- Attitudes towards science during the COVID-19 pandemic: A psychological network approach -
A better understanding of the public attitude towards science could be crucial to tackle the spread of mis- and disinformation related to the COVID-19 pandemic and beyond. We here contribute to this understanding by conceptualizing and analyzing the attitude toward science as a psychological network. For this analysis, we utilized data from a German probability sample (N = 1,009), the “Science Barometer”, collected during the first wave of the COVID-19 pandemic. Overall, our network analysis revealed that especially the perceived value of science for curbing the pandemic is central to the attitude towards science. Beliefs about this value are related to trust in science and trust in scientific information and to positive and negative evaluations of scientific controversy and complexity. Further, valuing common sense over science was related to seeking less scientific information on official websites, suggesting that this belief, in particular, may drive mis- and disinformation and could be a promising target for interventions. Finally, we found no evidence that seeking scientific information on social media had detrimental consequences for the attitude towards science. Implications for health communication and science communication, limitations, and future directions are discussed.
- How do Good and Bad News Impact Mood During the Covid-19 Pandemic? The Role of Similarity -
How do media reports about the Covid-19 pandemic influence our mood? Building on the social comparison theory, we predicted that reading negative news affecting a similar group would result in an impaired mood. In contrast, reading negative news about a dissimilar group should lead to improved mood. To test this, 150 undergraduate students read positive or negative news about the well-being of a similar or dissimilar group during the pandemic. As predicted, a mood assimilation effect occurred for similar groups, whilst a contrast effect occurred for a dissimilar group. The findings suggest that media reports can have a strong impact on mood. The direction of these effects, however, seems to depend strongly on social comparison processes.
- The Perception of Infection Risks during the Early and Later Outbreak of COVID-19 in Germany: Consequences and Recommendations -
In three studies (N = 1,055), we investigated the determinants and consequences of the perception of infection risks during the early and later outbreak of COVID-19 in Germany. Individuals’ perceived COVID-19 infection risk was reasonably in line with experts’ assessment but changed over time. The probability of the rare event of getting severely sick and hospitalized was overestimated. Overestimation increased in the exponential growth phase of the pandemic and later on decreased again, showing an inverse U-shaped pattern. Individuals showed biases in their risk perception concerning overconfidence and the underestimation of exponential growth of infection cases in the early phase of the pandemic. Forecasts were more accurate after the growth curve had flattened. Risk perceptions increased with perceived dread and tended to increase with perceived control over infection, the evaluation of scientific and own knowledge about the pandemic. Approval for the introduction of stricter governmental measures and acceptance of future vaccination measures was mainly influenced by rational utilitarian factors of risk perception (probabilities and utilities of outcomes). These rational influences were mediated by dread, but dread had an additional potentially irrational effect. Adherence to governmental recommendations was mainly driven by dread and positive expected long-term consequences of the measures. To a smaller degree, adherence increased with perceived personal consequences of infection and decreased with negative expected short-term consequences of these measures. Implications for theory development are discussed and recommendations to handle virus outbreaks are derived.
- Prolonged viral shedding from noninfectious individuals confounds wastewater-based epidemiology -
Wastewater surveillance has been widely used to track and estimate SARS-CoV-2 incidence. While both infectious and recovered individuals shed virus into wastewater, epidemiological inferences using wastewater often only consider the viral contribution from the former group. Yet, the persistent shedding in the latter group could confound wastewater-based epidemiological inference, especially during the late stage of an outbreak when the recovered population outnumbers the infectious population. To determine the impact of recovered individuals9 viral shedding on the utility of wastewater surveillance, we develop a quantitative framework that incorporates population-level viral shedding dynamics, measured viral RNA in wastewater, and an epidemic dynamic model. We find that the viral shedding from the recovered population can become higher than the infectious population after the transmission peak, which leads to a decrease in the correlation between wastewater viral RNA and case report data. Furthermore, the inclusion of recovered individuals9 viral shedding into the model predicts earlier transmission dynamics and slower decreasing trends in wastewater viral RNA. The prolonged viral shedding also induces a potential delay in the detection of new variants due to the time needed to generate enough new cases for a significant viral signal in an environment dominated by virus shed by the recovered population. This effect is most prominent toward the end of an outbreak and is greatly affected by both the recovered individuals9 shedding rate and shedding duration. Our results suggest that the inclusion of viral shedding from non-infectious recovered individuals into wastewater surveillance research is important for precision epidemiology.
