Covid-19 Sentry

Contents

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

From Preprints

• DiSCERN - Deep Single Cell Expression ReconstructioN for improved cell clustering and cell subtype and state detection -
  Single cell sequencing provides detailed insights into biological processes including cell differentiation and identity. While providing deep cell-specific information, the method suffers from technical constraints, most notably a limited number of expressed genes per cell, which leads to suboptimal clustering and cell type identification. Here we present DISCERN, a novel deep generative network that reconstructs missing single cell gene expression using a reference dataset. DISCERN outperforms competing algorithms in expression inference resulting in greatly improved cell clustering, cell type and activity detection, and insights into the cellular regulation of disease. We used DISCERN to detect two unseen COVID-19-associated T cell types, cytotoxic CD4 + and CD8 + Tc2 T helper cells, with a potential role in adverse disease outcome. We utilized T cell fraction information of patient blood to classify mild or severe COVID-19 with an AUROC of 81 % that can serve as a biomarker of disease stage. DISCERN can be easily integrated into existing single cell sequencing workflows and readily adapted to enhance various other biomedical data types.
  🖺 Full Text HTML: DiSCERN - Deep Single Cell Expression ReconstructioN for improved cell clustering and cell subtype and state detection
• Inactivation of Influenza A virus by pH conditions encountered in expiratory aerosol particles results from localized conformational changes within Haemagglutinin and Matrix 1 proteins. -
  Multiple respiratory viruses including Influenza A virus (IAV) can be transmitted via expiratory aerosol particles, and many studies have established that indoor environmental conditions can affect viral infectivity during this transmission. Aerosol pH was recently identified as a major factor influencing the infectivity of aerosol-borne IAV and SARS-CoV-2, and for indoor room air, modelling indicates that small exhaled aerosols will undergo rapid acidification (pH below 5.5). However, there is a fundamental lack of understanding as to the mechanisms leading to viral inactivation within an acidic aerosol micro-environment. Here, we identified that transient exposure to acidic conditions impacted the early stages of the IAV infection cycle, which was primarily attributed to loss of binding function of the viral protein haemagglutinin. Viral capsid integrity was also partially affected by transient acidic exposures. The structural changes associated with loss of viral infectivity were then characterized using whole-virus hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS), and we observed discrete regions of unfolding in the external viral protein haemagglutinin and the internal matrix protein 1. Viral nucleoprotein structure appeared to be unaffected by exposure to acidic conditions. Protein analyses were complemented by genome and lipid envelope characterizations, and no acid-mediated changes were detected using our whole-virus methods. Improved understanding of the fate of respiratory viruses within exhaled aerosols constitutes a global public health priority, and information gained here could aid the development of novel strategies or therapeutics to control the airborne persistence of seasonal and/or pandemic influenza in the future. This study also provides proof-of-concept that HDX-MS is a highly effective method for characterization of both internal and external proteins for whole enveloped viruses such as IAV.
  🖺 Full Text HTML: Inactivation of Influenza A virus by pH conditions encountered in expiratory aerosol particles results from localized conformational changes within Haemagglutinin and Matrix 1 proteins.
• Post-COVID Phenotypic Manifestations are Associated with New-Onset Psychiatric Disease: Findings from the NIH N3C and RECOVER Studies -

  Acute COVID-19 infection can be followed by diverse clinical manifestations referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Studies have shown an increased risk of being diagnosed with new-onset psychiatric disease following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of new-onset psychiatric disease following COVID-19. A retrospective EHR cohort study of 1,603,767 individuals with acute COVID-19 was performed to evaluate whether non-psychiatric PASC-AMs are associated with new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 65 clinical organizations. EHR codes were mapped to 151 non-psychiatric PASC-AMs recorded 28-120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. Association of newly diagnosed psychiatric disease with age, sex, race, pre-existing comorbidities, and PASC-AMs in seven categories was assessed by logistic regression. There was a significant association between six categories and newly diagnosed anxiety, mood, and psychotic disorders, with odds ratios highest for cardiovascular (1.35, 1.27-1.42) PASC-AMs. Secondary analysis revealed that the proportions of 95 individual clinical features significantly differed between patients diagnosed with different psychiatric disorders. Our study provides evidence for association between non-psychiatric PASC-AMs and the incidence of newly diagnosed psychiatric disease. Significant associations were found for features related to multiple organ systems. This information could prove useful in understanding risk stratification for new-onset psychiatric disease following COVID-19. Prospective studies are needed to corroborate these findings.

