinology</a>
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<li><strong>Real-time forecasting of COVID-19-related hospital strain in France using a non-Markovian mechanistic model</strong> -
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Background The COVID-19 pandemic emphasised the importance of access to reliable real-time forecasts for key epidemiological indicators. Given the strong heterogeneity between regions, providing forecasts at the local level is essential for health professionals. Methods We developed a SARS-CoV-2 transmission model in France, COVIDici, that performs parameter estimation using up-to-date vaccination coverage and hospital data to provide forecasts up to a four-week horizon based on the current epidemic trend. We present the model, its associated online tool and perform a retrospective evaluation of the forecasts provided from January to December 2021 by comparing to three standard statistical forecasting methods (auto-regression, exponential smoothing, and ARIMA) at the national and regional levels. Results COVIDici allowed simultaneous real-time visualisation of several indicators of the COVID-19 epidemic at the sub-national level. For anticipating risk of critical care unit overload, it performed worse compared to the baseline methods for forecasts under the three-week horizon, but had better point forecasts at the longest horizons (e.g. four weeks) for 8 of the 13 regions considered depending on the metric. Conclusions Effective communication between modelers and clinicians is essential for utilising forecasts for health care planning. Online visualisation tools and consideration of how metrics can be affected by distortion from non-pharmaceutical government interventions facilitate this dialogue.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.21.23286228v1" target="_blank">Real-time forecasting of COVID-19-related hospital strain in France using a non-Markovian mechanistic model</a>
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<li><strong>Performance of Rapid Antigen Tests Based on Symptom Onset and Close Contact Exposure: A secondary analysis from the Test Us At Home prospective cohort study</strong> -
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Abstract Background: The performance of rapid antigen tests for SARS-CoV-2 (Ag-RDT) in temporal relation to symptom onset or exposure is unknown, as is the impact of vaccination on this relationship. Objective: To evaluate the performance of Ag-RDT compared with RT-PCR based on day after symptom onset or exposure in order to decide on when to test. Design, Setting, and Participants: The Test Us at Home study was a longitudinal cohort study that enrolled participants over 2 years old across the United States between October 18, 2021 and February 4, 2022. All participants were asked to conduct Ag-RDT and RT-PCR testing every 48 hours over a 15-day period. Participants with one or more symptoms during the study period were included in the Day Post Symptom Onset (DPSO) analyses, while those who reported a COVID-19 exposure were included in the Day Post Exposure (DPE) analysis. Exposure: Participants were asked to self-report any symptoms or known exposures to SARS-CoV-2 every 48-hours, immediately prior to conducting Ag-RDT and RT-PCR testing. The first day a participant reported one or more symptoms was termed DPSO 0, and the day of exposure was DPE 0. Vaccination status was self-reported. Main Outcome and Measures: Results of Ag-RDT were self-reported (positive, negative, or invalid) and RT-PCR results were analyzed by a central laboratory. Percent positivity of SARS-CoV-2 and sensitivity of Ag-RDT and RT-PCR by DPSO and DPE were stratified by vaccination status and calculated with 95% confidence intervals. Results: A total of 7,361 participants enrolled in the study. Among them, 2,086 (28.3%) and 546 (7.4%) participants were eligible for the DPSO and DPE analyses, respectively. Unvaccinated participants were nearly twice as likely to test positive for SARS-CoV-2 than vaccinated participants in event of symptoms (PCR+: 27.6% vs 10.1%) or exposure (PCR+: 43.8% vs. 22.2%). The highest proportion of vaccinated and unvaccinated individuals tested positive on DPSO 2 and DPE 5-8. Performance of RT-PCR and Ag-RDT did not differ by vaccination status. Ag-RDT detected 78.0% (95% Confidence Interval: 72.56-82.61) of PCR-confirmed infections by DPSO 4. For exposed participants, Ag-RDT detected 84.9% (95% CI: 75.0-91.4) of PCR-confirmed infections by day five post-exposure (DPE 5). Conclusions and Relevance: Performance of Ag-RDT and RT-PCR was highest on DPSO 0-2 and DPE 5 and did not differ by vaccination status. These data suggests that serial testing remains integral to enhancing the performance of Ag-RDT.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.21.23286239v1" target="_blank">Performance of Rapid Antigen Tests Based on Symptom Onset and Close Contact Exposure: A secondary analysis from the Test Us At Home prospective cohort study</a>
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<li><strong>COVID-19 preventive measures in Rohingya refugee camps: An assessment of knowledge, attitude and practice toward COVID-19</strong> -
