Covid-19 Sentry

Contents

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

From Preprints

• Palestinian Attitudes Towards Settlers in the West Bank -
  We present survey data from 1,573 West Bank Palestinians with which we estimate that the average Palestinian lives 14 km (UI 11 to 18 km) from the closest Israeli settlement. We also show with this data that while Palestinians in general hold negative attitudes towards settlers in the West Bank, Palestinians living in closer proximity to a settlement report more neutral attitudes towards settlers. Multivariate analysis shows that this effect appears to be driven by social and professional contact: Palestinians who have interacted with a settler or worked in a settlement present more positive attitudes towards settlers while distance loses its ability to predict attitudes. Since the onset of the COVID-19 global pandemic, the majority of respondents stated that they have lost either a job or a business from COVID-related restrictions, suggesting that this positive contact effect could dissipate as Palestinians have less reason to interact with Israelis.
  🖺 Full Text HTML: Palestinian Attitudes Towards Settlers in the West Bank
• CoronaNet: A Dyadic Dataset of Government Responses to the COVID-19 Pandemic -
  As the COVID-19 pandemic spreads around the world, governments have implemented a broad set of policies to limit the spread of the pandemic. In this paper we present an initial release of a large hand-coded dataset of more than 4,500 separate policy announcements from governments around the world. This data is being made publicly available, in combination with other data that we have collected (including COVID-19 tests, cases, and deaths) as well as a number of country-level covariates. Due to the speed of the COVID-19 outbreak, we will be releasing this data on a daily basis with a 5-day lag for record validity checking. In a truly global effort, our team is comprised of more than 190 research assistants across 18 time zones and makes use of cloud-based managerial and data collection technology in addition to machine learning coding of news sources. We analyze the dataset with a Bayesian time-varying ideal point model showing the quick acceleration of more harsh policies across countries beginning in mid-March and continuing to the present. While some relatively low-cost policies like task forces and health monitoring began early, countries generally adopted more harsh measures within a narrow time window, suggesting strong policy diffusion effects.
  🖺 Full Text HTML: CoronaNet: A Dyadic Dataset of Government Responses to the COVID-19 Pandemic
• Getting Off the Gold Standard: A Holistic Approach to Causal Inference with Entropic Causal Graphs -
  While many classify studies as either descriptive or causal, I argue that causality is a continuous construct, and different inference modes–experimental, observational and mechanistic–can at best provide only partial causal information. To discriminate between the relative value of different inference modes, I employ statistical entropy as a possible yardstick for evaluating research designs as different operations on causal graphs. Rather than dichotomize studies as either causal or descriptive, the concept of entropy instead emphasizes the relative causal knowledge gained from a given research finding. I employ this theory to clarify why and when researchers relied on divergent modes of inference to determine the efficacy of vaccines over the course of the COVID-19 pandemic.
  🖺 Full Text HTML: Getting Off the Gold Standard: A Holistic Approach to Causal Inference with Entropic Causal Graphs
• Relationship Satisfaction in the Early Stages of the COVID-19 Pandemic: A Cross-National Examination of Situational, Dispositional, and Relationship Factors -
  The outbreak of the COVID-19 pandemic has had a large impact on various aspects of life, but questions about its effect on close relationships remain largely unanswered. In the present study, we examined changes in relationship satisfaction at the beginning of the COVID-19 pandemic by using a sample of 3,243 individuals from 68 different countries. Participants responded to an online survey that included questions about relationship aspects (e.g., shared time, housework division), special circumstances (e.g., exit restrictions), and enduring dispositions (e.g., insecure attachment). A decline in time shared with one’s partner was the strongest predictor of decreases in relationship satisfaction, resulting in a different pattern of findings for cohabiting and non-cohabiting individuals. Among the most influential moderators were lockdown policies and insecure attachment. Differential involvement of men and women in household duties remained largely unchanged. The findings offer insights into aggravating and/or protecting factors in couples’ responses to pandemic-related stressors.
  🖺 Full Text HTML: Relationship Satisfaction in the Early Stages of the COVID-19 Pandemic: A Cross-National Examination of Situational, Dispositional, and Relationship Factors
• Did knowledge, attitudes, and practices matter during the second wave of COVID-19 pandemic in Bangladesh? Results from a web-based cross-sectional study -

