Covid-19 Sentry

Contents

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

From Preprints

• The People’s Vaccine: Intellectual Property, Access to Essential Medicines, and the Coronavirus COVID-19 -
  This paper explores intellectual property and access to essential medicines in the context of the coronavirus COVID-19 public health crisis. It considers policy solutions to counteract vaccine nationalism and profiteering by pharmaceutical companies and vaccine developers. This paper considers the campaign for the development of a People’s Vaccine led by the People’s Vaccine Alliance, UNAIDS, Oxfam and Public Citizen. The WHO has established the ACT Accelerator in order to boost research, development, and deployment of COVID-19 technologies. However, the operation of COVAX thus far has been falling short of its original ambitions. The Medicines Patent Pool has expanded its jurisdiction to include the sharing of intellectual property related to COVID-19. Meanwhile, Costa Rica has proposed a COVID-19 Technology Access Pool – an idea for a new institutional structure which has been taken up by the WHO. In the context of the coronavirus public health crisis, there has also been discussion of the use of compulsory licensing and crown use to counteract profiteering and anti-competitive behavior. There has been a push by Universities Allied for Essential Medicines (UAEM) and others for the public licensing of COVID-19 technologies developed with government funding. The Open COVID Pledge has been taken by a number of intellectual property owners. In response to the assertion of proprietary rights in respect of COVID-19 technologies, the open movement has championed the development of Open Science models of science. India and South Africa have put forward a waiver proposal in the TRIPS Council to enable countries to take action in respect of COVID-19 without fear of retribution under trade laws. While the United States has been willing to support a TRIPS Waiver for vaccines, there remain a number of opponents to a TRIPS Waiver – including the European Union, Germany, Japan, and Switzerland. This paper makes the case that international intellectual property law should accommodate a People’s Vaccine.
  🖺 Full Text HTML: The People’s Vaccine: Intellectual Property, Access to Essential Medicines, and the Coronavirus COVID-19
• Do Citizens Reward European Union Funding? Evidence from Three Local Studies -
  The European Union redistributes ever larger shares of its budget to enhance the economic performance of specific areas within its jurisdiction. However, there is little evidence of one of the most fundamental questions arising from this effort: Do citizens reward the European Union for funding that benefits their local environment? To answer this question, I leverage quasi-experimental data from an initiative that distributed vouchers to European municipalities to establish free and high-quality Wi-Fi connectivity before the European Parliament election in 2019.Moreover, I analyze geolocated data on beneficiaries of two major EuropeanUnion funds, European Parliament election results along with register data from polling stations, and a citywide survey experiment in Denmark. The results show that European place-based funding has little to no impact on turnout and Eurosceptic voting in European Parliament elections. The findings are discussed in light of the recently introduced EuropeanUnion recovery fund to combat economic downturn caused by the COVID-19 pandemic.
  🖺 Full Text HTML: Do Citizens Reward European Union Funding? Evidence from Three Local Studies
• North American Transportation During COVID-19: What Really Changed? -
  COVID-19 arrived in the United States and Canada at a time when the future of sustainable urban travel across the continent looked uncertain. A decade-long trend in transit ridership growth appeared to have stalled in many cities (Boisjoly et al., 2018), while automobile ownership grew. This chapter synthesizes unfolding evidence on how COVID-19 disrupted some of these existing trends in North American urban transportation while accelerating others. This synthesis is organized around three themes emerging from COVID-19 in the region: declining transit ridership, increased auto ownership or auto purchase plans, and a possible ‘new normal’ of increased telecommuting. I evaluate each theme in the context of prior trends and public policy choices feeding those trends. Untangling hype from data, the chapter concludes with recommendations on how to support travelers in the region while calling for clearer thinking from urban thought leaders and researchers on the likely long-term impact of the crisis.
  🖺 Full Text HTML: North American Transportation During COVID-19: What Really Changed?
• Social value at a distance: Higher identification with all of humanity is associated with reduced social discounting -
  How much we value the welfare of others has critical implications for the collective good. Yet, it is unclear what leads people to make more or less equal decisions about the welfare of those from whom they are socially distant. The current research sought to explore the psychological mechanisms that might underlie welfare judgments across social distance. Here, a social discounting paradigm was used to measure the tendency for the value of a reward to be discounted as the social distance of its recipient increased. Across two cohorts (one discovery, one replication), we found that a more expansive identity with all of humanity was associated with reduced social discounting. Additionally, we investigated the specificity of this association by examining whether this relationship extended to delay discounting, the tendency for the value of a reward to be discounted as the temporal distance to its receipt increases. Our findings suggest that the observed association with identity was unique to social discounting, thus underscoring a distinction in value-based decision-making processes across distances in time and across social networks. As data were collected during the COVID-19 pandemic, we also considered how stress associated with this global threat might influence welfare judgements across social distances. We found that, even after controlling for COVID-19 related stress, correlations between identity and social discounting held. Together these findings elucidate the psychological processes that are associated with a more equal distribution of generosity.
  🖺 Full Text HTML: Social value at a distance: Higher identification with all of humanity is associated with reduced social discounting
• Structural basis of nirmatrelvir and ensitrelvir resistance profiles against SARS-CoV-2 Main Protease naturally occurring polymorphisms -
  SARS-CoV-2 is the causative agent of COVID-19. Mpro is the main viral protease, with a critical role in replication and, therefore, an attractive target for antiviral drug discovery. The clinically approved drug nirmatrelvir from Pfizer, and the clinical candidate ensitrelvir from Shionogi Pharmaceuticals had so far showed great potential for treatment of viral infections. Despite the importance of new therapeutics, the broad use of antivirals is often associated with mutation selection and resistance generation. Herein, we characterized 14 naturally occurring polymorphisms that are already in circulation and are within the radius of action of these two antivirals. Nirmatrelvir retained most of its in vitro activity against most polymorphism tested, while mutants G143S and Q189K were associated with higher resistance. For ensitrelvir, higher resistance was observed for polymorphisms M49I, G143S and R188S, but not for Q189K, suggesting a distinct resistance profile difference between the two inhibitors. The crystal structures of selected polymorphism reveal the structural basis for resistance generation. Our data will assist the monitoring of potential resistant strains, support the design of combined therapy to avoid resistance, as well as assist the development of a next generation of Mpro inhibitors.
  🖺 Full Text HTML: Structural basis of nirmatrelvir and ensitrelvir resistance profiles against SARS-CoV-2 Main Protease naturally occurring polymorphisms
• Impact of COVID-19 and Effects of Vaccination with BNT162b2 on Patient-Reported Health-Related Quality of Life, Symptoms, and Work Productivity Among US Adult Outpatients with SARS-CoV-2 -