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Background: Although many studies were conducted on COVID-19 knowledge, attitude, and practice among the general population in many countries, very little is known about refugees, particularly Rohingya refugees in Cox9s Bazar. A vast array of Risk Communication and Community Engagement (RCCE) interventions were implemented in Cox’s Bazar with the intent of reducing disease transmission by empowering the community to adopt public health measures. Objectives: The study aimed to evaluate the current state of knowledge, attitude, and practice among Rohingya refugees as a result of RCCE initiatives. Materials and Methods: A cross-sectional study was conducted with 500 Rohingya individuals. Participants in the study were Rohingya refugees residing in five randomly selected camps where IOM health was operating. Using a structured questionnaire, skilled community health workers surveyed the Rohingya population. In addition to the survey on knowledge, attitude, and practice, the study gathered information on the perspectives and relevance of sociodemographic factors that influence KAP. Results: The study findings indicate that the mean scores for knowledge, attitude, and practice were 9.93 (out of 14), 7.55 (out of 11), and 2.71 (out of 7) respectively. Association was found between knowledge and practice level and age group – elderly age group (>/= 61 years) had less level of knowledge (AOR 0.42, P value= 0.05) and the late mid age group (46 – 60 years) had better practice level (AOR 2.67, P value <0.001). A significant association was also found between good knowledge level and medium family size (5 – 6 members) (P value= 0.02). Conclusions: The study reveals that the Cox9s Bazar Rohingya refugee community has a low knowledge and attitude score about COVID-19 prevention measures. Especially the KAP scores were found significantly low in elderly population. Despite RCCE interventions, the practice level of these measures exhibited a considerably low score. Poor implementation of preventive measures must be identified and remedied, involving the community in future outbreaks of a similar nature.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.21.23286227v1" target="_blank">COVID-19 preventive measures in Rohingya refugee camps: An assessment of knowledge, attitude and practice toward COVID-19</a>
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<li><strong>Genomic surveillance reveals early detection and transition of Delta to Omicron Lineages of SARS-CoV-2 Variants in wastewater treatment plants of Pune, India</strong> -
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The COVID-19 pandemic has emphasized the urgency for rapid public health surveillance methods in early detection and monitoring of the transmission of infectious diseases. The wastewater-based epidemiology (WBE) has emerged as a promising tool to analyze and enumerate the prevalence of infectious pathogens in a population ahead of time. In the present study, real time quantitative polymerase chain reaction (RT-qPCR) and Illumina sequencing was performed to determine the SARS-CoV-2 load trend and dynamics of variants over a longitudinal scale in 442 wastewater (WW) samples collected from 10 sewage treatment plants (STPs) of Pune city, India, during November 2021 to April-2022. In total 426 distinct lineages representing 17 highly transmissible variants of SARS-CoV-2 were identified. The SARS-CoV-2 Omicron variant fragments were detected in WW samples prior to its detection in clinical cases. Moreover, highly contagious sub-lineages of Omicron, such as BA.2.12 (0.8-0.25%), BA.2.38 (0.8-1.0%), BA.2.75 (0.01-0.02%), BA.3 (0.09-6.3%), BA.4 (0.24-0.29%), and XBB (0.01-13.7%) fragments were significantly detected. The longitudinal analysis also suggested the presence of the BA.5 lineage in November 2021, which was not reported in the clinical settings throughout the duration of this study, indicative of silent variant persistence. Overall, the present study demonstrated the practicality of WBE in early detection of SARS CoV-2 variants, which could be useful in tracking future outbreaks of SARS-CoV-2. Such approaches could be implicated in the monitoring of the infectious agents before they appear in clinical cases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.21.23286222v1" target="_blank">Genomic surveillance reveals early detection and transition of Delta to Omicron Lineages of SARS-CoV-2 Variants in wastewater treatment plants of Pune, India</a>
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<li><strong>Pathways to altered virulence of SARS-CoV-2</strong> -
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The recently emerged SARS-CoV-2 virus has led to a prolonged pandemic characterized by ongoing viral evolution. Vaccines have been an important piece in the strategy to combat the virus but have been insufficient to contain it as the virus continues to evolve to evade immunity developed by vaccination and infection. A consistent argument is that vaccination or prior immunity will lead to less severe infections. In this review, we address the question of whether the virus can evolve to become more virulent, despite prior infection. We describe the intrinsic characteristics of the virus and their relationship to altered virulence. We show that it is likely that viral evolution is subject to evolutionary drift, and it cannot be assumed that the virus will necessarily evolve to be less virulent, or that prior immunity will offer durable protection against severe disease. This has strong implications for public health strategies to confront the ongoing challenges presented by SARS-CoV-2 and implies that there are significant risks to a strategy based on the assumption of waning virulence.
