Covid-19 Sentry

Contents

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

From Preprints

• The blending of bending: how we engage with the world of Avatar: The Last Airbender through memes -
  People often use memes to express their ideological stance on real world events. This study departs from a recent COVID-19-related meme which makes use of elements known from the animated television series Avatar: The Last Airbender (ATLA) and Avatar: Legend of Korra (LOK), and asks how it came to be and how stance is conveyed through them. After acknowledging the impact of the series, conceptual blending theory is adopted to investigate the worldbuilding of the macrocosm in ATLA. This is identified as a correlative network, which acts as the blended space of multiple input spaces consisting of intertextual references. The world of ATLA then functions as a new input space which is updated with modern elements, resulting in the blend of LOK. Minor blends are identified in the hybrid animals that occupy the fictional world. Lastly, it is shown how the selection of a particular input element for participation in meme blends already conveys an ideological stance, rather than only emerging through readers’ eyes.
  🖺 Full Text HTML: The blending of bending: how we engage with the world of Avatar: The Last Airbender through memes
• Legal hunting for conservation of highly threatened species: The case of African rhinos -
  Legal hunting of highly threatened species – and especially the recreational practice of ‘trophy hunting’ – is controversial with selected ethical objections being increasingly voiced. Less attention has been paid to how hunting (even of threatened species) can be useful as a conservation tool, and likely outcomes if this was stopped. As case studies, we examine the regulated legal hunting in South Africa and Namibia of two African rhino species. Counter-intuitively, removing a small number of specific males can enhance population demography and genetic diversity, encourage range expansion, and generate meaningful socio-economic benefits to help fund effective conservation (facilitated by appropriate local institutional arrangements). Legal hunting of these species has been sustainable, as very small proportions of the populations of both species are hunted each year, and numbers of both today are higher in these countries than when controlled recreational hunting began. Terminating this management option and funding source could have negative consequences at a time when rhinos are being increasingly viewed as liabilities and COVID-19 has significantly impacted revenue generation for wildlife areas. Provided that there is appropriate governance and management, conservation of certain highly threatened species can be supported by cautiously selective and limited legal hunting.
  🖺 Full Text HTML: Legal hunting for conservation of highly threatened species: The case of African rhinos
• Human complement Factor H and Properdin act as soluble pattern recognition receptors and differentially modulate SARS-CoV-2 Infection -
  Severe cases of SARS-CoV-2 infection are characterised by an imbalanced immune response, excessive inflammation, and the development of acute respiratory distress syndrome, which can lead to multiorgan failure and death. Several studies have demonstrated dysregulated complement activity as an indicator of immunopathogenesis in the SARS-CoV-2 infection. Notably, the complement alternative pathway has been implicated in driving the excessive inflammation during severe SARS-CoV-2 infection. Reduced levels of factor H (FH), a down-regulator of the alternative pathway, and increased levels of properdin (Factor P/FP), the only known up-regulator of the alternative pathway, have been observed in individuals with severe COVID-19 infection. The present study investigated the complement activation-independent, and a more direct role of FH and FP against SARS-CoV-2 infection. Using direct ELISA, the interactions of FH and FP with the SARS-CoV-2 spike (S) and receptor binding domain (RBD) were assessed. Using S protein expressing lentiviral pseudotypes, the cell binding and luciferase-based virus entry assays were employed to assess the potential modulatory effects of FH, FP, and recombinant thrombospondin repeats 4 and 5 (TSR4+5) on SARS-CoV-2 cell entry. We also evaluated the immunomodulatory functions of FH and FP in the cytokine response triggered by SARS-CoV-2 pseudotypes via RT-qPCR. SARS-CoV-2 S and RBD proteins were found to bind both FH and FP. Treatment of