Covid-19 Sentry

Contents

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

From Preprints

• Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies -
  SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) {beta} sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. Highly expanded 199 TCR clonotypes upon stimulation with S peptide pools were reconstituted into a reporter T cell line for the determination of epitopes and restricting HLAs. Among them, we could determine 78 S epitopes, most of which were conserved in variants of concern (VOCs). In donors exhibiting sustained anti-S antibody titers (designated as "sustainers"), S-reactive T cell clonotypes detected immediately after 2nd vaccination polarized to follicular helper T (Tfh) cells, which was less obvious in "decliners". Even before vaccination, S-reactive CD4+ T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic bacteria. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly-responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest that de novo acquisition of memory Tfh cells upon vaccination contributes to the longevity of anti-S antibody titers.
  🖺 Full Text HTML: Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies
• A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic -
  Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges.
  🖺 Full Text HTML: A Global Experiment on Motivating Social Distancing during the COVID-19 Pandemic
• A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic -
  The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion regulation strategy which modifies how one thinks about a situation. Participants from 87 countries/regions (N = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vs. both control conditions) had consistent effects in reducing negative emotions and increasing positive emotions across different measures. Reconstrual and repurposing had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world to build resilience during the pandemic and beyond.
  🖺 Full Text HTML: A global test of brief reappraisal interventions on emotions during the COVID-19 pandemic
• In COVID-19 health messaging, loss framing increases anxiety with little-to-no concomitant benefits: Experimental evidence from 84 countries -
  The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., “If you do not practice these steps, you can endanger yourself and others”) or potential gains (e.g., “If you practice these steps, you can protect yourself and others”)? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions.
  🖺 Full Text HTML: In COVID-19 health messaging, loss framing increases anxiety with little-to-no concomitant benefits: Experimental evidence from 84 countries
• Current Perception of Epidemic between Traditional and Social Media: an Italian Case Study -
  Aim. More than two years after the beginning of the global epidemic period, most governments have adopted questionable strategies, aimed at the progressive reduction of the people freedom and pushing in a non-transparent way on the forced use of genic drugs, improperly called vaccines. The purpose of this work concerns the different way in which news relating to the epidemic reached citizens from traditional media (main TV channels and main national newspapers) and from social media, in particular from Telegram. Methods. The paper considers the situation perceived in Italy up to the first months of 2022 by analyzing the news appearing on mainstream TV channels and how they are described by national newspapers, as opposed to what can be deduced from some social media platforms who are still enough free from censorship. Results. The analysis underlines that there is a clear discrepancy between traditional and social media; the official narration of the traditional media is not only questionable, but does not give rise to the possibility of a free discussion on the hottest issues of this epidemic. Only Telegram appears to be the most censorship free channel among the studied traditional/social media in this paper. Conclusions. The attention placed on the official narrative of Covid-19, on the use of the methodology still in force in Italy for fighting the epidemic, on the strong nonsanitary limitation of individual freedom and on a possible underlying plan about what is globally happening leads to the conclusion that in Italy there is an attempt to give an ambiguous, equivocal and inconsistent version of the facts, contradicted by experimental data and scientific papers appearing more and more numerous in qualified international journals.
  🖺 Full Text HTML: Current Perception of Epidemic between Traditional and Social Media: an Italian Case Study
• The Potential Role of ACEi and ARBs in COVID-19; A Perpsective -
  COVID-19 pandemic has caused significant morbidity and mortality around the world. The disease severity ranges from mild upper respiratory infection to severe lower respiratory and cardiac illness. Acute respiratory distress syndrome (ARDS) is the most serious complication and results in diffuse inflammatory alveolar damage, respiratory failure, and death. Components of the Renin-Angiotensin-Aldosterone-System (RAAS) are involved in an inflammatory reaction in the lungs. Various studies have shown that blocking RAAS peptides in the lungs especially angiotensin-converting enzyme (ACE) and type-1 angiotensin receptor (ATR1) reduces lung injury, improves respiratory function, and is associated with better clinical outcomes in the COVID-19 patients. We suggest that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) – drugs that block RAAS peptides – be considered for a repurposed use in COVID-19 induced lung injury.
  🖺 Full Text HTML: The Potential Role of ACEi and ARBs in COVID-19; A Perpsective
• Exploring psychosocial impacts of COVID-19 mandates in children with and without autism spectrum disorder -
  Children with autism spectrum disorder (ASD) are particularly at risk for adverse psychosocial consequences as a result of unexpected challenges such as the COVID-19 pandemic. These children experience a higher prevalence of depression and anxiety, difficulties with cognitive flexibility, and a reduction in support services during the pandemic. Higher executive function (EF) has been previously found to be protective against negative mental health outcomes. Here we probed the psychosocial impacts of pandemic responses in children with ASD by relating pre-pandemic (EF) measures with mental health outcomes measured several months into the pandemic. We found that pre-existing inhibition and shift difficulties measured by the Behavior Rating Inventory of Executive Function predicted higher risk of anxiety symptoms, with shift difficulties also predicting elevated depressive symptoms during the pandemic. These findings are critical for promoting community recovery and maximizing clinical preparedness to support children at increased risk for adverse psychosocial outcomes.