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🖺 Full Text HTML: <a href="https://osf.io/k4hb3/" target="_blank">Pathways to altered virulence of SARS-CoV-2</a>
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<li><strong>Integrating autoethnography and dynamic p-technique: A convergent explanatory bidirectional single-subject study on embodying mindfulness as an instructor</strong> -
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This article contributes to the mixed methods research (MMR) field a description of utilizing MMR in a single-subject design. The example utilizes a convergent intensive longitudinal data collection strategy and an explanatory bidirectional framework for data merging analysis to examine one female faculty member’s practices of incorporating social-emotional learning (SEL) and mindfulness during the COVID-19 pandemic to reduce burnout. By examining results from the dynamic p-technique (a special case of structural equation modeling) and reflexive journaling resulting in autoethnography, a clearer, longitudinal picture of one faculty member’s lived experience emerged. The study is a concrete demonstration of how structural equation modeling and autoethnography methods can be combined within a convergent data collection strategy and explanatory bidirectional analytic framework. Readers interested in replicating the dynamic p-technique analyses can access our tutorial and supplemental materials at https://bit.ly/osfburnout.
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🖺 Full Text HTML: <a href="https://osf.io/4jhgb/" target="_blank">Integrating autoethnography and dynamic p-technique: A convergent explanatory bidirectional single-subject study on embodying mindfulness as an instructor</a>
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<li><strong>Durable reprogramming of neutralising antibody responses following breakthrough Omicron infection</strong> -
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SARS-CoV-2 breakthrough infection of vaccinated individuals is increasingly common with the circulation of highly immune evasive and transmissible Omicron variants. Here, we report the dynamics and durability of recalled spike-specific humoral immunity following BA.1 or BA.2 breakthrough infection, with longitudinal sampling up to 8 months post-infection. Both BA.1 and BA.2 infection robustly boosted neutralisation activity against the infecting strain while expanding breadth against other Omicron strains. Cross-reactive memory B cells against both ancestral and Omicron spike were predominantly expanded by infection, with limited recruitment of de novo Omicron-specific B cells or antibodies. Modelling of neutralisation titres predicts that protection from symptomatic reinfection against antigenically similar strains will be remarkably durable, but is undermined by novel emerging strains with further neutralisation escape.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.19.23286159v1" target="_blank">Durable reprogramming of neutralising antibody responses following breakthrough Omicron infection</a>
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<li><strong>Bivalent COVID-19 vaccine antibody responses to Omicron variants suggest that responses to divergent variants would be improved with matched vaccine antigens</strong> -
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We compared neutralizing antibody responses to BA.4/5, BQ.1.1, XBB, and XBB.1.5 Omicron SARS-CoV-2 variants after a bivalent or ancestral COVID-19 mRNA booster vaccine or post-vaccination infection. We found that the bivalent booster elicited moderately high antibody titers against BA.4/5 that were approximately two-fold higher against all Omicron variants than titers elicited by the monovalent booster. The bivalent booster elicited low but similar titers against both XBB and XBB.1.5 variants. These findings inform risk assessments for future COVID-19 vaccine recommendations and suggest that updated COVID-19 vaccines containing matched vaccine antigens to circulating divergent variants may be needed.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.22.23286320v1" target="_blank">Bivalent COVID-19 vaccine antibody responses to Omicron variants suggest that responses to divergent variants would be improved with matched vaccine antigens</a>
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<li><strong>Was access and quality of healthcare affected during COVID-19 pandemic? A qualitative enquiry into healthcare access for non-communicable diseases in Central India</strong> -