- Intragroup differences in COVID-19 vaccine attitudes among Black Americans -
COVID-19 vaccine hesitancy among Black Americans threatens to further magnify racial inequities in COVID-19 related health outcomes that emerged in the earliest stages of the pandemic. Here we shed new light on attitudes towards COVID-19 vaccines by considering intragroup variation. Rather than analyzing Blacks as a homogenous group, we examine the relationship between COVID-19 vaccine attitudes and the extent to which participants are aligned with African American versus White culture (i.e., level of “acculturation”). In a sample of N=997 Black Americans, we find that stronger alignment with African American culture predicts substantially more negative attitudes towards COVID-19 vaccination, above and beyond variation explained by age, gender, education, and socioeconomic status. This relationship was substantially attenuated when controlling for suspicion of the healthcare system, but not perceptions that healthcare system treats Blacks unfairly, science knowledge, or cognitive reflection. The intragroup differences among Blacks in COVID-19 vaccine perceptions uncovered here provide insights into designing interventions that provide health information that targets the relevant factors for vaccine hesitancy in differing subgroups.
- On the disposition to think analytically: Four distinct intuitive-analytic thinking styles -
Many measures have been developed to index intuitive versus analytic thinking. Yet it remains an open question whether people primarily vary along a single dimension or if there are genuinely different types of thinking styles. We distinguish between four distinct types of thinking styles: Actively Open-minded Thinking, Close-minded Thinking, Preference for Intuitive Thinking, and Preference for Effortful Thinking. We discovered strong predictive validity across several outcome measures (e.g., epistemically suspect beliefs, bullshit receptivity, empathy, moral judgments), with some subscales having stronger predictive validity for some outcomes but not others. Furthermore, Actively Open-minded Thinking, in particular, strongly outperformed the Cognitive Reflection Test in predicting misperceptions about COVID-19 and the ability to discern between vaccination-related true and false news. Our results indicate that people do, in fact, differ along multiple dimensions of intuitive-analytic thinking styles and that these dimensions have consequences for understanding a wide range of beliefs and behaviors.
- Concerns about data integrity of 30 randomized clinical trials from one author. -
Introduction In 2021, we learnt about the problems in studies on ivermectin and hydrocholoroquine in COVID-19. We noticed an appreciable number of unfunded randomised clinical trials (RCTs) on the treatment of COVID-19 conducted across three centres in Egypt (Tanta University, Assiut University, Ain-shams University) on COVID-19 patients with similar inclusion criteria and overlapping time frames. Dr Sherief M Abd-Elsalam ran seven such RCTs across these three centres; four of these RCTs have since been retracted. We therefore set out to systematically analyse the integrity of all RCTs (co-)authored by Dr Abd-Elsalam, in particular 23 RCTs on Gastroenterology and Hepatology. Methods We searched PubMed, Google Scholar, Scopus and clinical trial registries for RCTs published by Dr Sherief M Abd-Elsalam, affiliated with the Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt. We assessed trial registration, tables for identical data values, statistical errors, and improbable data trends. We assessed the probability of true randomization by assessing baseline characteristics through a Monte Carlo Analysis. Results We report on 30 published randomized control trials (RCTs) of Dr. Sherief Abd-Elsalam, in particular 23 RCTs on Gastroenterology and Hepatology. We found important issues in all RCTs examined. Of these 23 RCTs, 10 RCTs had substantial trial registration inconsistencies. Only one of these 10 RCTs has been retracted to date. We found nine RCTs with substantial statistical mistakes, five RCTs with similarities between tables unlikely to happen by chance, four RCTs with implausible Gaussian distributions, three RCTs in which almost all dichotomous variables had even values, while part of at least one study was plagiarized. Monte Carlo analysis indicated that the probability that distribution of baseline characteristics due to randomisation was 0.0000228. According to the trial registration, Dr. Abd-Elsalam is coordinating 76 clinical trials with 45 trials currently marked as ‘Recruiting’ and 17 trials marked as ‘Unknown Status’ as of November 2022. Interpretation We strongly recommend a thorough investigation of the data integrity of all RCTs by Dr Sherief M Abd-Elsalam by journal editors. Until the completion of such an investigation, we suggest that none of these studies are used to inform clinical practice.