  🖺 Full Text HTML: Exploring psychosocial impacts of COVID-19 mandates in children with and without autism spectrum disorder
• COVID-19 first lockdown as a window into language acquisition: associations between caregiver-child activities and vocabulary gains. -
  The COVID-19 pandemic, and the resulting closure of daycare centers worldwide, led to unprecedented changes in children’s learning environments. This period of increased time at home with caregivers, with limited access to external sources (e.g., daycares) provides a unique opportunity to examine the associations between the caregiver-child activities and children’s language development. The vocabularies of 1742 children aged 8-36 months across 13 countries and 12 languages were evaluated at the beginning and end of the first lockdown period in their respective countries (from March to September 2020). Children who had less passive screen exposure and whose caregivers read more to them showed larger gains in vocabulary development during lockdown, after controlling for SES and other caregiver-child activities. Children also gained more words than expected (based on normative data) during lockdown; either caregivers were more aware of their child’s development, or vocabulary development benefited from intense caregiver-child interaction during lockdown or both. We discuss these results in the context of the extraordinary circumstances of the COVID-19 pandemic and highlight limitations of the study.
  🖺 Full Text HTML: COVID-19 first lockdown as a window into language acquisition: associations between caregiver-child activities and vocabulary gains.
• H3K4 methylation regulates development, DNA repair, and virulence in Mucorales -
  Mucorales are basal fungi that opportunistically cause a fatal infection known as mucormycosis (black fungus disease), which poses a significant threat to human health due to its high mortality rate and its recent association with SARS-CoV-2 infections. On the other hand, histone methylation is a regulatory mechanism with pleiotropic effects, including the virulence of several pathogenic organisms. However, the role of epigenetic changes at the histone level never has been studied in Mucorales. Here, we dissected the functional role of Set1, a histone methyltransferase that catalyzes the methylation of H3K4, which is associated with the activation of gene transcription and virulence. A comparative analysis of the Mucor lusitanicus genome (previously known as Mucor circinelloides f. lusitanicus) identified only one homolog of Set1 from Candida albicans and Saccharomyces cerevisiae that contains the typical SET domain. Knockout strains in the gene set1 lacked H3K4 monomethylation, dimethylation, and trimethylation enzymatic activities. These strains also showed a significant reduction in vegetative growth and sporulation. Additionally, set1 null strains were more sensitive to SDS, EMS, and UV light, indicating severe impairment in the repair process of the cell wall and DNA lesions and a correlation between Set1 and these processes. During pathogen-host interactions, strains lacking the set1 gene exhibited shortened polar growth within the phagosome and attenuated virulence both in vitro and in vivo. Our findings suggest that the histone methyltransferase Set1 coordinates several cell processes related to the pathogenesis of M. lusitanicus and may be an important target for future therapeutic strategies against mucormycosis.
  🖺 Full Text HTML: H3K4 methylation regulates development, DNA repair, and virulence in Mucorales
• Species and habitat specific changes in bird activity in an urban environment during Covid 19 lockdown -
  Covid-19 lockdowns provided ecologists with a rare opportunity to examine how animals behave when humans are absent. Indeed many, sometimes contradicting, studies reported various effects of lockdowns on animal activity, especially in urban areas and other human-dominated habitats. We explored how Covid-19 lockdowns in Israel have influenced bird activity in an urban environment by using continuous acoustic recordings to monitor three common bird species that differ in their level of adaptation to the urban ecosystem: (1) the hooded crow, an urban exploiter, which depends heavily on anthropogenic resources; (2) the rose-ringed parakeet, an invasive alien species that has adapted to exploit human resources; and (3) the graceful prinia, an urban adapter, which is relatively shy of humans can be found urban habitats with shrubs and prairies. Acoustic recordings provided continuous monitoring of bird activity without an effect of the observer on the animal. We performed dense sampling of a 1.3 square km area in northern Tel-Aviv by placing 17 recorders for more than a month in different micro-habitats within this region including roads, residential areas and urban parks. We monitored both lockdown and no-lockdown periods. We portray a complex dynamic system where the activity of specific bird species decreases or increases in a habitat-dependent manner during lockdown. Specifically, urban exploiter species decreased their activity in most urban habitats during lockdown, while human adapter species increased their activity during lockdown especially in parks where humans were absent. Our results also demonstrate the value of different habitats within urban environments for animal activity, specifically highlighting the importance of urban parks. These species- and habitat-specific changes in activity might explain the contradicting results reported by others who have not performed a habitat specific analysis.
  🖺 Full Text HTML: Species and habitat specific changes in bird activity in an urban environment during Covid 19 lockdown
• Population age and household structures shape transmission dynamics of emerging infectious diseases: a longitudinal microsimulation approach -

