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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>08 November, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<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>Stress, coping, and quality of life in the United States during the COVID-19 pandemic</strong> -
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While research has widely explored stress, coping, and quality of life (QOL) individually and the potential links between them, there is a critical dearth in the literature regarding these constructs in the context of the COVID-19 pandemic. Our study aims to identify the salient stressors experienced, describe the coping strategies used, and examine the relationships between stress, coping, and current QOL among individuals during the pandemic. Data are from a nationally representative sample of 1,004 respondents who completed an online survey. Key measures included stressful life events (SLEs), coping strategies, and the physical and psychological health domains of QOL. Staged multivariate linear regression analyses examined the relationships between the two QOL domains and SLEs, controlling for sociodemographic and pre-existing health conditions and testing for the effects of coping strategies on these relationships. The most common SLEs experienced during the pandemic were a decrease in financial status, personal injury or illness, and change in living conditions. Problem-focused coping and emotion-focused coping were significantly related to higher levels of QOL, whereas avoidant coping was associated with lower QOL. Avoidant coping partially mediated the relationship between experiencing SLEs and reduced physical and psychological QOL. Our study informs clinical interventions to help individuals adopt healthy behaviors to effectively manage stressors, especially large-scale traumatic events like the pandemic. Our findings also call for public health and clinical interventions to address the long-term impacts of the most prevalent stressors experienced during the pandemic among vulnerable groups.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.03.22281899v1" target="_blank">Stress, coping, and quality of life in the United States during the COVID-19 pandemic</a>
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<li><strong>Changes in Alcohol Consumption during the COVID-19 Pandemic: Evidence from Wisconsin</strong> -
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Introduction: The COVID-19 pandemic increased stress levels broadly in the general population. Patterns of alcohol consumption are known to increase in times of increased stress like natural disasters, disease outbreaks, and economic turmoil. Wisconsin is an important place to study changes in alcohol consumption because it is one of the heaviest-drinking states in the United States. The primary aim of this study is to identify changes in alcohol use at three distinct timepoints during the COVID-19 pandemic in a statewide sample. Methods: An online survey was sent to 5,502 previous Survey of the Health of Wisconsin (SHOW) participants to ask about a wide range of topics related to COVID-19. The timepoints were taken May through June 2020 (Wave 1), January to February 2021 (Wave 2), and June 2021 (Wave 3) The sample included 1,290, 1,868, and 1,585 participants in each of the three waves respectively. Changes in alcohol consumption (whether they drank more, about the same, or less) were examined by race, age, gender, educational attainment, annual income, anxiety and depression status, remote work status, whether the participant experienced employment changes due to COVID-19, and whether there were children present in the home. Within-wave univariate changes in alcohol consumption were evaluated by demographics using a chi-squared test. Results: In all three waves, those with anxiety, a bachelors degree or higher, two younger age groups, and those with children in the home were significantly more likely to increase alcohol consumption. Those reporting depression, those in the highest income quartile, and those working remotely were more likely to report increased drinking in the first two surveys, but not in the third survey. Participants reporting changes in employment due to COVID-19 were more likely to increase drinking in the first survey only. Non-white participants were more likely to report decreased drinking in the first survey only. Conclusions: There may be subpopulations in Wisconsin at higher risk for the negative effects of heavy drinking during the pandemic like those with anxiety, those with children in the home, those with a bachelors degree or higher, and those in younger age groups, as these groups had consistently higher alcohol use that did not subside 15 months after lockdowns began.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.07.22282029v1" target="_blank">Changes in Alcohol Consumption during the COVID-19 Pandemic: Evidence from Wisconsin</a>
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<li><strong>Systematic review of the prevalence of Long Covid</strong> -