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Objective: COVID-19 pandemic has had significant impacts on healthcare systems across the world. However, its impact on healthcare systems in Low- and Middle-Income Countries (LMICs) has been especially devastating, resulting in restricted access to healthcare. The present study was conducted to assess healthcare access for non-communicable diseases (NCDs) in Central India. Design: Inductive and deductive thematic analysis of in-depth semi-structured interviews. Setting: Study was conducted in communities of two urban and rural districts of central India. Participants: Interviewed participants included PLNCDs, their caregivers, community dwellers, CHWs such as, Accredited Social Health Activists (ASHAs) and Anganwadi Workers (AWWs), Medical Officers, and Community Leaders. Recruitment of the participants was done via purposive and convenience sampling. Result: A total of fifty Key Informant Interviews were (KIIs) conducted. All participants reported facing considerable difficulties while trying to access care from both public as well as private healthcare facilities. Absence of staff, equipment and medicines, restricted commute, misconceptions regarding the spread of COVID-19, and the stigma attached to COVID-19 infection acted as major barriers to accessing care, while door-to-door visits by community health workers, community support, and presence of privately owned healthcare facilities in the vicinity acted as facilitators. Conclusion: In our study, we found that continued functioning of primary healthcare centres, ensuring uninterrupted supply of medicine and effective dissemination of information regarding COVID-19 could have acted to ease access to healthcare. Going ahead, capacity building to offset the impact of future emergencies and pandemics should be a crucial consideration while developing resilient healthcare systems.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.23.23286390v1" target="_blank">Was access and quality of healthcare affected during COVID-19 pandemic? A qualitative enquiry into healthcare access for non-communicable diseases in Central India</a>
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<li><strong>COVID-19 Booster Vaccination Strategy</strong> -
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Despite the fact that medical specialists believe COVID-19 vaccinations are successful in regulating the virus’s health consequences, demand in such vaccines among various communities has been quite low. On that basis, experts have questioned whether combining influenza vaccinations might improve vaccine uptake. The key reason for their hypothesis is that the number of persons obtaining influenza vaccinations outnumbers those interested in various COVID-19 vaccines. As a result, the current work entails a systematic review and meta-analysis of various research studies focusing on combining influenza and COVID-19 booster immunization to enhance vaccine uptake among groups severely impacted by the health pandemic. It is the appropriate time to undertake such systematic review and meta-analysis mainly because of the need to make informed health decisions on mitigating the health implications of such viruses, especially among diverse populations that are majorly affected by them.
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🖺 Full Text HTML: <a href="https://osf.io/2ye9p/" target="_blank">COVID-19 Booster Vaccination Strategy</a>
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<li><strong>Personalized and privacy-preserving federated heterogeneous medical image analysis with PPPML-HMI</strong> -
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Heterogeneous data is endemic due to the use of diverse models and settings of devices by hospitals in the field of medical imaging. However, there are few open-source frameworks for federated heterogeneous medical image analysis with personalization and privacy protection without the demand to modify the existing model structures or to share any private data. In this paper, we proposed PPPML-HMI, a novel open-source learning paradigm for personalized and privacy-preserving federated heterogeneous medical image analysis. To our best knowledge, personalization and privacy protection were achieved simultaneously for the first time under the federated scenario by integrating the PerFedAvg algorithm and designing the novel cyclic secure aggregation with the homomorphic encryption algorithm. To show the utility of PPPML-HMI, we applied it to a simulated classification task namely the classification of healthy people and patients from the RAD-ChestCT Dataset, and one real-world segmentation task namely the segmentation of lung infections from COVID-19 CT scans. For the real-world task, PPPML-HMI achieved $$5% higher Dice score on average compared to conventional FL under the heterogeneous scenario. Meanwhile, we applied the improved deep leakage from gradients to simulate adversarial attacks and showed the strong privacy-preserving capability of PPPML-HMI. By applying PPPML-HMI to both tasks with different neural networks, a varied number of users, and sample sizes, we further demonstrated the strong generalizability of PPPML-HMI.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.19.22279631v1" target="_blank">Personalized and privacy-preserving federated heterogeneous medical image analysis with PPPML-HMI</a>
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</div></li>
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<li><strong>COVID-19 Booster Vaccination Strategy</strong> -