  Host population demographics and patterns of host-to-host interactions are important drivers of heterogeneity in infectious disease transmission. To improve our understanding of how population structures and changes therein influence disease transmission dynamics at the individual and population level, we model a dynamic age- and household-structured population using longitudinal microdata drawn from Belgian census and population registers. At different points in time, we simulate the spread of a close-contact infectious disease and vary the age profiles of infectiousness and susceptibility to reflect specific infections (e.g. influenza and SARS-CoV-2) using a two-level mixing model, which distinguishes between exposure to infection in the household and exposure in the community. We find a strong relationship between age and household structures, which, in combination with social mixing patterns and epidemiological parameters, shape the spread of an emerging infection. Disease transmission in the adult population in particular is explained by differential household compositions and not just household size. Moreover, we highlight how demographic processes alter population structures in an ageing population and how these in turn affect disease transmission dynamics across population groups.

  🖺 Full Text HTML: Population age and household structures shape transmission dynamics of emerging infectious diseases: a longitudinal microsimulation approach
• How could a pooled testing policy have performed in managing the early stages of the COVID-19 pandemic? Results from a simulation study -

  A coordinated testing policy is an essential tool for responding to emerging epidemics, as was seen with COVID-19. However, it is very difficult to agree on the best policy when there are multiple conflicting objectives. A key objective is minimising cost, which is why pooled testing (a method that involves pooling samples taken from multiple individuals and analysing this with a single diagnostic test) has been suggested. In this paper, we present results from an extensive and realistic simulation study comparing testing policies based on individually testing subjects with symptoms (a policy resembling the UK strategy at the start of the COVID-19 pandemic), individually testing subjects at random or pools of subjects randomly combined and tested. To compare these testing methods, a dynamic model compromised of a relationship network and an extended SEIR model is used. In contrast to most existing literature, testing capacity is considered as fixed and limited rather than unbounded. This paper then explores the impact of the proportion of symptomatic infections on the expected performance of testing policies. Only for less than 50% of infections being symptomatic does pooled testing outperform symptomatic testing in terms of metrics such as total infections and length of epidemic. Additionally, we present the novel feature for testing of non-compliance and perform a sensitivity analysis for different compliance assumptions. Our results suggest for the pooled testing scheme to be superior to testing symptomatic people individually, only a small proportion of the population (>2%) needs to not comply with the testing procedure.