  Globally, health promotion measures have been undertaken in preventing the emergence and spread of coronavirus disease 2019 (COVID-19). However, whether these measures influence public awareness and behaviors is unclear and evidence is limited in particular in low-and-middle income country. We conducted an online survey among internet users in Bangladesh to understand the status and attributes of their knowledge, attitudes and practices towards COVID-19 during second wave of the pandemic when COVID educational information was more accessible to the public. Survey data were analyzed using descriptive statistics, Chi-square tests, and multivariate logistic regression analysis. Of 964 respondents, 40.2%, 51.5%, and 64.3% had good knowledge, confident attitudes, and proper practices towards COVID-19, respectively. The multivariate regression analysis found that the knowledge and practice scores were associated (p<0.05) with gender, age, and occupation. Females had better knowledge and practices compared to males (p<0.05). There were major gaps in awareness, attitudes, and practices among internet users in particular males and elders that needs to be addressed to control the further spread of COVID-19 infections before at least COVID-19 vaccine become accessible at population level in Bangladesh.

  🖺 Full Text HTML: Did knowledge, attitudes, and practices matter during the second wave of COVID-19 pandemic in Bangladesh? Results from a web-based cross-sectional study
• Becoming A Resilient Scientist Series: An Intervention Program -

  Compared to the general population, science trainees experience significant challenges and stressors that increase negative mental health outcomes. With COVID-19, the stressors of social distancing, isolation, truncated lab time, and uncertainty about the future have all likely exacerbated the effect. Now, more than ever, practical and effective interventions are vitally needed to address the core causes of science trainee stress and to increase resilience amongst trainee populations. This paper discusses a new resilience program targeted to biomedical trainees and scientists - Becoming a Resilient Scientist Series (BRS), a 5-part workshop coupled with facilitated group discussions dedicated to increasing resilience, specifically focusing on academic and research environments. Results show that BRS increases trainee resilience (primary outcome), with reductions in perceived stress, anxiety, and work presenteeism, and increases in ability to shift and persist, self-awareness, and self-efficacy (secondary outcomes). Furthermore, participants in the program reported high level of satisfaction, would highly recommend the program to others, and perceived positive changes in their resilience skills. To our knowledge, this is the first resilience program explicitly targeted for biomedical trainees and scientists, catering to the unique professional culture and environment in which these individuals work.

  🖺 Full Text HTML: Becoming A Resilient Scientist Series: An Intervention Program
• Sex and age-dependent alterations of drug consumption during the COVID-19 lockdown in Spain: Lessons learned for the future -

  In order to reduce the spread of COVID-19, lockdown has been one of the most implemented measures worldwide. Spain had one of the harshest lockdowns in Europe, impacting the social and psychological health of the population. The aim of this paper is to study how the lockdown has affected drug consumption patterns and the extent to which age and sex are influential factors. We have developed an online survey in which people were asked about their consumption of alcohol, marihuana, cocaine, and sedative and tranquilizers before and during the COVID-19 lockdown. Data revealed a general reduction in the consumption of all the drugs surveyed. Interestingly, when data was analysed by sex or age, we detected alterations in the consumption patterns depending on these variables that were of special relevance in the case of alcohol, marihuana and non-prescription sedatives and tranquilizers. Our data revealed a general decrease in the use of these drugs in the case of young adults, revealing that their use is strongly linked to social life, whereas the middle-aged population has experienced alterations in their consumption patterns, whereby their use has increased to daily. In addition, the use of non-prescription sedatives and tranquilizers has increased in specific populations. In conclusion, our data reveals important alterations during the lockdown in the consumption pattern of both legal and illegal drugs (sex and age dependent) in the Spanish population, and these alterations might be considered for future national strategies of preventative actions.

