Covid-19 Sentry

Contents

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

From Preprints

• A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients -
  The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis and comparisons with healthy controls revealed extensive changes in the cellular composition and expression states in COVID-19 liver, reflecting hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis. We also observed Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas, resembling similar responses in liver injury in mice and in sepsis, respectively. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition was dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.
  🖺 Full Text HTML: A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients
• Dynamics of SARS-CoV-2 seroassay sensitivity: a systematic review and modeling study -

  Background Serological surveys have been the gold standard to estimate the numbers of SARS-CoV-2 infections, epidemic dynamics, and disease severity throughout the pandemic. Serological assays are known to have decaying sensitivity with time that can strongly bias their results, but there is a lack of guidelines to account for this phenomenon. Aim Assess the sensitivity decay of seroassays for detecting infections, its dependence on assay characteristics, and provide a simple tool to correct for this phenomenon. Methods We performed a systematic review and meta-analysis of SARS-CoV-2 serology studies. We included studies testing previously diagnosed individuals, without any SARS-CoV-2 vaccines, and excluded studies of cohorts highly unrepresentative of the general population (e.g. hospitalised patients). Results Of the 488 screened studies, 76 studies reporting on 50 different seroassays were included in the analysis. Sensitivity decay depends strongly on the antigen and the analytic technique used by the assay, with average sensitivities ranging between 26% and 98% at 6 months after infection, depending on assay characteristics. We find that a third of the included assays depart significantly from manufacturer specifications after 6 months. Conclusions Seroassay sensitivity decay depends on assay characteristics, and for some types of assays it can make manufacturer specifications highly unreliable. We provide a tool to correct for this phenomenon, and to assess the risk of decay for a given assay. This can be used to design better serosurveys, and quantify systematic biases in the existing serology literature.

  🖺 Full Text HTML: Dynamics of SARS-CoV-2 seroassay sensitivity: a systematic review and modeling study
• Tocilizumab treatment leads to early resolution of myeloid dysfunction and lymphopenia in patients hospitalized with COVID-19 -
  Tocilizumab, an anti-interleukin-6 receptor inhibitor, is recommended in global treatment guidelines for patients hospitalized with severe COVID-19. Using proteomic and transcriptomic analysis, we characterized the immune profile and identified cellular and molecular pathways directly modified by tocilizumab in peripheral blood samples collected from patients enrolled in the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial, to assess the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19 pneumonia. We identified factors predicting disease severity and clinical outcomes, including markers of inflammation, lymphopenia, myeloid dysfunction, and organ injury. Proteomic analysis confirmed a pharmacodynamic effect for tocilizumab. Transcriptomic analysis revealed that tocilizumab treatment leads to faster resolution of lymphopenia and myeloid dysfunction associated with severe COVID-19, thus defining an anti-inflammatory mechanism of action for the beneficial effects of tocilizumab in patients hospitalized with COVID-19.
  🖺 Full Text HTML: Tocilizumab treatment leads to early resolution of myeloid dysfunction and lymphopenia in patients hospitalized with COVID-19
• Natural heteroclitic-like peptides are generated by SARS-CoV-2 mutations -
  Mutations carried by SARS-CoV-2 spike protein variants may promote viral escape from immune protection. Humoral immunity is sensitive to evasion by SARS-CoV-2 mutants, but the impact of viral evolution on the interplay between virus and host CD8 T cell reactivity remains uncertain. By a systematic functional analysis of 30 spike variant mutations, we show that in vaccinated as well as convalescent subjects, mutated epitopes can have not only a neutral or abrogating effect on the recognition by CD8 T cells but can also enhance or even generate de novo CD8 T cell responses. Large pools of peptides spanning the entire spike sequence and comprising previously identified CD8 T cell epitopes were then used in parallel with variant peptides to define strength and multispecificity of total anti-spike CD8 responses. In some individuals, CD8 cells were narrowly focused on a few epitopes indicating that in this context of weak and oligospecific responses the overall antiviral protection can likely benefit of the function enhancing effect of heteroclitic-like mutations. In conclusion, appearance of mutated stimulatory epitopes likely reflects an epiphenomenon of SARS-CoV-2 evolution driven by antibody evasion and increased transmissibility, that might bear clinical relevance in a subset of individuals with weak and oligospecific CD8 T cell responses.
  🖺 Full Text HTML: Natural heteroclitic-like peptides are generated by SARS-CoV-2 mutations
• The impact of COVID-19 pandemic on influenza surveillance: a systematic review and meta-analysis -