- The Your COVID-19 Risk Assessment Tool and the Accompanying Open Access Data and Materials Repositories -
In March 2020, the Your COVID-19 Risk tool was developed in response to the global spread of SARS-CoV-2. The tool is an online resource based on key behavioural evidence-based risk factors related to contracting and spreading SARS-CoV-2. This article describes the development of the tool, the produced resources, the associated open repository, and initial results. This tool was developed by a multidisciplinary research team consisting of more than 150 international experts. This project leverages knowledge obtained in behavioural science, aiming to promote behaviour change by assessing risk and supporting individuals completing the assessment tool to protect themselves and others from infection. To enable iterative improvements of the tool, tool users can optionally answer questions about behavioural determinants. The data and results are openly shared to support governments and health agencies developing behaviour change interventions. Over 60 000 users in more than 150 countries have assessed their risk and provided data.
- Anti-Viral and Anti-Inflammatory Therapeutic Effect of RAGE-Ig Protein Against Multiple SARS-CoV-2 Variants of Concern Demonstrated in K18-hACE2 Mouse and Syrian Golden Hamster Models -
Significance: SARS-CoV-2 Variants of Concern (VOCs) continue to evolve and re-emerge with chronic inflammatory long-COVID sequelae necessitating the development of anti-inflammatory therapeutic molecules. Therapeutic effects of the Receptor for Advanced Glycation End products (RAGE) were reported in many inflammatory diseases. However, a therapeutic effect of the RAGE in COVID-19 has not been reported. In the present study, we investigated whether and how the RAGE-Ig fusion protein would have an anti-viral and anti-inflammatory therapeutic effect in the COVID-19 system. Methods: The protective therapeutic effect of RAGE-Ig was determined in vitro in K18-hACE2 transgenic mice and Syrian golden hamsters infected with six various VOCs of SARS-CoV-2. The underlying anti-viral mechanism of RAGE-Ig was determined in vitro in SARS-CoV-2-infected human lung epithelial cells (BEAS-2B). Results: Following treatment of K18-hACE2 mice and hamsters infected with various SARS-CoV-2 VOCs with RAGE-Ig, we demonstrated: (i) significant dose-dependent protection (i.e. greater survival, less weight loss, lower virus replication in the lungs); (ii) a reduction of inflammatory macrophages (F4/80+/Ly6C+) and neutrophils (CD11b+/Ly6G+) infiltrating the infected lungs; (iii) a RAGE-Ig dose-dependent increase in the expression of type I interferons (IFN-alpha;, and IFN-beta) and type III interferon (IFN lambda2) and a decrease in the inflammatory cytokines (IL-6 and IL-8) in SARS-CoV-2-infected human lung epithelial cells; and (iv) a dose-dependent decrease in the expression of CD64 (FcgR1) on monocytes and lung epithelial cells from symptomatic COVID-19 patients. Conclusion: Our pre-clinical findings revealed type I and III interferons-mediated anti-viral and anti-inflammatory therapeutic effects of RAGE-Ig protein against COVID-19 caused by multiple SARS-CoV-2 VOCs.
- Potential for bias in (sero)prevalence estimates when not accounting for test sensitivity and specificity -
Objectives: The COVID-19 has led to many studies of seroprevalence. A number of methods exist in the statistical literature to correctly estimate disease prevalence in the presence of diagnostic test misclassification, but these methods seem to be less known and not routinely used in the public health literature. We aimed to show how widespread the problem is in recent publications, and to quantify the magnitude of bias introduced when correct methods are not used. Methods: We examined a sample of recent literature to determine how often public health researcher did not account for test performance in estimates of seroprevalence. Using straightforward calculations, we estimated the amount of bias introduced when reporting the proportion of positive test results instead of using sensitivity and specificity to estimate disease prevalence. Results: Of the seroprevalence studies sampled, 80% failed to account for sensitivity and specificity. Expected bias is often more than is desired in practice, ranging from 1% to 10%. Conclusions: Researchers conducting studies of prevalence should correctly account for test sensitivity and specificity in their statistical analysis.
- COVFlow: performing virus phylodynamics analyses from selected SARS-CoV-2 genome sequences -
Phylodynamic analyses generate important and timely data to optimise public health response to SARS-CoV-2 outbreaks and epidemics. However, their implementation is hampered by the massive amount of sequence data and the difficulty to parameterise dedicated software packages. We introduce the COVFlow pipeline, accessible at https://gitlab.in2p3.fr/ete/CoV-flow, which allows a user to select sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database according to user-specified criteria, to perform basic phylogenetic analyses, and to produce an XML file to be run in the Beast2 software package. We illustrate the potential of this tool by studying two sets of sequences from the Delta variant in two French regions. This pipeline can facilitate the use of virus sequence data at the local level, for instance, to track the dynamics of a particular lineage or variant in a region of interest.