  Background: Although there is extensive literature on the clinical benefits of COVID-19 vaccination, data on humanistic effects are limited. This study evaluated the impact of SARS-CoV-2 infection on symptoms, Health Related Quality of Life (HRQoL) and Work Productivity and Impairment (WPAI) prior to and one month following infection, and compared results between individuals vaccinated with BNT162b2 and those unvaccinated. Methods: Subjects with ≥1 self-reported symptom and positive RT-PCR for SARS-CoV-2 at CVS Health US test sites were recruited between 01/31/2022-04/30/2022. Socio-demographics, clinical characteristics and vaccination status were evaluated. Self-reported symptoms, HRQoL, and WPAI outcomes were assessed using questionnaires and validated instruments (EQ-5D-5L, WPAI-GH) across acute COVID time points from pre-COVID to Week 4, and between vaccination groups. Mixed models for repeated measures were conducted for multivariable analyses, adjusting for several covariates. Effect size (ES) of Cohen9s d was calculated to quantify the magnitude of outcome changes within and between vaccination groups. Results: The study population included 430 subjects: 197 unvaccinated and 233 vaccinated with BNT162b2. Mean (SD) age was 42.4 years (14.3), 76.0% were female, 38.8% reported prior infection and 24.2% at least one comorbidity. Statistically significant differences in outcomes were observed compared with baseline and between groups. The EQ-Visual analogue scale scores and Utility Index dropped in both cohorts at Day 3 and increased by Week 4, but did not return to pre-COVID levels. The mean changes were statistically lower in the BNT162b2 cohort at Day 3 and Week 4. The BNT162b2 cohort reported lower prevalence and fewer symptoms at index date and Week 4. At Week 1, COVID-19 had a large impact on all WPAI-GH domains: the work productivity time loss among unvaccinated and vaccinated was 65.0% and 53.8%, and the mean activity impairment was 50.2% and 43.9%, respectively. With the exception of absenteeism at Week 4, the BNT162b2 cohort was associated with statistically significant less worsening in all WPAI-GH scores at both Week 1 and 4. Conclusions: COVID-19 negatively impacted HRQoL and work productivity among mildly symptomatic outpatients. Compared with unvaccinated, those vaccinated with BNT162b2 were less impacted by COVID-19 infection and recovered faster.