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Background: Long Covid occurs in those infected with SARSCoV2 whose symptoms persist or develop beyond the acute phase. We conducted a systematic review to determine the prevalence of persistent symptoms, functional disability or pathological changes in adults or children at least 12 weeks post-infection. Methods: We searched MEDLINE (Ovid), Embase (OVID), the Cochrane Covid-19 Study register, WHO ICTRP, medRxiv, Cochrane CENTRAL, MEDLINE (PubMed), ClinicalTrials.gov, and the WHO Global research on coronavirus disease (COVID-19) database from 1st January 2020 to 2nd November 2021, limited to publications in English. We included studies with at least 100 participants. Studies where all participants were critically ill were excluded. Articles were screened independently by two reviewers, with disagreements resolved by a third. Long Covid (primary outcome) was extracted as prevalence of at least one symptom or pathology, or prevalence of the most common symptom or pathology, at 12 weeks or later. Heterogeneity was quantified in absolute terms and as a proportion of total variation and explored across pre-defined subgroups (PROSPERO ID CRD42020218351). Findings: In total 120 studies in 130 publications were included. Length of follow-up varied from 12 weeks to over 12 months. Few studies had low risk of bias. All complete and subgroup analyses except one had I2 ≥ 90%, with prevalence of persistent symptoms ranging between 0% and 93%. Studies using routine healthcare records tended to report lower prevalence of persistent symptoms/pathology than self-report. However, studies systematically investigating pathology in all participants at follow up tended to report the highest estimates of all three. Studies of hospitalised cases had generally higher estimates than community-based studies. Interpretation: The way in which Long Covid is defined and measured affects prevalence estimation. Given the widespread nature of SARSCoV2 infection globally, the burden of chronic illness is likely to be substantial even using the most conservative estimates.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.06.22281979v1" target="_blank">Systematic review of the prevalence of Long Covid</a>
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<li><strong>Systematic review of the clinical effectiveness of Tixagevimab/Cilgavimab for prophylaxis of COVID-19 in immunocompromised patients</strong> -
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Background and aims Immunocompromised patients have a reduced ability to generate antibodies after COVID-19 vaccination and are at higher risk of SARS-CoV-2 infection, complications and mortality. Tixagevimab/Cilgavimab (Evusheld) is a monoclonal antibody combination which bind to the SARS-CoV-2 spike protein, preventing the virus entering human cells. The phase III PROVENT trial reported that immunocompromised patients given Tixagevimab/Cilgavimab had a significantly reduced risk of COVID-19 infection. However, PROVENT was conducted before the SARS-CoV-2 Omicron became prevalent. This systematic review provides an updated summary of real-world clinical evidence of Tixagevimab/Cilgavimab effectiveness in immunocompromised patients. Methods Two independent reviewers conducted PubMed and medRxiv searches for the period of 01/01/2021 to 01/10/2022. Clinical studies which reported the primary outcome of breakthrough COVID-19 infections after Tixagevimab/Cilgavimab administration were included in the review. COVID-19-related hospitalisations, ITU admissions and mortality were assessed as secondary outcomes. Clinical effectiveness was determined using the case-control clinical effectiveness methodology. The GRADE tool was used to ascertain the level of certainty for the primary outcome in each study. Results 17 clinical studies were included, comprising 24,773 immunocompromised participants of whom 10,775 received Tixagevimab/Cilgavimab. Most studies reported clinical outcomes during the SARS-CoV-2 Omicron wave. Six studies compared a Tixagevimab/Cilgavimab intervention group to a control group. Overall, the clinical effectiveness of prophylactic Tixagevimab/Cilgavimab against COVID-19 breakthrough infection, hospitalisation and ITU admission were 40.47%, 69.23% and 87.89%, respectively. For prevention of all-cause and COVID-19-specifc mortality, overall clinical effectiveness was 81.29% and 86.36%, respectively. Conclusions There is a growing body of real-world evidence validating the original PROVENT phase III study regarding the clinical effectiveness of Tixagevimab/Cilgavimab as prophylaxis for immunocompromised patients, notably demonstrating effectiveness during the Omicron wave. This review demonstrates the clinical effectiveness of prophylactic Tixagevimab/Cilgavimab at reducing COVID-19 infection, hospitalisation, ITU admission and mortality for immunosuppressed individuals. It is important that ongoing larger-scale and better-controlled real world studies are initiated and evaluated to provide ongoing certainty of the clinical benefit of prophylactic antibody treatment for immunocompromised patients in the face of new variants.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.07.22281786v1" target="_blank">Systematic review of the clinical effectiveness of Tixagevimab/Cilgavimab for prophylaxis of COVID-19 in immunocompromised patients</a>
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<li><strong>A comprehensive knowledgebase of known and predicted human genetic variants associated with COVID-19 susceptibility and severity</strong> -
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Host genetic susceptibility is a key risk factor for severe illness associated with COVID-19. Despite numerous studies of COVID-19 host genetics, our knowledge of COVID-19-associated variants is still limited, and there is no resource comprising all the published variants and categorizing them based on their confidence level. Also, there are currently no computational tools available to predict novel COVID-19 severity variants. Therefore, we collated 820 host genetic variants reported to affect COVID-19 susceptibility by means of a systematic literature search and confidence evaluation, and obtained 196 high-confidence variants. We then developed the first machine learning classifier of severe COVID-19 variants to perform a genome-wide prediction of COVID-19 severity for 82,468,698 missense variants in the human genome. We further evaluated the classifier9s predictions using feature importance analyses to investigate the biological properties of COVID-19 susceptibility variants, which identified conservation scores as the most