- A Solution to the Kermack and McKendrick Integro-Differential Equations -
In this manuscript, we derive a closed form solution to the full Kermack and McKendrick integro-differential equations (Kermack and McKendrick 1927) which we call the KMES. The KMES can be cast in the form of a step function response to the input of new infections; and that response is the time series of the total infections. We demonstrate the veracity of the KMES using independent data from the Covid 19 pandemic and derive many previously unknown and useful analytical expressions for diagnosing and managing an epidemic. These include new expressions for the viral load, the final size, the effective reproduction number, and the time to the peak in infections. Since the publication of the Kermack and McKendrick seminal paper (1927), thousands of authors have utilized the Susceptible, Infected, and Recovered (SIR) approximations; expressions which are putatively derived from the integro-differential equations, to model epidemic dynamics. Implicit in the use of the SIR approximation are the beliefs that there is no closed form solution to the more complex integro-differential equations, that the approximation adequately reproduces the dynamics of the integro-differential equations, and that herd immunity always exists. However, as we explicate in this manuscript, the KMES demonstrates that the SIR models are not adequate representations of the integro-differential equations, and herd immunity is not guaranteed. Our conclusion is that the KMES obsoletes the need for the SIR approximations; and provides a new level of understanding of epidemic dynamics.
- Psychometric validation of the Portuguese Obsession with COVID-19 Scale (PT-OCS) -
The COVID-19 pandemic had relevant psychological effects on the Portuguese population, partially related to repetitive and disruptive thoughts about the disease. Successive lockdowns contributed to an additional burden on parents’ family-work-life balance. This study intends to validate the Portuguese version of the Obsession with COVID-19 Scale (OCS; Lee, 2020), drew upon a general sample from diverse country regions (n = 531) and a specific sample of Portuguese parents (n = 109). Confirmatory factor analysis’ results ensure the PT-OCS excellent psychometric properties both for the general sample [X2 (1) = 0.446, p = 0.504; CFI = 1.0; GFI = 1.0; RMSEA = 0.0; Standardized RMR = 0.003] and for the parents’ group [X2 (2) = 1.816, p = 0.403; CFI = 1.0; GFI = 0.99; RMSEA = 0.0; Standardized RMR = 0.016; p Bollen-Stine bootstrap = 0.65]. The scale had very good reliability results (0.84 < α / ⍵ < 0.88). As expected, obsession with COVID-19 was highly correlated with COVID-19 anxiety and women had higher PT-OCS scores. Findings suggest the PT-OCS as a reliable and valid measure to evaluate persistent and disruptive thinking about COVID-19, namely in different groups of the Portuguese population, with potentialities for future epidemic events.
- Emotional distress and affective knowledge representation one year after the Covid-19 outbreak -
This study examines whether the detrimental effects of the COVID-19 pandemic on the affectivity of the population extend one year after the outbreak. In an online-mobile session, participants completed surveys (i.e. demographic characteristics, positive-negative affectivity, interoceptive awareness) and a similarity judgment task of triplets of emotional concepts, from which we derived 2D maps of their affective knowledge representation. Compared with pre-pandemic data derived from a comparable population, we report three main findings. First, we observed enhanced negative affectivity during the pandemic, but no changes in positive affectivity levels. Second, increased self-reported interoceptive awareness compared to pre-pandemic data, with greater attention to bodily sensations and adaptive aspects of interoceptive sensitivity. Furthermore, female participants reported higher scores than males on the questionnaire subscales of Emotional Awareness and Attention Regulation. Third, the effect of pandemic-related conditions is also apparent in the mental organization of emotional concepts, especially for female participants (i.e., reduced coherence in the organization of the concepts along the arousal dimension and more misclassification of concepts based on arousal) and participants who did not perform physical activity (a collapse of the arousal dimension). Some of the effects of the pandemic, thus, persist about a year after the outbreak. These results advise providing programs of psychological and emotional assistance throughout the pandemic beyond the outbreak, and that age-dependent gender differences should be accounted for to define tailored interventions. Physical activity might relieve pandemic-related stressors, so it should be promoted during particularly stressful periods for the population.
