Covid-19 Sentry

Contents

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

From Preprints

• Impact of News Related to Covid-19 on Stock Market Returns in Five Major ASEAN Countries -
  The sudden tightening of global finances, unprecedented and dominating news of how negative COVID-19 is has affected the global monetary, and how pessimistic the public sentiment towards the COVID-19 virus pandemic is itself has caused uncertainty in the stock market. The purpose of this study is to analyze the relationship between COVID-19-related news and stock market returns. RavenPack Coronavirus Media Monitor was used to explain important news issues related to COVID-19 with news indices such as panic, media hype, fake news, country sentiment, infodemic, and media coverage. With the quantile regression analysis technique, the results of the study were divided into three research periods. For the research period of January 2020 to March 2020, it was found that the variables that affect stock market returns are media hype, fake news, country sentiment and infodemic index; for the research period of April 2020 to December 2020, it was found that the variables that affect stock market returns are panic, fake news and country sentiment index; while for the period January 2020 to December 2020 the variables that affect stock market returns are panic, fake news, country sentiment and infodemic index.
  🖺 Full Text HTML: Impact of News Related to Covid-19 on Stock Market Returns in Five Major ASEAN Countries
• SARS-CoV-2 and its variants, but not Omicron, induces thymic atrophy and impaired T cell development -
  Pathogenic infections cause thymic atrophy, perturb thymic-T cell development and alter immunological response. Previous studies reported dysregulated T cell function and lymphopenia in coronavirus disease-19 (COVID-19) patients. However, immune-pathological changes, in the thymus, post severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have not been elucidated. Here, we report SARS-CoV-2 infects thymocytes, depletes CD4+CD8+ (double positive DP) T cell population associated with an increased apoptosis of thymocytes, which leads to severe thymic atrophy in K18-hACE2-Tg mice. CD44+CD25- T cells were found to be enriched in infected thymus, indicating an early arrest in the T cell developmental pathway. Further, Interferon gamma was crucial for thymic atrophy, as anti- IFN{gamma}; antibody neutralization rescued the loss of thymic involution. Therapeutic use of remdesivir (prototype anti-viral drug) was also able to rescue thymic atrophy. While Omicron variant of SARS-CoV2 caused marginal thymic atrophy, delta variant of SARS-CoV-2 exhibited most profound thymic atrophy characterized by severely depleted DP T cells. Recently characterized broadly SARS-CoV-2 neutralizing monoclonal antibody P4A2 was able to rescue thymic atrophy and restore thymic developmental pathway of T cells. Together, we provide the first report of SARS-CoV-2 associated thymic atrophy resulting from impaired T cell developmental pathway and also explains dysregulated T cell function in COVID-19.
  🖺 Full Text HTML: SARS-CoV-2 and its variants, but not Omicron, induces thymic atrophy and impaired T cell development
• SARS-CoV-2 mutations affect proteasome processing to alter CD8+ T cell responses -
  Viral CD8+ epitopes are generated by the cellular turnover of viral proteins, predominantly by the proteasome. Mutations located within viral epitopes can result in escape from memory T cells but the contribution of mutations in flanking regions of epitopes in SARS-CoV-2 has not been investigated. Focusing on two of the most dominant SARS-CoV-2 nucleoprotein CD8+ epitopes, we identified mutations in epitope flanking regions and investigated the contribution of these mutations to antigen processing and T cell activation using SARS-CoV-2 nucleoprotein transduced B cell lines and in vitro proteasomal processing of peptides. We found that decreased NP9-17-B27:05 CD8+ T cell responses to the NP-Q7K mutation correlated with lower epitope surface expression, likely due to a lack of efficient epitope production by the proteasome, suggesting immune escape caused by this mutation. In contrast, NP-P6L and NP-D103N/Y mutations flanking the NP9-17-B27:05 and NP105-113-B*07:02 epitopes, respectively, increased CD8+ T cell responses associated with enhanced epitope production by the proteasome. Our results provide evidence that SARS-CoV-2 mutations outside the epitope could have a significant impact on antigen processing and presentation, thereby contributing to escape from immunodominant T cell responses. Alternatively, mutations could enhance antigen processing and efficacy of T cell recognition, opening new avenues for improving future vaccine designs.
  🖺 Full Text HTML: SARS-CoV-2 mutations affect proteasome processing to alter CD8+ T cell responses
• Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike -
  The BA.2 lineage of the SARS-CoV-2 Omicron variant has gained in proportion relative to BA.1. As differences in their spike (S) proteins may underlie differences in their pathobiology, here we determined cryo-EM structures of a BA.2 S protein ectodomain and compared these to previously determined BA.1 S structures. BA.2 Receptor Binding Domain (RBD) mutations induced remodeling of the internal RBD structure resulting in its improved thermostability and tighter packing within the 3-RBD-down spike. In the S2 subunit, the fusion peptide in the BA.2 was less accessible to antibodies than in BA.1. Pseudovirus neutralization and spike binding assays revealed extensive immune evasion while defining epitopes of two RBD-directed antibodies, DH1044 and DH1193, that bound the outer RBD face to neutralize both BA.1 and BA.2. Taken together, our results indicate that stabilization of the 3-RBD-down state through interprotomer RBD-RBD packing is a hallmark of the Omicron lineages, and reveal differences in key functional regions in the BA.1 and BA.2 S proteins.
  🖺 Full Text HTML: Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike
• The Delta variant SARS-CoV-2 spike protein uniquely promotes aggregation of pseudotyped viral particles -
  Individuals infected with the SARS-CoV-2 Delta variant, lineage B.1.617.2, exhibit faster initial infection with a higher viral load than prior variants, and pseudotyped particles bearing the SARS-CoV-2 Delta variant spike protein induce a faster initial infection rate of target cells compared to those bearing other SARS-CoV-2 variant spikes. Here, we show that pseudotyped particles bearing the Delta variant spike form unique aggregates, as evidenced by negative stain and cryogenic electron microscopy (EM), flow cytometry, and nanoparticle tracking analysis. Viral particles pseudotyped with other SARS-CoV-2 spike variants do not show aggregation by any of these criteria. The contribution to infection kinetics of the Delta spike’s unique property to aggregate is discussed with respect to recent evidence for collective infection by other viruses. Irrespective of this intriguing possibility, spike-dependent aggregation is a new functional parameter of spike-expressing viral particles to evaluate in future spike protein variants.
  🖺 Full Text HTML: The Delta variant SARS-CoV-2 spike protein uniquely promotes aggregation of pseudotyped viral particles
• Hippo Signaling Pathway Activation during SARS-CoV-2 Infection Contributes to Host Antiviral Response -
  SARS-CoV-2, responsible for the COVID-19 pandemic, causes respiratory failure and damage to multiple organ systems. The emergence of viral variants poses a risk of vaccine failures and prolongation of the pandemic. However, our understanding of the molecular basis of SARS-CoV-2 infection and subsequent COVID-19 pathophysiology is limited. In this study, we have uncovered a critical role for the evolutionarily conserved Hippo signaling pathway in COVID-19 pathogenesis. Given the complexity of COVID-19 associated cell injury and immunopathogenesis processes, we investigated Hippo pathway dynamics in SARS-CoV-2 infection by utilizing COVID-19 lung samples, and human cell models based on pluripotent stem cell-derived cardiomyocytes (PSC-CMs) and human primary lung air-liquid interface (ALI) cultures. SARS- CoV-2 infection caused activation of the Hippo signaling pathway in COVID-19 lung and in vitro cultures. Both parental and Delta variant of concern (VOC) strains induced Hippo pathway. The chemical inhibition and gene knockdown of upstream kinases MST1/2 and LATS1 resulted in significantly enhanced SARS-CoV-2 replication, indicating antiviral roles. Verteporfin a pharmacological inhibitor of the Hippo pathway downstream transactivator, YAP, significantly reduced virus replication. These results delineate a direct antiviral role for Hippo signaling in SARS-CoV-2 infection and the potential for this pathway to be pharmacologically targeted to treat COVID-19.
  🖺 Full Text HTML: Hippo Signaling Pathway Activation during SARS-CoV-2 Infection Contributes to Host Antiviral Response
• Plant-produced RBD and cocktail-based vaccine candidates are highly effective against SARS-CoV-2, independently of its emerging variants -
  SARS-CoV-2 is a novel and highly pathogenic coronavirus, which has caused an outbreak in Wuhan City, China, in 2019 and then spread rapidly throughout the world. Although several COVID-19 vaccines are currently available for mass immunization, they are less effective against emerging SARS-CoV-2 variants, especially the Omicron (B.1.1.529). Recently, we successfully produced receptor-binding domain (RBD) variants of spike (S) protein of SARC-CoV-2 and an antigen cocktail in Nicotiana benthamiana, which are highly produced in plants and elicited high-titer antibodies with potent neutralizing activity against SARS-CoV-2. In this study, we demonstrate that these protein-based vaccine candidates are highly effective against Delta and Omicron variants. These data support that plant produced RBD and cocktail-based antigens are most promising vaccine candidates and may protect against Delta and Omicron-mediated COVID-19. Based on the neutralization ability, plant produced RBD and cocktail-based vaccine candidates are highly effective against SARS-CoV-2, independently of its emerging variants.
  🖺 Full Text HTML: Plant- produced RBD and cocktail-based vaccine candidates are highly effective against SARS-CoV-2, independently of its emerging variants
• CHANGES IN LIFE EXPECTANCY BETWEEN 2019 AND 2021: UNITED STATES AND 19 PEER COUNTRIES -