impactful predictive features. The results of enrichment analyses revealed that genes carrying high-confidence COVID-19 susceptibility variants shared pathways, networks, diseases and biological functions, with the immune system and infectious disease being the most significant categories. Additionally, we investigated the pleiotropic effects of COVID-19-associated variants using phenome-wide association studies (PheWAS) in ~40,000 BioMe BioBank genotyped individuals, revealing pre-existing conditions that could serve to increase the risk of severe COVID-19 such as chronic liver disease and thromboembolism. Lastly, we generated a web-based interface for exploring, downloading and submitting genetic variants associated with COVID-19 susceptibility for use in both research and clinical settings (https://itanlab.shinyapps.io/COVID19webpage/). Taken together, our work provides the most comprehensive COVID-19 host genetics knowledgebase to date for the known and predicted genetic determinants of severe COVID-19, a resource that should further contribute to our understanding of the biology underlying COVID-19 susceptibility and facilitate the identification of individuals at high risk for severe COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.03.22281867v1" target="_blank">A comprehensive knowledgebase of known and predicted human genetic variants associated with COVID-19 susceptibility and severity</a>
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<li><strong>4-Fluorouridine mitigates lethal infection with pandemic human and highly pathogenic avian influenza viruses</strong> -
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Influenza outbreaks are associated with substantial morbidity, mortality and economic burden. Next generation antivirals are needed to treat seasonal infections and prepare against zoonotic spillover of avian influenza viruses with pandemic potential. Having previously identified oral efficacy of the nucleoside analog 4-Fluorouridine (4-FlU, EIDD-2749) against SARS-CoV-2 and respiratory syncytial virus, we explored activity of the compound against seasonal and highly pathogenic influenza (HPAI) viruses in cell culture, human airway epithelium organoids, and/or two animal models, ferrets and mice, that assess IAV transmission and lethal viral pneumonia, respectively. 4-FlU inhibited a panel of relevant influenza A and B viruses with nanomolar potency in organoids. In vitro polymerase assays revealed immediate chain termination of IAV polymerase after 4-FlU incorporation, in contrast to delayed chain termination of SARS-CoV-2 and RSV polymerase. Once-daily oral treatment of ferrets with 2 mg/kg 4-FlU initiated 12 hours after infection rapidly stopped virus shedding and prevented direct-contact transmission to untreated sentinels. Treatment of mice infected with a lethal inoculum of pandemic A/CA/07/2009 (H1N1) (Ca09) with 2 mg/kg 4-FlU alleviated pneumonia. Three doses mediated complete survival when treatment was initiated up to 60 hours after infection, indicating an unusually broad window for effective intervention. Therapeutic oral 4-FlU ensured survival of animals infected with HPAI A/VN/12/2003 (H5N1) and of immunocompromised mice infected with pandemic Ca09. Recoverees were fully protected against homologous reinfection. This study defines the mechanistic foundation for high sensitivity of influenza viruses to 4-FlU and supports 4-FlU as developmental candidate for the treatment of seasonal and pandemic influenza.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.05.515296v1" target="_blank">4-Fluorouridine mitigates lethal infection with pandemic human and highly pathogenic avian influenza viruses</a>
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<li><strong>ARF6 is a host factor for SARS-CoV-2 infection in vitro</strong> -
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SARS-CoV-2 is a newly emerged beta-coronavirus that enter cells via two routes, direct fusion at the plasma membrane or endocytosis followed by fusion with the late endosome/lysosome. While the viral receptor, ACE2, multiple entry factors, and the mechanism of fusion of the virus at the plasma membrane have been extensively investigated, viral entry via the endocytic pathway is less understood. By using a human hepatocarcinoma cell line, Huh-7, which is resistant to the antiviral action of the TMPRSS2 inhibitor camostat, we discovered that SARS-CoV-2 entry is not dependent on dynamin but dependent on cholesterol. ADP-ribosylation factor 6 (ARF6) has been described as a host factor for SARS-CoV-2 replication and it is involved in the entry and infection of several pathogenic viruses. Using CRISPR-Cas9 genetic deletion, we observed that ARF6 is important for SARS-CoV-2 uptake and infection in Huh-7. This finding was corroborated using a pharmacologic inhibitor, whereby the ARF6 inhibitor NAV-2729 showed a dose-dependent inhibition of viral infection. Importantly, NAV-2729 reduced SARS-CoV-2 viral loads also in more physiologic models of infection: Calu-3 and kidney organoids. This highlighted the importance of ARF6 in multiple cell contexts. Together, these experiments points to ARF6 as a putative target to develop antiviral strategies against SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.09.495482v2" target="_blank">ARF6 is a host factor for SARS-CoV-2 infection in vitro</a>
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<li><strong>Mathematical Modeling of Impacts of Patient Differences on COVID-19 Lung Fibrosis Outcomes</strong> -