  Background Influenza activity was reported to be below the seasonal levels during the COVID-19 pandemic globally. However, during the SARS-CoV-2 outbreak, the routine real-time surveillance of influenza like illness (ILI) and acute respiratory infection (ARI) was adversely affected due to the changes in priorities, economic constraints, repurposing of hospitals for COVID care and closure of outpatient services. Methods A systematic review and meta-analysis were carried out to assess the pooled proportion of symptomatic cases tested for influenza virus before the current pandemic in 2019 and during the pandemic in 2020/21. An electronic search of PubMed/MEDLINE, Scopus and Google Scholar was carried out for the articles reporting the impact of the COVID-19 pandemic on Influenza surveillance among humans using search terms. The study was designed based on PRISMA guidelines and the meta-analysis was performed to synthesise the pooled proportion of patients sampled for influenza with 95% confidence interval (CI). Results The nine qualified studies from the WHO-European region, Canada, Japan, Germany, Italy, Spain, South Africa and the United States were pooled by random-effects meta-analysis. The overall pooled proportion of symptomatic cases sampled for influenza surveillance before and during the pandemic was 2.38% (95% CI 2.08%-2.67%) and 4.18% (95% CI 3.8%-4.52%) respectively. However, the pooled proportion of samples tested for influenza before the pandemic was 0.69% (95% CI 0.45-0.92%) and during the pandemic was 0.48% (95% CI 0.28-0.68%) when studies from Canada were excluded. Conclusion: The meta-analysis concludes that globally there was a decline in influenza surveillance during the COVID-19 pandemic except in Canada.

  🖺 Full Text HTML: The impact of COVID-19 pandemic on influenza surveillance: a systematic review and meta-analysis
• The SARS-CoV-2 cellular receptor ACE2 is expressed in oropharyngeal cells and is modulated in vitro by the bacterial lysate Lantigen B -
  Angiotensin-converting enzyme2 (ACE2) is the main cell surface receptor of the SARS-CoV-2 spike protein and is expressed in a variety of cell types, including cells of the respiratory tract. A bacterial lysate used for the prophylaxis of respiratory infections (OM-85), was recently shown to downregulate the expression of ACE2 in epithelial cells, suggesting its possible role as a prophylaxis of the onset of COVID19. Another bacterial lysate (Lantigen B, administered sublingually) is used in the prophylaxis of recurrent respiratory tract infections. It contains antigens obtained by chemical lysis from the most representative microbes of the respiratory tract. In this in vitro study, the capacity of Lantigen B to decrease ACE2 in human oropharyngeal cells was evaluated. The study was carried out in 40 healthy donors undergoing oropharyngeal swab for routine SARS-CoV-2 detection. Cells were treated in vitro with a 1:2 of Lantigen B. ACE2 expression was evaluated using a fluorescent anti-ACE2 monoclonal antibody and flow cytometry. A reduction in the number of positive cells was observed in 72% of the patients, while a modulation of ACE2 expression was observed in 62% of the samples. As a control, the expression of the CD54 rhinovirus receptor in the same cells was unaffected. To evaluate the functional effects of down regulation, in a subset of samples, the same oropharynx cells were incubated with Lantigen B and infected with wild-type SARS-CoV-2. After 24 hours, viral RNA, as assessed by rt-PCR, was significantly lower in samples treated with Lantigen B. In conclusion, this study demonstrates that Lantigen B, at a pharmacological dose, modulates the expression of the main SARS-CoV-2 receptor in oropharyngeal cells, and reduces viral yield. This activity could be synergistic with other approaches (vaccination and therapy) by reducing the number of potentially infected cells and thus reducing the effects of SARS-CoV-2 infection.
  🖺 Full Text HTML: The SARS-CoV-2 cellular receptor ACE2 is expressed in oropharyngeal cells and is modulated in vitro by the bacterial lysate Lantigen B
• Where to Look? Alcohol, Affect, and Gaze Behavior During a Virtual Social Interaction -
  COVID-19 forced social interactions to move online. Yet researchers have little understanding of the mental health consequences of this shift. Given pandemic-related surges in emotional disorders and problematic drinking, it becomes imperative to understand the cognitive and affective processes involved in virtual interactions and the impact of alcohol in virtual social spaces. Participants (N=246) engaged in an online video call while their gaze behavior was tracked. Prior to the interaction, participants were randomly assigned to receive an alcoholic or control beverage. Participants’ affect was repeatedly assessed. Results indicated that a proportionally larger amount of time spent gazing at oneself (vs. one’s interaction partner) predicted significantly higher negative affect after the exchange. Further, alcohol independently increased self-directed attention, failing to demonstrate its typically potent social-affective enhancement in this virtual context. Results carry potential implications for understanding factors that increase risk for hazardous drinking and negative affect in our increasingly virtual world.
  🖺 Full Text HTML: Where to Look? Alcohol, Affect, and Gaze Behavior During a Virtual Social Interaction
• Estimating the impact of implementation and timing of COVID-19 vaccination programme in Brazil: a counterfactual analysis -