  BACKGROUND Prior studies reported large decreases in US life expectancy during 2020 as a result of the COVID-19 pandemic, disproportionately affecting Hispanic and Black populations and vastly exceeding the average change in life expectancy in other high-income countries. Life expectancy estimates for 2021 have not been reported. This study estimated changes in life expectancy during 2019-2021 in the US population, in three US racial/ethnic groups, and in 19 peer countries. METHODS US and peer country death data for 2019-2021 were obtained from the National Center for Health Statistics, the Human Mortality Database, and overseas statistical agencies. The 19 peer countries included Austria, Belgium, Denmark, England and Wales, Finland, France, Germany, Israel, Italy, Netherlands, New Zealand, Northern Ireland, Norway, Portugal, Scotland, South Korea, Spain, Sweden, and Switzerland. Life expectancy was calculated for 2019 and 2020 and estimated for 2021 using a previously validated modeling method. RESULTS US life expectancy decreased from 78.86 years in 2019 to 76.99 years in 2020 and 76.60 years in 2021, a net loss of 2.26 years. In contrast, peer countries averaged a smaller decrease in life expectancy between 2019 and 2020 (0.40 years) and a 0.28-year increase between 2020 and 2021, widening the gap in life expectancy between the United States and peer countries to more than five years. The decrease in US life expectancy was highly racialized: whereas the largest decreases in 2020 occurred among Hispanic and non-Hispanic Black populations, in 2021 only the non-Hispanic White population experienced a decrease in life expectancy. DISCUSSION The US mortality experience during 2020 and 2021 was more severe than in peer countries, deepening a US disadvantage in health and survival that has been building for decades. Over the two-year period between 2019 and 2021, US Hispanic and non-Hispanic Black populations experienced the largest losses in life expectancy, reflecting the legacy of systemic racism and inadequacies in the US handling of the pandemic. Reasons for the crossover in racialized outcomes between 2020 and 2021, in which life expectancy decreased only in the non-Hispanic White population, could have multiple explanations.

  🖺 Full Text HTML: CHANGES IN LIFE EXPECTANCY BETWEEN 2019 AND 2021: UNITED STATES AND 19 PEER COUNTRIES
• Immunity post-COVID-19 recovery boosts the antibody immune response to SARS-CoV-2 vaccination -

  Measurement of strength and durability of SARSCOV2 antibody response is important to understand the waning dynamics of immune response to both vaccines and infection. The study aimed to evaluate the level of IgG antibodies against SARSCoV2 and their persistence in recovered, naive and vaccinated individuals. We randomly investigate Antispike RBD IgG antibody responses in 10,000 individuals, both following infection with SARSCoV2 and immunization with SARSCOV2 adenoviral vector and killed vaccines. Overall, antibody titres in recovered vaccinated individuals and naive vaccinee persists beyond 20 weeks. The mean levels of antispike IgG antibodies were higher in vaccinated participants with prior COVID19 infections than in individuals without prior infection. Decline for IgG antibodies were faster in vaccinated individuals without previous COVID19 infection compared to those with previous COVID19 infection. Vaccination with adenoviral vector vaccines generates higher antibody titers than for killed virus vaccine. Slightly over half of asymptomatic unvaccinated individuals develops antibody response. Previous COVID19 infection elicited robust and sustained levels of SARSCoV2 antibodies in vaccinated individuals. A single dose of the vaccine is likely to provide greater protection against SARSCoV2 infection in individuals with prior SARSCoV2 infection, than in SARSCoV2 naive individuals. This study also underlines that asymptomatic infection equally generates antibodies as symptomatic infection. Those vaccinated with inactivated vaccine may require more frequent boosters than those vaccinated with an adenoviral vaccine. These findings are important for formulating public health vaccination strategies during COVID19 pandemic.