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Patient-specific premorbidity, age, and sex are significant heterogeneous factors that influence the severe manifestation of lung diseases, including COVID-19 fibrosis. The renin-angiotensin system (RAS) plays a prominent role in regulating effects of these factors. Recent evidence suggests that patient-specific alteration of RAS homeostasis with premorbidity and the expression level of angiotensin converting enzyme 2 (ACE2), depending on age and sex, is correlated with lung fibrosis. However, conflicting evidence suggests decreases, increases, or no changes in RAS after SARS-CoV-2 infection. In addition, detailed mechanisms connecting the patient-specific conditions before infection to infection-induced fibrosis are still unknown. Here, a mathematical model is developed to quantify the systemic contribution of heterogeneous factors of RAS in the progression of lung fibrosis. Three submodels are connected - a RAS model, an agent-based COVID-19 in-host immune response model, and a fibrosis model - to investigate the effects of patient-group-specific factors in the systemic alteration of RAS and collagen deposition in the lung. The model results indicate cell death due to inflammatory response as a major contributor to the reduction of ACE and ACE2, whereas there are no significant changes in ACE2 dynamics due to viral-bound internalization of ACE2. Reduction of ACE reduces the homeostasis of RAS including angiotensin II (ANGII), while the decrease in ACE2 increases ANGII and results in severe lung injury and fibrosis. The model explains possible mechanisms for conflicting evidence of RAS alterations in previously published studies. Also, the results show that ACE2 variations with age and sex significantly alter RAS peptides and lead to fibrosis with around 20% additional collagen deposition from systemic RAS with slight variations depending on age and sex. This model may find further applications in patient-specific calibrations of tissue models for acute and chronic lung diseases to develop personalized treatments.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.06.515367v1" target="_blank">Mathematical Modeling of Impacts of Patient Differences on COVID-19 Lung Fibrosis Outcomes</a>
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<li><strong>Motivational factors were more important than perceived risk or optimism for compliance to infection control measures in the early stage of the COVID-19 pandemic</strong> -
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Compliance to infection control measures may be influenced both by the fear of negative consequences of a pandemic, but also by the expectation to be able to handle the pandemic’s challenges. We performed a survey on a representative sample for Norway (N = 4,083) in the first weeks of the COVID-19 lock-down in March 2020. We had preregistered hypotheses to test the effect of optimism and perceived risk on compliance. Perceived risk had small effects on increasing compliance and on leading to more careful information gathering. The expected negative association between optimism and compliance was not supported, and there was instead a small positive association. We found a small effect that optimism was associated with seeing less risk from the pandemic and with a larger optimistic bias. Finally, an exploratory analysis showed that seeing the infection control measures as being effective in protecting others explained a substantial proportion of the variation in compliance. The study indicates that how we think about pandemic risk has complex and non-intuitive relationships with compliance. Our beliefs and motivations toward infection control measures appears to be important for compliance.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/njhvu/" target="_blank">Motivational factors were more important than perceived risk or optimism for compliance to infection control measures in the early stage of the COVID-19 pandemic</a>
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<li><strong>A Systematic Review on Medical Oxygen Ecosystem: Current State and Recent Advancements</strong> -
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<b>Background:</b> Medical oxygen is an essential component of modern healthcare, with a wide variety of applications ranging from supplemental use in surgery and trauma patients to the primary medication in oxygen therapy. This is the most effective treatment for any respiratory illness. Despite the importance of oxygen for public health and its demand as a life-saving drug, research on the subject is limited, with the majority of studies conducted following the outbreak of the COVID-19 pandemic. Due to the lack of empirical studies, we aimed to compile the recent research efforts with the current state of the field through a systematic review. <b>Methods:</b> We have performed a systematic review targeting the medical oxygen ecosystem, following the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P). For the study, we have limited our scope to healthcare facilities and domiciliary applications of medical oxygen. We considered the articles published in the last twenty years, starting from the SARS outbreak in November 2002. <b>Results:</b> Our systematic search resulted in thirty-nine preliminary articles, with three more articles appended for a complete outlook on the topic. Based on the selected articles, the current state of the topic was presented through detailed discussion and analysis. <b>Conclusion:</b> We have presented an in-depth discussion of the research works found through the systematic search while extrapolating to provide insights on the current subject scenario. We have highlighted the areas with inadequate contemporary studies and presented some research gaps in the field.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.23.22281394v2" target="_blank">A Systematic Review on Medical Oxygen Ecosystem: Current State and Recent Advancements</a>
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<li><strong>Effective screening strategies for safe opening of universities under Omicron and Delta variants of COVID-19</strong> -