  🖺 Full Text HTML: Impact of COVID-19 and Effects of Vaccination with BNT162b2 on Patient-Reported Health-Related Quality of Life, Symptoms, and Work Productivity Among US Adult Outpatients with SARS-CoV-2
• COVID-19 individual participant data meta-analyses. Can there be too many? Results from a rapid systematic review -

  Background Individual participant data meta-analyses (IPD-MAs), which include harmonising and analysing participant-level data from related studies, provide several advantages over aggregate data meta-analyses, which pool study-level findings. IPD-MAs are especially important for building and evaluating diagnostic and prognostic models, making them an important tool for informing the research and public health responses to COVID-19. Methods We conducted a rapid systematic review of protocols and publications from planned, ongoing, or completed COVID-19-related IPD-MAs to identify areas of overlap and maximise data request and harmonisation efforts. We searched four databases using a combination of text and MeSH terms. Two independent reviewers determined eligibility at the title-abstract and full-text stage. Data were extracted by one reviewer into a pretested data extraction form and subsequently reviewed by a second reviewer. Data were analysed using a narrative synthesis approach. A formal risk of bias assessment was not conducted. Results We identified 31 COVID-19-related IPD-MAs, including five living IPD-MAs and ten IPD-MAs that limited their inference to published data (e.g., case reports). We found overlap in study designs, populations, exposures, and outcomes of interest. For example, 26 IPD-MAs included RCTs; 17 IPD-MAs were limited to hospitalised patients. Sixteen IPD-MAs focused on evaluating medical treatments, including six IPD-MAs for antivirals, four on antibodies, and two that evaluated convalescent plasma. Conclusions Collaboration across related IPD-MAs can leverage limited resources and expertise by expediting the creation of cross-study participant-level data datasets, which can, in turn, fast-track evidence synthesis for the improved diagnosis and treatment of COVID-19.

  🖺 Full Text HTML: COVID-19 individual participant data meta-analyses. Can there be too many? Results from a rapid systematic review
• A Novel Dry-Stabilized Whole Blood Microsampling and Protein Extraction Method for Testing of SARS-CoV-2 Antibody Titers -

  The COVID-19 pandemic has revealed a crucial need for rapid, straightforward collection and testing of biological samples. Serological antibody assays can analyze patient blood samples to confirm immune response following mRNA vaccine administration or to verify past exposure to the SARS-CoV-2 virus. While blood tests provide vital information for clinical analysis and epidemiology, sample collection is not uncomplicated. This process requires a visit to the doctors office, a professionally trained phlebotomist to draw several milliliters of blood, processing to yield plasma or serum, and necessitates appropriate cold chain storage to preserve the specimen. The Covaris truCOLLECT Whole Blood Collection Kit allows for a lancet-based, decentralized capillary blood collection of exactly metered low volumes and eliminates the need for refrigerated transport and storage through the process of active desiccation. Anti-SARS CoV-2 spike and nucleocapsid protein antibody titers in plasma samples collected via venipuncture were compared to antibody titers in whole blood extracts obtained by treating desiccated whole blood samples stored in truCOLLECT sampling devices with Covaris Adaptive-focused Acoustics (AFA). Pearson correlation coefficients of 0.98, 95% CI [0.96, 0.99] for anti-SARS-CoV spike protein antibodies and 0.97, 95% CI [0.94, 0.99] for anti-SARS-CoV-2 nucleocapsid protein antibodies were observed. These data suggest that serology testing using desiccated whole blood samples collected and stored in truCOLLECT devices can be a convenient and cost-effective alternative to conventionally collected plasma.

