Covid-19 Sentry

Contents

• From Preprints
• From Clinical Trials
• From PubMed
• From Patent Search

From Preprints

• Attitudes, behaviours and experiences of authors of COVID-19 preprints -
  The COVID-19 pandemic caused a rise in preprinting, apparently triggered by the need for open and rapid dissemination of research outputs. We surveyed authors of COVID-19 preprints to learn about their experience of preprinting as well as publishing in a peer-reviewed journal. A key aim was to consider preprints in terms of their effectiveness for authors to receive feedback on their work. We also aimed to compare the impact of feedback on preprints with the impact of comments of editors and reviewers on papers submitted to journals. We observed a high rate of new adopters of preprinting who reported positive intentions regarding preprinting their future work. This allows us to posit that the boost in preprinting may have a structural effect that will last after the pandemic. We also saw a high rate of feedback on preprints but mainly through “closed” channels – directly to the authors. This means that preprinting was a useful way to receive feedback on research, but the value of feedback could be increased further by facilitating and promoting “open” channels for preprint feedback. At the same time, almost a quarter of the preprints that received feedback received comments resembling journal peer review. This shows the potential of preprint feedback to provide valuable detailed comments on research. However, journal peer review resulted in a higher rate of major changes in the papers surveyed, suggesting that the journal peer review process has significant added value compared to preprint feedback.
  🖺 Full Text HTML: Attitudes, behaviours and experiences of authors of COVID-19 preprints
• Molecular engineering of a cryptic epitope in Spike RBD improves manufacturability and neutralizing breadth against SARS-CoV-2 variants -
  There is a continued need for sarbecovirus vaccines that can be manufactured and distributed in low- and middle-income countries (LMICs). Subunit protein vaccines are manufactured at large scales at low costs, have less stringent temperature requirements for distribution in LMICs, and several candidates have shown protection against SARS-CoV-2. We previously reported an engineered variant of the SARS-CoV-2 Spike protein receptor binding domain antigen (RBD-L452K-F490W; RBD-J) with enhanced manufacturability and immunogenicity compared to the ancestral RBD. Here, we report a second-generation engineered RBD antigen (RBD-J6) with two additional mutations to a hydrophobic cryptic epitope in the RBD core, S383D and L518D, that further improved expression titers and biophysical stability. RBD-J6 retained binding affinity to human convalescent sera and to all tested neutralizing antibodies except antibodies that target the class IV epitope on the RBD core. K18-hACE2 transgenic mice immunized with three doses of a Beta variant of RBD-J6 displayed on a virus-like particle (VLP) generated neutralizing antibodies (nAb) to nine SARS-CoV-2 variants of concern at similar levels as two doses of Comirnaty. The vaccinated mice were also protected from challenge with Alpha or Beta SARS-CoV-2. This engineered antigen could be useful for modular RBD-based subunit vaccines to enhance manufacturability and global access, or for further development of variant-specific or broadly acting booster vaccines.
  🖺 Full Text HTML: Molecular engineering of a cryptic epitope in Spike RBD improves manufacturability and neutralizing breadth against SARS-CoV-2 variants
• Analysis and comprehensive lineage identification for SARS-CoV-2 genomes through scalable learning methods -
  Since its emergence in late 2019, SARS-CoV-2 has diversified into a large number of lineages and globally caused multiple waves of infection. Lineages have the potential to spread rapidly and internationally if they have higher intrinsic transmissibility and/or can evade host immune responses, as has been seen with the Alpha, Delta, and Omicron variants of concern (VoCs). Phylogenetic methods provide the gold standard for representing the global diversity of SARS-CoV-2 and to identify newly emerging lineages. However, these methods are computationally expensive, struggle when datasets get too large, and require manual curation to designate new lineages. These issues will only intensify as the vast number of SARS-CoV-2 genomes already available continues to grow. It will therefore be beneficial to develop complementary methods that can incorporate all of the genetic data available, without down sampling, to extract meaningful information rapidly and with minimal curation. Here, we demonstrate the utility of using algorithmic approaches based on word-statistics to represent whole sequences, bringing speed, scalability, and interpretability to the construction of genetic topologies, and that can be used to augment traditional classification practice based on phylogeny.
  🖺 Full Text HTML: Analysis and comprehensive lineage identification for SARS-CoV-2 genomes through scalable learning methods
• Pregnant women’s attitudes and behaviours towards antenatal vaccination against Influenza and COVID-19 in the Liverpool City Region, United Kingdom: cross-sectional survey -