  🖺 Full Text HTML: How could a pooled testing policy have performed in managing the early stages of the COVID-19 pandemic? Results from a simulation study
• Rapid and Multiplexed Nucleic Acid Detection using Programmable Aptamer-Based RNA Switches -

  Rapid, simple, and low-cost diagnostic technologies are crucial tools for combatting infectious disease. Here, we describe a class of aptamer-based RNA switches called aptaswitches that recognize specific target nucleic acid molecules and respond by initiating folding of a reporter aptamer. Aptaswitches can detect virtually any sequence and provide a fast and intense fluorescent readout, generating signals in as little as 5 minutes and enabling detection by eye with minimal equipment. We demonstrate that aptaswitches can be used to regulate folding of six different fluorescent aptamer/fluorogen pairs, providing a general means of controlling aptamer activity and an array of different reporter colors for multiplexing. By coupling isothermal amplification reactions with aptaswitches, we reach sensitivities down to 1 RNA copy/microL in one-pot reactions. Application of multiplexed one-pot reactions against RNA extracted from clinical saliva samples yields an overall accuracy of 96.67% for detection of SARS-CoV-2 in 30 minutes. Aptaswitches are thus versatile tools for nucleic acid detection that can be readily integrated into rapid diagnostic assays.

  🖺 Full Text HTML: Rapid and Multiplexed Nucleic Acid Detection using Programmable Aptamer-Based RNA Switches
• A prospective, single-center, randomized phase 2 trial of etoposide in severe COVID-19 -

  The systemic inflammatory response seen in patients with severe COVID-19 shares many similarities with the changes observed in hemophagocytic lymphohistiocytosis (HLH); a disease characterized by excessive immune activation. Many patients with severe COVID qualify for a diagnosis of HLH. Etoposide, an inhibitor of topoisomerase II is used to control inflammation in HLH. This randomized, open-label, single center phase II trial attempted to determine whether etoposide can be used to blunt the inflammatory response in severe COVID. This trial was closed early after eight patients were randomized. This underpowered trial did not meet its primary endpoint of improvement in pulmonary status by two categories on an 8 point ordinal scale of respiratory function. There were not significant differences in secondary outcomes including overall survival at 30 days, cumulative incidence of grade 2 through 4 adverse events during hospitalization, duration of hospitalization, duration of ventilation and improvement in oxygenation or paO2/FIO2 ratio or improvement in inflammatory markers associated with cytokine storm. A high rate of grade 3 myelosuppression was noted in this critically ill population despite dose reduction, a toxicity which will limit future attempts to explore the utility of etoposide for virally-driven cytokine storm or HLH.

  🖺 Full Text HTML: A prospective, single-center, randomized phase 2 trial of etoposide in severe COVID-19
• Association of Long COVID with housing insecurity in the United States, 2022-2023 -

  Objectives. To assess the association of Long COVID with housing insecurity in the United States. Methods. To compare the prevalence of 3 binary indicators of housing insecurity between people with Long COVID (symptoms > 3 months) and COVID-19 survivors who don9t report long-term symptoms, we used survey-weighted regression models on 203,807 responses from the Household Pulse Survey, a representative survey of US households collected September 2022 - April 2023. Among people with Long COVID, we assessed whether functional impairment, current COVID-19 related symptoms, and symptom impact on day-to-day life were associated with a higher prevalence of housing insecurity. Results. During the study period, 54,446 (27.2%) respondents with COVID-19 experienced symptoms lasting 3 months or longer, representing an estimated 27 million US adults. People with Long COVID were nearly twice as likely to experience significant difficulty with household expenses (Prevalence ratio [PR] 1.85, 95% CI 1.74-1.96), be behind on housing payments (PR 1.76, 95% CI 1.57-1.99), and face likely eviction or foreclosure (PR 2.12, 95% CI 1.58-2.86). Functional limitation and current symptoms which impact day-to-day life were associated with higher prevalence of housing insecurity. Conclusions. Compared with COVID-19 survivors who don9t experience long-term symptoms, people with Long COVID are more likely to report indicators housing insecurity, particularly those with functional limitations and long-term COVID-19 related symptoms impacting day-to-day life. Policies are needed to support people living with chronic illnesses following SARS-CoV-2 infection.