  🖺 Full Text HTML: Post-COVID Phenotypic Manifestations are Associated with New-Onset Psychiatric Disease: Findings from the NIH N3C and RECOVER Studies
• An optimised method for recovery and quantification of laboratory generated SARS-CoV-2 aerosols by plaque assay. -
  We present an optimised method for the recovery of laboratory generated SARS-CoV-2 aerosols and quantification by plaque assays. This method allows easy incorporation into existing standard operating procedures of biological containment level 3 (CL3) laboratories.
  🖺 Full Text HTML: An optimised method for recovery and quantification of laboratory generated SARS-CoV-2 aerosols by plaque assay.
• Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody to antigenically distinct omicron SARS-CoV-2 subvariants -
  The rapid evolution of SARS-CoV-2 Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identify S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) and derived from an individual previously infected with SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrates broad cross-neutralization of all dominant variants including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1). Furthermore, it protected hamsters against in vivo challenges with wildtype, Delta, and BA.1 viruses. Structural analysis reveals that this antibody targets a class 1 epitope via multiple hydrophobic and polar interactions with its CDR-H3, in addition to common class 1 motifs in CDR-H1/CDR-H2. Importantly, this epitope is more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared to diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential, and may inform target-driven vaccine design against future SARS-CoV-2 variants.
  🖺 Full Text HTML: Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody to antigenically distinct omicron SARS-CoV-2 subvariants
• mRNA bivalent booster enhances neutralization against BA.2.75.2 and BQ.1.1 -
  The emergence of the highly divergent SARS-CoV-2 Omicron variant has jeopardized the efficacy of vaccines based on the ancestral spike. The bivalent COVID-19 mRNA booster vaccine within the United States is comprised of the ancestral and the Omicron BA.5 spike. Since its approval and distribution, additional Omicron subvariants have been identified with key mutations within the spike protein receptor binding domain that are predicted to escape vaccine sera. Of particular concern is the R346T mutation which has arisen in multiple subvariants, including BA.2.75.2 and BQ.1.1. Using a live virus neutralization assay, we evaluated serum samples from individuals who had received either one or two monovalent boosters or the bivalent booster to determine neutralizing activity against wild-type (WA1/2020) virus and Omicron subvariants BA.1, BA.5, BA.2.75.2, and BQ.1.1. In the one monovalent booster cohort, relative to WA1/2020, we observed a reduction in neutralization titers of 9-15-fold against BA.1 and BA.5 and 28-39-fold against BA.2.75.2 and BQ.1.1. In the BA.5-containing bivalent booster cohort, the neutralizing activity improved against all the Omicron subvariants. Relative to WA1/2020, we observed a reduction in neutralization titers of 3.7- and 4-fold against BA.1 and BA.5, respectively, and 11.5- and 21-fold against BA.2.75.2 and BQ.1.1, respectively. These data suggest that the bivalent mRNA booster vaccine broadens humoral immunity against the Omicron subvariants.
  🖺 Full Text HTML: mRNA bivalent booster enhances neutralization against BA.2.75.2 and BQ.1.1
• Negligible peptidome diversity of SARS-CoV-2 and its higher taxonomic ranks -
  The unprecedented increase in SARS-CoV-2 sequence data limits the application of alignment-dependent approaches to study viral diversity. Herein, we applied our recently published UNIQmin, an alignment-free tool to study the protein sequence diversity of SARS-CoV-2 (sub-species) and its higher taxonomic lineage ranks (species, genus, and family). Only less than 0.5% of the reported SARS-CoV-2 protein sequences are required to represent the inherent viral peptidome diversity, which only increases to a mere ~2% at the family rank. This is expected to remain relatively the same even with further increases in the sequence data. The findings have important implications in the design of vaccines, drugs, and diagnostics, whereby the number of sequences required for consideration of such studies is drastically reduced, short-circuiting the discovery process, while still providing for a systematic evaluation and coverage of the pathogen diversity.
  🖺 Full Text HTML: Negligible peptidome diversity of SARS-CoV-2 and its higher taxonomic ranks
• Characteristics of Students Participating in Collegiate Recovery Programs and the Impact of COVID-19: An Updated National Longitudinal Study -
  The goals of the present study were to use data from the first national longitudinal study of students in collegiate recovery programs (CRPs) to 1) provide an updated characterization of CRP students, with respect to demographics and past problem severity; 2) characterize current psychosocial functioning and examine changes in functioning over time; and 3) examine the impact of COVID-19 on CRP students. Data came from a longitudinal cohort study focused on the impact of CRPs on participating students’ success initiated in fall 2020. Four-year universities and community colleges with CRPs were invited to be partners on this project. Three cohorts of participants were recruited. All participants who completed the baseline survey (N = 334) were invited to complete follow-up surveys. The sample was composed of mostly White, cisgender undergraduate students with an average age of 29 years at baseline. CRP students generally reported challenging personal and academic histories, including high levels of polysubstance use and substance problem severity. They evidenced high levels of current psychosocial functioning. Recovery-related functioning (i.e., recovery capital, quality of life) was generally high at baseline and decreased slightly over time. COVID-19 represented a substantial source of stress for many CRP students, impacting some individuals’ abstinence. These results from the first national longitudinal study of CRP students parallel findings from other cross-sectional and/or CRP-specific studies and provide novel insights into the stability of recovery functioning. These results can advance our understanding and characterization of the national CRP student population, with the ability to examine recovery-related constructs over time.
  🖺 Full Text HTML: Characteristics of Students Participating in Collegiate Recovery Programs and the Impact of COVID-19: An Updated National Longitudinal Study
• It-which-must-not-be-named: COVID-19 misinformation, tactics to profit from it and to evade content moderation on YouTube -
  COVID-19 misinformation became accessible and profitable through social media platforms, such as YouTube. Here we investigate if Brazilian YouTube channels previously identified as vaccine misinformation spreaders would also misinform their audience about COVID-19. Our analysis sample consists of 6 months of content (3,318 videos) from 50 Brazilian YouTube channels. We establish a protocol to classify the types of COVID-19 misinformation spread by the content creators, describing how the channels evade content moderation—disguising, replicating, and dispersing misinformation—and what tactics the content creators use to profit. Our analysis shows that these channels exploited COVID-19 misinformation to promote themselves, profiting in the process.
  🖺 Full Text HTML: It-which-must-not-be-named: COVID-19 misinformation, tactics to profit from it and to evade content moderation on YouTube
• Fluvoxamine for Outpatient Treatment of COVID-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial -

  Background: The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic coronavirus disease 2019 (COVID-19) is unclear. Design: ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial testing repurposed medications in outpatients with mild to moderate COVID-19. A total of 1288 non-hospitalized adults aged >=30 years with confirmed COVID-19 experiencing >=2 symptoms of acute infection for <=7 days prior to randomization were randomized to receive fluvoxamine 50 mg or placebo twice daily for 10 days. The primary outcome was time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Secondary outcomes included composites of hospitalization or death with or without urgent or emergency care visit by day 28. Results: Of 1331 participants randomized (mean [SD] age, 48.5 [12.8] years; 57% women; 67% reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (n=614 placebo, n=674 fluvoxamine). Median time to recovery was 13 days (IQR 12-13) in the placebo group and 12 days (IQR 11-14) in the fluvoxamine group (hazard ratio [HR] 0.96, 95% credible interval [CrI] 0.86-1.07; posterior probability for benefit [HR>1]=0.22). Twenty-six participants (3.9%) in the fluvoxamine group were hospitalized or had urgent or emergency care visits compared with 23 (3.8%) in the placebo group (HR 1.1, 95% CrI 0.6-1.8; posterior probability for benefit [HR<1]=0.340). One participant in the fluvoxamine group and 2 in the placebo group were hospitalized; no deaths occurred. Adverse events were uncommon in both groups. Conclusions: Treatment with fluvoxamine 50 mg twice daily for 10 days did not improve time to recovery, compared with placebo, among outpatients with mild to moderate COVID-19. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19.