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As new COVID-19 variants emerge, and disease and population characteristics change, screening strategies may also need to change. We develop a decision-making model that can assist a college to determine an optimal screening strategy based on their characteristics and resources, considering COVID-19 infections/hospitalizations/deaths; peak daily hospitalizations; and the tests required. We also use this tool to generate screening guidelines for the safe opening of college campuses. Our compartmental model simulates disease spread on a hypothetical college campus under co-circulating variants with different disease dynamics, considering: (i) the heterogeneity in disease transmission and outcomes for faculty/staff and students based on vaccination status and level of natural immunity; and (ii) variant- and dose-dependent vaccine efficacy. Using the Spring 2022 academic semester as a case study, we study routine screening strategies, and find that screening the faculty/staff less frequently than the students, and/or the boosted and vaccinated less frequently than the unvaccinated, may avert a higher number of infections per test, compared to universal screening of the entire population at a common frequency. We also discuss key policy issues, including the need to revisit the mitigation objective over time, effective strategies that are informed by booster coverage, and if and when screening alone can compensate for low booster coverage.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.04.22274667v2" target="_blank">Effective screening strategies for safe opening of universities under Omicron and Delta variants of COVID-19</a>
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<li><strong>Novel inhibitors against COVID-19 main protease suppressed viral infection</strong> -
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can cause severe disease with high mortality rates, especially among older and vulnerable populations. Despite the recent success of vaccines and approval of first-generation anti-viral inhibitor against SARS-CoV-2, an expanded arsenal of anti-viral compounds that limit viral replication and ameliorate disease severity is still urgently needed in light of the continued emergence of viral variants of concern (VOC). The main protease (Mpro) of SARS-CoV-2 is the major non-structural protein required for the processing of viral polypeptides encoded by the open reading frame 1 (ORF1) and ultimately replication. Structural conservation of Mpro among SARS-CoV-2 variants make this protein an attractive target for the anti-viral inhibition by small molecules. Here, we developed a structure-based in-silico screening of approximately 11 million compounds in ZINC15 database inhibiting Mpro, which prioritized 9 lead compounds for the subsequent in vitro validation in SARS-CoV-2 replication assays using both Vero and Calu-3 cells. We validated three of these compounds significantly inhibited SARS-CoV-2 replication in the micromolar range. In summary, our study identified novel small-molecules significantly suppressed infection and replication of SARS-CoV-2 in human cells.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.05.515305v1" target="_blank">Novel inhibitors against COVID-19 main protease suppressed viral infection</a>
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<li><strong>Wildlife exposure to SARS-CoV-2 across a human use gradient</strong> -
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The spillover of SARS-CoV-2 into humans has caused one of the most devastating pandemics in recorded history. Human-animal interactions have led to transmission events of SARS-CoV-2 from humans to wild and captive animals. However, many questions remain about how extensive SARS-CoV-2 exposure is in wildlife, the factors that influence wildlife transmission risk, and whether sylvatic cycles can generate novel variants with increased infectivity and virulence. We sampled 18 different wildlife species in the Eastern U.S. and detected widespread exposure to SARS-CoV-2 across wildlife species. Using quantitative reverse transcription polymerase chain reaction and whole genome sequencing, we conclusively detected SARS-CoV-2 in the Virginia opossum and had equivocal detections in six additional species. Species considered human commensals like squirrels, and raccoons had high seroprevalence, ranging between 62%-71%, and sites with high human use had three times higher seroprevalence than low human-use areas. SARS-CoV-2 genomic data from an infected opossum and molecular modeling exposed previously uncharacterized changes to amino acid residues observed in the receptor binding domain (RBD), which predicts improved binding between the spike protein and human angiotensin-converting enzyme (ACE2) compared to the dominant variant circulating at the time of isolation. These mutations were not identified in human samples at the time of collection. Overall, our results highlight widespread exposure to SARS-CoV-2 in wildlife and suggest that areas with high human activity may serve as important points of contact for cross-species transmission. Furthermore, this work highlights the potential role of wildlife in fueling de novo mutations that may eventually appear in humans.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.04.515237v1" target="_blank">Wildlife exposure to SARS-CoV-2 across a human use gradient</a>
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<li><strong>Pharmacological modulators of epithelial immunity uncovered by synthetic genetic tracing of SARS-CoV-2 infection responses</strong> -