  🖺 Full Text HTML: A Novel Dry-Stabilized Whole Blood Microsampling and Protein Extraction Method for Testing of SARS-CoV-2 Antibody Titers
• User Engagement with COVID-19 Visualizations on Twitter -
  Data visualizations have been a key component of online discourse during the COVID-19 pandemic. However, research on how they affect public engagement is scarce. Understanding this would aid creating of visualizations that maximize engagements by public officials and visualization specialists. In this paper, we analyze tweets from a sample of medical experts to investigate how they use data visualizations to convey information about COVID-19 on Twitter. By comparing tweets with and without visualizations, as well as the effects of using particular visualization types, we hope to quantify the impact of visualizations on audience engagement. We learn that only 4.025% of the tweets from the chosen sample of users included visualizations, and they experienced lower engagement when doing so. Although the line charts were the most commonly used, the authors used different types of visualizations to communicate different aspects of the pandemic.
  🖺 Full Text HTML: User Engagement with COVID-19 Visualizations on Twitter
• Effectiveness of the COVID-19 vaccines against severe disease with Omicron sub-lineages BA.4 and BA.5 in England -

  The Omicron sub-lineages BA.4 and BA.5 were first detected in England in April 2022. A case surge followed despite England having recently experienced waves with BA.1 and BA.2. This study used a whole population test-negative case-control study design to estimate the effectiveness of the vaccines currently in use as part of the UK COVID-19 vaccination programme against hospitalisation following infection with BA.4 and BA.5 as compared to BA.2 during a period of co-circulation. Incremental VE was estimated in those vaccinated with either a third or fourth dose as compared to individuals with waned immunity who had received their second dose at least 25 weeks prior. Vaccination status was included as an independent variable and effectiveness was defined as 1-odds of vaccination in cases/odds of vaccination in controls. During the study period, there were 32,845 eligible tests from hospitalised individuals. Of these, 25,862 were negative (controls), 3,432 were BA.2, 273 were BA.4, 947 were BA.5 and 2,331 were either BA.4 or BA.5 cases. There was no evidence of reduced VE against hospitalisation for BA.4 or BA.5 as compared to BA.2. The incremental VE was 56.8% (95% C.I.; 24.0-75.4%), 59.9% (95% C.I.; 45.6-70.5%) and 52.4% (95% C.I.; 43.2-60.1%) for BA.4, BA.5 and BA.2, respectively, at 2 to 14 weeks after a third or fourth dose. VE against hospitalisation with BA.4/5 or BA.2 was slightly higher for the mRNA-1273 booster than the BNT162b2 booster at all time-points investigated, but confidence intervals overlapped. These data provide reassuring evidence of the protection conferred by the current vaccines against severe disease with BA.4 and BA.5.

  🖺 Full Text HTML: Effectiveness of the COVID-19 vaccines against severe disease with Omicron sub-lineages BA.4 and BA.5 in England
• Periodic epidemic outbursts explained by local saturation of clusters -

  Adding the notion of spatial locality to the susceptible-infected-removed (or SIR) model, allows to capture local saturation of an epidemic. The resulting minimum model of an epidemic, consisting of five ordinar y differential equations with constant model coefficients, reproduces slowly decaying periodic outbursts, as observed in the COVID-19 or Spanish flu epidemic. It is shown that if immunity decays, even slowly, the model yields a fully periodic dynamics.

  🖺 Full Text HTML: Periodic epidemic outbursts explained by local saturation of clusters
• A Novel Dry-Stabilized Whole Blood Microsampling and Protein Extraction Method for Testing of SARS-CoV-2 Antibody Titers -

  The COVID-19 pandemic has revealed a crucial need for rapid, straightforward collection and testing of biological samples. Serological antibody assays can analyze patient blood samples to confirm immune response following mRNA vaccine administration or to verify past exposure to the SARS-CoV-2 virus. While blood tests provide vital information for clinical analysis and epidemiology, sample collection is not uncomplicated. This process requires a visit to the doctors office, a professionally trained phlebotomist to draw several milliliters of blood, processing to yield plasma or serum, and necessitates appropriate cold chain storage to preserve the specimen. The Covaris truCOLLECT Whole Blood Collection Kit allows for a lancet-based, decentralized capillary blood collection of exactly metered low volumes and eliminates the need for refrigerated transport and storage through the process of active desiccation. Anti-SARS CoV-2 spike and nucleocapsid protein antibody titers in plasma samples collected via venipuncture were compared to antibody titers in whole blood extracts obtained by treating desiccated whole blood samples stored in truCOLLECT sampling devices with Covaris Adaptive-focused Acoustics (AFA). Pearson correlation coefficients of 0.98, 95% CI [0.96, 0.99] for anti-SARS-CoV spike protein antibodies and 0.97, 95% CI [0.94, 0.99] for anti-SARS-CoV-2 nucleocapsid protein antibodies were observed. These data suggest that serology testing using desiccated whole blood samples collected and stored in truCOLLECT devices can be a convenient and cost-effective alternative to conventionally collected plasma.