  🖺 Full Text HTML: Fluvoxamine for Outpatient Treatment of COVID-19: A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial
• COVID-19 primary series and booster vaccination and immune imprinting -

  Background: Epidemiological evidence for immune imprinting was investigated in immune histories related to vaccination in Qatar from onset of the omicron wave, on December 19, 2021, through September 15, 2022. Methods: Matched, retrospective, cohort studies were conducted to investigate differences in incidence of SARS-CoV-2 reinfection in the national cohort of persons who had a primary omicron infection, but different vaccination histories. History of primary-series (two-dose) vaccination was compared to that of no vaccination, history of booster (three-dose) vaccination was compared to that of two-dose vaccination, and history of booster vaccination was compared to that of no vaccination. Associations were estimated using Cox proportional-hazards regression models. Results: The adjusted hazard ratio comparing incidence of reinfection in the two-dose cohort to that in the unvaccinated cohort was 0.43 (95% CI: 0.38-0.48). The adjusted hazard ratio comparing incidence of reinfection in the three-dose cohort to that in the two-dose cohort was 1.38 (95% CI: 1.16-1.65). The adjusted hazard ratio comparing incidence of reinfection in the three-dose cohort to that in the unvaccinated cohort was 0.53 (95% CI: 0.44-0.63). All adjusted hazard ratios appeared stable over 6 months of follow-up. Divergence in cumulative incidence curves in all comparisons increased markedly when incidence was dominated by BA.4/BA.5 and BA.2.75*. No reinfection in any cohort progressed to severe, critical, or fatal COVID-19. Conclusions: History of primary-series vaccination enhanced immune protection against omicron reinfection, but history of booster vaccination compromised protection against omicron reinfection. These findings do not undermine the short-term public health utility of booster vaccination.

  🖺 Full Text HTML: COVID-19 primary series and booster vaccination and immune imprinting
• Long-term Association between NO2 and Human Mobility: A Two-year Spatiotemporal Study during the COVID-19 Pandemic in Southeast Asia -

  Since the COVID-19 pandemic, governments have implemented lockdowns and movement restrictions to contain the disease outbreak. Previous studies have reported a significant positive correlation between NO2 and mobility level during the lockdowns in early 2020. Though NO2 level and mobility exhibited similar spatial distribution, our initial exploration indicated that the decreased mobility level did not always result in concurrent decreasing NO2 level during a two-year time period in Southeast Asia with human movement data at a very high spatial resolution (i.e., Facebook origin-destination data). It indicated that factors other than mobility level contributed to NO2 level decline. Our subsequent analysis used a trained Multi-Layer Perceptron model to assess mobility and other contributing factors (e.g., travel modes, temperature, wind speed) and predicted future NO2 levels in Southeast Asia. The model results suggest that, while as expected mobility has a strong impact on NO2 level, a more accurate prediction requires considering different travel modes (i.e., driving and walking). Mobility shows two-sided impacts on NO2 level: mobility above the average level has a high impact on NO2, whereas mobility at a relatively low level shows negligible impact. The results also suggest that spatio-temporal heterogeneity and temperature also have impacts on NO2 and they should be incorporated to facilitate a more comprehensive understanding of the association between NO2 and mobility in the future study.