  Objectives Influenza poses a serious health risk to pregnant women and their babies. Despite this risk, influenza vaccine uptake in pregnant women in the UK is less than 50%. Little is known about how COVID-19 affects pregnant women, but its management may affect attitudes and behaviours towards vaccination in pregnancy. The study objectives were to establish attitudes and knowledge of pregnant women towards influenza disease and influenza vaccination and to compare these to attitudes and knowledge about COVID-19 and COVID-19 vaccination. Design A cross-sectional survey was conducted using an online questionnaire distributed through local advertisement and social media outlets. Information was sought on attitudes and knowledge of influenza and COVID-19 and their respective vaccines. Participants and setting Pregnant women residing in Liverpool City Region, UK Results Of the 237 respondents, 73.8% reported receiving an influenza vaccine. Over half (56.5%) perceived themselves to be at risk from influenza, 70.5% believed that if they got influenza, their baby would get ill, and 64.6% believed getting influenza could hurt their baby, 60.3% believed that the influenza vaccine would prevent their baby from getting ill, and 70.8% believed it would protect their baby. Only 32.9% of respondents stated they would receive the COVID-19 vaccine if it were available to them. However, 80.2% stated they would receive a COVID-19 vaccine if they were not pregnant. Most of the women stated that they would accept a vaccine if recommended to them by healthcare professionals. Conclusions Acceptance of the influenza and COVID-19 vaccines during pregnancy seems to be more related to the safety of the baby rather than the mother. Women perceived their child to be more at risk than themselves. Information about influenza and COVID-19 vaccine safety as well as healthcare provider recommendations play an important role in vaccine uptake in pregnant women.

  🖺 Full Text HTML: Pregnant women’s attitudes and behaviours towards antenatal vaccination against Influenza and COVID-19 in the Liverpool City Region, United Kingdom: cross-sectional survey
• Excess mortality in the general population versus Veterans Healthcare System during the first year of the COVID-19 pandemic in the United States -

  Importance The COVID-19 pandemic had a substantial impact on the overall rate of death in the United States during the first year. It is unclear whether access to comprehensive medical care, such as through the VA healthcare system, altered death rates compared to the US population. Objective: Quantify the increase in death rates during the first year of the COVID-19 pandemic in the general US population and among individuals who receive comprehensive medical care through the Department of Veterans Affairs (VA). Design: Analysis of changes in all-cause death rates by quarter, stratified by age, sex race/ethnicity, and region, based on individual-level data. Hierarchical regression models were fit in a Bayesian setting. Standardized rates were used for comparison between populations. Setting and participants: General population of the United States, enrollees in the VA, and active users of VA healthcare. Exposure and main outcome: Changes in rates of death from any cause during the COVID-19 pandemic in 2020 compared to previous years. Results Sharp increases were apparent across all of the adult age groups (25 years and older) in both the general US population and the VA populations. Across all of 2020, the relative increase in death rates was similar in the general US population (RR: 1.20 (95% CI: 1.17, 1.22)), VA enrollees (RR: 1.20 (95% CI: 1.14, 1.29)), and VA active users (RR: 1.19 (95% CI: 1.14, 1.26)). Because the pre-pandemic standardized mortality rates were higher in the VA populations prior to the pandemic, the absolute rates of excess mortality were higher in the VA populations. Conclusions and Relevance: Despite access to comprehensive medical care, active users of the VA had similar relative mortality increases from all causes compared with the general US population. Factors that influenced baseline rates of death and that mitigated viral transmission in the community are more likely to have influenced the impact of the pandemic.

  🖺 Full Text HTML: Excess mortality in the general population versus Veterans Healthcare System during the first year of the COVID-19 pandemic in the United States
• The Effects of Long COVID-19, its Severity, and the Need for Immediate Attention: Analysis of Clinical Trials and Twitter data -