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<div>
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Despite the fact that medical specialists believe COVID-19 vaccinations are successful in regulating the virus’s health consequences, demand in such vaccines among various communities has been quite low. On that basis, experts have questioned whether combining influenza vaccinations might improve vaccine uptake. The key reason for their hypothesis is that the number of persons obtaining influenza vaccinations outnumbers those interested in various COVID-19 vaccines. As a result, the current work entails a systematic review and meta-analysis of various research studies focusing on combining influenza and COVID-19 booster immunization to enhance vaccine uptake among groups severely impacted by the health pandemic. It is the appropriate time to undertake such systematic review and meta-analysis mainly because of the need to make informed health decisions on mitigating the health implications of such viruses, especially among diverse populations that are majorly affected by them.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/jqvng/" target="_blank">COVID-19 Booster Vaccination Strategy</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Heterologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine in Children 12-17 Years of Age</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: SARS-CoV-2 subunit protein recombinant vaccine<br/><b>Sponsors</b>: PT Bio Farma; Faculty of Medicine Universitas Padjadjaran<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>Exercise Training Six-Months After Discharge in Post-COVID-19 Syndrome</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Other: Aerobic exercise and strength training<br/><b>Sponsor</b>: Ukbe Sirayder<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm C (Fluticasone)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluticasone; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm A (Ivmermectin 400)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Ivermectin; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>Counter-Regulatory Hormonal and Stress Systems in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: Blood sampling<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<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>Exploratory Efficacy of N-Acetylcysteine in Patients With History of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: N-Acetylcysteine; Drug: Placebo<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Specific miRNA Encoded by SARS-CoV-2 as a Diagnostic Tool to Predict Disease Severity in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: miRNA analysis in plasma<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<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>Application and Research of Mesenchymal Stem Cells in Alleviating Severe Development of COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Umbilical cord mesenchymal stem cells implantation; Other: Comparator<br/><b>Sponsor</b>: Hebei Medical University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cognitive Rehabilitation for People With Cognitive Covid19</strong> - <b>Condition</b>: Long Covid19<br/><b>Intervention</b>: Behavioral: Cognitive rehabilitation<br/><b>Sponsors</b>: University College, London; Bangor University; St George’s University Hospitals NHS Foundation Trust; University of Brighton; University Hospital Southampton NHS Foundation Trust; Greater Manchester Mental Health NHS Foundation Trust<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>MGC Health COVID-19 & Flu A+B Home Multi Test Usability Study</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza B<br/><b>Interventions</b>: Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test; Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test (2 to 13 y/o)<br/><b>Sponsors</b>: Medical Group Care, LLC; CSSi Life Sciences<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>Washing COVID-19 Away With a Hypertonic Seawater Nasal Irrigation Solution</strong> - <b>Condition</b>: SARS-CoV2 Infection<br/><b>Intervention</b>: Other: Hypertonic seawater solution<br/><b>Sponsor</b>: Larissa University Hospital<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>Exercise Intervention Using mHealth in Patients With Post-Acute COVID-19 Syndrome: a Randomized Clinical Trial</strong> - <b>Conditions</b>: Post-Acute COVID19 Syndrome; Long COVID; Post COVID-19 Condition<br/><b>Interventions</b>: Device: COVIDReApp Group; Other: Control Group<br/><b>Sponsor</b>: University of Cadiz<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>Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach</strong> - <b>Conditions</b>: Social Determinants of Health; Mental Health Issue; COVID-19<br/><b>Interventions</b>: Other: Individual Counseling; Other: Group Counseling; Other: Resources<br/><b>Sponsors</b>: New Mexico State University; National Institutes of Health (NIH)<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>To Evaluate the Safety, Efficacy,and Pharmacokinetics of Orally Administered Prolectin-M</strong> - <b>Conditions</b>: COVID-19; SARS CoV 2 Infection<br/><b>Intervention</b>: Drug: Prolectin-M<br/><b>Sponsor</b>: Bioxytran Inc.