  🖺 Full Text HTML: Sex and age-dependent alterations of drug consumption during the COVID-19 lockdown in Spain: Lessons learned for the future
• Hear my Voice: Understanding how community health workers in the Peruvian Amazon expanded their roles to mitigate the impact of the COVID-19 pandemic through Community-Based Participatory Action Research -

  Introduction: The COVID-19 pandemic led to the collapse of the Peruvian health system, which disrupted healthcare access for indigenous communities in the Amazon. We aimed to understand how the COVID-19 pandemic transformed the responsibilities of community health workers (CHWs) from indigenous communities in the Peruvian Amazon so policymakers can support indigenous health efforts. Methods: Fourteen CHWs from Loreto, Peru participated in a community-based Participatory Action Research (CBPR) project using Photovoice, a technique that encourages vulnerable groups to take photos and develop stories illustrating their lived experiences. Participants were recruited from Mamás del Río, a local university-based program, through purposive sampling. CHWs were trained in Photovoice and asked to photograph how the pandemic affected their lives and work. Participants met four times over five months to share photos and develop action items. Data were organized into key themes using a general inductive method. Final photos and action items were shared with policymakers during galleries in Iquitos and Lima. Results: CHWs took a total of 36 photos with 33 accompanying texts highlighting their roles during the pandemic. Four core themes emerged: (1) the collapse of social infrastructure, (2) the use of medicinal plants versus pharmaceuticals, (3) the community adaptations and struggles, and (4) the importance of CHWs. CHWs expanded their responsibilities or leveraged their leadership across these themes to support COVID-19 patients, vaccination, and mandates without training or resources from the government. CHWs asked policymakers for formal integration into the health system, standardization of CHW training, and better management of community pharmacies. Conclusion: CHWs, who work on a voluntary basis, took on additional roles during the pandemic with little to no training from the government. CHWs demonstrated how their roles could be better supported by the government to ameliorate future health catastrophes in the Peruvian Amazon.

  🖺 Full Text HTML: Hear my Voice: Understanding how community health workers in the Peruvian Amazon expanded their roles to mitigate the impact of the COVID-19 pandemic through Community-Based Participatory Action Research
• Association of SARS-CoV-2 Infection and Cardiopulmonary Long COVID with Exercise Capacity and Chronotropic Incompetence among People with HIV -

  Background: Long COVID has been associated with reduced exercise capacity, but whether SARS-CoV-2 infection or Long COVID is associated with reduced exercise capacity among people with HIV (PWH) has not been reported. We hypothesized that PWH with cardiopulmonary post-acute symptoms of COVID-19 (PASC) would have reduced exercise capacity due to chronotropic incompetence. Methods: We conducted cross-sectional cardiopulmonary exercise testing within a COVID recovery cohort that included PWH. We evaluated associations of HIV, prior SARS-CoV-2 infection, and cardiopulmonary PASC with exercise capacity (peak oxygen consumption, VO2) and adjusted heart rate reserve (AHRR, chronotropic measure) with adjustment for age, sex, and body mass index. Results: We included 83 participants (median age 54, 35% female). All 37 PWH were virally suppressed; 23 (62%) had prior SARS-CoV-2 infection, and 11 (30%) had PASC. Peak VO2 was reduced among PWH (80% predicted vs 99%; p=0.005), a difference of 5.5 ml/kg/min (95%CI 2.7-8.2, p<0.001). Chronotropic incompetence more prevalent among PWH (38% vs 11%; p=0.002), and AHRR was reduced among PWH (60% vs 83%, p<0.0001). Among PWH, exercise capacity did not vary by SARS-CoV-2 coinfection, but chronotropic incompetence was more common among PWH with PASC: 3/14 (21%) without SARS-CoV-2, 4/12 (25%) with SARS-CoV-2 without PASC, and 7/11 (64%) with PASC (p=0.04 PASC vs no PASC). Conclusions: Exercise capacity and chronotropy are lower among PWH compared to SARS-CoV-2 infected individuals without HIV. Among PWH, SARS-CoV-2 infection and PASC were not strongly associated with reduced exercise capacity. Chronotropic incompetence may be a mechanism limiting exercise capacity among PWH.