  Background: Vaccines developed between 2020 - 2021 against the SARS-CoV-2 virus were designed to diminish the severity and prevent deaths due to COVID-19. However, estimates of the effectiveness of vaccination campaigns in achieving these goals remain a methodological challenge. In this work, we developed a Bayesian statistical model to estimate the number of deaths and hospitalisations averted by vaccination of older adults (above 60 years old) in Brazil. Methods: We fit a linear model to predict the number of deaths and hospitalisations of older adults as a function of vaccination coverage in this group and casualties in younger adults. We used this model in a counterfactual analysis, simulating alternative scenarios without vaccination or with faster vaccination roll-out. We estimated the direct effects of COVID-19 vaccination by computing the difference between hypothetical and realised scenarios. Findings: We estimated that more than 165,000 individuals above 60 years of age were not hospitalised due to COVID-19 in the first seven months of the vaccination campaign. An additional contingent of 104,000 hospitalisations could have been averted if vaccination had started earlier. We also estimated that more than 58 thousand lives were saved by vaccinations in the period analysed for the same age group and that an additional 47 thousand lives could have been saved had the Brazilian government started the vaccination programme earlier. Interpretation: Our estimates provided a lower bound for vaccination impacts in Brazil, demonstrating the importance of preventing the suffering and loss of older Brazilian adults. Once vaccines were approved, an early vaccination roll-out could have saved many more lives, especially when facing a pandemic.

  🖺 Full Text HTML: Estimating the impact of implementation and timing of COVID-19 vaccination programme in Brazil: a counterfactual analysis
• Graph-based Fusion Modeling and Explanation for Disease Trajectory Prediction -

  We propose a relational graph to incorporate clinical similarity between patients while building personalized clinical event predictors with a focus on hospitalized COVID-19 patients. Our graph formation process fuses heterogeneous data, i.e., chest X-rays as node features and non-imaging EHR for edge formation. While node represents a snap-shot in time for a single patient, weighted edge structure encodes complex clinical patterns among patients. While age and gender have been used in the past for patient graph formation, our method incorporates complex clinical history while avoiding manual feature selection. The model learns from the patient9s own data as well as patterns among clinically-similar patients. Our visualization study investigates the effects of neighborhood of a node on its predictiveness and showcases the model9s tendency to focus on edge-connected patients with highly suggestive clinical features common with the node. The proposed model generalizes well by allowing edge formation process to adapt to an external cohort.