A549 cells expressing human ACE2 and TMPRSS2 with FP or TSR4+5 resulted in increased cell entry and binding of SARS-CoV-2 pseudotypes. In silico studies revealed that FP increases affinity between SARS-CoV-2 and host ACE2. The impact of FP on viral cell entry and binding was reversed by anti-FP antibody treatment in A549-hACE2+TMPRSS2 cells. However, FH treatment reduced the cell entry and binding of SARS-CoV-2 lentiviral pseudotypes. Furthermore, the A549-hACE2+TMPRSS2 cells challenged with SARS-CoV-2 spike, envelope, nucleoprotein, and membrane protein expressing alphaviral pseudotypes pre-treated with FP or TSR4+5, exhibited upregulation of the transcripts of pro-inflammatory cytokines, such as IL-1{beta}, IL-8, IL-6, TNF-, IFN- and RANTES (as well as NF-kB). Conversely, FH pre-treatment downregulated the expression of these pro-inflammatory cytokines. Treatment of A549-hACE2+TMPRSS2 cells with FP increased S protein-mediated NF-kB activation, while FH treatment reduced it. These findings suggest that FH may act as an inhibitor of SARS-CoV-2 cell entry and binding, thereby attenuating the infection-associated inflammatory response in a complement activation-independent manner. FP may contribute to viral cell entry, binding, and exacerbating the immune response. That may result in potentially influencing the severity of the infection.
  🖺 Full Text HTML: Human complement Factor H and Properdin act as soluble pattern recognition receptors and differentially modulate SARS-CoV-2 Infection
• Explaining viral pandemics with help from Theology and Physics - Alternative Hypotheses. -
  Pathogens have been plaguing humans since time immemorial. One characteristic feature is repetition of pandemics by the same pathogen(s) resulting in devastation. However, starting CE 1880, the offending pathogens have been different with every episode. Borrowing concepts from theology and physics, this article tries to proffer answers to some aspects observed regarding Viruses, Vectors, and Humans, and thereby tries to redefine our thinking on the concepts of viral infections. These aspects being: how pandemics occur in the first instance, the rapid global spread of the current Covid-19 Pandemic and will the humanity be able to control such pandemics in future.
  🖺 Full Text HTML: Explaining viral pandemics with help from Theology and Physics - Alternative Hypotheses.
• Neuron- and microglia-specific immunoexpression in steroid-independent male sexual behaviour in castrated B6D2F1 male mice -
  Sexual behaviour is necessary for procreation for several species and is traditionally viewed to be regulated by sex steroid hormones. However, several species exhibit steroid-independent sexual behaviour, and its molecular understanding is only beginning to be uncovered. The main goal of our experiment was to provide new insight into cell-specific roles that both neuronal and non-neuronal cells may play in steroid-independent male sexual behaviour. Forty B6D2F1 hybrid male mice underwent orchidectomy and were tested for reinstatement of steroid-independent male sexual behaviour after an extended period of social isolation caused by the COVID-19-mandated laboratory shutdown. After 62 weeks post-orchidectomy, 20.59% demonstrated reinstatement of steroid-independent male sexual behaviour (identified as steroid-independent persistent maters), while 23.53% of the males did not display steroid-independent male sexual behaviour (identified as steroid-independent non-maters). Using flow cytometry, we compared the preoptic area immunoexpression in NeuN+ neurons and Iba1+ microglia between steroid-independent persistent maters and steroid-independent non-maters (N = 5-6 per group). We found neuronal immunoexpression up-regulated for amyloid precursor protein and androgen receptor, as well as down-regulated for glucocorticoid receptor in steroid-independent persistent maters compared to steroid-independent non-maters. In conjunction, microglial immunoexpression of amyloid precursor protein was up-regulated in steroid-independent persistent maters compared to steroid-independent non-maters. These data suggest there are cell-specific immunoexpression differences, including the role of non-neuronal cells in steroid-independent male sexual behaviour.
  🖺 Full Text HTML: Neuron- and microglia-specific immunoexpression in steroid-independent male sexual behaviour in castrated B6D2F1 male mice
• Comparative Reconstruction of SARS-CoV-2 transmission in three African countries using a mathematical model integrating immunity data. -