  🖺 Full Text HTML: Association of SARS-CoV-2 Infection and Cardiopulmonary Long COVID with Exercise Capacity and Chronotropic Incompetence among People with HIV
• Discovery and characterization of highly potent and selective covalent inhibitors of SARS-CoV-2 PLpro -
  Coronavirus infections, such as the global COVID-19 pandemic, have had a profound impact on many aspects of our daily life including working style, economy, and the healthcare system. To prevent the rapid viral transmission and speed up recovery from the infection, many academic organizations and industry research labs have conducted extensive research on discovering new therapeutic options for SARS-CoV-2. Among those efforts, RNA-dependent RNA polymerase (RdRp) inhibitors such as Remdesivir, Molnupiravir and 3CLpro inhibitor such as Nirmatrelvir (PaxlovidTM) have been widely used as the therapeutic options. Given the recent emergence of several new variants that caused a resurgence of the virus, it would be beneficial to discover more diverse therapeutic options with novel anti-viral mechanisms. In this regard, PLpro has been highlighted since it, along with 3CLpro, is one of the two most important proteases that are required for SARS-CoV-2 viral processing. While 3CLpro inhibitors were extensively investigated in the light of Emergency Use Authorizations of Nirmatrelvir, PLpro inhibitors have not been thoroughly investigated even preclinically. Thus, discovery efforts on antivirals acting against PLpro will be valuable. PLpro inhibitors may exert their activity by inhibiting viral replication and enhancing the host defense system through blocking virus-induced cell signaling events for evading host immune response. In this study, we report the discovery and development of two covalent irreversible PLpro inhibitors, HUP0109 and its deuterated analog DX-027, out of our quest for novel anti-COVID 19 therapeutic agents for the past two and half years. HUP0109 selectively targets the viral catalytic cleft of PLpro and covalently modifies its active site cysteine residue (C111). Promising results from preclinical evaluation suggest that DX-027 can be developed as a potential COVID-19 treatment.
  🖺 Full Text HTML: Discovery and characterization of highly potent and selective covalent inhibitors of SARS-CoV-2 PLpro
• Diverging maternal and infant cord antibody functions from SARS-CoV-2 infection and vaccination in pregnancy -
  Immunization in pregnancy is a critical tool that can be leveraged to protect the infant with an immature immune system but how vaccine-induced antibodies transfer to the placenta and protect the maternal-fetal dyad remains unclear. Here, we compare matched maternal-infant cord blood from individuals who in pregnancy received mRNA COVID-19 vaccine, were infected by SARS-CoV-2, or had the combination of these two immune exposures. We find that some but not all antibody neutralizing activities and Fc effector functions are enriched with vaccination compared to infection. Preferential transport to the fetus of Fc functions and not neutralization is observed. Immunization compared to infection enriches IgG1-mediated antibody functions with changes in antibody post-translational sialylation and fucosylation that impact fetal more than maternal antibody functional potency. Thus, vaccine enhanced antibody functional magnitude, potency and breadth in the fetus are driven more by antibody glycosylation and Fc effector functions compared to maternal responses, highlighting prenatal opportunities to safeguard newborns as SARS-CoV-2 becomes endemic.
  🖺 Full Text HTML: Diverging maternal and infant cord antibody functions from SARS-CoV-2 infection and vaccination in pregnancy
• Computational fitness estimates of SARS-CoV-2 mutations affecting spike protein binding to antibodies and ACE2 -
  Predicting the impact of new emerging virus mutations is of major interest in surveillance and for understanding the evolutionary forces of the pathogen. The SARS-CoV-2 surface spike-protein (S-protein) binds to human ACE2 receptors as a critical step in host cell infection. At the same time, S-protein binding to human antibodies neutralizes the virus and prevents interaction with ACE2. Here we combine these two binding properties in a simple fitness model, using structure-based computation of all possible mutation effects averaged over 10 ACE2 complexes and 10 antibody complexes of the S-protein. The ACE2-antibody selectivity change caused by mutation (i.e., the change binding to ACE2 minus the change in binding to immunity-inducing antibodies) is proposed to be a key metric of virus fitness, which furthermore enables substantial systematic error cancelation when evaluated. In this model, new mutations become fixated if they increase the selective binding to ACE2 relative to circulating antibodies, assuming that both are present in the host in a competitive binding situation. We use this model to categorize viral mutations that may best reach ACE2 before being captured by antibodies. Our model may aid the understanding of variant-specific vaccines and molecular mechanisms of viral evolution in the context of a human host.
  🖺 Full Text HTML: Computational fitness estimates of SARS-CoV-2 mutations affecting spike protein binding to antibodies and ACE2
• Repeated Omicron infection alleviates SARS-CoV-2 immune imprinting -
  The continuous emergence of highly immune evasive SARS-CoV-2 variants, like XBB.1.5 and XBB.1.16, highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by wildtype (WT)-based vaccination would compromise the antibody response to Omicron-based boosters. Vaccination strategies that can counter immune imprinting are critically needed. In this study, we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. Our results show that in mice, the efficacy of single Omicron-boosting is heavily limited by immune imprinting, especially when using variants antigenically distinct from WT, like XBB, while the concerning situation could be largely mitigated by a second Omicron booster. Similarly, in humans, we found that repeated Omicron infections could also alleviate WT-vaccination-induced immune imprinting and generate high neutralizing titers against XBB.1.5 and XBB.1.16 in both plasma and nasal mucosa. By isolating 781 RBD-targeting mAbs from repeated Omicron infection cohorts, we revealed that double Omicron exposure alleviates immune imprinting by generating a large proportion of highly matured and potent Omicron-specific antibodies. Importantly, epitope characterization using deep mutational scanning (DMS) showed that these Omicron-specific antibodies target distinct RBD epitopes compared to WT-induced antibodies, and the bias towards non-neutralizing epitopes observed in single Omicron exposures due to imprinting was largely restored after repeated Omicron stimulation, together leading to a substantial neutralizing epitope shift. Based on the DMS profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated the combinations of these mutations could further boost XBB.1.5’s immune-evasion capability while maintaining high ACE2 binding affinity. Our findings suggest the WT component should be abandoned when updating COVID-19 vaccine antigen compositions to XBB lineages, and those who haven’t been exposed to Omicron yet should receive two updated vaccine boosters.
  🖺 Full Text HTML: Repeated Omicron infection alleviates SARS-CoV-2 immune imprinting
• Death, Inequality, and the Pandemic in the Nation’s Capital -