  🖺 Full Text HTML: Graph-based Fusion Modeling and Explanation for Disease Trajectory Prediction
• Viral load of SARS-CoV-2 Omicron BA.5 is lower than that of BA.2 despite the higher infectivity of BA.5 -

  Sublineage BA.5 of the SARS-CoV-2 Omicron variant rapidly spread and replaced BA.2 in July 2022 in Tokyo. A high viral load can be a possible cause of high transmissibility. Therefore, the copy numbers of SARS-CoV-2 in nasopharyngeal swab samples obtained from all patients visiting the hospital where this research was conducted were measured using quantitative polymerase chain reaction (qPCR). Viral genotypes were determined using PCR-based melting curve analysis. Next, whole-genome sequencing was performed using approximately one-fifth of the samples to verify the viral genotypes determined using PCR. Then, the copy numbers of the BA.1, BA.2, and BA.5 cases were compared. Contrary to expectations, the copy numbers of the BA.5 cases (median 4.7 X 10⁴ copies/uL, n = 290) were significantly (p = 0.001) lower than those of BA.2 cases (median 1.1 X 10⁵ copies/uL, n = 184). There was no significant difference between the BA.5 and BA.1 cases (median, 3.1 X 10⁴ copies/uL; n = 215). The results presented here suggest that the increased infectivity of BA.5 is not caused by higher viral loads, but presumably by other factors such as increased affinity to human cell receptors or immune escape due to its L452R mutation.

  🖺 Full Text HTML: Viral load of SARS-CoV-2 Omicron BA.5 is lower than that of BA.2 despite the higher infectivity of BA.5
• Post-acute symptoms four months after SARS-CoV-2 infection during the Omicron period: a nationwide Danish questionnaire study -

  Background Post-acute symptoms are not uncommon after SARS-CoV-2 infection with pre-Omicron variants. How the Omicron variant and COVID-19 booster vaccination influences the risk of post-acute symptoms is less clear. Objectives To evaluate the effects of the Omicron variant and COVID-19 booster vaccination on post-acute symptoms, four months after infection with SARS-CoV-2. Methods A nationwide Danish questionnaire study comprising 44,004 individuals aged 15 years or older with outcomes on post-acute symptoms and new-onset general health problems, four months after testing. Risk differences (RDs) were estimated by comparing Omicron -cases to controls, Omicron to Delta -cases, and Omicron vaccinated cases with three to -two doses, adjusted for age, sex, BMI, self-reported chronic diseases, Charlson comorbidity index, healthcare occupation, and vaccination status. Results Four months after testing for SARS-CoV-2 during the Omicron period, the largest RD comparing Omicron cases to controls was observed for memory issues (RD=7.2%, 95% CI: 6.4 to 8.1). Compared to cases from the Delta period, Omicron cases reported reduced risks of post-acute dysosmia (RD=-15.5%, 95% CI: -17.5 to -13.4) and dysgeusia (RD=-11.8%, 95% CI: -13.9 to -9.8). Cases vaccinated with three doses prior to Omicron infection reported reduced risk of 13/26 post-acute symptoms and of 4/5 new-onset general health problems, compared to those vaccinated with two doses. Conclusions Cases infected during the Omicron period experienced substantial post-acute symptoms and new-onset health problems, four months after testing, although milder than Delta cases. Booster vaccination was associated with fewer post-acute symptoms and new-onset health problems, four months after Omicron infection, compared to two doses of COVID-19 vaccine.