  The coronavirus disease 2019 (COVID-19) has been declared a pandemic since March 2020 by the World Health Organisation (WHO). The infection pathway follows symptoms of fever, cough, shortness of breath, dyspnea, and severe cases that lead to hospitalization, emergency life support, and even death. Identifying the disease progression and predicting patient outcomes early, precisely predicting the possibility of long-term adverse events through effective modeling, and use of real-world data such as longitudinal clinical trial data, electronic health records data, and health insurance data are of immense importance to effective treatment, resource allocation, and prevention of severe adverse events (SAE) of grades four or five. The main goal of the study is threefold. Firstly, we raise awareness about the different clinical trials that are being conducted concurrently on Long covid-19, and how these are beneficial. Secondly, we analyze the recent tweets on Long haul covid-19 and give an overview of the sentiments of the opinion of the people. Finally, we analyze the sentiment scores and find if they are associated with the demographics of the tweeters via a negative binomial regression model. The trials were selected with long Covid-19 available in ClinicalTrials.Gov. Also, the tweets obtained with the term #long covid-19 consisted of 8436 tweets. We utilized the NRC Emotion Lexicon method for sentiment analysis is a list of English words and their associations with eight basic emotions (anger, fear, anticipation, trust, surprise, sadness, joy, and disgust) and two sentiments (negative and positive) (11). We obtained a matrix of sentiment scores, as well as retweet counts and favorite counts which were analyzed. We regressed the retweet counts and the favorite counts with the sentiment scores and find if they are associated with the emotions and sentiments of the tweeters via a negative binomial regression model since the outcome variable is count data. Our results find that there are two types of clinical trials (a total of 298) being conducted 1)observational and b) interventional. The details about enrollment, time to completion, clinical trial phases, etc., are discussed. Sentiment analysis with the NRC method of the tweets shows that there are both positive and negative sentiments. The retweet counts and favorite counts are associated with the sentiments and emotions such as disgust, joy, sadness, surprise, trust, negative, positive, etc. Finally, to conclude we need resources, and further research needs to be conducted in this area of long Covid-19.

  🖺 Full Text HTML: The Effects of Long COVID-19, its Severity, and the Need for Immediate Attention: Analysis of Clinical Trials and Twitter data
• Real-World Effectiveness of Nirmatrelvir/Ritonavir in Preventing Hospitalization Among Patients With COVID-19 at High Risk for Severe Disease in the United States: A Nationwide Population-Based Cohort Study -

  Objectives: The aim of this analysis was to describe nirmatrelvir/ritonavir real-world effectiveness in preventing hospitalization among high-risk US COVID-19 patients during SARS-CoV-2 Omicron predominance. Design: An ongoing population-based cohort study with retrospective and prospective collection of electronic healthcare data in the United States. Methods: Data for this analysis were collected from the US Optum de-identified COVID-19 Electronic Health Record (EHR) dataset during December 22, 2021 to June 8, 2022. Key eligibility criteria for inclusion in the database analysis were at least 12-years-old; positive SARS-CoV-2 test, COVID-19 diagnosis, or nirmatrelvir/ritonavir prescription; and high risk of severe COVID-19 based on demographic/clinical characteristics. Potential confounders between groups were balanced using propensity score matching (PSM). Immortal time bias was addressed. Outcome measures: Hospitalization rates within 30 (primary analysis) or 15 (sensitivity analysis) days from COVID-19 diagnosis overall and within subgroups were evaluated. Results: Before PSM, the nirmatrelvir/ritonavir group (n=2811) was less racially diverse, older, and had higher COVID-19 vaccination rates and a greater number of comorbidities than the non-nirmatrelvir/ritonavir group (n=194,542). Baseline characteristics were well balanced across groups (n=2808 and n=10,849, respectively) after PSM. Incidence of hospitalization (95% CI) within 30 days was 1.21% (0.84%, 1.69%) for the nirmatrelvir/ritonavir group and 6.94% (6.03%, 7.94%) for the non-nirmatrelvir/ritonavir group, with a hazard ratio (95% CI) of 0.16 (0.11, 0.22; 84% relative risk reduction). Incidence within 15 days was 0.78% (0.49%, 1.18%) for the nirmatrelvir/ritonavir group and 6.54% (5.65%, 7.52%) for the non-nirmatrelvir/ritonavir group; hazard ratio 0.11 (0.07, 0.17; 89% relative risk reduction). Nirmatrelvir/ritonavir was effective in African American patients (hazard ratio, 0.35 [0.15, 0.83]; 65% relative risk reduction). Relative risk reductions were comparable with overall results across ages and among vaccinated patients. Conclusions: Real-world nirmatrelvir/ritonavir effectiveness against hospitalization during the Omicron era supports EPIC-HR efficacy among high-risk patients. Future research should confirm these early real-world results and address limitations.