<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>Post COVID-19 REspiratory Mechanisms and the Efficacy of a Breathing Exercise Intervention for DYsregulated Breathing</strong> - <b>Conditions</b>: COVID-19; Respiratory Disease<br/><b>Intervention</b>: Other: Breathing techniques over 12 sessions / 6 weeks inc yoga<br/><b>Sponsor</b>: University of Nottingham<br/><b>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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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>BA.1, BA.2 and BA.2.75 variants show comparable replication kinetics, reduced impact on epithelial barrier and elicit cross-neutralizing antibodies</strong> - The Omicron variant of SARS-CoV-2 is capable of infecting unvaccinated, vaccinated and previously-infected individuals due to its ability to evade neutralization by antibodies. With multiple sub-lineages of Omicron emerging in the last 12 months, there is inadequate information on the quantitative antibody response generated upon natural infection with Omicron variant and whether these antibodies offer cross-protection against other sub-lineages of Omicron variant. In this study, we…</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>SARS-CoV-2 ORF8 dimerization and binding mode analysis with class I MHC: computational approaches to identify COVID-19 inhibitors</strong> - SARS-CoV-2 encodes eight accessory proteins, one of which, ORF8, has a poorly conserved sequence with SARS-CoV and its role in viral pathogenicity has recently been identified. ORF8 in SARS-CoV-2 has a unique functional feature that allows it to form a dimer structure linked by a disulfide bridge between Cys20 and Cys20 (S-S). This study provides structural characterization of natural mutant variants as well as the identification of potential drug candidates capable of binding directly to 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>Nuclear export inhibitor Selinexor targeting XPO1 enhances coronavirus replication</strong> - Nucleocytoplasmic transport of proteins using XPO1 (exportin 1) plays a vital role in cell proliferation and survival. Many viruses also exploit this pathway to promote infection and replication. Thus, inhibiting XPO1-mediated nuclear export with selective inhibitors activates multiple antiviral and anti-inflammatory pathways. The XPO1 inhibitor, Selinexor, is an FDA-approved anticancer drug predicted to have antiviral function against many viruses, including SARS-CoV-2. Unexpectedly, we…</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>Use of the particle agglutination/particle agglutination inhibition test for antigenic analysis of SARS-CoV-2</strong> - CONCLUSIONS: The PAI test is an easy and rapid method to analyze the antigenicity of 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>Machine learning combines atomistic simulations to predict SARS-CoV-2 Mpro inhibitors from natural compounds</strong> - To date, the COVID-19 pandemic has still been infectious around the world, continuously causing social and economic damage on a global scale. One of the most important therapeutic targets for the treatment of COVID-19 is the main protease (Mpro) of SARS-CoV-2. In this study, we combined machine-learning (ML) model with atomistic simulations to computationally search for highly promising SARS-CoV-2 Mpro inhibitors from the representative natural compounds of the National Cancer Institute (NCI)…</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>Relapse of acquired hemophilia A following COVID-19</strong> - Acquired hemophilia A (AHA) is a rare disease in which an autoantibody causes bleeding by interacting with and inhibiting the coagulation activity of endogenous factor VIII (FⅧ). Most cases of AHA are idiopathic, and other causes include autoimmune diseases, malignant tumors, pregnancy, drugs, and viral infections. An 86-year-old man was diagnosed with AHA based on the following results: activated partial thromboplastin time (aPTT) extension of 130.7 seconds, inhibitor pattern by mixing study,…</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>HLA-E<em>01:01 + HLA-E</em>01:01 genotype confers less susceptibility to COVID-19, while HLA-E<em>01:03 + HLA-E</em>01:03 genotype is associated with more severe disease</strong> - BACKGROUND: HLA-E interaction with inhibitory receptor, NKG2A attenuates NK-mediated cytotoxicity. NKG2A overexpression by SARS-CoV-2 exhausts NK cells function, whereas virus-induced down-regulation of MHC-Ia reduces its derived-leader sequence peptide levels required for proper binding of HLA-E to NKG2A. This leads HLA-E to become more complex with viral antigens and delivers them to CD8^(+) T cells, which facilitates cytolysis of infected cells. Now, the fact that alleles of HLA-E have…</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>DiDang decoction improves mitochondrial function and lipid metabolism via the HIF-1 signaling pathway to treat atherosclerosis and hyperlipidemia</strong> - CONCLUSION: DDD exerts therapeutic effects on AS and HLP through multiple targets and pathways, and improves mitochondrial function, reduces ROS content, inhibits ferroptosis and apoptosis by activating the HIF-1 signaling pathway, which provides reliable theoretical and experimental support for DDD treatment of AS and HLP.