  🖺 Full Text HTML: Long-term Association between NO2 and Human Mobility: A Two-year Spatiotemporal Study during the COVID-19 Pandemic in Southeast Asia
• Evaluation of the Peterborough Public Health COVID-19 Rapid Antigen Test Self-Report Tool: Implications for COVID-19 Surveillance -

  Background: The ongoing COVID-19 pandemic has necessitated novel testing strategies, including the use of Rapid Antigen Tests (RATs). The widespread distribution of RATs to the public prompted Peterborough Public Health to launch a pilot RAT self-report tool to assess its utility in COVID-19 surveillance. Objective: To investigate the utility of a RAT self-report tool through an analysis of the temporal association between RAT results, PCR test results, and wastewater levels of COVID-19. Methods: We investigated the association between RAT results, PCR test results, and wastewater levels of COVID-19 using Pearson correlation coefficients. Percent positivity and count of positive tests for RATs and PCR tests were analyzed. Results: PCR percent positivity and wastewater were weakly correlated (r=0.33 p=0.022), as were RAT percent positivity and wastewater (r=0.33 p=0.002). RAT percent positivity and PCR percent positivity were not significantly correlated (r=-0.035, p=0.75). Count of positive RAT tests and count of positive PCR tests were moderately correlated (r=0.59, p<0.001). Wastewater was not significantly correlated to count of positive RAT tests (r=0.019, p=0.864) or count of positive PCR tests (r=0.004, p=0.971). Conclusion: Our results provide evidence in support of the use of RAT self-reporting as a low-cost simple adjunctive COVID-19 surveillance tool, and may suggest that its utility is greatest when considering an absolute count of positive RAT tests rather than percent positivity due to reporting bias towards positive tests. These results can help inform COVID-19 surveillance strategies of local Public Health Units and encourage the use of a RAT self-report tool.

  🖺 Full Text HTML: Evaluation of the Peterborough Public Health COVID-19 Rapid Antigen Test Self-Report Tool: Implications for COVID-19 Surveillance
• The global polarisation of remote work -
  The Covid-19 pandemic has led to the rise of digitally enabled remote work with consequences for the global division of labour. Remote work could connect labour markets, but it might also increase spatial polarisation. However, our understanding of the geographies of remote work is limited. Specifically, in how far could remote work connect employers and workers in different countries? Does it bring jobs to rural areas because of lower living costs, or does it concentrate in large cities? And how do skill requirements affect competition for employment and wages? We use data from a fully remote labour market - an online labour platform - to show that remote platform work is polarised along three dimensions. First, countries are globally divided: North American, European, and South Asian remote platform workers attract most jobs, while many Global South countries participate only marginally. Secondly, remote jobs are pulled to large cities; rural areas fall behind. Thirdly, remote work is polarised along the skill axis: workers with in-demand skills attract profitable jobs, while others face intense competition and obtain low wages. The findings suggest that agglomerative forces linked to the unequal spatial distribution of skills, human capital, and opportunities shape the global geography of remote work. These forces pull remote work to places with institutions that foster specialisation and complex economic activities, i.e. metropolitan areas focused on information and communication technologies. Locations without access to these enabling institutions - in many cases, rural areas - fall behind. To make remote work an effective tool for economic and rural development, it would need to be complemented by local skill-building, infrastructure investment, and labour market programmes.
  🖺 Full Text HTML: The global polarisation of remote work
• Disassociating conformity driven and self-interest driven dishonest behaviors -
  Learning from others’ dishonesty usually encompasses various motivations, for example, the destination to pursue self-interest and the tendency to conform to the group norm. However, these different processes were rarely dissociated previously, which impedes the understanding of how the individual dishonest behavior propagates and becomes popular in the community. We built a comprehensive model based on the reinforcement learning framework to depict both the processes of rational self-interest propensity and dishonesty conformity and examined their roles during the social learning of dishonesty. With an agent-based simulation and empirical studies in samples of diverse cultural backgrounds, we found rational self-interest propensity was the primary factor that drives dishonest acts of self-interest, whereas the effect of dishonesty conformity was conditional and context-dependent. With an fMRI experiment, we found the brain implemented dishonesty conformity differently when it serves distinct goals. Besides, these two processes of dishonesty were encoded by non-overlapping dynamic interactions between the brain regions. In the background of the COVID-19 pandemic where public coordination is highly demanded but at a cost of self-interest, we found that these two processes of dishonesty exerted discrepant effects on residents’ attitudes towards the local epidemic control and impacted the prevalence of pathogens unevenly.
  🖺 Full Text HTML: Disassociating conformity driven and self-interest driven dishonest behaviors