  🖺 Full Text HTML: Real-World Effectiveness of Nirmatrelvir/Ritonavir in Preventing Hospitalization Among Patients With COVID-19 at High Risk for Severe Disease in the United States: A Nationwide Population-Based Cohort Study
• Assessing the Impacts of COVID-19 and Social Isolation on Mental Health in the United States of America -

  The COVID-19 pandemic has had a devastating impact on the world at large with over 500 million cases and over 6 million deaths reported thus far. Of those, over 85 million cases and 1 million deaths have occurred in the United States of America (USA). The mental health of the general population has been impacted by several aspects of the pandemic including lockdowns, media sensationalism, social isolation, and spread of the disease. In this paper, we examine the effect that social isolation and COVID-19 infection and related death had on the prevalence of anxiety and depression in the general population of the USA in a state-by-state multiple time-series analysis. Vector Error Correction Models are estimated and we subsequently evaluated the coefficients of the estimated models and calculated their impulse response functions for further interpretation. We found that variables related to COVID-19 overall led to an increase both anxiety and depression across the studied period, while variables related to social isolation had a varied effect depending on the state being considered. Both conclusions have important implications for future pandemics.

  🖺 Full Text HTML: Assessing the Impacts of COVID-19 and Social Isolation on Mental Health in the United States of America
• Increasing Cases of SARS-CoV-2 Omicron Reinfection Reveals Ineffective Post-COVID-19 Immunity in Denmark and Conveys the Need for Continued Next-Generation Sequencing -

  Abstract SARS-CoV-2 has extensively mutated creating variants of concern (VOC) resulting in global infection surges. The Omicron VOC reinfects individuals exposed to earlier variants of SARS-CoV-2 at a higher frequency than previously seen for non-Omicron VOC. An analysis of the sub-lineages associated with an Omicron primary infection and Omicron reinfection reveals that the incidence of Omicron-Omicron reinfections is occurring over a shorter time interval than seen after a primary infection with a non-Omicron VOC. Our analysis suggests that a single infection from SARS-CoV-2 may not generate the protective immunity required to defend against reinfections from emerging Omicron lineages. This analysis was made possible by Next-generation sequencing (NGS), specifically of a Danish cohort with clinical metadata on both infections occurring in the same individual. We suggest that the continuation of COVID-19 NGS and inclusion of clinical metadata is necessary to ensure effective surveillance of SARS-CoV-2 genomics, assist in treatment and vaccine development, and guide public health recommendations.

  🖺 Full Text HTML: Increasing Cases of SARS-CoV-2 Omicron Reinfection Reveals Ineffective Post-COVID-19 Immunity in Denmark and Conveys the Need for Continued Next-Generation Sequencing
• Trends in Low-Value Cancer Care During the COVID-19 Pandemic -

  Background Low-value services are common in cancer care. The onset of the COVID-19 pandemic caused a dramatic decrease in health care utilization, leading many to suspect that low-value cancer services may decrease. Methods In this retrospective cohort study, we used administrative claims from the HealthCore Integrated Research Environment, a repository of medical and pharmacy data from US health plans representing over 80 million members, to identify 204,581 patients diagnosed with breast, colorectal, and/or lung cancer between January 1, 2015, and March 31, 2021. We used linear probability models to investigate the relation between the onset of COVID-19 pandemic and 5 guideline-based metrics of low-value cancer care: 1) Positron Emission Tomography/Computed Tomography (PET/CT) instead of conventional CT imaging for initial staging; 2) conventional fractionation instead of hypofractionation for early-stage breast cancer; 3) non-guideline-based antiemetic use for minimal-, low-, or moderate-to-high-risk chemotherapies; 4) off-pathway systemic therapy; and 5) aggressive end-of-life care. Results Among 204,581 patients, the mean [SD] age was 63.1 [13.2], 68.1% were female, 83,593 (40.8%) had breast cancer, 56,373 (27.5%) had colon cancer, and 64,615 (31.5%) had lung cancer. Rates of low-value cancer services did not exhibit meaningful declines during the pandemic: PET/CT imaging, adjusted percentage point difference 1.87 (95% CI -0.13 to 3.87); conventional radiotherapy, adjusted percentage point difference 3.93 (95% CI 1.50 to 6.36); off-pathway systemic therapy, adjusted percentage point difference 0.82 (95% CI -0.62 to 2.25); non-guideline-based antiemetics, adjusted percentage point difference -3.62 (95% CI -4.97 to -2.27); aggressive end-of-life care, adjusted percentage point difference 2.71 (95% CI -0.59 to 6.02). Discussion Low-value cancer care remained prevalent through the pandemic. Policymakers should consider changes to payment and incentive design to turn the tide toward higher-value cancer care.