  Objectives: Africa has experienced fewer coronavirus disease 2019 (COVID-19) cases and deaths than other regions, with a contrasting epidemiological situation between countries, raising questions regarding the determinants of disease spread in Africa. Method: We built a susceptible-exposed-infected-recovered model including COVID-19 mortality data where recovery class is structured by specific immunization and modeled by a partial differential equation considering the opposed effects of immunity decline and immunization. This model was applied to Tunisia, Senegal, and Madagascar. Finding: Senegal and Tunisia experienced two epidemic phases. Initially, infections emerged in naive individuals and were limited by social distancing. Variants of concern (VOCs) were also introduced. The second phase was characterized by successive epidemic waves driven by new VOCs that escaped host immunity. Meanwhile, Madagascar demonstrated a different profile, characterized by longer intervals between epidemic waves, increasing the pool of susceptible individuals who had lost their protective immunity. The impact of vaccination in Tunisia and Senegal on model parameters was evaluated. Interpretation: Loss of immunity and vaccination-induced immunity have played crucial role in controlling the African pandemic. Severe acute respiratory syndrome coronavirus 2 has become endemic now and will continue to circulate in African populations. However, previous infections provide significant protection against severe diseases, thus providing a basis for future vaccination strategies.

  🖺 Full Text HTML: Comparative Reconstruction of SARS-CoV-2 transmission in three African countries using a mathematical model integrating immunity data.
• Association of Chronotype and Shiftwork with COVID-19 Infection -

  Objective: This study assesses whether chronotype is related to COVID-19 infection and whether there is an interaction with shift work. Methods: Cross-sectional survey of 19,821 U.S. adults Results: COVID-19 infection occurred in 40% of participants, 32.6% morning and 17.2% evening chronotypes. After adjusting for demographic and socioeconomic factors, shift work, sleep duration and comorbidities, morning chronotype was associated with a higher (aOR: 1.15, 95% CI 1.10-1.21) and evening chronotype with a lower (aOR: 0.82, 95% CI: 0.78-0.87) prevalence of COVID-19 infection in comparison to an intermediate chronotype. Working exclusively night shifts was not associated with higher prevalence of COVID-19. Morning chronotype and working some evening shifts was associated with the highest prevalence of previous COVID-19 infection (aOR: 1.87, 95% CI: 1.28-2.74). Conclusion: Morning chronotype and working a mixture of shifts increase risk of COVID-19 infection.

  🖺 Full Text HTML: Association of Chronotype and Shiftwork with COVID-19 Infection
• Increasing burden of opioid overdose mortality in the United States: Years of life lost by age, race, and state from 2019-2021 -

  The United States9 opioid crisis is worsening, but the nationwide burden has not been characterized during the COVID-19 pandemic. In this study we calculate years of life lost to opioid overdose deaths by demographic group and examine trends from 2019 to 2021. Using the Multiple Cause of Death dataset from CDC WONDER, we extracted opioid overdose deaths stratified by race/ethnicity, age, and state, and estimated crude and age-adjusted mortality rates, years of life lost, and reduction in life expectancy at birth. Increasing annually, opioid overdose deaths reached 80,411 in 2021, leading to 3 million years of life lost, and reducing life expectancy by 0.65 years. From 2019 to 2021, opioid overdose death rates increased across all groups. American Indian/Alaska Native and Black/African American men now experience the highest burden, with 1,500 years of life lost per 100,000, life expectancies at birth reduced by almost 1 year, and 46 and 51 deaths per 100,000, respectively. This study highlights the continued growth of the opioid crisis, and the surge in years of life lost coinciding with COVID-19. There is an urgent need for more effective interventions, particularly in light of this epidemic9s changing demographics.

  🖺 Full Text HTML: Increasing burden of opioid overdose mortality in the United States: Years of life lost by age, race, and state from 2019-2021
• The impact of digital health insurance for low-income women in Kenya -

  Objective: This study evaluates how a subsidized, mobile phone-based health insurance program affected insurance uptake, healthcare utilization and health expenditures for low-income women and their family members in Western Kenya. The program, targeting pregnant women and mothers of children below age four, addressed both demand- and supply-side constraints, providing subsidies through mobile money and support in digital registration while upgrading selected facilities and digitally training community health workers. Methods: The research was based on a cluster-RCT conducted between 2019 and 2021 in 24 villages in Kakamega County. After a baseline survey, 240 households (more than 1,300 individuals) were interviewed every week during 18 months to collect detailed financial and health data while the program was rolled out in the treatment communities, moving to phone-based interviewing after the onset of COVID-19. Results: The intervention had a significant impact on individual insurance uptake of 65.8 percentage points (from a baseline control mean 18.9 percent). We find weak positive impacts on formal healthcare utilization, and substantial increases in financial coverage of medical costs and associated reductions in out-of-pocket expenditures, particularly for medicines. Results are strongest for women, young children and individuals living closest to the clinics. Dynamic analyses show that impacts become increasingly pronounced over time, suggesting that women may need some time to get used to the digital insurance scheme. Conclusion: The program not only reduced the costs of enrolment, but also eliminated other (administrative, logistical, trust) barriers. The introduction of the scheme by trusted local agents, the hands-on assistance with the digital registration procedures at women9s homes, and support in retrieving the necessary documentation such as children9s birth certificates, have likely all contributed to the high enrolment rates, thereby improving access to good-quality care. Digital insurance has the potential to substantially enhance universal health coverage and financial protection for poor households.