  🖺 Full Text HTML: Immunity post-COVID-19 recovery boosts the antibody immune response to SARS-CoV-2 vaccination
• Distinguishing Admissions Specifically for COVID-19 from Incidental SARS-CoV-2 Admissions: A National EHR Research Consortium Study -

  Background: Admissions are generally classified as COVID-19 hospitalizations if the patient has a positive SARS- CoV-2 polymerase chain reaction (PCR) test. However, because 35% of SARS-CoV-2 infections are asymptomatic, patients admitted for unrelated indications with an incidentally positive test could be misclassified as a COVID-19 hospitalization. EHR-based studies have been unable to distinguish between a hospitalization specifically for COVID-19 versus an incidental SARS-CoV-2 hospitalization. Although the need to improve classification of COVID-19 disease vs.  incidental SARS-CoV-2 is well understood, the magnitude of the problems has only been characterized in small, single- center studies. Furthermore, there have been no peer-reviewed studies evaluating methods for improving classification. Objective: The aims of this study were to: first, quantify the frequency of incidental hospitalizations over the first fifteen months of the pandemic in multiple hospital systems in the United States; and second, to apply electronic phenotyping techniques to automatically improve COVID-19 hospitalization classification. Methods: From a retrospective EHR-based cohort in four US healthcare systems in Massachusetts, Pennsylvania, and Illinois, a random sample of 1,123 SARS-CoV-2 PCR-positive patients hospitalized between 3/2020-8/2021 was manually chart-reviewed and classified as admitted-with-COVID-19 (incidental) vs. specifically admitted for COVID-19 (for-COVID-19). EHR-based phenotyping was used to find feature sets to filter out incidental admissions. Results: EHR-based phenotyped feature sets filtered out incidental admissions, which occurred in an average of 26% of hospitalizations (although this varied widely over time, from 0%-75%). The top site-specific feature sets had 79-99% specificity with 62-75% sensitivity, while the best performing across-site feature set had 71-94% specificity with 69-81% sensitivity. Conclusions: A large proportion of SARS-CoV-2 PCR-positive admissions were incidental. Straightforward EHR-based phenotypes differentiated admissions, which is important to assure accurate public health reporting and research.

  🖺 Full Text HTML: Distinguishing Admissions Specifically for COVID-19 from Incidental SARS-CoV-2 Admissions: A National EHR Research Consortium Study
• Impact of the COVID-19 pandemic on mental healthcare consultations among children and adolescents in Norway: a nationwide registry study -

  The COVID-19 pandemic and its associated restrictions may have affected children and adolescent`s mental health adversely. We cast light on this question using primary and specialist consultations data for the entire population of children 6-19 years in Norway (N=908 272). Our outcomes are the monthly likelihood of having a consultation or hospitalization related to mental health problems and common mental health diagnoses. We compared a pandemic (2019-2021) to a pre-pandemic (2017-2019) cohort using event study and difference-in-difference designs that separate the shock of the pandemic from linear period trends and seasonal variation. We found temporary reductions in all mental health consultations during lockdown in spring 2020. In fall 2020 and winter 2021, consultation volumes in primary care increased, stabilizing at a higher level in 2021. Consultations in specialist care increased from spring

2021. Our findings could suggest a worsening of mental health among adolescents.
      🖺 Full Text HTML: Impact of the COVID-19 pandemic on mental healthcare consultations among children and adolescents in Norway: a nationwide registry study

• Reports of myocarditis and pericarditis following mRNA COVID-19 vaccines: A systematic review of spontaneously reported data from the UK, Europe, and the US and of the literature -

  Objectives: To bring together spontaneously reported data from multiple countries to estimate reporting rate, and better understand risk factors for myocarditis and pericarditis following COVID-19 mRNA vaccines. Design: Systematic review of spontaneously reported data from United Kingdom (UK), United States (US), and European Union/European Economic Area (EU/EEA) and of the literature. Data sources: UK Yellow Card scheme, Vaccine Adverse Event Reporting System (VAERS), EudraVigilance were searched from date of vaccine launch to 14-16 March 2022. PubMed/MEDLINE and Embase were searched to 15 March 2022. Eligibility criteria: We included publicly available spontaneous reporting data for ″Myocarditis″ and ″Pericarditis″ from UK, US, and EU/EEA following COVID-19 mRNA vaccines. Pharmacoepidemiological observational studies investigating myocarditis/pericarditis following mRNA COVID-19 vaccines were included (no restrictions on language or date). Critical Appraisal Skills Programme (CASP) tools assessed study quality. Data extraction and synthesis: Two researchers extracted data. Spontaneously reported events of myocarditis and pericarditis were presented for each data source, stratified by vaccine, age, sex, and dose (where available). Reporting rates were calculated for myocarditis and pericarditis for each population. For published pharmacoepidemiological studies, design, participant characteristics, and study results were tabulated. Results: Overall, 18,204 myocarditis and pericarditis events have been submitted to the UK, US, and EU/EEA regulators during the study period. Males represented 62.24% (n=11,331) of myocarditis and pericarditis reports. Most reports concerned vaccinees aged <40 years and were more frequent following a second dose. Reporting rates were consistent between the data sources. Thirty-two pharmacoepidemiological studies were included; results were consistent with our spontaneous report analyses. Conclusions: Younger vaccinees more frequently report myocarditis and pericarditis following mRNA COVID-19 vaccines than older vaccinees. Results from published literature supported the results of our analyses.