  🖺 Full Text HTML: A Novel Dry-Stabilized Whole Blood Microsampling and Protein Extraction Method for Testing of SARS-CoV-2 Antibody Titers
• Heterogeneity in vaccinal immunity to SARS-CoV-2 can be addressed by a personalized booster strategy -

  The ongoing COVID-19 pandemic has placed an unprecedented burden on global health. Crucial for managing this burden, the existing SARS-CoV-2 vaccines have substantially reduced the risk of severe disease and death up to this point. The induction of neutralizing antibodies (nAbs) by these vaccines leads to protection against both infection and severe disease. However, pharmacokinetic (PK) waning and rapid viral evolution degrade neutralizing antibody binding titers, leading to a rapid loss of vaccinal protection against infection occurring on the order of months after vaccination. Additionally, inter-individual heterogeneity in the strength and durability of the vaccine-induced neutralizing response to SARS-CoV-2 can create a further public-health risk by placing a subset of the population at risk. Here we incorporate the heterogeneity in inter-individual response into a pharmacokinetic/ pharmacodynamic (PK/PD) model to project the degree of heterogeneity in immune protection. We extend our model-based approach to examine the impact of evolutionary immune evasion on vaccinal protection. Our findings suggest that viral evolution can be expected to impact the effectiveness of vaccinal protection against severe disease, particularly for individuals with a shorter duration of immune response. One possible solution to immune heterogeneity may be more frequent boosting for individuals with a weaker immune response. We demonstrate a model-based approach to targeted boosting that involves the use of the ECLIA RBD assay to identify individuals whose immune response is insufficient for protection against severe disease. Our work suggests that vaccinal protection against severe disease is not assured and provides a path forward to reducing the risk to immunologically vulnerable individuals.

  🖺 Full Text HTML: Heterogeneity in vaccinal immunity to SARS-CoV-2 can be addressed by a personalized booster strategy
• Zero-COVID policy or Living-with-COVID policy? Analysis Based on Percent Excess Mortality -

  Background: Since the outbreak of the SARS-CoV-2 variant B.1.1.529 (Omicron) in late 2021, many countries adopted the living-with-COVID (LWC) policy instead of the zero-COVID (ZC) policy to restore pre-COVID-19 normalcy. However, given that the Omicron variant is much more contagious, whether the mortality burden under the LWC policy is tolerable to the society remains under debate. Methods: In this study, four countries (Singapore, South Korea, Australia, and New Zealand) that have shifted to the LWC policy and one region (Hong Kong) with a significant Omicron outbreak were selected as research objects. Percent excess mortality (PEM), which is the percentage of excess mortality over expected mortality, was selected to assess the effectiveness of different anti-pandemic policies in controlling the mortality burden within the same country/region during the pandemic. In addition, confirmed COVID cases, COVID-associated deaths, percent COVID-excess mortality, expected and observed mortality over time were collected or calculated for further comparisons. Results: In the examined four countries, PEM fluctuated around 0 and was lower than 10% most of the time under the ZC policy. After shifting to the LWC policy, PEM usually exceeded 10%, and countries with high population density experienced a peak PEM of 20-70%. New Zealand was the only country in our analysis that achieved approximately 10% average PEM during the Omicron outbreak under the LWC policy. Hong Kong, under a specialized ZC policy, attained a significant high PEM during the Omicron outbreak. Conclusion: Our analysis demonstrated that PEM was significantly higher during the LWC policy period than that during the ZC policy period. Thus, the precondition of the policy transition needs to be cautiously examined, and the current LWC policy should be revised to achieve a lower PEM.

  🖺 Full Text HTML: Zero-COVID policy or Living-with-COVID policy? Analysis Based on Percent Excess Mortality
• Effects of inbound attendees of a mass gathering event on the COVID-19 epidemic using individual-based simulations -

  Given that mass gathering events involve heterogeneous and time-varying contact between residents and visitors, we sought to identify possible measures to prevent the potential acceleration of the outbreak of an emerging infectious disease induced by such events. An individual-based simulator was built based on a description of the reproduction rate among people infected with the infectious disease in a hypothetical city. Three different scenarios were assessed using our simulator, in which controls aimed at reduced contact were assumed to be carried out only in the main event venue or at subsequent additional events, or in which behavior restrictions were carried out among the visitors to the main event. The simulation results indicated that the increase in the number of patients with COVID-19 could possibly be suppressed to a level equivalent to that if the event were not being held so long as the prevalence among visitors was only slightly higher than that among domestic residents and strict requirements were applied to the activities of visitors.