  🖺 Full Text HTML: The impact of digital health insurance for low-income women in Kenya
• Poor Hemorrhagic Stroke Outcomes During the COVID-19 Pandemic Are Driven by Socioeconomic Disparities -

  Background Nationally representative data demonstrating the impact of the COVID-19 pandemic on hemorrhagic stroke outcomes are lacking. Methods In this pooled cross-sectional analysis, we used the National Inpatient Sample (2016-2020) to identify adults (>=18 years) with primary intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH). We fit segmented logistic regression models to evaluate the differences in the rates of in-hospital outcomes (in-hospital mortality, home discharge, and receiving neurosurgical procedures) between the pre-pandemic (January 2016-February 2020) and pandemic periods (March 2020-December 2020). We used multivariable logistic regression models to evaluate the differences in mortality between patients admitted from April to December 2020, with and without COVID-19, and those admitted during a similar period in 2019. Stratified analyses were conducted among patients residing in low and high-income zip codes and among patients with extreme loss of function (E-LoF) and those with minor to major loss of function (MM-LoF). Results Overall, 309,965 ICH patients (mean age [SD]: 68[14.8], 47% female, 56% low-income) and 112,210 SAH patients (mean age [SD]: 60.2[15.4], 62% female, 55% low-income) were analyzed. Pre-pandemic, ICH mortality was decreasing by ≈1% per month (adjusted odds ratio, 95% confidence interval: 0.99, 0.99-1.00). However, during the pandemic, the overall ICH mortality rate increased by ≈2% per month (1.02, 1.00-1.02) and ≈4% per month among low-income patients (1.04, 1.01-1.07). However, there was no change in trend among high-income ICH patients during the pandemic (1.00, 0.97-1.03). Patients with comorbid COVID-19 in 2020 had significantly higher odds of mortality compared to the 2019 comparison cohort, overall (ICH: 1.83, 1.33-2.51; SAH: 2.76, 1.68-4.54), and among patients with MM-LoF (ICH: 2.15, 1.12-4.16; SAH: 5.77, 1.57-21.17). However, patients with E-LoF and comorbid COVID-19 had similar mortality rates with the 2019 cohort. Conclusion Sustained efforts are needed to address socioeconomic disparities in healthcare access, quality, and outcomes during public health emergencies.