  🖺 Full Text HTML: Reports of myocarditis and pericarditis following mRNA COVID-19 vaccines: A systematic review of spontaneously reported data from the UK, Europe, and the US and of the literature
• Racism, Posttraumatic Stress Symptoms, and Racial Disparity in the U.S. COVID-19 Syndemic -
  The COVID-19 syndemic, with a disproportionately higher adverse impact on communities of color (i.e., COVID-19 infection and death), will likely exacerbate the existing health disparities in trauma-related symptoms between people of color (POC) and White Americans. However, no studies have examined the racial disparities in posttraumatic stress symptoms (PTSS) during COVID-19. Grounded in ecological theory and racial trauma framework, we investigated rates of racial disparities in PTSS and three possible mechanisms, 1) COVID stress, 2) direct racism, and 3) indirect racism, for these discrepancies using a large U.S. national sample (N = 2,019). Results indicated that POC reported higher levels of PTSS than White Americans (d =.21). The PTSS racial disparity was accounted more by direct and indirect racism than by the COVID-19-specific stressors, after controlling for age, gender, education, income, parent status, adverse childhood experiences (ACEs), and intimate partner violence (IPV). Additional fine-grained analyses for Hispanic/Latinx Americans (n = 283), Black/African Americans (n = 279), and Asian American and Pacific Islanders (n = 123) by and large corroborated the above findings. Our findings highlighted the deleterious impact of the ongoing racism pandemic on the POC community as a public health crisis in addition to the COVID-19 pandemic.
  🖺 Full Text HTML: Racism, Posttraumatic Stress Symptoms, and Racial Disparity in the U.S. COVID-19 Syndemic
• Gambling on Others’ Health: Risky Pro-social Decision-Making in the Era of Covid19 -
  The ongoing Covid-19 pandemic has demanded a degree of sacrifice from individuals for the sake of the greater good. Individuals have taken costly actions, both volitional and imposed, to reduce harm to strangers. While many studies have examined health decision-making by experts, the study of individual, non-expert decision-making on a stranger’s health has been left to the wayside, as ordinary citizens are usually not tasked with such decisions. The recent pandemic has brought this dilemma to the fore however, as life-saving decisions fell to ordinary citizens in the form of social restrictions, decreased work activity and, ultimately, economic loss. We administered two surveys where we applied models of probabilistic decision-making to investigate health-related choices for oneself, a loved one and a stranger. We found converging evidence that participants were risk-seeking overall, privileging risky treatments that could heal someone over treatments that reduce disease severity with certainty. Nonetheless, risk-seeking decreased with expected disutility of disease, regardless of target. However, distinctions across targets emerged when decisions were conditioned on treatment cost, with participants preferring cheaper options for strangers. Overall our data suggest that

1. individuals apply an expected utility model to quantify disease; 2) risk preferences for others parallel those for the self; and 3) decisions for strangers’ health differ from those of self and loved ones only in terms of their associated cost. These findings provide a descriptive model of individual risky decision-making for self and others, in the case of a novel disease; and inform on the limits of what can be asked of an individual in service to a stranger.
   🖺 Full Text HTML: Gambling on Others’ Health: Risky Pro-social Decision-Making in the Era of Covid19