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Epithelial immune responses govern tissue homeostasis and offer drug targets against maladaptation. Here, we report a framework to generate drug discovery-ready reporters of cellular responses to viral infection. We reverse engineered epithelial cell responses to SARS- CoV-2, the viral agent fueling the ongoing COVID-19 pandemic and designed synthetic transcriptional reporters whose molecular logic comprises interferon-a/b/g-, and NF-kB pathways. Such regulatory potential reflected single-cell data from experimental models to severe COVID-19 patient epithelial cells infected by SARS-CoV-2. SARS-CoV-2, type-I interferons, and RIG-I drive reporter activation. Live-cell-image-based phenotypic drug screens identified JAK inhibitors and DNA damage inducers as antagonistic modulators of epithelial cell response to interferons, RIG-I stimulation, and SARS-CoV-2. Synergistic or antagonistic modulation of the reporter by drugs underscored their similar mechanism of action. Thus, this study describes a tool for dissecting antiviral responses to infection and sterile cues, and a rapid approach to other emerging viruses of public health concern in order to discover rational drug combinations.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.05.515197v1" target="_blank">Pharmacological modulators of epithelial immunity uncovered by synthetic genetic tracing of SARS-CoV-2 infection responses</a>
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<li><strong>The Impact of COVID-19 on Families’ Home Literacy Practices with Young Children</strong> -
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The practice of shared book reading is a nurturing support for early language, literacy and socio-emotional development within young children’s typical care. However, the closures of childcare, early education programs, and centers for family activities in the Spring of 2020 due to COVID-19 brought many sudden changes to the everyday lives of families with young children. In order to explore the impact of COVID-19 on shared reading, we surveyed parents of children between ages 2 and 5 (n = 85) about their children’s frequency of shared reading engagement in February and October, 2020 as well as the frequency of screen-mediated reading, the number of readers their children read with, and book preferences at both time points. Parents were also asked about changes in their children’s regular care and whether and how they had tried new kinds of (virtual) literacy activities during their increased time at home. Findings showed that there were no significant changes in frequency of shared reading from February to October, but there was a significant increase in frequency of screen-mediated reading, especially among families who lost outside-the-home childcare. There was also a significant decrease in the number of adults regularly reading with the children. Caregivers described adapting to virtual options for storytime. Ultimately, while families were still able to provide consistent amounts of shared reading with their children throughout COVID-19, the nature of that shared reading was changed. Future research will investigate whether these changes may have an impact on children’s typical learning from shared reading.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/dvcqm/" target="_blank">The Impact of COVID-19 on Families’ Home Literacy Practices with Young Children</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Bivalent Booster Megastudy</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: COVID Booster text messages<br/><b>Sponsor</b>: University of Pennsylvania<br/><b>Enrolling by invitation</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>Using a Community-level Just-in-Time Adaptive Intervention to Address COVID-19 Testing Disparities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Multi-Level Multi-Component Intervention (MLI); Behavioral: Community Just-In-Time Adaptive Intervention (Community JITAI)<br/><b>Sponsors</b>: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)<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>Safety and Efficacy of Medications COVID-19</strong> - <b>Condition</b>: Severe Covid-19<br/><b>Intervention</b>: Drug: Oral bedtime melatonin<br/><b>Sponsor</b>: Hospital San Carlos, Madrid<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>Use of Multiple Doses of Convalescent Plasma in Mechanically Intubated Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Multiple doses of anti-SARS-CoV-2 Convalescent Plasma<br/><b>Sponsors</b>: Hospital Regional Dr. Rafael Estévez; Complejo Hospitalario Dr. Arnulfo Arias Madrid; Hospital Santo Tomas; Hospital Punta Pacífica, Pacífica Salud; Insituto Conmemorativo Gorgas de Estudios para la Salud; Sociedad Panameña de Hematología; Institute of Scientific Research and High Technology Services (INDICASAT AIP); University of Panama; Sistema Nacional de Investigación de Panamá<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>Examining How a Facilitated Self-Sampling Intervention and Testing Navigation Intervention Influences COVID-19 Testing</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Facilitated Self-Sampling Intervention (FSSI); Behavioral: Testing Navigation Intervention (TNI).; Behavioral: Control<br/><b>Sponsors</b>: The University of Texas Health Science Center, Houston; National Center for Advancing Translational Sciences (NCATS)<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>A Phase III of COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: EuCorVac-19; Biological: ChAdOx1<br/><b>Sponsor</b>: EuBiologics Co.,Ltd<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>Open Multicenter Study for Assessment of Efficacy and Safety of Molnupiravir in Adult Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Molnupiravir (Esperavir); Drug: Standard of care<br/><b>Sponsor</b>: Promomed, LLC<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>Open Multicentre Study of the Safety and Efficacy Against COVID-19 of Nirmatrelvir/Ritonavir in the Adult Population</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: nirmatrelvir/ritonavir; Drug: Standard of care<br/><b>Sponsors</b>: Promomed, LLC; Sponsor GmbH<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>Study Evaluating GS-5245 in Participants With COVID-19 Who Have a High Risk of Developing Serious or Severe Illness</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GS-5245; Drug: GS-5245 Placebo<br/><b>Sponsor</b>: Gilead 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>Effects of Respiratory Muscle Training in Individuals With Long-term Post-COVID-19 Symptoms</strong> - <b>Conditions</b>: Covid19; Post-acute COVID-19 Syndrome<br/><b>Interventions</b>: Other: Inspiratory + expiratory muscle training group; Other: Inspiratory + expiratory muscle training sham group; Other: Exercise training program<br/><b>Sponsors</b>: Universidad Complutense de Madrid; Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid<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>Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) Phase III Clinical Trial</strong> - <b>Conditions</b>: COVID-19; Coronavirus Infections<br/><b>Interventions</b>: Biological: LIBP-Rec-Vaccine; Biological: BIBP-Rec-Vaccine; Biological: placebo<br/><b>Sponsors</b>: National Vaccine and Serum Institute, China; China National Biotec Group Company Limited; Lanzhou Institute of Biological Products Co., Ltd; Beijing Institute of Biological Products Co Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza</strong> - <b>Conditions</b>: Influenza, Human; COVID-19<br/><b>Interventions</b>: Biological: bivalent BNT162b2 (original/Omi BA.4/BA.5); Biological: qIRV (22/23); Biological: QIV<br/><b>Sponsors</b>: BioNTech SE; Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate Safety, Tolerability, Efficacy and Pharmacokinetics of ASC10 in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>: SARS CoV 2 Infection<br/><b>Interventions</b>: Drug: ASC10; Drug: Placebo<br/><b>Sponsor</b>: Ascletis Pharmaceuticals Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Nitric Oxide Nasal Spray (NONS) To Treat and Prevent the Exacerbation of Infection in Individuals With Mild COVID-19</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Intervention</b>: Drug: Nitric Oxide<br/><b>Sponsors</b>: Sanotize Research and Development corp.; Glenmark Pharmaceuticals Ltd. India<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>A Phase I/II Study of GLB-COV2-043 as a COVID-19 Vaccine Booster</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GLB-COV2-043; Drug: BNT162b2/COMIRNATY®<br/><b>Sponsor</b>: GreenLight Biosciences, Inc.<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Advances And Challenges In Using Nirmatrelvir And Its Derivatives Against Sars-Cov-2 Infection</strong> - On 22 December 2021, the United States Food and Drug Administration (FDA) approved the first M^(pro) inhibitor, i.e., oral antiviral nirmatrelvir (PF-07321332)/ritonavir (Paxlovid), for the treatment of early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nirmatrelvir inhibits SARS-CoV-2 infection, but high doses or long-term treatment may cause embryonic developmental toxicity and changes in host gene expression. The chiral structure of nirmatrelvir plays a key role in…</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>Protocol for characterizing the inhibition of SARS-CoV-2 infection by a protein of interest in cultured cells</strong> - Here, we present a protocol to characterize the antiviral ability of a protein of interest to SARS-CoV-2 infection in cultured cells, using MUC1 as an example. We use SARS-CoV-2 ΔN trVLP system, which utilizes transcription and replication-competent SARS-CoV-2 virus-like particles lacking nucleocapsid gene. We describe the optimized procedure to analyze protein interference of viral attachment and entry into cells, and qRT-PCR-based quantification of viral infection. The protocol can be applied…</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>Current insights and molecular docking studies of the drugs under clinical trial as rdrp inhibitors in COVID-19 treatment</strong> - CONCLUSION: The drug repurposing approach provides a new avenue in COVID-19 treatment.</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>Insight into the role of clathrin-mediated endocytosis inhibitors in SARS-CoV-2 infection</strong> - Emergence of SARS-CoV-2 variants warrants sustainable efforts to upgrade both the diagnostic and therapeutic protocols. Understanding the details of cellular and molecular basis of the virus-host cell interaction is essential for developing variant-independent therapeutic options. The internalization of SARS-CoV-2, into lung epithelial cells, is mediated by endocytosis, especially clathrin-mediated endocytosis (CME). Although vaccination is the gold standard strategy against viral infection,…</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 randomized clinical trial of lipid metabolism modulation with fenofibrate for acute coronavirus disease 2019</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cytotoxicity may involve inhibition of peroxisome proliferator-activated receptor alpha. Fenofibrate activates peroxisome proliferator-activated receptor alpha and inhibits SARS-CoV-2 replication in vitro. Whether fenofibrate can be used to treat coronavirus disease 2019 (COVID-19) infection in humans remains unknown. Here, we randomly assigned inpatients and outpatients with COVID-19 within 14 d of symptom onset to 145 mg of oral…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 public health and social measures: a comprehensive picture of six Asian countries</strong> - The COVID-19 pandemic will not be the last of its kind. As the world charts a way towards an equitable and resilient recovery, Public Health and Social Measures (PHSMs) that were implemented since the beginning of the pandemic need to be made a permanent feature of health systems that can be activated and readily deployed to tackle sudden surges in infections going forward. Although PHSMs