  🖺 Full Text HTML: Poor Hemorrhagic Stroke Outcomes During the COVID-19 Pandemic Are Driven by Socioeconomic Disparities
• Temporal Pattern of Mutation Accumulation in SARS-CoV-2 Proteins: Insights from Whole Genome Sequences Pan-India Using Data Mining Approach -
  Mutation is a fundamental factor that affects host-pathogen biology and consequently viral survival and spread. Close monitoring and observation of such mutation help decipher essential changes in the SARS Cov2 genome. A plethora of mutations have been documented owing to increased whole genomic sequencing. Understanding how conserved the specific mutations are and the temporal pattern of mutation accumulation is of paramount interest. Using an in-house data mining approach, pan-India data was mined and analysed for 26 proteins expressed by SARS-CoV-2 to understand the spread of mutations over 28 months (January 2021- April 2023). It was observed that proteins such as Nsp3, Nsp4, ORF9b, among others, acquired mutations over the period. In contrast, proteins such as Nsp6-10 were highly stable, with no detectable conserved mutations. Further, it was observed that many of the mutations that were highly prevalent in the delta variants were not observed in the omicron variants, which probably influenced the host-pathogen relationship. The study attempts to catalogue and focus on well-conserved mutations across all the SARS-CoV-2 proteins, highlighting the importance of understanding non-spike mutations.
  🖺 Full Text HTML: Temporal Pattern of Mutation Accumulation in SARS-CoV-2 Proteins: Insights from Whole Genome Sequences Pan-India Using Data Mining Approach
• First Eurasian cases of SARS-CoV-2 seropositivity in a free-ranging urban population of wild fallow deer -
  Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects wildlife. Recent studies highlighted that variants of concern (VOC) may expand into novel animal reservoirs with the potential for reverse zoonosis. North American white-tailed deer are the only deer species in which SARS-CoV-2 has been documented, raising the question whether further reservoir species exist as new VOC emerge. Here, we report the first cases of deer SARS-CoV-2 seropositivity in Eurasia, in a city population of fallow deer in Dublin, Ireland. Deer were seronegative in 2020 (circulating variant in humans: Alpha), one animal was seropositive in 2021 (Delta variant), and 57% of animals tested in 2022 were seropositive (Omicron variant). Ex vivo, a clinical isolate of Omicron BA.1 infected fallow deer precision cut lung slice type-2 pneumocytes, also a major target of infection in human lungs. Our findings suggest a change in host tropism as new variants emerged in the human reservoir, highlighting the importance of continued wildlife disease monitoring and limiting human-wildlife contacts.
  🖺 Full Text HTML: First Eurasian cases of SARS-CoV-2 seropositivity in a free-ranging urban population of wild fallow deer
• Single cell susceptibility to SARS-CoV-2 infection is driven by variable cell states -
  The ability of a virus to infect a cell type is at least in part determined by the presence of host factors required for the viral life cycle. However, even within cell types that express known factors needed for infection, not every cell is equally susceptible, suggesting that our knowledge of the full spectrum of factors that promote infection is incomplete. Profiling the most susceptible subsets of cells within a population may reveal additional factors that promote infection. However, because viral infection dramatically alters the state of the cell, new approaches are needed to reveal the state of these cells prior to infection with virus. Here, we used single-cell clone tracing to retrospectively identify and characterize lung epithelial cells that are highly susceptible to infection with SARS-CoV-2. The transcriptional state of these highly susceptible cells includes markers of retinoic acid signaling and epithelial differentiation. Loss of candidate factors identified by our approach revealed that many of these factors play roles in viral entry. Moreover, a subset of these factors exert control over the infectable cell state itself, regulating the expression of key factors associated with viral infection and entry. Analysis of patient samples revealed the heterogeneous expression of these factors across both cells and patients in vivo. Further, the expression of these factors is upregulated in particular inflammatory pathologies. Altogether, our results show that the variable expression of intrinsic cell states is a major determinant of whether a cell can be infected by SARS-CoV-2.
  🖺 Full Text HTML: Single cell susceptibility to SARS-CoV-2 infection is driven by variable cell states
• Establishing thresholds for cytokine storm and defining their relationship to disease severity in respiratory viral infections -
  Previous studies have identified cytokines associated with respiratory virus infection illness outcome. However, few studies have included comprehensive cytokine panels, longitudinal analyses, and/or simultaneous assessment across the severity spectrum. This, coupled with subjective definitions of cytokine storm syndrome (CSS), have contributed to inconsistent findings of cytokine signatures, particularly with COVID severity. Here, we measured 38 plasma cytokines and compared profiles in healthy, SARS-CoV-2 infected, and multisystem inflammatory syndrome in children (MIS-C) patients (n = 169). Infected patients spanned the severity spectrum and were classified as Asymptomatic, Mild, Moderate or Severe. Our results showed acute cytokine profiles and longitudinal dynamics of IL1Ra, IL10, MIP1b, and IP10 can differentiate COVID severity groups. Only 4% of acutely infected patients exhibited hypercytokinemia. Of these subjects, 3 were Mild, 3 Moderate, and 1 Severe, highlighting the lack of association between CSS and COVID severity. Additionally, we identified IL1Ra and TNFa as potential biomarkers for patients at high risk for long COVID. Lastly, we compare hypercytokinemia profiles across COVID and influenza patients and show distinct elevated cytokine signatures, wherein influenza induces the most elevated cytokine profile. Together, these results identify key analytes that, if obtained at early time points, can predict COVID illness outcome and/or risk of complications, and provide novel insight for improving the conceptual framework of hypercytokinemia, wherein CSS is a subgroup that requires concomitant severe clinical manifestations, and including a list of cytokines that can distinguish between subtypes of hypercytokinemia.
  🖺 Full Text HTML: Establishing thresholds for cytokine storm and defining their relationship to disease severity in respiratory viral infections
• Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant. -
  Most COVID-19 vaccines are based on the SARS-CoV-2 Spike glycoprotein (S) or their subunits. However, the S shows some structural instability that limits its immunogenicity and production, hampering the development of recombinant S-based vaccines. The introduction of the K986P and V987P (S-2P) mutations increases the production of the recombinant S trimer and, more importantly, its immunogenicity, suggesting that these two parameters are related. However, S-2P still shows some molecular instability and it is produced with low yield. Thus, S-2P production can be further optimized. Here we described a novel set of mutations identified by molecular modelling and located in the S2 region of the Spike that increase S-2P production up to five-fold. Besides their immunogenicity, the efficacy of two representative S-2P-based mutants, S-29 and S-21, protecting from a heterologous SARS-CoV-2 Beta variant challenge was assayed in K18-hACE2 mice (an animal model of severe SARS-CoV-2 disease) and golden Syrian hamsters (GSH) (a moderate disease model). S-21 induced higher level of WH1 and Delta variants neutralizing antibodies than S-2P in K18-hACE2 mice three days after challenge. Viral load in nasal turbinate and oropharyngeal samples were reduced in S-21 and S-29 vaccinated mice. Despite that, only the S-29 protein protected 100% of K18-hACE2 mice from severe disease. When GSH were analyzed, all immunized animals were protected from disease development irrespectively of the immunogen they received. Therefore, the higher yield of S-29, as well as its improved immunogenicity and efficacy protecting from the highly pathogenic SARS-CoV-2 Beta variant, pinpoint the S-29 spike mutant as an alternative to the S-2P protein for future SARS-CoV-2 vaccine development.
  🖺 Full Text HTML: Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant.