  🖺 Full Text HTML: Post-acute symptoms four months after SARS-CoV-2 infection during the Omicron period: a nationwide Danish questionnaire study
• Vitamin D deficiency and SARS-CoV-2 infection: Big-data analysis from March 2020 to March 2021. D-COVID study -
  Methods: Using big-data analytics and artificial intelligence through the SAVANA Manager clinical platform, we analysed clinical data from patients with COVID-19 atended in a terciary university hospital from March 2020 to March 2021. Results: Of the 143.157 analysed patients, 36.261 subjects had COVID-19 infection (25.33%); during this period; of these 2588 had vitamin D deficiency (7.14%). Among subjects with COVID-19 and vitamin D deficiency, there was a higher proportion of women OR 1.45 [95% CI 1.33-1.57], adults older than 80 years OR 2.63 [95%CI 2.38-2.91], people living in nursing homes OR 2.88 [95%CI 2.95-3.45] and walking dependence OR 3.45 [95%CI 2.85-4.26]. Regarding clinical course, a higher number of subjects with COVID-19 and vitamin D deficiency required hospitalitation OR 2.41 [95%CI 2.22-2-61], intensive unit care (ICU) OR 2.22 [95% CI 1.64-3.02], had a longer mean hospital stay 3.94 (2.29) p=0.02 and higher mortality OR 1.82 [95%CI 1.66-2.01].) Conclusion: Low serum 25 (OH) Vitamin-D level was significantly associated with a worse clinical evolution and prognosis of COVID-19 infection. We found a higher proportion of institutionalised and dependent people over 80 years of age among patients with COVID-19 and vitamin D deficiency.
  🖺 Full Text HTML: Vitamin D deficiency and SARS-CoV-2 infection: Big-data analysis from March 2020 to March 2021. D-COVID study
• Tailored interventions into broad attitude networks towards the COVID-19 pandemic -
  This study examines how broad attitude networks are affected by tailored interventions aimed at variables selected based on their connectiveness with other variables. We first computed a broad attitude network based on a large-scale cross-sectional COVID-19 survey (N = 6,093). Over a period of approximately 10 weeks, participants were invited five times to complete this survey, with the third and fifth wave including interventions aimed at manipulating specific variables in the broad COVID-19 attitude network. Results suggest that targeted interventions that yield relatively strong effects on variables central to a broad attitude network have downstream effects on connected variables, which can be partially explained by the variables the interventions were aimed at. We conclude that broad attitude network structures can reveal important relations between variables that can help to design new interventions.
  🖺 Full Text HTML: Tailored interventions into broad attitude networks towards the COVID-19 pandemic
• Intranasal virus-particle mimicking vaccine enhances SARS-CoV-2 clearance in the Syrian hamster model -
  Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a pandemic and multiple vaccines have been developed and authorized for human use. While these vaccines reduce disease severity, they do not prevent infection allowing SARS-CoV-2 to continue to spread and evolve. To confer protection against infection and limit transmission, vaccines must be developed that induce mucosal immunity in the respiratory tract. Therefore, we performed proof-of-principle pre-clinical vaccine and challenge studies with a virus-particle mimicking intranasal vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4A using cryo-EM, and established RBD decoration through both SDS-PAGE and negative stain TEM. Using this RBD grafted SpyCage scaffold (RBD+SpyCage), we performed two vaccination studies in Syrian hamsters using an intranasal prime and boost vaccine regiment followed by SARS-CoV-2 challenge. The initial study focused on assessing the immunogenicity of RBD+SpyCage, which indicated that vaccination of hamsters induced a non-neutralizing antibody response that enhanced viral clearance but did not prevent infection. In an expanded study, we demonstrated that covalent bonding of RBD to the scaffold was required to induce an antibody response. Consistent with the initial study, animals vaccinated with RBD+SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract, whereas admixtures of SpyCage and RBD, or either component alone did not. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile and adaptable system for the development of intranasal vaccines targeting respiratory pathogens.
  🖺 Full Text HTML: Intranasal virus-particle mimicking vaccine enhances SARS-CoV-2 clearance in the Syrian hamster model
• Can Artificial Intelligence Detect Monkeypox from Digital Skin Images? -
  An outbreak of Monkeypox has been reported in 75 countries so far, and it is spreading at a fast pace around the world. The clinical attributes of Monkeypox resemble those of Smallpox, while skin lesions and rashes of Monkeypox often resemble those of other poxes, for example, Chickenpox and Cowpox. These similarities make Monkeypox detection challenging for healthcare professionals by examining the visual appearance of lesions and rashes. Additionally, there is a knowledge gap among healthcare professionals due to the rarity of Monkeypox before the current outbreak. Motivated by the success of artificial intelligence (AI) in COVID-19 detection, the scientific community has shown an increasing interest in using AI in Monkeypox detection from digital skin images. However, the lack of Monkeypox skin image data has been the bottleneck of using AI in Monkeypox detection. Therefore, in this paper, we used a web-scrapping-based Monkeypox, Chickenpox, Smallpox, Cowpox, Measles, and healthy skin image dataset to study the feasibility of using state-of-the-art AI deep models on skin images for Monkeypox detection. Our study found that deep AI models have great potential in the detection of Monkeypox from digital skin images (precision of 85%). However, achieving a more robust detection power requires larger training samples to train those deep models.
  🖺 Full Text HTML: Can Artificial Intelligence Detect Monkeypox from Digital Skin Images?