• Investigating the impact of COVID-19 on eating behaviours in the general public and an eating disorder population -
  Research suggests that the COVID-19 pandemic is negatively impacting mental health, with rates of eating disorder referrals in particular rising steeply during the pandemic. This study aimed to examine 8-month changes in body image and disordered eating during the COVID-19 pandemic, and explore whether any changes were moderated by gender, age, or eating disorder history. This study used a longitudinal survey design in which 587 adults living in the UK (85% women; mean age = 32.87 years) completed assessments every two months over five timepoints from May/June 2020 to January/February 2021. Measures included body esteem (Body Esteem Scale for Adults and Adolescence), disordered eating (Eating Disorder Examination – Questionnaire Short Form) and psychological distress (Patient Health Questionnaire – 4). Mixed effect models showed small but significant improvements in body esteem and disordered eating symptoms from May/June 2020 to January/February 2021. These improvements were independent of changes in psychological distress, and did not vary by gender, age or eating disorder history. Whilst poor body image and disordered eating may have been elevated in the early period of the pandemic, this study suggest improvements, rather than worsening, of these outcomes over time. This may reflect adaptation to this changing context.
  🖺 Full Text HTML: Investigating the impact of COVID-19 on eating behaviours in the general public and an eating disorder population

From Clinical Trials

• Randomized Controlled Clinical Trial to Evaluate The Efficacy and Safety of Healthtone as Prophylaxis for COVID-19 - Condition:   COVID-19
  Intervention:   Dietary Supplement: Rhea® Health Tone
  Sponsor:   Indonesia University
  Completed

• Aerobic Exercise in People With Post-COVID-19 - Condition:   COVID-19
  Interventions:   Other: Conventional rehabilitation;   Other: Aerobic exercise
  Sponsor:   Istituti Clinici Scientifici Maugeri SpA
  Recruiting

• The Effect of Home-based Rehabilitation Program After COVID-19 Infection - Condition:   COVID-19
  Interventions:   Behavioral: Add-on telerehabilitation and home-based rehabilitation;   Behavioral: Home-based rehabilitation alone
  Sponsor:  
  National Taiwan University Hospital
  Recruiting

• Efficacy, Safety and Immunogenicity Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition:   COVID-19
  Interventions:   Biological: SARS-CoV-2 protein subunit recombinant vaccine;   Biological: placebo
  Sponsors:   PT Bio Farma;   Faculty of Medicine, Universitas Indonesia, Jakarta;   Faculty of Medicine, Diponegoro University, Semarang;   Faculty of Medicine, Universitas Andalas, Padang;   Faculty of Medicine, Universitas Hassanudin, Makassar
  Not yet recruiting

• COVID-19 Treatment Cascade Optimization Study - Condition:   COVID-19
  Interventions:   Behavioral: Navigation Services;   Behavioral: Brief Counseling;   Behavioral: Critical Dialogue;   Behavioral: Referral and Digital Brochure
  Sponsors:   University of Illinois at Urbana-Champaign;   National Institute of Allergy and Infectious Diseases (NIAID);   Comprehensive Behavioral Health Center;   North Jersey Community Research Initiative;   University of Michigan
  Not yet recruiting

• A Study to Evaluate the Effectiveness and Safety of SCTV01E (a Recombinant Protein COVID-19 Vaccine) in Population Aged ≥12 Years - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01E;   Biological: CoronaVac;   Biological: Sinopharm inactivated COVID-19 vaccine;   Biological: other approved COVID-19 vaccines
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• A Study to Evaluate the Immunogenicity and Safety of SCTV01C and SCTV01E (Two Recombinant Protein COVID-19 Vaccines) in Population Aged ≥12 Years - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01C;   Biological: SCTV01E;   Biological: mRNA vaccine manufactured by Pfizer or Moderna;   Biological: Sinopharm inactivated COVID-19 vaccine
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• Phase 1/2 Study to Evaluate the Efficacy and Safety of Inhaled IBIO123 in Participants With Mild to Moderate COVID-19 Illness - Condition:   COVID-19
  Interventions:   Biological: IBIO123;   Other: Placebo
  Sponsor:   Immune Biosolutions Inc
  Recruiting

• Phase 1&2 Study to Evaluate the Safety & Efficacy of Inhaled IBIO123 in Severe COVID-19 Illness - Condition:   COVID-19
  Interventions:   Biological: IBIO123;   Other: Placebo
  Sponsor:   Immune Biosolutions Inc
  Recruiting

• A Study to Evaluate the Efficacy and Safety of Ivermectin in COVID-19 Prevention - Condition:   COVID-19
  Interventions:   Drug: Ivermectin Tablets;   Drug: Matching placebo tablets
  Sponsor:   MedinCell S.A
  Recruiting

• Tele-Rehabilitation in Individuals With Covid-19 - Condition:   COVID-19
  Intervention:   Other: Exercise
  Sponsor:  
  Hacettepe University
  Completed