From Clinical Trials

• Homologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition:   COVID-19
  Intervention:   Biological: SARS-CoV-2 Subunit Recombinant Protein Vaccine
  Sponsor:   PT Bio Farma
  Not yet recruiting

• Role of Ivermectin and Colchicine in Treatment of COVID-19: Randomized Controlled Clinical Trial - Condition:   COVID-19
  Interventions:   Drug: Ivermectin Tablets;   Drug: Colchicine 0.5 MG;   Drug: Standared managment
  Sponsor:   Ain Shams University
  Completed

• A Study to Evaluate the Immunogenicity and Safety of A Recombinant Protein COVID-19 Vaccine as Booster Vaccines - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01E-2;   Biological: SCTV01E
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• COVID-19 Vaccine Hesitancy Counseling Intervention for Pharmacists - Condition:   COVID-19
  Interventions:   Behavioral: Standard implementation webinar and online training;   Behavioral: Virtual facilitation
  Sponsors:   University of North Carolina, Chapel Hill;   University of Arkansas;   University of South Carolina;   National Institute on Minority Health and Health Disparities (NIMHD)
  Not yet recruiting

• Developing an Effective Intervention to Address Post-Corona-Virus-Disease-2019 Balance Disorders, Weakness and Muscle Fatigue in Individuals Aged 65+ - Condition:   COVID-19
  Intervention:   Device: Resistance Training
  Sponsor:   Józef Piłsudski University of Physical Education
  Recruiting

• LUSZ Treatment Efficacy in Hospitalized COVID-19 Patients - Conditions:   COVID-19;   Hospitalized COVID-19 Patients
  Interventions:   Drug: Lopinavir / Ritonavir;   Drug: Remdesivir (RDV);   Drug: Tocilizumab;   Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)
  Sponsors:   Lebanese University;   Hospital Saydet Zgharta University Medical Center
  Recruiting

• Multimodal Long Covid19 - Condition:   Long COVID-19 Syndrome
  Intervention:   Other: Multimodal intervention in Long Covid19
  Sponsors:   Universidad de Magallanes;   Teaching Assistance and Research Center of the University of Magallanes CADI-UMAG;   Clinical Hospital Dr. Lautaro Navarro Avaria
  Active, not recruiting

• Comprehensive Imaging Exam of Convalesced COVID-19 Patients - Conditions:   COVID-19;   COVID Long-Haul
  Interventions:   Other: Magnetic Resonance Imaging;   Other: Ultra-High Resolution Computed Tomography (CT) Scan
  Sponsors:   Johns Hopkins University;   Canon Medical Systems, USA
  Enrolling by invitation

• UNAIR Inactivated COVID-19 Vaccine as Heterologue Booster (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-1 9 Vaccine 3 µg
  Sponsors:   Dr. Soetomo General Hospital;   Indonesia-MoH;   Universitas Airlangga;   Biotis Pharmaceuticals, Indonesia
  Recruiting

• Immunogenicity and Safety Study of SCB-2023 Vaccine as a Booster in Adults - Condition:   COVID-19
  Interventions:   Biological: SCB-2023 vaccine (trivalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection;   Biological: SCB-2019 (monovalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection
  Sponsor:   Clover Biopharmaceuticals AUS Pty Ltd
  Not yet recruiting

• The Safety and Immunogenicity Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB002 - Condition:   COVID-19
  Interventions:   Biological: LYB002V14;   Biological: LYB002V14A;   Biological: LYB002CA
  Sponsors:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.;   Affiliated Hospital of North Sichuan Medical College
  Active, not recruiting