  🖺 Full Text HTML: Trends in Low-Value Cancer Care During the COVID-19 Pandemic
• SARS-CoV-2 containment was achievable during the early stage of the pandemic: a retrospective modelling study of the Xinfadi outbreak in Beijing -

  Prior to the emergence of the Omicron variant, many cities in China had been able to maintain a “Zero-COVID” policy. They were able to achieve this without blanket city-wide lockdown and through widespread testing and an extensive set of nonpharmaceutical interventions (NPIs), such as mask wearing, contact tracing, and social distancing. We wanted to examine the effectiveness of such a policy in containing SARS-CoV-2 in the early stage of the pandemic. Therefore, we developed a fully stochastic, spatially structured, agent-based model of SARS-CoV-2 ancestral strain and reconstructed the Beijing Xinfadi outbreak through computational simulations. We found that screening for symptoms and among high-risk populations served as methods to discover cryptic community transmission in the early stage of the outbreak. Effective contact tracing could greatly reduce transmission. Targeted community lockdown and temporal mobility restriction could slow down the spatial spread of the virus, with much less of the population being affected. Population-wide mass testing could further improve the speed at which the outbreak is contained. Our analysis suggests that the containment of SARS-CoV-2 ancestral strains was certainly possible. Outbreak suppression and containment at the beginning of the pandemic, before the virus had the opportunity to undergo extensive adaptive evolution with increasing fitness in the human population, could be much more cost-effective in averting the overall pandemic disease burden and socioeconomic cost.

  🖺 Full Text HTML: SARS-CoV-2 containment was achievable during the early stage of the pandemic: a retrospective modelling study of the Xinfadi outbreak in Beijing
• The epidemiology of long COVID in US adults two years after the start of the US SARS-CoV-2 pandemic -

  Objectives: To characterize prevalence and impact of long COVID. Methods: We conducted a population-representative survey, June 30-July 2, 2022, of a random sample of 3,042 United States adults. Using questions developed by the United Kingdom9s Office of National Statistics, we estimated the prevalence by sociodemographics, adjusting for gender and age. Results: An estimated 7.3% (95% CI: 6.1-8.5%) of all respondents reported long COVID, approximately 18,533,864 adults. One-quarter (25.3% [18.2-32.4%]) of respondents with long COVID reported their day-to-day activities were impacted 9a lot9 and 28.9% had SARS-CoV-2 infection >12 months ago. The prevalence of long COVID was higher among respondents who were female (aPR: 1.84 [1.40-2.42]), had comorbidities (aPR: 1.55 [1.19-2.00]) or were not (versus were) boosted (aPR: 1.67 [1.19-2.34]) or not vaccinated (versus boosted) (aPR: 1.41 (1.05-1.91)). Conclusions: We observed a high burden of long COVID and substantial variability in prevalence of SARS-CoV-2. Population-based surveys are an important surveillance tool and supplement to ongoing efforts to monitor long COVID.