  Abrupt changes in mortality rates and life expectancy allow us to understand how shocks like COVID-19 can exacerbate health inequalities across groups. We look at Washington, D.C., a major city with a diverse population and long-standing socio-economic divisions, to describe the all-cause mortality trends from 2015 to 2021 by age, sex, race, and ward of residence. We report differences in cause-specific mortality pre- and post-COVID-19 outbreak and estimate the Years of Life Lost (YLL) attributable to COVID-19. We compute death rates using information from death certificates and the Census, and we calculate YLL using the life table approach, comparing the life expectancy of people with and without COVID-19. We find that in 2020 and 2021, there were respectively 1,128 and 629 excess deaths (158 per 100K and 94 per 100K) compared to the annual average over the previous five years, and 689 and 363 deaths in 2020 and 2021, respectively (97 per 100K and 54 per 100K) listing COVID-19 as a cause of death. Death rates in 2020 and 2021, compared to the five previous years, were higher for men than women by about 12pp and 5pp and occurred almost entirely among residents 45 and older. Excess deaths between 2020 and 2021 were higher for Black and Hispanic residents by about 286 and 97 per 100K, respectively–with the highest proportional increase (almost twofold) for Hispanics in 2020. YLL was highest for Hispanic males and lowest for White females.

  🖺 Full Text HTML: Death, Inequality, and the Pandemic in the Nation’s Capital
• Too WEIRD, Too Fast? Preprints about COVID-19 in psychology -
  That behavioral sciences are overrepresented by some countries, in terms of samples and authors, is a well-documented finding. Considering the immediate policy implications, the present study aimed to scope whether this is true in the context of understanding the effects of the coronavirus as well. We assessed relevant preprints with “coronavirus” or “COVID-19” as keywords published on PsyArxiv between March-April, 2020, as well as between May-December, 2020 in terms of samples, participants, and authors. We found that some countries, such as the US, were overrepresented in both waves; papers based on authors from such countries, and employing samples from such countries were also more likely to be published in journals with higher impact factors, and were also more likely to be cited more. Implications, especially regarding a reductionist bifurcation of research as “WEIRD” or “non-WEIRD,” are discussed.
  🖺 Full Text HTML: Too WEIRD, Too Fast? Preprints about COVID-19 in psychology

From Clinical Trials

• Long COVID-19 Syndrome Lifestyle Intervention Study - Condition:   Long COVID-19 Syndrome
  Intervention:   Dietary Supplement: Low carbohydrate diet intervention
  Sponsor:   University of Southern California
  Not yet recruiting