  🖺 Full Text HTML: Association of Long COVID with housing insecurity in the United States, 2022-2023

From Clinical Trials

• Extracorporeal Photopheresis as a Possible Therapeutic Approach to Adults With Severe and Critical COVID-19 - Condition:   COVID-19
  Intervention:   Procedure: Extracorporeal photopheresis
  Sponsor:   Del-Pest Central Hospital - National Institute of Hematology and Infectious Diseases
  Recruiting

• A Clinical Trial on Booster Immunization of Two COVID-19 Vaccines Constructed From Different Technical Routes - Condition:   COVID-19
  Interventions:   Biological: Prototype and Omicron BA.4/5 Bivalent Recombinant COVID-19 Vaccine(Adenovirus Type 5 Vector) For Inhalation;   Biological: Bivalent COVID-19 mRNA Vaccine;   Biological: Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) For Inhalation
  Sponsors:   Zhongnan Hospital;   Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China
  Recruiting

• Evaluation of Safety, Tolerability, Reactogenicity, Immunogenicity of Baiya SARS-CoV-2 Vax 2 as a Booster for COVID-19 - Conditions:   COVID-19 Vaccine;   COVID-19
  Interventions:   Biological: 50 μg Baiya SARS-CoV-2 Vax 2;   Other: Placebo
  Sponsor:   Baiya Phytopharm Co., Ltd.
  Not yet recruiting

• Safety Study of COVID19 Vaccine on the Market - Condition:   COVID-19
  Intervention:   Biological: Recombinant new coronavirus vaccine (CHO cell)
  Sponsors:   Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.;   Hunan Provincial Center for Disease Control and Prevention;   Guizhou Center for Disease Control and Prevention;   Hainan Center for Disease Control & Prevention
  Recruiting

• ACTIV-6: COVID-19 Study of Repurposed Medications - Arm B (Fluvoxamine) - Condition:   Covid19
  Interventions:   Drug: Fluvoxamine;   Other: Placebo
  Sponsors:   Susanna Naggie, MD;   National Center for Advancing Translational Sciences (NCATS);   Vanderbilt University Medical Center
  Completed

• Physiotherapy in Mutated COVID-19 Patients - Condition:   COVID-19 Pandemic
  Intervention:   Behavioral: Physiotherapy
  Sponsor:   Giresun University
  Completed

• Evaluation of Home Use COVID-19 Frequent Antigen Testing and Data Reporting - Condition:   COVID-19 Respiratory Infection
  Intervention:   Diagnostic Test: SARS CoV-2 antigen tests
  Sponsors:   IDX20 Inc;   National Institute on Minority Health and Health Disparities (NIMHD)
  Recruiting

• Mitoquinone/Mitoquinol Mesylate as Oral and Safe Postexposure Prophylaxis for Covid-19 - Conditions:   SARS-CoV Infection;   COVID-19
  Interventions:   Drug: Mitoquinone/mitoquinol mesylate;   Other: Placebo
  Sponsor:   University of Texas Southwestern Medical Center
  Not yet recruiting

• Pycnogenol® in Post-COVID-19 Condition - Conditions:   Post COVID-19 Condition;   Long COVID
  Interventions:   Drug: Pycnogenol®;   Drug: Placebo
  Sponsor:   University of Zurich
  Not yet recruiting

• To Explore the Regulatory Effect of Combined Capsule FMT on the Levels of Inflammatory Factors in Peripheral Blood of Patients With COVID-19 During Treatment. - Conditions:   Fecal Microbiota Transplantation;   COVID-19 Infection
  Intervention:   Procedure: Fecal microbiota transplantation
  Sponsor:   Shanghai 10th People’s Hospital
  Completed

• Efficacy of Bailing Capsule on Pulmonary Fibrosis After COVID-19 - Conditions:   Pulmonary Fibrosis;   COVID-19 Pneumonia
  Intervention:   Drug: Bailing capsule
  Sponsor:   Second Affiliated Hospital, School of Medicine, Zhejiang University
  Not yet recruiting

• Evaluating Emetine for Viral Outbreaks (EVOLVE) - Condition:   COVID-19
  Interventions:   Drug: Emetine Hydrochloride;   Drug: Placebo
  Sponsors:   Johns Hopkins University;   Nepal Health Research Council;   Bharatpur Hospital Chitwan;   Stony Brook University;   Rutgers University
  Not yet recruiting

• Phase 3 Study of Novavax Vaccine(s) as Booster Dose After mRNA Vaccines - Condition:   COVID-19
  Interventions:   Biological: NVX-CoV2373;   Biological: SARS-CoV-2 rS antigen/Matrix-M Adjuvant
  Sponsor:   Novavax
  Active, not recruiting