  🖺 Full Text HTML: The epidemiology of long COVID in US adults two years after the start of the US SARS-CoV-2 pandemic
• PARNAS: Objectively Selecting the Most Representative Taxa on a Phylogeny -
  The use of next-generation sequencing technology has enabled phylogenetic studies with hun- dreds of thousands of taxa. Such large-scale phylogenies have become a critical component in genomic epidemiology in pathogens such as SARS-CoV-2 and influenza A virus. However, de- tailed phenotypic characterization of pathogens or generating a computationally tractable dataset for detailed phylogenetic analyses requires bias free subsampling of taxa. To address this need, we propose parnas, an objective and flexible algorithm to sample and select taxa that best repre- sent observed diversity by solving a generalized k-medoids problem on a phylogenetic tree. parnas solves this problem efficiently and exactly by novel optimizations and adapting algorithms from operations research. For more nuanced selections, taxa can be weighted with metadata or genetic sequence parameters, and the pool of potential representatives can be user-constrained. Motivated by influenza A virus genomic surveillance and vaccine design, parnas can be applied to identify representative taxa that optimally cover the diversity in a phylogeny within a specified distance radius. We demonstrated that parnas is more efficient and flexible than current approaches, and applied it to select representative influenza A virus in swine genes derived from over 5 years of genomic surveillance data. Our objective selection of 4 to 6 strains selected every two years from the 16 distinct genetic clades were sufficient to cover 80% of diversity circulating in US swine. We suggest that this method, through the objective selection of representatives in a phylogeny, provides criteria for rational multivalent vaccine design and for quantifying diversity. PARNAS is available at https://github.com/flu-crew/parnas.
  🖺 Full Text HTML: PARNAS: Objectively Selecting the Most Representative Taxa on a Phylogeny
• Validation and Establishment of a SARS-CoV-2 Lentivirus Surrogate Neutralization Assay as a pre-screening tool for the Plaque Reduction Neutralization Test -
  Neutralization assays are important in understanding and quantifying neutralizing antibody responses towards SARS-CoV-2. The SARS-CoV-2 Lentivirus Surrogate Neutralization Assay (SCLSNA) can be used in biosafety level 2 (BSL-2) laboratories and has been shown to be a reliable, alternative approach to the plaque reduction neutralization test (PRNT). In this study, we optimized and validated the SCLSNA to assess its ability as a comparator and pre-screening method to support the PRNT. Comparability between the PRNT and SCLSNA was determined through clinical sensitivity and specificity evaluations. Clinical sensitivity and specificity produced acceptable results with 100% (95% CI: 94-100) specificity and 100% (95% CI: 94-100) sensitivity against ancestral Wuhan spike pseudotyped lentivirus. The sensitivity and specificity against B.1.1.7 spike pseudotyped lentivirus resulted in 88.3% (95% CI: 77.8 to 94.2) and 100% (95% CI: 94-100), respectively. Assay precision measuring intra-assay variability produced acceptable results for High (1:[≥]640 PRNT50), Mid (1:160 PRNT50) and Low (1:40 PRNT50) antibody titer concentration ranges based on the PRNT50, with %CV of 14.21, 12.47, and 13.28 respectively. Intermediate precision indicated acceptable ranges for the High and Mid concentrations, with %CV of 15.52 and 16.09, respectively. However, the Low concentration did not meet the acceptance criteria with a %CV of 26.42. Acceptable ranges were found in the robustness evaluation for both intra-assay and inter-assay variability. In summary, the validation parameters tested met the acceptance criteria, making the SCLSNA method fit for its intended purpose, which can be used to support the PRNT.
  🖺 Full Text HTML: Validation and Establishment of a SARS-CoV-2 Lentivirus Surrogate Neutralization Assay as a pre-screening tool for the Plaque Reduction Neutralization Test
• The SARS-CoV-2 spike N-terminal domain engages 9-O-acetylated α2-8-linked sialic acids -
  SARS-CoV-2 viruses engage ACE2 as a functional receptor with their spike protein. The S1 domain of the spike protein contains a C-terminal receptor-binding domain (RBD) and an N-terminal domain (NTD) which, in other coronaviruses, includes a glycan-binding cleft. However, for the SARS-CoV-2 NTD protein-glycan binding was only observed weakly for sialic acids with highly sensitive methods. Amino acid changes in the NTD of Variants of Concern (VoC) shows antigenic pressure, which can be an indication of functionality. To analyze gain or loss of glycan-binding in VoC, trimeric fluorescent NTD proteins were used. Binding properties were analyzed biochemically on Vero E6 cells and tissue samples. Unexpectedly, the SARS-CoV-2 Beta (501Y.V2-1) NTD binding to Vero E6 cells was sensitive to sialidase pretreatment. Glycan microarray analyses identified a putative 9-O-acetylated sialic acid as a ligand, which was confirmed by catch-and-release ESI-MS, STD-NMR analyses, and a graphene-based electrochemical sensor. The Beta (501Y.V2-1) variant attained an enhanced glycan binding modality in the NTD with specificity towards 9-O-acetylated structures, suggesting a dual-receptor functionality of the SARS-CoV-2 S1 domain, which was quickly selected against. This demonstrates plasticity for improved engagement to sialic acids, possibly under immunological pressure.
  🖺 Full Text HTML: The SARS-CoV-2 spike N-terminal domain engages 9-O-acetylated α2-8-linked sialic acids

From Clinical Trials

• Booster Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition:   COVID-19
  Interventions:   Biological: SARS-CoV-2 subunit protein recombinant vaccine;   Biological: Active Comparator
  Sponsors:   PT Bio Farma;   Universitas Padjadjaran;   Udayana University
  Recruiting

• Association Between Smell Training and Quality of Life in Patients With Impaired Sense of Smell Following COVID-19 - Condition:   COVID-19
  Interventions:   Other: Olfactory training with essential oils;   Other: Olfactory training with fragrance-free oils
  Sponsor:   Ditte Gertz Mogensen
  Recruiting