• Phase 2/3 Heterologous Boosting Study With Different Dose Levels of Monovalent SARS-CoV-2 rS Vaccines - Condition:   COVID-19
  Interventions:   Biological: NVX-CoV2373 (5μg);   Biological: NVX-CoV2601 (5μg);   Biological: NVX-CoV2601(5μg);   Biological: NVX-CoV2601 (35μg);   Biological: NVX-CoV2601(35μg);   Biological: NVX-CoV2601(50μg);   Biological: Bivalent BA.4/5
  Sponsor:   Novavax
  Not yet recruiting

• The Immunogenicity and Safety Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB001 - Conditions:   COVID-19;   Vaccine Reaction
  Interventions:   Biological: LYB001;   Biological: CoronaVac
  Sponsors:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.;   Affiliated Hospital of North Sichuan Medical College
  Active, not recruiting

• Safety and Efficacy of Anakinra Treatment for Patients With Post Acute Covid Syndrome - Condition:   Post-Acute COVID-19 Syndrome
  Interventions:   Drug: Placebo;   Drug: Anakinra 149 MG/ML Prefilled Syringe [Kineret]
  Sponsor:   Hellenic Institute for the Study of Sepsis
  Not yet recruiting

• The Effect of Smart Sensor Combined With APP for Individualized Precise Exercise Training in Long Covid-19 - Conditions:   Coronavirus Disease;   COVID-19;   Long Covid-19;   Telerehabilitation
  Interventions:   Device: KNEESUP smart knee assistive device + KNEESUP care APP;   Device: KNEESUP care APP;   Behavioral: Healthy consulation
  Sponsor:   Shang-Lin Chiang
  Recruiting

From PubMed

• Patch-clamp studies and cell viability assays suggest a distinct site for viroporin inhibitors on the E protein of SARS-CoV-2 - CONCLUSIONS: This study demonstrates direct inhibition of the SARS-CoV-2 E protein by classical viroporin inhibitors. Ivermectin and milbemycin inhibit the E protein channel but their cytotoxicity argues against clinical application.

• Structural basis for the inhibition of coronaviral main proteases by ensitrelvir - Main protease (M^(pro)) is a highly conserved cysteine protease that plays a vital role in the replication of coronaviruses, making it an attractive pan-coronaviral therapeutic target. Ensitrelvir (S-217622), developed by Shionogi, is the first orally active non-covalent, non-peptidic SARS-CoV-2 M^(pro) inhibitor, which also displays antiviral efficacy against other human coronaviruses as well as SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs). Here, we report the crystal…

• Kaempferol inhibits SARS-CoV-2 invasion by impairing heptad repeats-mediated viral fusion - CONCLUSIONS: Kae prevents SARS-CoV-2 infection by blocking membrane fusion and possesses a broad-spectrum anti-fusion ability. These findings provide valuable insights into potential benefits of Kae-containing botanical products as a complementary prophylaxis, especially during the waves of breakthrough infections and re-infections.

• Prologue: Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2022 Annual Meeting - The 2022 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) was held from July 14 to 17, 2022, in New York City, New York, USA, and was attended by 420 rheumatologists, dermatologists, basic scientists, allied health professionals, patient research partners, and industry partners from 31 countries. A GRAPPA executive retreat, a Trainee Symposium, and the Patient Research Partners Network meeting were held prior to the annual meeting….

• NETosis promotes chronic inflammation and fibrosis in systemic lupus erythematosus and COVID-19 - Pulmonary fibrosis, a serious complication of systemic lupus erythematosus (SLE) and coronavirus disease 2019 (COVID-19), leads to irreversible lung damage. However, the underlying mechanism of this condition remains unclear. In this study, we revealed the landscape of transcriptional changes in lung biopsies from individuals with SLE, COVID-19-induced pulmonary fibrosis, and idiopathic pulmonary fibrosis (IPF) using histopathology and RNA sequencing, respectively. Despite the diverse etiologies…

• Structure basis of two nanobodies neutralizing SARS-CoV-2 Omicron variant by targeting ultra-conservative epitopes - The evolving SARS-CoV-2 Omicron strain has repeatedly caused widespread disease epidemics, and effective antibody drugs continue to be in short supply. Here, we identified a batch of nanobodies with high affinity for receptor binding domain (RBD) of SARS-CoV-2 spike protein, separated them into three classes using high performance liquid chromatography (HPLC), and then resolved the crystal structures of the ternary complexes of two non-competing nanobodies (NB1C6 and NB1B5) with RBD using X-ray…