  🖺 Full Text HTML: Effects of inbound attendees of a mass gathering event on the COVID-19 epidemic using individual-based simulations

From Clinical Trials

• Booster Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition:   COVID-19
  Interventions:   Biological: SARS-CoV-2 subunit protein recombinant vaccine;   Biological: Active Comparator
  Sponsors:   PT Bio Farma;   Faculty of Medicine Universitas Padjadjaran;   Faculty of Medicine Universitas Udayana
  Recruiting

• A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine SCTV01E-1 in Population Aged Above 18 Years - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01E-1 on D0;   Biological: SCTV01E-1 on D28;   Biological: SCTV01E-1 on D150;   Biological: SCTV01E on D0;   Biological: SCTV01E on D28;   Biological: SCTV01E on D150;   Biological: SCTV01E-1 on D120;   Biological: SCTV01E on D120
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• The Role of BCG Vaccine in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 Vaccines - Condition:   COVID-19
  Interventions:   Biological: BCG (Bacillus Calmette-Guérin) vaccine;   Other: Placebo
  Sponsors:   Oswaldo Cruz Foundation;   University of Sao Paulo;   Federal University of Juiz de Fora
  Recruiting

• A Novel Parameter LIT/N That Predicts Survival in COVID-19 ICU Patients - Condition:   COVID-19 Pneumonia
  Intervention:   Diagnostic Test: the LIT test
  Sponsors:   Gazi University;   Oxford MediStress
  Completed

• Efficacy and Safety of ES16001 in Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: ES16001 40 mg;   Drug: ES16001 80 mg;   Drug: ES16001 160 mg;   Drug: Placebo
  Sponsor:   Genencell Co. Ltd.
  Recruiting

• Phase 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults. - Condition:   COVID-19
  Intervention:   Drug: Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine, SARS-CoV-2 rS (CovovaxTM), BNT162b2 (Pfizer)
  Sponsors:   The Aurum Institute NPC;   Coalition for Epidemic Preparedness Innovations
  Recruiting

• UNAIR Inactivated COVID-19 Vaccine Phase III (Immunobridging Study) - Conditions:   COVID-19 Pandemic;   COVID-19 Vaccines
  Interventions:   Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg;   Biological: CoronaVac Biofarma COVID-19 Vaccine
  Sponsors:   Dr. Soetomo General Hospital;   Indonesia-MoH;   Universitas Airlangga;   Biotis Pharmaceuticals, Indonesia
  Recruiting

• COVID Protection After Transplant - Sanofi GSK (CPAT-SG) Study - Conditions:   COVID-19;   Kidney Transplant
  Intervention:   Biological: Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   PPD;   Johns Hopkins University;   Sanofi Pasteur, a Sanofi Company
  Not yet recruiting

• Safety and Immunogenicity of COVID-19 Vaccine, AdCLD-CoV19-1 - Conditions:   COVID-19;   Vaccines
  Intervention:   Biological: AdCLD-CoV19-1
  Sponsors:   International Vaccine Institute;   Cellid Co., Ltd.
  Not yet recruiting

• Clinical Trial of Jinzhen Oral Liquid in Treating Children With COVID-19 Infection - Conditions:   COVID-19;   Child, Only
  Intervention:   Drug: Jinzhen oral liquid or Jinhuaqinggan granules
  Sponsor:   The Affiliated Hospital of Qingdao University
  Recruiting

• Smartphone Intervention for Overdose and COVID-19 - Conditions:   Substance Use Disorders;   Overdose;   COVID-19
  Intervention:   Device: iThrive WI Intervention
  Sponsors:   University of Wisconsin, Madison;   National Institute on Drug Abuse (NIDA)
  Not yet recruiting

• Phase 2 Study of the Safety and Immunogenicity of COVID-19 and Influenza Combination Vaccine - Conditions:   COVID-19;   Influenza
  Interventions:   Drug: CIC Vaccine;   Drug: qNIV Vaccine;   Drug: SARS-CoV-2 rS Vaccine;   Drug: Influenza Vaccine
  Sponsor:   Novavax
  Not yet recruiting