• Study to Monitor the Occurrence of Viral Variants in Patients With Compromised Immune Systems Being Treated for COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Sotrovimab
  Sponsor:   GlaxoSmithKline
  Not yet recruiting

• Assessment of the Efficacy of Calcium Dobesilate vs. Placebo on SARS-CoV-2 Viral Load Amongst Outpatients With COVID-19. - Condition:   COVID-19 Virus Disease
  Interventions:   Drug: Calcium Dobesilate;   Drug: Mannitol
  Sponsors:   Hervé SPECHBACH;   OM Pharma
  Not yet recruiting

• A Phase I Study to Evaluate Safety, Tolerability, and Immunogenicity of a PIKA COVID-19 Vaccine in Healthy Individuals - Condition:   COVID-19 Pandemic
  Interventions:   Biological: PIKA COVID-19 Vaccine (CHO cell, S-protein), Arm A;   Biological: PIKA COVID-19 Vaccine (CHO cell, S-protein), Arm B
  Sponsor:  
  Yisheng Biopharma (Singapore) Pte. Ltd.
  Active, not recruiting

• SARS-CoV-2 Specific Immune Response After COVID-19 Vaccination in Cancer Patients - Conditions:   COVID-19;   Cancer
  Intervention:   Biological: CoronaVac vaccine
  Sponsors:   National Cancer Institute, Thailand;   Mahidol University
  Completed

From PubMed

• A critical evaluation of risk to reward ratio of quercetin supplementation for COVID-19 and associated comorbid conditions - The interim results of the large, multinational trials on coronavirus disease 2019 (COVID-19) using a combination of antiviral drugs appear to have little to no effect on the 28-day mortality or the in-hospital course. Therefore, there is a still vivid interest in finding alternate re-purposed drugs and nutrition supplements, which can halt or slow the disease severity. We review here the multiple preclinical studies, partially supported by clinical evidence showing the quercetin’s possible…

• Characterization, in-silico, and in-vitro study of a new steroid derivative from Ophiocoma dentata as a potential treatment for COVID-19 - The medicinal potential of marine invertebrates’ bioactive components that may act as anti-COVID-19 demonstrated promising results. Ophiocoma dentata, which is common in the Red Sea, is one such source. Therefore, this study aimed to isolate a new compound from the brittle star, Ophiocoma dentata, and evaluate its efficacy as anti-COVID-19 in-silico and in-vitro. Standard procedures were followed in order to assess the isolated compound’s preliminary toxicity and anti-inflammatory properties….

• Development of optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for treatment of COVID-19 - The SARS-CoV-2 3CL protease is a critical drug target for small molecule COVID-19 therapy, given its likely druggability and essentiality in the viral maturation and replication cycle. Based on the conservation of 3CL protease substrate binding pockets across coronaviruses and using screening, we identified four structurally distinct lead compounds that inhibit SARS-CoV-2 3CL protease. After evaluation of their binding specificity, cellular antiviral potency, metabolic stability, and water…

• Activated CD8(+)CD38(+) Cells Are Associated With Worse Clinical Outcome in Hospitalized COVID-19 Patients - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that spread around the world during the past 2 years, has infected more than 260 million people worldwide and has imposed an important burden on the healthcare system. Several risk factors associated with unfavorable outcome were identified, including elderly age, selected comorbidities, immune suppression as well as laboratory markers. The role of immune system in the pathophysiology of SARS-CoV-2 infection is indisputable: while an…

• Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19 - The ongoing COVID-19 pandemic has affected millions of people worldwide and caused substantial socio-economic losses. Few successful vaccine candidates have been approved against SARS-CoV-2; however, their therapeutic efficacy against the mutated strains of the virus remains questionable. Furthermore, the limited supply of vaccines and promising antiviral drugs have created havoc in the present scenario. Plant-based phytochemicals (bioactive molecules) are promising because of their low side…

• Red blood cells-hitchhiking mediated pulmonary delivery of ivermectin: effects of nanoparticles properties - Recent studies have demonstrated that ivermectin (IVM) exhibits antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of coronavirus disease (COVID-19). However, the repurposing of IVM for treatment of COVID-19 has presented challenges primarily due to the low IVM plasma concentration after oral administration, which was well below IC(50). Here, a red blood cells (RBCs)-hitchhiking strategy was used for the targeted delivery of IVM-loaded…