• Safety and Effects of an Investigational COVID-19 Vaccine as a Booster in Healthy People - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Interventions:   Biological: BNT162b5 Bivalent or BNT162b2 Bivalent 30 µg;   Biological: BNT162b4 5 µg;   Biological: BNT162b4 10 µg;   Biological: BNT162b4 15 µg
  Sponsors:   BioNTech SE;   Pfizer
  Not yet recruiting

• Trial of 2nd Booster Dose of COVID-19 Vaccine - Condition:   COVID-19
  Intervention:   Other: Invitation to get a 2nd booster dose of COVID-19 vaccine
  Sponsor:   Norwegian Institute of Public Health
  Not yet recruiting

• Efficacy and Safety of ES16001 in Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: ES16001 40 mg;   Drug: ES16001 80 mg;   Drug: ES16001 160 mg;   Drug: Placebo
  Sponsor:   Genencell Co. Ltd.
  Recruiting

• SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Text Message Study - Condition:   COVID-19
  Interventions:   Behavioral: Text-Messaging (TM);   Behavioral: Patient Navigation (PN)
  Sponsors:   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)
  Not yet recruiting

• SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Conversational Agent Study - Condition:   COVID-19
  Interventions:   Behavioral: Text-Messaging (TM);   Behavioral: Conversational Agent (CA);   Behavioral: Patient Navigation (PN)
  Sponsors:   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)
  Not yet recruiting

• Evaluating the Safety and Efficacy of AD17002 Intranasal Spray in Treating Participants With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Biological: AD17002 + Formulation buffer;   Biological: Placebo
  Sponsors:   Advagene Biopharma Co. Ltd.;   Gadjah Mada University
  Not yet recruiting

• 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 - Condition:   COVID-19
  Interventions:   Behavioral: Community-based Health Education based on core intervention package;   Behavioral: Health Information Sharing Group
  Sponsors:   The Hong Kong Polytechnic University;   Food and Health Bureau, Hong Kong
  Recruiting

• Multidisciplinary Day-hospital Versus Waiting List Management of Post-COVID-19 Persistent Symptoms (ECHAP-COVID) - Condition:   Post COVID-19 Condition
  Intervention:   Behavioral: Personalized multidisciplinary day-hospital intervention
  Sponsor:   Assistance Publique - Hôpitaux de Paris
  Not yet recruiting

• Simvastatin Nasal Rinses for the Treatment of COVID-19 Mediated Dysomsia - Conditions:   Olfactory Disorder;   COVID-19
  Intervention:   Drug: Simvastatin
  Sponsors:   Washington University School of Medicine;   Duke University
  Not yet recruiting

• Efficacy and Safety Evaluation of Paxlovid for COVID-19: a Real-world Case-control Study - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: standard-of-care plus Paxlovid;   Drug: standard-of-care
  Sponsor:   Ruijin Hospital
  Recruiting

• Booster Study of PTX-COVID19-B in Adults Aged 18 Years and Older - Condition:   SARS-CoV-2 Infection
  Interventions:   Biological: PTX-COVID19-B;   Biological: Comirnaty®
  Sponsor:   Everest Medicines (Singapore) Pte. Ltd.
  Not yet recruiting

• Booster Superiority Study of PTX-COVID19-B Compared to Vaxzevria® in Adults Aged 18 Years and Older - Condition:   SARS-CoV-2 Infection
  Interventions:   Biological: PTX-COVID19-B;   Biological: Vaxzevria®
  Sponsor:   Everest Medicines (Singapore) Pte. Ltd.
  Not yet recruiting

• Engaging Church Health Ministries to Decrease Coronavirus Disease-19 Vaccine Hesitancy in Underserved Populations - Condition:   COVID-19
  Intervention:   Behavioral: Active Intervention Group
  Sponsor:   Pennington Biomedical Research Center
  Not yet recruiting

From PubMed

• Therapeutic properties and molecular docking study of some phenolic compounds as anti-human lung cancer potential: A biochemical approach - 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…

• In silico studies of M^pro and PL^pro from SARS-CoV-2 and a new class of cephalosporin drugs containing 1,2,4-thiadiazole - 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…

• Remdesivir analog as SARS-CoV-2 polymerase inhibitor: virtual screening of a database generated by scaffold replacement - 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….