From Clinical Trials

• Safety and Efficacy of Medications COVID-19 - Condition:   Severe Covid-19
  Intervention:   Drug: Oral bedtime melatonin
  Sponsor:   Hospital San Carlos, Madrid
  Completed

• Use of Multiple Doses of Convalescent Plasma in Mechanically Intubated Patients With COVID-19 - Condition:   COVID-19
  Intervention:   Biological: Multiple doses of anti-SARS-CoV-2 Convalescent Plasma
  Sponsors:   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
  Completed

• Open Multicenter Study for Assessment of Efficacy and Safety of Molnupiravir in Adult Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Molnupiravir (Esperavir);   Drug: Standard of care
  Sponsor:   Promomed, LLC
  Completed

• COVID-19 Testing and Vaccine Literacy for Women With Criminal Legal System Involvement - Condition:   COVID-19 Pandemic
  Intervention:   Behavioral: Tri-City COVID Attitudes Study
  Sponsor:   University of Kansas Medical Center
  Recruiting

• Effects of Respiratory Muscle Training in Individuals With Long-term Post-COVID-19 Symptoms - Conditions:   Covid19;   Post-acute COVID-19 Syndrome
  Interventions:   Other: Inspiratory + expiratory muscle training group;   Other: Inspiratory + expiratory muscle training sham group;   Other: Exercise training program
  Sponsors:   Universidad Complutense de Madrid;   Colegio Profesional de Fisioterapeutas de la Comunidad de Madrid
  Enrolling by invitation

• JT001 (VV116) for the Treatment of COVID-19 - Condition:   Mild to Moderate COVID-19
  Interventions:   Drug: JT001;   Drug: Placebo
  Sponsors:   Shanghai Vinnerna Biosciences Co., Ltd.;   Sponsor GmbH
  Not yet recruiting

• Boost Intentions and Facilitate Action to Promote COVID-19 Booster Take-up - Conditions:   COVID-19;   Vaccines
  Interventions:   Behavioral: Eligibility reminder;   Behavioral: Link to a narrow set of vaccine venues;   Behavioral: Link to a broad set of vaccine venues;   Behavioral: Doctors’ recommendation and value of vaccine
  Sponsor:   University of California, Los Angeles
  Not yet recruiting

• Effects of Prompt to Bundle COVID-19 Booster and Flu Shot - Conditions:   COVID-19;   Vaccines
  Interventions:   Behavioral: Reminder to boost protection against COVID-19;   Behavioral: Flu Tag Along;   Behavioral: COVID-19 Booster & Flu Bundle
  Sponsor:   University of California, Los Angeles
  Not yet recruiting

• Information Provision and Consistency Framing to Increase COVID-19 Booster Uptake - Conditions:   COVID-19;   Vaccines
  Interventions:   Behavioral: Reminder that facilitates action;   Behavioral: Consistency framing;   Behavioral: Information provision about the uniqueness of the bivalent booster;   Behavioral: Information provision about bivalent booster eligibility;   Behavioral: Information provision about the severity of COVID-19 symptoms
  Sponsor:   University of California, Los Angeles
  Not yet recruiting

• Respiratory Muscles After Inspiratory Muscle Training After COVID-19 - Conditions:   COVID-19;   Diaphragm Injury
  Intervention:   Device: Inspiratory Muscle Training (IMT)
  Sponsors:   RWTH Aachen University;   Philipps University Marburg Medical Center
  Recruiting

• OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial - Conditions:   COVID-19;   Immunodeficiency
  Interventions:   Drug: Paxlovid 5 days;   Drug: Paxlovid 10 days;   Drug: Tixagevimab and Cilgavimab
  Sponsors:   ANRS, Emerging Infectious Diseases;   University Hospital, Geneva
  Not yet recruiting

• A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza - Conditions:   Influenza, Human;   COVID-19
  Interventions:   Biological: bivalent BNT162b2 (original/Omi BA.4/BA.5);   Biological: qIRV (22/23);   Biological: QIV
  Sponsors:   BioNTech SE;   Pfizer
  Not yet recruiting