• A Coping and Resilience Intervention for Adolescents - Condition:   COVID-19 Pandemic
  Interventions:   Behavioral: Coping and Resilience Intervention for Adolescents;   Other: Printing materials of Coping and Resilience Intervention for Adolescents
  Sponsor:   Taipei Medical University
  Enrolling by invitation

• Effectiveness of Modified Diaphragmatic Training for Gastroesophageal Reflux Disease Post Covid-19 - Conditions:   GERD;   Post COVID-19 Condition;   Diaphragm Issues
  Interventions:   Other: modified diaphragmatic training;   Other: standard diaphragmatic training
  Sponsor:   Indonesia University
  Completed

• The Safety, Tolerability and Pharmacokinetics Study of RAY1216 in Healthy Adult Participants - Condition:   COVID-19 (Coronavirus Disease 2019)
  Interventions:   Drug: RAY1216 dose 1;   Drug: RAY1216 dose 2;   Drug: RAY1216 dose 3;   Drug: RAY1216 dose 4 &ritonavir   Drug: RAY1216 dose 5;   Drug: RAY1216 dose 6;   Drug: RAY1216 dose 7;   Drug: RAY1216 dose 8;   Drug: RAY1216 dose 9;   Drug: RAY1216 dose 10
  Sponsor:   Guangdong Raynovent Biotech Co., Ltd
  Completed

• Computerized Training of Attention and Working Memory in Post COVID-19 Patients With Cognitive Complaints - Conditions:   COVID-19;   Cognitive Impairment;   Cognition Disorder;   Memory Disorders;   Attention Deficit;   Memory Impairment;   Memory Loss;   Attention Impaired
  Intervention:   Device: RehaCom
  Sponsor:   Erasmus Medical Center
  Not yet recruiting

• Strategies and Treatments for Respiratory Infections &Amp; Viral Emergencies (STRIVE): Immune Modulation Strategy Trial - Condition:   COVID-19
  Interventions:   Drug: abatacept infusion;   Drug: Placebo group
  Sponsor:   University of Minnesota
  Not yet recruiting

• Evaluation of the Efficacy and Safety of Nano-S1 - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: NANOS1 , argent colloïdal ,
  Sponsor:   General Administration of Military Health, Tunisia
  Completed

• Digital Mental Health Care for COVID-19 High-Risk Populations - Phase 2 - Conditions:   Stigma, Social;   Help-Seeking Behavior
  Interventions:   Other: Adjusted Content Intervention;   Other: Non-Adjusted Intervention Video
  Sponsors:   Research Foundation for Mental Hygiene, Inc.;   Columbia University
  Not yet recruiting

• Vaccine Hesitancy in Black/African Americans With Rheumatic Diseases - Conditions:   Rheumatic Diseases;   COVID-19 Vaccine;   COVID-19;   SLE
  Intervention:   Behavioral: COVID-19 vaccine and booster training, and importance
  Sponsors:   Northwestern University;   Brigham and Women’s Hospital;   Boston Children’s Hospital;   Boston Medical Center
  Not yet recruiting

• A Study of mRNA-based Influenza and SARS-CoV-2 (COVID-19) Multi-component Vaccines in Healthy Adults - Conditions:   SARS-CoV-2;   Influenza
  Interventions:   Biological: Fluarix;   Biological: mRNA-1083.1;   Biological: mRNA-1083.2;   Biological: mRNA-1083.3;   Biological: mRNA-1010.4;   Biological: mRNA-1283.222;   Biological: mRNA-1273.222;   Biological: mRNA-1010;   Biological: Fluzone HD
  Sponsor:   ModernaTX, Inc.
  Recruiting

• imPROving Quality of LIFe In the Long COVID Patient - Conditions:   Post-COVID-19 Syndrome;   Long COVID;   Long Covid19;   COVID-19;   POTS - Postural Orthostatic Tachycardia Syndrome;   Post COVID-19 Condition;   Post-COVID Syndrome;   Post COVID-19 Condition, Unspecified;   Postinfectious Inflammation;   Postinfectious Disorder
  Interventions:   Drug: Nirmatrelvir/ritonavir;   Drug: Placebo/ritonavir
  Sponsors:   Karolinska Institutet;   Karolinska University Hospital;   Pfizer
  Not yet recruiting