• A Study to Learn About How Loss of Liver Function Affects the Blood Levels of the Study Medicine Called PF-07817883. - Condition:   COVID-19
  Intervention:   Drug: PF-07817883
  Sponsor:   Pfizer
  Not yet recruiting

• Anti-SARS-CoV-2 Monoclonal Antibodies for Long COVID (COVID-19) - Conditions:   Long COVID;   Post-Acute Sequela of COVID-19;   Post-Acute COVID-19
  Interventions:   Drug: AER002;   Other: Placebo
  Sponsors:   Michael Peluso, MD;   Aerium Therapeutics
  Not yet recruiting

From PubMed

• Ebselen derivatives inhibit SARS-CoV-2 replication by inhibition of its essential proteins: PL^pro and M^pro proteases, and nsp14 guanine N7-methyltransferase - Proteases encoded by SARS-CoV-2 constitute a promising target for new therapies against COVID-19. SARS-CoV-2 main protease (M^(pro), 3CL^(pro)) and papain-like protease (PL^(pro)) are responsible for viral polyprotein cleavage-a process crucial for viral survival and replication. Recently it was shown that 2-phenylbenzisoselenazol-3(2H)-one (ebselen), an organoselenium anti-inflammatory small-molecule drug, is a potent, covalent inhibitor of both the proteases and its potency was evaluated in…

• One Week of Oral Camostat Versus Placebo in Non-Hospitalized Adults with Mild-to-Moderate COVID-19: A Randomized Controlled Phase 2 Trial - CONCLUSIONS: In a phase 2 study of non-hospitalized adults with mild-to-moderate COVID-19, oral camostat did not accelerate viral clearance nor time to symptom improvement, nor reduce hospitalizations or deaths. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT04518410.).

• A clinical pharmacokinetic drug-drug interaction study between dextromethorphan and emvododstat, a potent anti-SARS-CoV-2 dihydroorotate dehydrogenase inhibitor - CONCLUSION: Emvododstat appears to be a strong CYP2D6 inhibitor. No drug-related treatment emergent adverse effects (TEAEs) were considered to be severe or serious.

• The PRMT5/WDR77 complex restricts hepatitis E virus replication - Hepatitis E virus (HEV) is one of the main pathogenic agents of acute hepatitis in the world. The mechanism of HEV replication, especially host factors governing HEV replication is still not clear. Here, using HEV ORF1 trans-complementation cell culture system and HEV replicon system, combining with stable isotope labelling with amino acids in cell culture (SILAC) and mass spectrometry (MS), we aimed to identify the host factors regulating HEV replication. We identified a diversity of host…

• Gasdermin D-mediated pyroptosis: mechanisms, diseases, and inhibitors - Gasdermin D (GSDMD)-mediated pyroptosis and downstream inflammation are important self-protection mechanisms against stimuli and infections. Hosts can defend against intracellular bacterial infections by inducing cell pyroptosis, which triggers the clearance of pathogens. However, pyroptosis is a double-edged sword. Numerous studies have revealed the relationship between abnormal GSDMD activation and various inflammatory diseases, including sepsis, coronavirus disease 2019 (COVID-19),…

• Anti-SARS-CoV-2 Activity of Adamantanes In Vitro and in Animal Models of Infection - Coronavirus disease 2019 (COVID-19) has had devastating effects worldwide, with particularly high morbidity and mortality in outbreaks on residential care facilities. Amantadine, originally licensed as an antiviral agent for therapy and prophylaxis against influenza A virus, has beneficial effects on patients with Parkinson’s disease and is used for treatment of Parkinson’s disease, multiple sclerosis, acquired brain injury, and various other neurological disorders. Recent observational data…

• In silico evidence implicating novel mechanisms of Prunella vulgaris L. as a potential botanical drug against COVID-19-associated acute kidney injury - COVID-19-associated acute kidney injury (COVID-19 AKI) is an independent risk factor for in-hospital mortality and has the potential to progress to chronic kidney disease. Prunella vulgaris L., a traditional Chinese herb that has been used for the treatment of a variety of kidney diseases for centuries, could have the potential to treat this complication. In this study, we studied the potential protective role of Prunella vulgaris in COVID-19 AKI and explored its specific mechanisms applied by…