• Study to Evaluate Safety, Tolerability, Efficacy and Pharmacokinetics of ASC10 in Mild to Moderate COVID-19 Patients - Condition:   SARS CoV 2 Infection
  Interventions:   Drug: ASC10;   Drug: Placebo
  Sponsor:   Ascletis Pharmaceuticals Co., Ltd.
  Not yet recruiting

• A Preliminary Exploratory Study to Evaluate the Safety and Immunogenicity of Omicron Variant Bivalent Vaccine V-01-B5 - Condition:   COVID-19 Pandemic
  Interventions:   Biological: V-01/V-01-B5;   Biological: V-01-351/V-01-B5;   Biological: V-01
  Sponsor:   Livzon Pharmaceutical Group Inc.
  Active, not recruiting

• Exploratory Clinical Study to Evaluation of the Safety and Immunogenicity of Bivalent Vaccine V-01D-351 - Condition:   COVID-19 Pandemic
  Interventions:   Biological: V-01D-351;   Biological: CoronaVac
  Sponsor:   Livzon Pharmaceutical Group Inc.
  Active, not recruiting

From PubMed

• Discovery of host-directed modulators of virus infection by probing the SARS-CoV-2-host protein-protein interaction network - The ongoing coronavirus disease 2019 (COVID-19) pandemic has highlighted the need to better understand virus-host interactions. We developed a network-based method that expands the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-host protein interaction network and identifies host targets that modulate viral infection. To disrupt the SARS-CoV-2 interactome, we systematically probed for potent compounds that selectively target the identified host proteins with high expression in…

• Ligand-based discovery of coronavirus main protease inhibitors using MACAW molecular embeddings - Ligand-based drug design methods are thought to require large experimental datasets to become useful for virtual screening. In this work, we propose a computational strategy to design novel inhibitors of coronavirus main protease, M^(pro). The pipeline integrates publicly available screening and binding affinity data in a two-stage machine-learning model using the recent MACAW embeddings. Once trained, the model can be deployed to rapidly screen large libraries of molecules in silico. Several…

• Resistance profile and mechanism of severe acute respiratory syndrome coronavirus-2 variants to LCB1 inhibitor targeting the spike receptor-binding motif - LCB1 is a 56-mer miniprotein computationally designed to target the spike (S) receptor-binding motif of SARS-CoV-2 with potent in vitro and in vivo inhibitory activities (Cao et al., 2020; Case et al., 2021). However, the rapid emergence and epidemic of viral variants have greatly impacted the effectiveness of S protein-targeting vaccines and antivirals. In this study, we chemically synthesized a peptide-based LCB1 inhibitor and characterized the resistance profile and underlying mechanism of…

• A multi-task FP-GNN framework enables accurate prediction of selective PARP inhibitors - PARP (poly ADP-ribose polymerase) family is a crucial DNA repair enzyme that responds to DNA damage, regulates apoptosis, and maintains genome stability; therefore, PARP inhibitors represent a promising therapeutic strategy for the treatment of various human diseases including COVID-19. In this study, a multi-task FP-GNN (Fingerprint and Graph Neural Networks) deep learning framework was proposed to predict the inhibitory activity of molecules against four PARP isoforms (PARP-1, PARP-2, PARP-5A,…

• Screening of Potent Phytochemical Inhibitors Against SARS-CoV-2 Main Protease: An Integrative Computational Approach - Coronavirus disease 2019 (COVID-19) is a potentially lethal and devastating disease that has quickly become a public health threat worldwide. Due to its high transmission rate, many countries were forced to implement lockdown protocols, wreaking havoc on the global economy and the medical crisis. The main protease (M^(pro)) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus for COVID-19, represent an effective target for the development of a new drug/vaccine…

• Acetylshikonin inhibits inflammatory responses and Papain-like protease activity in murine model of COVID-19 - No abstract

• Efficient synthesis of novel colchicine-magnolol hybrids and evaluation of their inhibitory activity on key proteases of 2019-nCoV replication and acute lung injury - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV), is a life-threatening infectious condition. Acute lung injury is a common complication in patients with COVID-19. 3-chymotrypsin-like protease (3CL^(pro)) of 2019-nCoV and neutrophil elastase are critical targets of COVID-19 and acute lung injury, respectively. Colchicine and magnolol are reported to exert inhibitory effects on inflammatory response, the severe comorbidity in…