• A Study to Learn About How Itraconazole Affects the Blood Level of Study Medicine (PF-07817883) in Healthy Adults. - Condition:   Healthy
  Interventions:   Drug: PF-07817883;   Drug: Itraconazole
  Sponsor:   Pfizer
  Not yet recruiting

• Obesity, Insulin Resistance, and PASC: Persistent SARS-CoV-2 - Conditions:   Long COVID;   Insulin Resistance;   Insulin Sensitivity
  Interventions:   Procedure: Adipose Tissue Biopsy;   Diagnostic Test: Steady State Plasma Glucose (SSPG) Test
  Sponsor:   Stanford University
  Not yet recruiting

From PubMed

• Impaired potency of neutralizing antibodies against cell-cell fusion mediated by SARS-CoV-2 - The SARS-CoV-2 Omicron subvariants have dominated the pandemic due to their high transmissibility and immune evasion conferred by the spike mutations. The Omicron subvariants can spread by cell-free virus infection and cell-cell fusion, the latter of which is more effective but has not been extensively investigated. In this study, we developed a simple and high-throughput assay that provides a rapid readout to quantify cell-cell fusion mediated by the SARS-CoV-2 spike proteins without using live…

• In silico Study of Antiviral Activity of Polyphenol Compounds from Ocimum basilicum by Molecular Docking, ADMET, and Drug-Likeness Analysis - CONCLUSION: Based on the data obtained, Apigenin-7-glucuronide and dihydrokaempferol-3-glucoside are compounds that have more potential to have an antiviral effect on the main protease enzyme than aesculetin. Based on pharmacokinetic parameters and drug-likeness, three compounds can be used as lead compounds for further research.

• Targeting the vital non-structural proteins (NSP12, NSP7, NSP8 and NSP3) from SARS-CoV-2 and inhibition of RNA polymerase by natural bioactive compound naringenin as a promising drug candidate against COVID-19 - The prevalence of SARS-CoV-2-induced respiratory infections is now a major challenge worldwide. There is currently no specific antiviral drug to prevent or treat this disease. Infection with COVID-19 seriously needs to find effective therapeutic agents. In the present study, naringenin, as a potential inhibitor candidate for RNA Polymerase SARS-CoV-2 was compared with remdesivir (FDA-approved drug) and GS-441,524 (Derivative of the drug remdesivir) by screening with wild-type and mutant…

• A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication and pathogenesis in vivo - Despite unprecedented efforts, our therapeutic arsenal against SARS-CoV-2 remains limited. The conserved macrodomain 1 (Mac1) in NSP3 is an enzyme exhibiting ADP-ribosylhydrolase activity and a possible drug target. To determine the therapeutic potential of Mac1 inhibition, we generated recombinant viruses and replicons encoding catalytically inactive NSP3 Mac1 domain by mutating a critical asparagine in the active site. While substitution to alanine (N40A) reduced activity by ∼10-fold,…

• An in vitro experimental pipeline to characterize the binding specificity of SARS-CoV-2 neutralizing antibodies - The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has led to over 760 million cases and >6.8 million deaths worldwide. We developed a panel of human neutralizing monoclonal antibodies (mAbs) targeting the SARS-CoV-2 Spike protein using Harbour H2L2 transgenic mice immunized with Spike receptor binding domain (RBD) (1). Representative antibodies from genetically-distinct families were evaluated for inhibition of…

• An ex vivo human precision-cut lung slice platform provides insight into SARS-CoV-2 pathogenesis and antiviral drug efficacy - COVID-19 has claimed millions of lives since the emergence of SARS-CoV-2, and lung disease appears the primary cause of the death in COVID-19 patients. However, the underlying mechanisms of COVID-19 pathogenesis remain elusive, and there is no existing model where the human disease can be faithfully recapitulated and conditions for the infection process can be experimentally controlled. Herein we report the establishment of an ex vivo human precision-cut lung slice (hPCLS) platform for studying…

• Ruxolitinib as an Effective Treatment for Hemophagocytic Lymphohistiocytosis Secondary to SARS-Cov-2 Infection: A Case Report - CONCLUSION: Clinicians should be aware of the possibility of HLH secondary to mild SARS-CoV-2 infection and take timely therapeutic measures to inhibit an inflammatory factor storm. Ruxolitinib is a potential choice for COVID-19 related HLH.