- Towards Pandemic-Scale Ancestral Recombination Graphs of SARS-CoV-2 -
Recombination is an ongoing and increasingly important feature of circulating lineages of SARS-CoV-2, challenging how we represent the evolutionary history of this virus and giving rise to new variants of potential public health concern by combining transmission and immune evasion properties of different lineages. Detection of new recombinant strains is challenging, with most methods looking for breaks between sets of mutations that characterise distinct lineages. In addition, many basic approaches fundamental to the study of viral evolution assume that recombination is negligible, in that a single phylogenetic tree can represent the genetic ancestry of the circulating strains. Here we present an initial version of sc2ts, a method to automatically detect recombinants in real time and to cohesively integrate them into a genealogy in the form of an ancestral recombination graph (ARG), which jointly records mutation, recombination and genetic inheritance. We infer two ARGs under different sampling strategies, and study their properties. One contains 1.27 million sequences sampled up to June 30, 2021, and the second is more sparsely sampled, consisting of 657K sequences sampled up to June 30, 2022. We find that both ARGs are highly consistent with known features of SARS-CoV-2 evolution, recovering the basic backbone phylogeny, mutational spectra, and recapitulating details on the majority of known recombinant lineages. Using the well-established and feature-rich tskit library, the ARGs can also be stored concisely and processed efficiently using standard Python tools. For example, the ARG for 1.27 million sequences—encoding the inferred reticulate ancestry, genetic variation, and extensive metadata—requires 58MB of storage, and loads in less than a second. The ability to fully integrate the effects of recombination into downstream analyses, to quickly and automatically detect new recombinants, and to utilise an efficient and convenient platform for computation based on well-engineered technologies makes sc2ts a promising approach.
Extracorporeal Photopheresis as a Possible Therapeutic Approach to Adults With Severe and Critical COVID-19 - Condition: COVID-19
Intervention: Procedure: Extracorporeal photopheresis
Sponsor: Del-Pest Central Hospital - National Institute of Hematology and Infectious Diseases
Recruiting
A Clinical Trial on Booster Immunization of Two COVID-19 Vaccines Constructed From Different Technical Routes - Condition: COVID-19
Interventions: Biological: Prototype and Omicron BA.4/5 Bivalent Recombinant COVID-19 Vaccine(Adenovirus Type 5 Vector) For Inhalation; Biological: Bivalent COVID-19 mRNA Vaccine; Biological: Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) For Inhalation
Sponsors: Zhongnan Hospital; Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China
Recruiting
Safety Study of COVID19 Vaccine on the Market - Condition: COVID-19
Intervention: Biological: Recombinant new coronavirus vaccine (CHO cell)
Sponsors: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention; Guizhou Center for Disease Control and Prevention; Hainan Center for Disease Control & Prevention
Recruiting
Community-engaged Optimization of COVID-19 Rapid Evaluation And TEsting Experiences - Conditions: COVID-19; COVID-19 Pandemic
Interventions: Behavioral: COVID-19 walk-up, on-site testing strategy; Behavioral: Community Health Worker (CHW) leading testing navigation and general preventive care reminders; Behavioral: No-cost self-testing kit vending machines
Sponsors: University of California, San Diego; San Ysidro Health Center
Not yet recruiting
Evaluation of Home Use COVID-19 Frequent Antigen Testing and Data Reporting - Condition: COVID-19 Respiratory Infection
Intervention: Diagnostic Test: SARS CoV-2 antigen tests
Sponsors: IDX20 Inc; National Institute on Minority Health and Health Disparities (NIMHD)
Recruiting
Mitoquinone/Mitoquinol Mesylate as Oral and Safe Postexposure Prophylaxis for Covid-19 - Conditions: SARS-CoV Infection; COVID-19
Interventions: Drug: Mitoquinone/mitoquinol mesylate; Other: Placebo
Sponsor: University of Texas Southwestern Medical Center
Not yet recruiting
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm F (Montelukast) - Condition: Covid19
Interventions: Other: Placebo; Drug: Montelukast
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Recruiting
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm B (Fluvoxamine) - Condition: Covid19
Interventions: Drug: Fluvoxamine; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm D (Ivermectin 600) - Condition: Covid19