• 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 - 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,…

• Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture - 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…

• 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 - 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…

• Disinfection effect of hexadecyl pyridinium chloride on SARS-CoV-2 in vitro - The novel coronavirus (COVID-19 or 2019-nCoV) is a respiratory virus that can exist in the mouth and saliva of patients and spreads through aerosol dispersion. Therefore, stomatological hospitals and departments have become high-infection-risk environments. Accordingly, oral disinfectants that can effectively inactivate the virus have become a highly active area of research. Hexadecyl pyridinium chloride, povidone-iodine, and other common oral disinfectants are the natural primary choices for…

• Computational exploration of the dual role of the phytochemical fortunellin: Antiviral activities against SARS-CoV-2 and immunomodulatory abilities against the host - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections generate approximately one million virions per day, and the majority of available antivirals are ineffective against it due to the virus’s inherent genetic mutability. This necessitates the investigation of concurrent inhibition of multiple SARS-CoV-2 targets. We show that fortunellin (acacetin 7-O-neohesperidoside), a phytochemical, is a promising candidate for preventing and treating coronavirus disease (COVID-19) by…

• The cumulative effect of fibromyalgia symptoms on cognitive performance: The mediating role of pain - Fibromyalgia (FMS) is a chronic condition that encompasses widespread pain associated with cognitive impairment and significant emotional distress related to functional disability. This study aimed to obtain evidence of the role of pain in the effect of time since FMS diagnosis and cognitive performance using a novel online protocol of neuropsychological evaluation since the COVID-19 pandemic has challenged traditional neuropsychology testing leading to the need for novel procedures…

• Identification of immunomodulatory drugs that inhibit multiple inflammasomes and impair SARS-CoV-2 infection - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces mild or asymptomatic COVID-19 in most cases, but some patients develop an excessive inflammatory process that can be fatal. As the NLRP3 inflammasome and additional inflammasomes are implicated in disease aggravation, drug repositioning to target inflammasomes emerges as a strategy to treat COVID-19. Here, we performed a high-throughput screening using a 2560 small-molecule compound library and identified FDA-approved drugs…

• Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerases (PARPs), blocks in vitro replication of SARS-CoV-2 variants - We recently published a preliminary assessment of the activity of a poly (ADP-ribose) polymerase (PARP) inhibitor, stenoparib, also known as 2X-121, which inhibits viral replication by affecting pathways of the host. Here we show that stenoparib effectively inhibits a SARS-CoV-2 wild type (BavPat1/2020) strain and four additional variant strains; alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2) and gamma (P.1) in vitro, with 50% effective concentration (EC50) estimates of 4.1 μM, 8.5 μM, 24.1…

• Utilization of Receptor-Binding Domain of SARS-CoV-2 Spike Protein Expressed in Escherichia coli for the Development of Neutralizing Antibody Assay - The ongoing COVID-19 pandemic has resulted from widespread infection by the SARS-CoV-2 virus. As new variants of concern continue to emerge, understanding the correlation between the level of neutralizing antibodies (NAb) and clinical protection from SAR-CoV-2 infection could be critical in planning the next steps in COVID-19 vaccine programs. This study explored the potential usefulness of E. coli as an alternative expression system that can be used to produce a SARS-CoV-2 receptor-binding…

• Calpain-1: a Novel Antiviral Host Factor Identified in Porcine Small Intestinal Mucus - The thick mucus layer covering of the intestinal epithelium has received increasing attention, owing to its protective role in intestinal infection. However, the exact mechanisms by which the mucus increases intestinal resistance against viral infection remain largely unclear. Here, we identify prominent antiviral activity of the small intestinal mucus and extracted total mucus proteins, as evidenced by their inhibitory effects against porcine epidemic diarrhea virus (PEDV) infection. Of all the…

• Synthesis, characterization, molecular docking, and anticancer activities of new 1,3,4-oxadiazole-5-fluorocytosine hybrid derivatives - Analogs of pyrimidine and 1,3,4-oxadiazole are two well established class of molecules proven as potent antiviral and anticancer agents in the pharmaceutical industry. We envisioned designing new molecules where these two heterocycles were conjugated with the goal of enhancing biological activity. In this vein, we synthesized a series of novel pyrimidine-1,3,4-oxadiazole conjugated hybrid molecules as potential anticancer and antiviral agents. Herein, we present a new design for…

• SARS-CoV-2 main protease (3CL^pro) interaction with acyclovir antiviral drug/methyl-β-cyclodextrin complex: Physiochemical characterization and molecular docking - During the current outbreak of the novel coronavirus disease 2019 (COVID-19), researchers have examined several antiviral drugs with the potential to inhibit the proliferation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The antiviral drug acyclovir (AVR), which is used to treat COVID-19, in complex with methyl-β-cyclodextrin (Mβ-CD) was examined in the solution and solid phases. UV-visible and fluorescence spectroscopic analyses confirmed that the guest (AVR) was…

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