• The SARS-CoV-2 papain-like protease suppresses type I interferon responses by deubiquitinating STING - The SARS-CoV-2 papain-like protease (PLpro), which has deubiquitinating activity, suppresses the type I interferon (IFN-I) antiviral response. We investigated the mechanism by which PLpro antagonizes cellular antiviral responses. In HEK392T cells, PLpro removed K63-linked polyubiquitin chains from Lys^(289) of the stimulator of interferon genes (STING). PLpro-mediated deubiquitination of STING disrupted the STING-IKKε-IRF3 complex that induces the production of IFN-β and IFN-stimulated cytokines…

• Mucin-Inspired Single-Chain Polymer (MIP) Fibers as Potent SARS-CoV-2 Inhibitors - Mucins are the key component of the defensive mucus barrier. They are extended fibers of very high molecular weight with diverse biological functions depending strongly on their specific structural parameters. Here, we present a mucin-inspired nanostructure, produced via a synthetic methodology to prepare methacrylate-based dendronized polysulfates (MIP-1) on a multi gram scale with relatively high molecular weight (MW = 450 kDa) and thiol end-functionalized mucin-inspired polymer (MIP) via RAFT…

• Effectiveness of estrogen and its derivatives over dexamethasone in the treatment of COVID-19 - Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus and dexamethasone is a glucocorticoid widely used for its treatment. Dexamethasone is not used in non-severe cases due to its immunosuppressant action. So, considering this, Estrogen and Estetrol were tested for the treatment of COVID-19 as they all possess a common steroid ring and dislike dexamethasone, they are immunoenhancer. Virtual screening of test ligands was performed through molecular docking,…

• Oridonin inhibits SARS-CoV-2 replication by targeting viral proteinase and polymerase - COVID-19 has become a global public health crisis since its outbreak in China in December 2019. Currently there are few clinically effective drugs to combat SARS-CoV-2 infection. The main protein (M^(pro)), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 are involved in the viral replication, and might be prospective targets for anti-coronavirus drug development. Here, we investigated the antiviral activity of oridonin, a natural small-molecule compound,…

• Advanced Nitric Oxide Generating Nanomedicine for Therapeutic Applications - Nitric oxide (NO), a gaseous transmitter extensively present in the human body, regulates vascular relaxation, immune response, inflammation, neurotransmission, and other crucial functions. Nitrite donors have been used clinically to treat angina, heart failure, pulmonary hypertension, and erectile dysfunction. Based on NO’s vast biological functions, it further can treat tumors, bacteria/biofilms and other infections, wound healing, eye diseases, and osteoporosis. However, delivering NO is…

• Identification of diphenylurea derivatives as novel endocytosis inhibitors that demonstrate broad-spectrum activity against SARS-CoV-2 and influenza A virus both in vitro and in vivo - Rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) poses enormous challenge in the development of broad-spectrum antivirals that are effective against the existing and emerging viral strains. Virus entry through endocytosis represents an attractive target for drug development, as inhibition of this early infection step should block downstream infection processes, and potentially inhibit viruses sharing the same entry route. In this study,…

• The Role of Mitochondria in Phytochemically Mediated Disease Amelioration - Mitochondrial dysfunction may cause cell death, which has recently emerged as a cancer prevention and treatment strategy mediated by chemotherapy drugs or phytochemicals. However, most existing drugs cannot target cancerous cells and may adversely affect normal cells via side effects. Mounting studies have revealed that phytochemicals such as resveratrol could ameliorate various diseases with dysfunctional or damaged mitochondria. For instance, resveratrol can regulate mitophagy, inhibit…

• Fighting cytokine storm and immunomodulatory deficiency: By using natural products therapy up to now - A novel coronavirus strain (COVID-19) caused severe illness and mortality worldwide from 31 December 2019 to 21 March 2023. As of this writing, 761,071,826 million cases have been diagnosed worldwide, with 6,879,677 million deaths accorded by WHO organization and has spread to 228 countries. The number of deaths is closely connected to the growth of innate immune cells in the lungs, mainly macrophages, which generate inflammatory cytokines (especially IL-6 and IL-1β) that induce "cytokine storm…

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