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

• A Phase III of COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older - Condition:   COVID-19
  Interventions:   Biological: EuCorVac-19;   Biological: ChAdOx1
  Sponsor:   EuBiologics Co.,Ltd
  Recruiting

• 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

• Open Multicentre Study of the Safety and Efficacy Against COVID-19 of Nirmatrelvir/Ritonavir in the Adult Population - Condition:   COVID-19
  Interventions:   Drug: nirmatrelvir/ritonavir;   Drug: Standard of care
  Sponsors:   Promomed, LLC;   Sponsor GmbH
  Completed

• Study Evaluating GS-5245 in Participants With COVID-19 Who Have a High Risk of Developing Serious or Severe Illness - Condition:   COVID-19
  Interventions:   Drug: GS-5245;   Drug: GS-5245 Placebo
  Sponsor:   Gilead Sciences
  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
  Recruiting

• Recombinant COVID-19 Vaccine (CHO Cell, NVSI-06-09) Phase III Clinical Trial - Conditions:   COVID-19;   Coronavirus Infections
  Interventions:   Biological: LIBP-Rec-Vaccine;   Biological: BIBP-Rec-Vaccine;   Biological: placebo
  Sponsors:   National Vaccine and Serum Institute, China;   China National Biotec Group Company Limited;   Lanzhou Institute of Biological Products Co., Ltd;   Beijing Institute of Biological Products Co Ltd.
  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

• 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 Phase I/II Study of GLB-COV2-043 as a COVID-19 Vaccine Booster - Condition:   COVID-19
  Interventions:   Drug: GLB-COV2-043;   Drug: BNT162b2/COMIRNATY®
  Sponsor:   GreenLight Biosciences, Inc.
  Not yet recruiting

From PubMed

• Anti-SARS-CoV-2 and cytotoxic activity of two marine alkaloids from green alga Caulerpa cylindracea Sonder in the Dardanelles - Caulerpa cylindracea Sonder is a green alga belonging to the Caulerpaceae family. This is the first chemical investigation of C. cylindracea in the Dardanelles which resulted in the isolation of four compounds, caulerpin (1), monomethyl caulerpinate (2), beta-sitosterol (3), and palmitic acid (4). Their structures were elucidated by spectroscopic analyses including 1D- and 2D NMR and mass. The isolated compounds 1 and 2 were tested against the SARS-CoV-2 viral targets spike protein and main…

• Withholding methotrexate after vaccination with ChAdOx1 nCov19 in patients with rheumatoid or psoriatic arthritis in India (MIVAC I and II): results of two, parallel, assessor-masked, randomised controlled trials - BACKGROUND: There is a necessity for an optimal COVID-19 vaccination strategy for vulnerable population groups, including people with autoimmune inflammatory arthritis on immunosuppressants such as methotrexate, which inhibit vaccine-induced immunity against SARS-CoV-2. Thus, we aimed to assess the effects of withholding methotrexate for 2 weeks after each dose of ChAdOx1 nCov-19 (Oxford-AstraZeneca) vaccine (MIVAC I) or only after the second dose of vaccine (MIVAC II) compared with continuation…