Interventions: Drug: Ivermectin; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm E (Fluvoxamine 100) - Condition: Covid19
Interventions: Drug: Fluvoxamine; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
Evaluating Emetine for Viral Outbreaks (EVOLVE) - Condition: COVID-19
Interventions: Drug: Emetine Hydrochloride; Drug: Placebo
Sponsors: Johns Hopkins University; Nepal Health Research Council; Bharatpur Hospital Chitwan; Stony Brook University; Rutgers University
Not yet recruiting
Pycnogenol® in Post-COVID-19 Condition - Conditions: Post COVID-19 Condition; Long COVID
Interventions: Drug: Pycnogenol®; Drug: Placebo
Sponsor: University of Zurich
Not yet recruiting
Efficacy of Bailing Capsule on Pulmonary Fibrosis After COVID-19 - Conditions: Pulmonary Fibrosis; COVID-19 Pneumonia
Intervention: Drug: Bailing capsule
Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Not yet recruiting
To Evaluate the Immunogenicity and Safety of Sequential Booster Immunization of Recombinant Novel Coronavirus Vaccine (CHO Cells) for SARS-CoV-2 - Condition: COVID-19
Intervention: Biological: Recombinant Novel Coronavirus vaccine (CHO Cells)
Sponsor: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
Completed
A Study to Learn About How Loss of Liver Function Affects the Blood Levels of the Study Medicine Called PF-07817883. - Condition: COVID-19
Intervention: Drug: PF-07817883
Sponsor: Pfizer
Not yet recruiting
Multiscale Simulations of the Covalent Inhibition of the SARS-CoV-2 Main Protease: Four Compounds and Three Reaction Mechanisms - We report the results of computational modeling of the reactions of the SARS-CoV-2 main protease (M^(Pro)) with four potential covalent inhibitors. Two of them, carmofur and nirmatrelvir, have shown experimentally the ability to inhibit M^(Pro). Two other compounds, X77A and X77C, were designed computationally in this work. They were derived from the structure of X77, a non-covalent inhibitor forming a tight surface complex with M^(Pro). We modified the X77 structure by introducing warheads…
Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence - Alpha-1-antitrypsin (AAT), a serine protease inhibitor (serpin), is increasingly recognized to inhibit SARS-CoV-2 infection and counter many of the pathogenic mechanisms of COVID-19. Herein, we reviewed the epidemiologic evidence, the molecular mechanisms, and the clinical evidence that support this paradigm. As background to our discussion, we first examined the basic mechanism of SARS-CoV-2 infection and contend that despite the availability of vaccines and anti-viral agents, COVID-19 remains…
Serum proteomics hint at an early T-cell response and modulation of SARS-CoV-2-related pathogenic pathways in COVID-19-ARDS treated with Ruxolitinib - CONCLUSION: Our results indicate that the mechanism of action of Ruxo in COVID-19-ARDS can be related to both known effects of this drug as a modulator of T-cells and the SARS-CoV-2-infection.
Elucidation of novel compounds and epitope-based peptide vaccine design against C30 endopeptidase regions of SARS-CoV-2 using immunoinformatics approaches - There has been progressive improvement in immunoinformatics approaches for epitope-based peptide design. Computational-based immune-informatics approaches were applied to identify the epitopes of SARS-CoV-2 to develop vaccines. The accessibility of the SARS-CoV-2 protein surface was analyzed, and hexa-peptide sequences (KTPKYK) were observed having a maximum score of 8.254, located between amino acids 97 and 102, whereas the FSVLAC at amino acids 112 to 117 showed the lowest score of 0.114. The…
Host microRNA interactions with the SARS-CoV-2 viral genome 3’-untranslated region - The 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has marked the spread of a novel human coronavirus. While the viral life cycle is well understood, most of the interactions at the virus-host interface remain elusive. Furthermore, the molecular mechanisms behind disease severity and immune evasion are still largely unknown. Conserved elements of the viral genome such as secondary structures within the 5’- and 3’-untranslated regions (UTRs) serve as…
Vascular Endothelial-derived SPARCL1 Exacerbates Viral Pneumonia Through Pro-Inflammatory Macrophage Activation - Inflammation upon infectious lung injury is a double-edged sword: while tissue-infiltrating immune cells and cytokines are necessary to control infection, these same factors often aggravate injury. Full appreciation of both the sources and targets of inflammatory mediators is required to facilitate strategies to maintain antimicrobial effects while minimizing off-target epithelial and endothelial damage. Recognizing that the vasculature is centrally involved in tissue responses to injury and…