aim to blunt the spread of the virus, and in turn protect lives and preserve health system capacity, there…</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 a Bacterial Artificial Chromosome to Generate Recombinant SARS-CoV-2 Expressing Robust Levels of Reporter Genes</strong> - Reporter-expressing recombinant virus represents an excellent option and a powerful tool to investigate, among others, viral infection, pathogenicity, and transmission, as well as to identify therapeutic compounds that inhibit viral infection and prophylactic vaccines. To combat the ongoing coronavirus disease 2019 (COVID-19) pandemic, we have established a robust bacterial artificial chromosome (BAC)-based reverse genetics (RG) system to rapidly generate recombinant severe acute respiratory…</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>Geneticin shows selective antiviral activity against SARS-CoV-2 by interfering with programmed -1 ribosomal frameshifting</strong> - SARS-CoV-2 is currently causing an unprecedented pandemic. While vaccines are massively deployed, we still lack effective large-scale antiviral therapies. In the quest for antivirals targeting conserved structures, we focused on molecules able to bind viral RNA secondary structures. Aminoglycosides are a class of antibiotics known to interact with the ribosomal RNA of both prokaryotes and eukaryotes and have previously been shown to exert antiviral activities by interacting with viral RNA. Here…</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>New thiophene-derived <em>α</em>-aminophosphonic acids: Synthesis under microwave irradiations, antioxidant and antifungal activities, DFT investigations and SARS-CoV-2 main protease inhibition</strong> - Four new α-aminophosphonic acids containing thiophene ring have been synthesized using simple, neat and catalyst-free conditions, more convenient and eco-friendly method under microwave irradiations. The structures of the title molecules have been confirmed by UV-Vis, FT-IR, ¹H NMR, ^(13)C NMR and ^(31)P NMR. Moreover, their antioxidant activity was evaluated using DPPH, ABTS and phenantroline methods; the obtained results indicate that the title molecules exhibit excellent activity better than…</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>Antifungal activity of Taurolidine against Mucorales: An in vitro study on clinical isolates</strong> - CONCLUSION: In conclusion, this is an updated experience of using taurolidine against Mucorales. However, our in-vitro findings need to be confirmed in well-designed clinical trials aimed at treating invasive Mucormycosis infections.</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>Dual-targeting cyclic peptides of receptor-binding domain (RBD) and main protease (Mpro) as potential drug leads for the treatment of SARS-CoV-2 infection</strong> - The receptor-binding domain (RBD) and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) play a crucial role in the entry and replication of viral particles, and co-targeting both of them could be an attractive approach for the treatment of SARS-CoV-2 infection by setting up a “double lock” in the viral lifecycle. However, few dual RBD/Mpro-targeting agents have been reported. Here, four novel RBD/Mpro dual-targeting peptides, termed as MRs 1-4, were…</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>Polyphenolic promiscuity, inflammation-coupled selectivity: Whether PAINs filters mask an antiviral asset</strong> - The Covid-19 pandemic has elicited much laboratory and clinical research attention on vaccines, mAbs, and certain small-molecule antivirals against SARS-CoV-2 infection. By contrast, there has been comparatively little attention on plant-derived compounds, especially those that are understood to be safely ingested at common doses and are frequently consumed in the diet in herbs, spices, fruits and vegetables. Examining plant secondary metabolites, we review recent elucidations into 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>Benchmarked molecular docking integrated molecular dynamics stability analysis for prediction of SARS-CoV-2 papain-like protease inhibition by olive secoiridoids</strong> - CONCLUSION: AutoDock Vina retrieved the active molecules accurately and predicted Demethyloleuropein aglycone as the best inhibitor of PLpro. The Arabian diet consisting of olive products rich in secoiridoids benefits from the PLpro inhibition property and reduces the risk of viral infection.</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>Antimicrobial activity effects of electrolytically generated hypochlorous acid-treated pathogenic microorganisms by isothermal kinetic simulation</strong> - This study involves isothermal kinetic simulation to evaluate the parameters of inhibition conditions for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) of high-risk pathogens. This is because the new type of the 2019 novel coronavirus (2019-nCoV) is continuously spreading and the importance of public health issues. Environmental disinfection and personal wearing of masks have become important epidemic prevention measures. Selection of concentration kinetics could be estimated…</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>Vimentin is an important ACE2 co-receptor for SARS-CoV-2 in epithelial cells</strong> - Vimentin is a type III intermediate filament protein, widely expressed in mesenchymal cells. Mainly located in the cytoplasm, vimentin can also appear at extracellular locations, where it may interact with bacterial or viral pathogens. In this study, we aimed at investigating the implication of vimentin in SARS-CoV-2 viral entry and the consequences on viral replication and cellular response. We showed that upon infection, vimentin was upregulated at the cell surface, where it interacts with…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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