• In silico analyses of betulin: DFT studies, corrosion inhibition properties, ADMET prediction, and molecular docking with a series of SARS-CoV-2 and monkeypox proteins - We report detailed computational studies of betulin - a pentacyclic naturally occuring triterpene, which is a precursor for a broad family of biologically active derivatives. The structure, electronic, and optical properties of betulin were studied by the density functional theory (DFT) calculations in gas phase. The reactivity and the reactive centers of betulin were revealed through its global reactivity descriptors and molecular electrostatic potential (MEP). The DFT calculations were also…

• Irradiation accelerates SARS-CoV-2 infection by enhancing sphingolipid metabolism - Cancer patients who receive radiotherapy have a high risk of SARS-CoV-2 infection, but the concrete reason remains unclear. Herein, we investigated the influence of irradiation on the vulnerability of cancer cells to SARS-CoV-2 using S pseudovirions and probed the underlying mechanism via RNA-seq and other molecular biology techniques. Owing to the enhancement of sphingolipid metabolism, irradiation accelerated pseudovirion infection. Mechanistically, irradiation induced the expression of acid…

• LY3041658/ interleukin-8 complex structure as targets for IL-8 small molecule inhibitors discovery using a combination of in silico methods - Since interleukin-8 (IL-8/CXCL8) and its receptor, CXCR1 and CXCR2, were known in the early 1990s, biological pathways related to these proteins were proven to have high clinical value in cancer and inflammatory/autoimmune conditions treatment. Recently, IL-8 has been identified as biomarker for severe COVID-19 patients and COVID-19 prognosis. Boyles et al. (mAbs 12 (2020), pp. 1831880) have published a high-resolution X-ray crystal structure of the LY3041658 Fab in a complex human CXCL8. They…

• Chemical Compositions of Clove (Syzygium aromaticum (L.) Merr. & L.) Extracts and Their Potentials in Suppressing SARS-CoV-2 Spike Protein-ACE2 Binding, Inhibiting ACE2, and Scavenging Free Radicals - COVID-19 is initiated by binding the SARS-CoV-2 spike protein to angiotensin-converting enzyme 2 (ACE2) on host cells. Food factors capable of suppressing the binding between the SARS-CoV-2 spike protein and ACE2 or reducing the ACE2 availability through ACE2 inhibitions may potentially reduce the risk of SARS-CoV-2 infection and COVID-19. In this study, the chemical compositions of clove water and ethanol extracts were investigated, along with their potentials in suppressing SARS-CoV-2 spike…

• hnRNP K Degrades Viral Nucleocapsid Protein and Induces Type I IFN Production to Inhibit Porcine Epidemic Diarrhea Virus Replication - Porcine epidemic diarrhea virus (PEDV) is a re-emerging enteric coronavirus currently spreading in several nations and inflicting substantial financial damages on the swine industry. The currently available coronavirus vaccines do not provide adequate protection against the newly emerging viral strains. It is essential to study the relationship between host antiviral factors and the virus and to investigate the mechanisms underlying host immune response against PEDV infection. This study shows…

• Antiviral drug design based on structural insights into the N-terminal domain and C-terminal domain of the SARS-CoV-2 nucleocapsid protein - Nucleocapsid (N) protein plays crucial roles in the life cycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including the formation of ribonucleoprotein (RNP) complex with the viral RNA. Here we reported the crystal structures of the N-terminal domain (NTD) and C-terminal domain (CTD) of the N protein and an NTD-RNA complex. Our structures reveal a unique tetramer organization of NTD and identify a distinct RNA binding mode in the NTD-RNA complex, which could contribute to…

• SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein - Coronavirus disease-2019 (COVID-19) is primarily a respiratory disease, however, an increasing number of reports indicate that SARS-CoV-2 infection can also cause severe neurological manifestations, including precipitating cases of probable Parkinson’s disease. As microglial NLRP3 inflammasome activation is a major driver of neurodegeneration, here we interrogated whether SARS-CoV-2 can promote microglial NLRP3 inflammasome activation. Using SARS-CoV-2 infection of transgenic mice expressing…

• BC-11 is a covalent TMPRSS2 fragment inhibitor that impedes SARS-CoV-2 host cell entry - Host cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is facilitated via priming of its spike glycoprotein by the human transmembrane protease serine 2 (TMPRSS2). Although camostat and nafamostat are two highly potent covalent TMPRSS2 inhibitors, they nevertheless did not hold promise in COVID-19 clinical trials, presumably due to their short plasma half-lives. Herein, we report an integrative chemogenomics approach based on computational modeling and in vitro enzymatic…

• High-Throughput Assay for Identifying Diverse Antagonists of the Binding Interaction between the ACE2 Receptor and the Dynamic Spike Proteins of SARS-CoV-2 - SARS-CoV-2, a coronavirus strain that started a worldwide pandemic in early 2020, attaches to human cells by binding its spike (S) glycoprotein to a host receptor protein angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between the S protein and ACE2 has emerged as an important strategy for preventing viral infection. We systematically developed and optimized an AlphaLISA assay to investigate binding events between ACE2 and the ectodomain of the SARS-CoV-2 S protein (S-614G:…

• P38 kinases mediate NLRP1 inflammasome activation after ribotoxic stress response and virus infection - Inflammasomes integrate cytosolic evidence of infection or damage to mount inflammatory responses. The inflammasome sensor NLRP1 is expressed in human keratinocytes and coordinates inflammation in the skin. We found that diverse stress signals induce human NLRP1 inflammasome assembly by activating MAP kinase p38: While the ribotoxic stress response to UV and microbial molecules exclusively activates p38 through MAP3K ZAKα, infection with arthropod-borne alphaviruses, including Semliki Forest and…

• 25-Hydroxycholesterol Mediates Cholesterol Metabolism to Restrict Porcine Deltacoronavirus Infection via Suppression of Transforming Growth Factor β1 - Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus in pigs, is one of the major pathogens for lethal watery diarrhea in piglets and poses a threat to public health because of its potential for interspecies transmission to humans. 25-Hydroxycholesterol (25HC), a derivative of cholesterol, exhibits multiple potential modulating host responses to pathogens, including viruses and bacteria, as well as pathogen-induced inflammation, while its antiviral effect on PDCoV and how…

• Generation of Angiotensin-Converting Enzyme 2/Transmembrane Protease Serine 2-Double-Positive Human Induced Pluripotent Stem Cell-Derived Spheroids for Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Drug Evaluation - We newly generated two human induced pluripotent stem cell (hiPSC)-derived spheroid lines, termed Spheroids_(4M)^(ACE2-TMPRSS2) and Spheroids_(15M63)^(ACE2-TMPRSS2), both of which express angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), which are critical for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Both spheroids were highly susceptible to SARS-CoV-2 infection, and two representative anti-SARS-CoV-2 agents, remdesivir and 5h…

• Enhanced Inactivation of Pseudoparticles Containing SARS-CoV-2 S Protein Using Magnetic Nanoparticles and an Alternating Magnetic Field - Severe acute respiratory syndrome coronavirus 2’s (SARS-CoV-2) rapid global spread has posed a significant threat to human health, and similar outbreaks could occur in the future. Developing effective virus inactivation technologies is critical to preventing and overcoming pandemics. The infection of SARS-CoV-2 depends on the binding of the spike glycoprotein (S) receptor binding domain (RBD) to the host cellular surface receptor angiotensin-converting enzyme 2 (ACE2). If this interaction is…

From Patent Search