• Study to Assess Efficacy and Safety of Treamid for Patients With Reduced Exercise Tolerance After COVID-19 - Conditions:   SARS-CoV-2 Infection;   Lung Fibrosis
  Interventions:   Drug: Treamid;   Drug: Treamid twice a day;   Drug: Treamid once a day;   Drug: Placebo
  Sponsor:   PHARMENTERPRISES LLC
  Not yet recruiting

• Self-proning and Repositioning in COVID-19 Outpatients at Risk of Complicated Illness - Conditions:   COVID-19;   COVID-19 Pneumonia;   Proning;   Hospitalization;   Death;   Outpatient;   Complication
  Intervention:   Other: Self-proning
  Sponsors:   Unity Health Toronto;   Applied Health Research Centre
  Recruiting

• Effects of Immulina TM Supplements With PASC Patients - Condition:   Post Acute COVID-19 Syndrome
  Interventions:   Dietary Supplement: Immulina TM;   Dietary Supplement: Placebo
  Sponsors:   University of Mississippi Medical Center;   National Institute of General Medical Sciences (NIGMS)
  Not yet recruiting

From PubMed

• Eugenol alleviates transmissible gastroenteritis virus-induced intestinal epithelial injury by regulating NF-κB signaling pathway - Increasing evidence supports the ability of eugenol to maintain intestinal barrier integrity and anti-inflammatory in vitro and in vivo; however, whether eugenol alleviates virus-mediated intestinal barrier damage and inflammation remains a mystery. Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Here, we found that eugenol could alleviate TGEV-induced intestinal functional…

• Blood-brain Barrier Damage is Pivotal for SARS-CoV-2 Infection to the Central Nervous System - Transsynaptic transport is the most accepted proposal to explain the SARS-CoV-2 infection of the CNS. Nevertheless, emerging evidence shows that neurons do not express the SARS-CoV-2 receptor ACE2, which highlights the importance of the blood-brain barrier (BBB) in preventing virus entry to the brain. In this study, we examine the presence of SARS-CoV-2 messenger ribonucleic acid (mRNA) and the cytokine profile in cerebrospinal fluids (CSF) from two patients with a brain tumor and COVID-19. To…

• Insights into functional connectivity in mammalian signal transduction pathways by pairwise comparison of protein interaction partners of critical signaling hubs - Growth factors and cytokines activate signal transduction pathways and regulate gene expression in eukaryotes. Intracellular domains of activated receptors recruit several protein kinases as well as transcription factors that serve as platforms or hubs for the assembly of multi-protein complexes. The signaling hubs involved in a related biologic function often share common interaction proteins and target genes. This functional connectivity suggests that a pairwise comparison of protein…

• Molecular Docking Study of Several Seconder Metabolites from Medicinal Plants as Potential Inhibitors of COVID-19 Main Protease - CONCLUSION: Our results obtained from docking studies suggest that pycnamine should be examined in vitro to combat 2019-CoV. Moreover, pycnamine might be a promising lead compound for anti-CoV drugs.

• Withania somnifera (L.) Dunal (Ashwagandha) for the possible therapeutics and clinical management of SARS-CoV-2 infection: Plant-based drug discovery and targeted therapy - Coronavirus disease 2019 (COVID-19) pandemic has killed huge populations throughout the world and acts as a high-risk factor for elderly and young immune-suppressed patients. There is a critical need to build up secure, reliable, and efficient drugs against to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Bioactive compounds of Ashwagandha [Withania somnifera (L.) Dunal] may implicate as herbal medicine for the management and treatment of patients infected…

• Antibodies against the SARS-CoV-2 S1-RBD cross-react with dengue virus and hinder dengue pathogenesis - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally since December 2019. Several studies reported that SARS-CoV-2 infections may produce false-positive reactions in dengue virus (DENV) serology tests and vice versa. However, it remains unclear whether SARS-CoV-2 and DENV cross-reactive antibodies provide cross-protection against each disease or promote disease severity. In this study, we confirmed that antibodies against the SARS-CoV-2 spike protein and its…

• Promising Marine Natural Products for Tackling Viral Outbreaks: A Focus on Possible Targets and Structure-Activity Relationship - Recently, people worldwide have experienced several outbreaks caused by viruses that have attracted much interest globally, such as HIV, Zika, Ebola, and the one being faced, SARSCoV-2 viruses. Unfortunately, the availability of drugs giving satisfying outcomes in curing those diseases is limited. Therefore, it is necessary to dig deeper to provide compounds that can tackle the causative viruses. Meanwhile, the efforts to explore marine natural products have been gaining great interest as the…