• Applying Modeling and Simulations for Rational Dose Selection of Novel Toll-like Receptor 7/8 Inhibitor Enpatoran for Indications of High Medical Need - Dual toll-like receptor (TLR) 7 and TLR8 inhibitor enpatoran is under investigation as a treatment for lupus and coronavirus disease 2019 (COVID-19) pneumonia. Population pharmacokinetic/pharmacodynamic (popPK/PD) model-based simulations, using PK and PD (inhibition of ex vivo-stimulated interleukin-6 [IL-6] and interferon-α [IFN-α] secretion) data from a phase I study of enpatoran in healthy participants, were leveraged to inform dose selection for lupus and repurposed for accelerated…

• Chloroquine and COVID-19-A systems biology model uncovers the drug’s detrimental effect on autophagy and explains its failure - The COVID-19 pandemic caused by SARS-CoV-2 has resulted in an urgent need for identifying potential therapeutic drugs. In the first half of 2020 tropic antimalarial drugs, such as chloroquine (CQ) or hydroxochloroquine (HCQ) were the focus of tremendous public attention. In the initial periods of the pandemic, many scientific results pointed out that CQ/HCQ could be very effective for patients with severe COVID. While CQ and HCQ have successfully been used against several diseases (such as…

• SARS-CoV-2 -specific immune responses in boosted vaccine recipients with breakthrough infections during the Omicron variant surge - CONCLUSIONS: Our data suggest that breakthrough infections with the Omicron variant can occur despite robust immune responses to the vaccine strain spike protein.

• SARS-CoV-2 nsp5 Exhibits Stronger Catalytic Activity and Interferon Antagonism than Its SARS-CoV Ortholog - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose an enormous threat to economic activity and public health worldwide. Previous studies have shown that the nonstructural protein 5 (nsp5, also called 3C-like protease) of alpha- and deltacoronaviruses cleaves Q231 of the NF-κB essential modulator (NEMO), a key kinase in the RIG-I-like receptor pathway, to inhibit type I interferon (IFN) production. In this study, we found that both SARS-CoV-2 nsp5 and SARS-CoV nsp5…

• Structural Basis of the Main Proteases of Coronavirus Bound to Drug Candidate PF-07321332 - The high mutation rate of COVID-19 and the prevalence of multiple variants strongly support the need for pharmacological options to complement vaccine strategies. One region that appears highly conserved among different genera of coronaviruses is the substrate-binding site of the main protease (M^(pro) or 3CL^(pro)), making it an attractive target for the development of broad-spectrum drugs for multiple coronaviruses. PF-07321332, developed by Pfizer, is the first orally administered inhibitor…

• Potential plants for inflammatory dysfunction in the SARS-CoV-2 infection - The inflammatory process is a biological response of the organism to remove injurious stimuli and initiate homeostasis. It has been recognized as a key player in the most severe forms of SARS-CoV-2, characterized by significantly increased pro-inflammatory cytokine levels, the so-called “cytokine storm” that appears to play a pivotal role in this disease. Therefore, the aim of this systematic review was to select clinical trials with anti-inflammatory plants and relate the activity of these…

• Elucidating Design Principles for Engineering Cell-Derived Vesicles to Inhibit SARS-CoV-2 Infection - The ability of pathogens to develop drug resistance is a global health challenge. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an urgent need wherein several variants of concern resist neutralization by monoclonal antibody (mAb) therapies and vaccine-induced sera. Decoy nanoparticles-cell-mimicking particles that bind and inhibit virions-are an emerging class of therapeutics that may overcome such drug resistance challenges. To date, quantitative understanding as to how…

• Innovative Randomized Phase 1 Study and Dosing Regimen Selection to Accelerate and Inform Pivotal COVID-19 Trial of Nirmatrelvir - COVID-19 is a continued leading cause of hospitalization and death. Safe, efficacious COVID-19 antivirals are needed urgently. Nirmatrelvir (PF-07321332), the first orally bioavailable, SARS-CoV-2 M^(pro) inhibitor against the coronaviridae family, has demonstrated potent preclinical antiviral activity and benign safety profile. We report safety, tolerability, and pharmacokinetic data of nirmatrelvir with and without ritonavir as a pharmacokinetic enhancer, from an accelerated randomized,…

• Imatinib inhibits SARS-CoV-2 infection by an off-target-mechanism - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of the COVID-19 pandemic. More than 274 million individuals have suffered from COVID-19 and over five million people have died from this disease so far. Therefore, there is an urgent need for therapeutic drugs. Repurposing FDA approved drugs should be favored since evaluation of safety and efficacy of de-novo drug design are both costly and time consuming. We report that imatinib, an Abl tyrosine kinase…

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