• Analyzing immune responses to varied mRNA and protein vaccine sequences - In response to the COVID-19 pandemic, different types of vaccines, such as inactive, live-attenuated, messenger RNA (mRNA), and protein subunit, have been developed against SARS-CoV-2. This has unintentionally created a unique scenario where heterologous prime-boost vaccination against a single virus has been administered to a large human population. Here, we aimed to analyze whether the immunization order of vaccine types influences the efficacy of heterologous prime-boost vaccination,…

• Recent topics in the pathophysiology and treatment of immune thrombocytopenic purpura - Increased and impaired platelet productions via immunological abnormalities are the main pathophysiological mechanisms of primary immune thrombocytopenia (ITP). Recent studies have revealed that platelet removal from circulation involves not only Fc receptor-mediated phagocytosis of immunoglobulin G autoantibodies-bound platelets but also complement-dependent mechanism and platelet glycoprotein desialylation. Understanding the molecular mechanism of ITP pathophysiology has helped develop many…

• Prospective evaluation of the efficacy, safety, and optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock (ASTONISH): a double-blind, randomised, controlled, phase 2b trial - BACKGROUND: Activation of the triggering receptor expressed on myeloid cells-1 (TREM-1) pathway is associated with septic shock outcomes. Data suggest that modulation of this pathway in patients with activated TREM-1 might improve survival. Soluble TREM-1 (sTREM-1), a potential mechanism-based biomarker, might facilitate enrichment of patient selection in clinical trials of nangibotide, a TREM-1 modulator. In this phase 2b trial, we aimed to confirm the hypothesis that TREM1 inhibition might…

• Isolation of Anti-SARS-CoV-2 Natural Products Extracted from Mentha canadensis and the Semi-synthesis of Antiviral Derivatives - Traditional herbal medicine offers opportunities to discover novel therapeutics against SARS-CoV-2 mutation. The dried aerial part of mint (Mentha canadensis L.) was chosen for bioactivity-guided extraction. Seven constituents were isolated and characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). Syringic acid and methyl rosmarinate were evaluated in drug combination treatment. Ten amide derivatives of methyl rosmarinate were synthesized, and the dodecyl (13) and…

• Computational design of medicinal compounds to inhibit RBD-hACE2 interaction in the Omicron variant: unveiling a vulnerable target site - The COVID-19 pandemic, caused by SARS-CoV-2, has globally affected both human health and economy. Several variants with a high potential for reinfection and the ability to evade immunity were detected shortly after the initial reported case of COVID-19. A total of 30 mutations in the spike protein (S) have been reported in the SARS-CoV-2 (BA.2) variant in India and South Africa, while half of these mutations are in the receptor-binding domain and have spread rapidly throughout the world. Drug…

• In silico screening, ADMET analysis and MD simulations of phytochemicals of Onosma bracteata Wall. as SARS CoV-2 inhibitors - Being attracted with their cardiotonic, antidiabetic, cough relieving activity, treatment of fever, absorbent, anti-asthmatic, etc. activities reported in ancient Ayurvedic literature, phytochemicals of Onosma bracteata wall should be evaluated for their activity against SARS-CoV-2 virus. The main objective of this study is to identify a hit molecule for the inhibition of entry, replication, and protein synthesis of SARS CoV-2 virus into the host. To achieve given objective, computational…

• In silico Antivirus Repurposing and its Modification to Organoselenium Compounds as SARS-CoV-2 Spike Inhibitors - <b>Background and Objective:</b> The COVID-19, which has been circulating since late 2019, is caused by SARS-CoV-2. Because of its high infectivity, this virus has spread widely throughout the world. Spike glycoprotein is one of the proteins found in SARS-CoV-2. Spike glycoproteins directly affect infection by forming ACE-2 receptors on host cells. Inhibiting glycoprotein spikes could be one method of treating COVID-19. In this study, the antivirus marketed as a database will be…

• PACT inhibits the replication of SARS-CoV-2 through the blockage of GSK-3β-N-nsp3 cascade - The protein activator of protein kinase R (PKR) (PACT) has been shown to play a crucial role in stimulating the host antiviral response through the activation of PKR, retinoic acid-inducible gene I, and melanoma differentiation-associated protein 5. Whether PACT can inhibit viral replication independent of known mechanisms is still unrevealed. In this study, we show that, like many viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks GSK-3β to facilitate its replication….

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