• Structural Insights into Binding of Remdesivir Triphosphate within the Replication-Transcription Complex of SARS-CoV-2 - Remdesivir is an adenosine analogue that has a cyano substitution in the C1’ position of the ribosyl moiety and a modified base structure to stabilize the linkage of the base to the C1’ atom with its strong electron-withdrawing cyano group. Within the replication-transcription complex (RTC) of SARS-CoV-2, the RNA-dependent RNA polymerase nsp12 selects remdesivir monophosphate (RMP) over adenosine monophosphate (AMP) for nucleotide incorporation but noticeably slows primer extension after the…

• The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial - CONCLUSIONS: The primary end point did not reach statistical significance, indicating that there was no difference between Aviptadil versus placebo. However, Aviptadil improves the likelihood of survival from respiratory failure at day 60 in critical COVID-19 across all sites of care. Given the absence of drug-related serious adverse events and acceptable safety profile, we believe the benefit versus risk for the use of Aviptadil is favorable for patient treatment.

• Pirfenidone and post-Covid-19 pulmonary fibrosis: invoked again for realistic goals - Pirfenidone (PFN) is an anti-fibrotic drug with significant anti-inflammatory property used for treatment of fibrotic conditions such as idiopathic pulmonary fibrosis (IPF). In the coronavirus disease 2019 (Covid-19) era, severe acute respiratory syndrome 2 (SARS-CoV-2) could initially lead to acute lung injury (ALI) and in severe cases may cause acute respiratory distress syndrome (ARDS) which is usually resolved with normal lung function. However, some cases of ALI and ARDS are progressed to…

• S2 Subunit of SARS-CoV-2 Spike Protein Induces Domain Fusion in Natural Pulmonary Surfactant Monolayers - Pulmonary surfactant has been attempted as a supportive therapy to treat COVID-19. Although it is mechanistically accepted that the fusion peptide in the S2 subunit of the S protein plays a predominant role in mediating viral fusion with the host cell membrane, it is still unknown how the S2 subunit interacts with the natural surfactant film. Using combined bio-physicochemical assays and atomic force microscopy imaging, it was found that the S2 subunit inhibited the biophysical properties of the…

• Synthesis, Molecular Docking, c-Met inhibitions of 2,2,2-Trichloro-ethylidene-cyclohexane-1,3-dione Derivatives Together With Their Application as Target SARS-CoV-2 main Protease (Mpro) And as Potential Anti-Covid-19 - CONCLUSION: The results showed that compounds 10a, 10b, 10c, 10e, 10f, 10g and 10h showed high % inhibitions against SARs-Covnsp 14. Whereas, compounds 5a, 7a, 8b, 10a, 10b, 10c and 10i showed high inhibitions against hRNMT. This study explored the binding affinity of twenty two halogenated compounds to the SARS-CoV-2 MPro and discovered fifteen compounds with higher binding affinity than Nelfinavir, of which three showed remarkable results. c-Met kinase inhibitions of 10a, 10f, 10g and 10h…

• Cannabinoids receptors in Covid-19: Perpetrators and victims - COVID-19 is caused by SARS-CoV-2 and leads to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and extrapulmonary manifestations in severely affected cases. However, most of the affected cases are mild or asymptomatic. Cannabinoids (CBs) such as tetrahydrocannabinol (THC) and cannabidiol (CBD), which act on G-protein-coupled receptors called CB1 and CB2, have anti-inflammatory effects. Many published studies show that CBs are effective in various inflammatory disorders, viral…

• Homologous and Heterologous Boosting of the Chadox1-S1-S COVID-19 Vaccine With the SCB-2019 Vaccine Candidate: A Randomized, Controlled, Phase 2 Study - CONCLUSIONS: Boosting ChAdOx1-S-primed adults with SCB-2019 induced higher levels of antibodies against a wild-type strain and SARS-CoV-2 variants than a homologous ChAdOx1-S booster, with the highest responses being with the 30-μg SCB-2019 + CpG + aluminium hydroxide formulation.

• 5-HT/CGRP pathway and Sumatriptan role in Covid-19 - Coronavirus disease 2019 (Covid-19) is a pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In Covid-19, there is uncontrolled activation of immune cells with a massive release of pro-inflammatory cytokines and the development of cytokine storm. These inflammatory changes induce impairment of different organ functions, including the central nervous system (CNS), leading to acute brain injury and substantial changes in the neurotransmitters, including serotonin…

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