• The impact of COVID-19 on student learning during the transition from remote to in-person learning: Using mind mapping to identify and address faculty concerns - The COVID-19 pandemic led to suspension of in-person learning at many higher education institutions (HEIs) in March 2020. In response, HEIs transitioned most courses to online formats immediately and continued this mode of instruction through the 2020-2021 academic year. In fall 2021, numerous HEIs resumed in-person courses and some hybrid courses, and faculty began noting academic-related behavior deficiencies not previously observed in students. Focus groups of teaching faculty (n=8) from one…

• The potential for traditional Chinese therapy in treating sleep disorders caused by COVID-19 through the cholinergic anti-inflammatory pathway - Since the outbreak of Coronavirus disease (COVID-19) in 2019, it has spread rapidly across the globe. Sleep disorders caused by COVID-19 have become a major concern for COVID-19 patients and recovered patients. So far, there’s no effective therapy on this. Traditional Chinese therapy (TCT) has a great effect on sleep disorders, with rare side effects and no obvious withdrawal symptoms. The cholinergic anti-inflammatory pathway, a neuroregulatory pathway in the central nervous system that uses…

• Temporal proteomic analyses of human lung cells distinguish high pathogenicity influenza viruses and coronaviruses from low pathogenicity viruses - Newly re-emerging viruses are of significant global concern. In late 2019, a new coronavirus, SARS-CoV-2, emerged in China and soon spread worldwide, causing the COVID-19 pandemic, which to date has caused >6 M deaths. There has been a wealth of studies on this new virus since its emergence. The coronaviruses consist of many animal and human pathogens, with some of the human coronavirus, such as strain OC43, normally causing only mild cold-like symptoms. Viruses usurp host cellular processes to…

• Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis - We and others have previously shown that the SARS-CoV-2 accessory protein ORF6 is a powerful antagonist of the interferon (IFN) signaling pathway by directly interacting with Nup98-Rae1 at the nuclear pore complex (NPC) and disrupting bidirectional nucleo-cytoplasmic trafficking. In this study, we further assessed the role of ORF6 during infection using recombinant SARS-CoV-2 viruses carrying either a deletion or a well characterized M58R loss-of-function mutation in ORF6. We show that ORF6…

• Heterologous SARS-CoV-2 IgA neutralising antibody responses in convalescent plasma - CONCLUSION: Overall, convalescent plasma IgA contributed to the neutralising antibody response of wild-type SARS-CoV-2 RBD and various RBD mutations. However, this response displayed large heterogeneity and was less potent than IgG.

• Small-Molecule RAF265 as an Antiviral Therapy Acts against PEDV Infection - Porcine epidemic diarrhea virus (PEDV), a member of the family Coronaviridae, causes acute diarrhea, vomiting, dehydration, and high mortality in newborn piglets, and has caused significant economic losses in the pig industry. There are currently no specific drugs available to treat PEDV. Viruses depend exclusively on the cellular machinery to ensure an efficient replication cycle. In the present study, we found that small-molecule RAF265, an anticancer drug that has been shown to be a potent…

• Antiviral Activity of Ficus rubiginosa Leaf Extracts against HSV-1, HCoV-229E and PV-1 - Ficus rubiginosa plant extract showed antimicrobial activity, but no evidence concerning its antiviral properties was reported. The antiviral activity of the methanolic extract (MeOH) and its n-hexane (H) and ethyl acetate (EA) fractions against Herpes simplex virus-1 (HSV-1), Human coronavirus (HCoV) -229E, and Poliovirus-1 (PV-1) was investigated in the different phases of viral infection in the VERO CCL-81 cell line. To confirm the antiviral efficacy, a qPCR was conducted. The recorded…

• A Syntenin Inhibitor Blocks Endosomal Entry of SARS-CoV-2 and a Panel of RNA Viruses - Viruses are dependent on host factors in order to efficiently establish an infection and replicate. Targeting the interactions of such host factors provides an attractive strategy to develop novel antivirals. Syntenin is a protein known to regulate the architecture of cellular membranes by its involvement in protein trafficking and has previously been shown to be important for human papilloma virus (HPV) infection. Here, we show that a highly potent and metabolically stable peptide inhibitor…

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