</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>Investigating the competition between ACE2 natural molecular interactors and SARS-CoV-2 candidate inhibitors</strong> - The SARS-CoV-2 pandemic still poses a threat to the global health as the virus continues spreading in most countries. Therefore, the identification of molecules capable of inhibiting the binding between the ACE2 receptor and the SARS-CoV-2 spike protein is of paramount importance. Recently, two DNA aptamers were designed with the aim to inhibit the interaction between the ACE2 receptor and the spike protein of SARS-CoV-2. Indeed, the two molecules interact with the ACE2 receptor in the region…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of the mitochondrial pyruvate carrier simultaneously mitigates hyperinflammation and hyperglycemia in COVID-19</strong> - The relationship between diabetes and COVID-19 is bi-directional: while individuals with diabetes and high blood glucose (hyperglycemia) are predisposed to severe COVID-19, SARS-CoV-2 infection can also cause hyperglycemia and exacerbate underlying metabolic syndrome. Therefore, interventions capable of breaking the network of SARS-CoV-2 infection, hyperglycemia, and hyper-inflammation, all factors that drive COVID-19 pathophysiology, are urgently needed. Here, we show that genetic ablation or…</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>Arabincoside B isolated from Caralluma arabica as a potential anti-pneumonitis in LPS mice model</strong> - Acute lung injury (ALI) is a life-threatening condition usually associated with poor therapeutic outcomes and a high mortality rate. Since 2019, the situation has worsened due to the COVID-19 pandemic. ALI had approximately 40% of deaths before COVID-19, mainly due to the dysfunction of the blood-gas barrier that led to lung edema, failure of gas exchange, and dyspnea. Many strategies have been taken to mitigate the disease condition, such as diuretics, surfactants, antioxidants,…</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>Azapeptide activity-based probes for the SARS-CoV-2 main protease enable visualization of inhibition in infected cells</strong> - The COVID-19 pandemic has revealed the vulnerability of the modern, global society. With expected waves of future infections by SARS-CoV-2, treatment options for infected individuals will be crucial in order to decrease mortality and hospitalizations. The SARS-CoV-2 main protease is a validated drug target, for which the first inhibitor has been approved for use in patients. To facilitate future work on this drug target, we designed a solid-phase synthesis route towards azapeptide activity-based…</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>Plant-derived Ren’s oligopeptide has antiviral effects on influenza virus and SARS-CoV-2</strong> - Influenza virus and SARS-CoV-2 virus are two important viruses that cause respiratory tract diseases. The high-frequency mutation of the two types of viruses leads to failure of the durable immune protection of vaccines, meanwhile it also poses continuous challenges to the development of antiviral drugs. Traditional Chinese medicine contains large number of biologically active compounds, and some of them contain broad-spectrum antiviral ingredients. In this study, we extracted antiviral active…</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 epidemic voluntary vaccinating behavior based on information-driven decisions and benefit-cost analysis</strong> - A complex dynamic interplay exists between epidemic transmission and vaccination, which is significantly influenced by human behavioral responses. We construct a research framework combining both the function modeling of the cumulative global COVID-19 information and limited individuals’ information processing capacity employing the Gompertz model for growing processes. Meanwhile, we built a function representing the decision to get vaccinated following benefit-cost analysis considered 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>Synthesis of non-symmetric <em>N</em>-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus</strong> - Based on the data obtained by molecular modeling of the non-covalent interaction of non-symmetric N-benzylbispidin-9-ol amides with the active site of the main protease 3CLpro of the SARS-CoV-2 virus, a series of compounds was synthesized, and their inhibitory activity against 3CLpro was studied and compared with that of the known inhibitor ML188 (IC(50) = 1.56±0.55 µmol L^(-1)). It was found that only compound 1g containing the 1,4-dihydroindeno[1,2-c]pyrazole fragment showed moderate activity…</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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