In vitro reconstitution of SARS CoV-2 Nsp1-induced mRNA cleavage reveals the key roles of the N-terminal domain of Nsp1 and the RRM domain of eIF3g - SARS CoV-2 nonstructural protein 1 (Nsp1) is the major pathogenesis factor that inhibits host translation using a dual strategy of impairing initiation and inducing endonucleolytic cleavage of cellular mRNAs. To investigate the mechanism of cleavage, we reconstituted it in vitro on β-globin, EMCV IRES and CrPV IRES mRNAs that use unrelated initiation mechanisms. In all instances, cleavage required Nsp1 and only canonical translational components (40S subunits and initiation factors), arguing…
A Novel Viral Assembly Inhibitor Blocks SARS-CoV-2 Replication in Airway Epithelial Cells - The ongoing evolution of SARS-CoV-2 to evade vaccines and therapeutics underlines the need for novel therapies with high genetic barriers to resistance. The small molecule PAV-104, identified through a cell-free protein synthesis and assembly screen, was recently shown to target host protein assembly machinery in a manner specific to viral assembly. Here, we investigated the capacity of PAV-104 to inhibit SARS-CoV-2 replication in human airway epithelial cells (AECs). Our data demonstrate that…
Virtual Health Promotion Work-Integrated Learning Placements: A COVID-19 Consequence or Preparation for the Future? - We explored student and industry supervisors’ experiences of virtual work-integrated learning (vWIL) health promotion placements during the COVID-19 pandemic. Using a descriptive phenomenological qualitative methodology, we conducted semi-structured interviews with eight students and eight supervisors of undergraduate health promotion-related placements at community, not-for-profit and government organizations. We asked participants about the aspects of their placement they found most enjoyable…
Designing for digital transformation of residency education - a post-pandemic pedagogical response - CONCLUSIONS: The study reflects the course leaders’ pedagogical response to the pandemic, as remote teaching became the only way to provide residency education. Initially, the sudden shift was perceived as constraining, but over time they found new affordances through the enforced use of digital technology that helped them not only to cope with the transition but also to innovate their pedagogical methods. After a rapid, forced shift from on-site to digital courses, it is crucial to utilize…
Eco-friendly and effective antimicrobial Melaleuca alternifolia essential oil Pickering emulsions stabilized with cellulose nanofibrils against bacteria and SARS-CoV-2 - Melaleuca alternifolia essential oil (MaEO) is a green antimicrobial agent suitable for confection eco-friendly disinfectants to substitute conventional chemical disinfectants commonly formulated with toxic substances that cause dangerous environmental impacts. In this contribution, MaEO-in-water Pickering emulsions were successfully stabilized with cellulose nanofibrils (CNFs) by a simple mixing procedure. MaEO and the emulsions presented antimicrobial activities against Staphylococcus aureus…
Porcine Deltacoronavirus Infection Disrupts the Intestinal Mucosal Barrier and Inhibits Intestinal Stem Cell Differentiation to Goblet Cells via the Notch Signaling Pathway - Goblet cells and their secreted mucus are important elements of the intestinal mucosal barrier, which allows host cells to resist invasion by intestinal pathogens. Porcine deltacoronavirus (PDCoV) is an emerging swine enteric virus that causes severe diarrhea in pigs and causes large economic losses to pork producers worldwide. To date, the molecular mechanisms by which PDCoV regulates the function and differentiation of goblet cells and disrupts the intestinal mucosal barrier remain to be…
SARS-CoV-2 infection impairs NK cell functions via activation of the LLT1-CD161 axis - CONCLUSION: We propose a novel mechanism of SARS-CoV-2 inhibition of NK cell functions via activation of the LLT1-CD161 axis.
DPP-4 inhibitors for treating T2DM - hype or hope? an analysis based on the current literature - DPP-4 inhibition is an interesting line of therapy for treating Type 2 Diabetes Mellitus (T2DM) and is based on promoting the incretin effect. Here, the authors have presented a brief appraisal of DPP-4 inhibitors, their modes of action, and the clinical efficiency of currently available drugs based on DPP-4 inhibitors. The safety profiles as well as future directions including their potential application in improving COVID-19 patient outcomes have also been discussed in detail. This review also…
Failure of TRPC6 inhibition to prevent COVID-19 deterioration: more questions than answers - No abstract