• Targeting 2-Oxoglutarate-Dependent Dioxygenases Promotes Metabolic Reprogramming That Protects against Lethal SARS-CoV-2 Infection in the K18-hACE2 Transgenic Mouse Model - Dysregulation of host metabolism is a feature of lethal SARS-CoV-2 infection. Perturbations in α-ketoglutarate levels can elicit metabolic reprogramming through 2-oxoglutarate-dependent dioxygenases (2-ODDGs), leading to stabilization of the transcription factor HIF-1α. HIF1-α activation has been reported to promote antiviral mechanisms against SARS-CoV-2 through direct regulation of ACE2 expression (a receptor required for viral entry). However, given the numerous pathways HIF-1α serves to…

• Individuals at risk for severe COVID-19 in whom ritonavir-containing therapies are contraindicated or may lead to interactions with concomitant medications: a retrospective analysis of German health insurance claims data - CONCLUSION: Administering ritonavir-containing COVID-19 therapy can be challenging as thorough medical record review and close monitoring are required. In some cases, ritonavir-containing treatment may not be appropriate due to contraindications, risk of pDDIs, or both. For those individuals, an alternative ritonavir-free treatment should be considered.

• e-Pharmacophore modeling and in silico study of CD147 receptor against SARS-CoV-2 drugs - Coronavirus has left severe health impacts on the human population, globally. Still a significant number of cases are reported daily as no specific medications are available for its effective treatment. The presence of the CD147 receptor (human basigin) on the host cell facilitates the severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection. Therefore, the drugs that efficiently alter the formation of CD147 and spike protein complex could be the right drug candidate to inhibit the…

• Investigating theobromine as a potential anti-human coronaviral agent - Coronaviruses (CoVs) have long been known to infect humans, mainly alpha-CoV and beta-CoV. The vaccines developed for SARS-CoV-2 are likely not effective against other coronavirus species, whereas the risk of the emergence of new strains that may cause the next epidemic/pandemic is high. The development of antiviral drugs that are effective across different CoVs represents a viable strategy for improving pandemic preparedness. In this study, we aim to identify pan-coronaviral agents by targeting…

• SARS-CoV-2 Nsp1 mediated mRNA degradation requires mRNA interaction with the ribosome - Nsp1 is a SARS-CoV-2 host shutoff factor that both represses cellular translation and promotes host RNA decay. However, it is unclear how these two activities are connected and interact with normal translation processes. Here, we performed mutational analyses of Nsp1, and these revealed that both the N and C terminal domains of Nsp1 are important for translational repression. Furthermore, we demonstrate that specific residues in the N terminal domain are required for cellular RNA degradation but…

• Repurposing Polyether Ionophores as a New-Class of Anti-SARS-Cov-2 Agents as Adjunct Therapy - The emergence of SARS-CoV-2 and its variants have posed a significant threat to humankind in tackling the viral spread. Furthermore, currently repurposed drugs and frontline antiviral agents have failed to cure severe ongoing infections effectively. This insufficiency has fuelled research for potent and safe therapeutic agents to treat COVID-19. Nonetheless, various vaccine candidates have displayed a differential efficacy and need for repetitive dosing. The FDA-approved polyether ionophore…

• Prolonged Exposure to Remdesivir Inhibits the Human Ether-A-Go-Go-Related Gene Potassium Current - Remdesivir, approved for the treatment of coronavirus disease (COVID-19), has been associated with QTc interval prolongation and torsade de pointes (TdP) in case reports. However, data are conflicting regarding the ability of remdesivir to inhibit the human ether-a-go-go-related (hERG)-related current. The objective of this study was to investigate the effects remdesivir and its primary metabolite, GS-441524, on hERG-related currents. Human embryonic kidney (HEK 293) cells stably expressing hERG…

• The KDM6A-KMT2D-p300 axis regulates susceptibility to diverse coronaviruses by mediating viral receptor expression - Identification of host determinants of coronavirus infection informs mechanisms of pathogenesis and may provide novel therapeutic targets. Here, we demonstrate that the histone demethylase KDM6A promotes infection of diverse coronaviruses, including SARS-CoV, SARS-CoV-2, MERS-CoV and mouse hepatitis virus (MHV) in a demethylase activity-independent manner. Mechanistic studies reveal that KDM6A promotes viral entry by regulating expression of multiple coronavirus receptors, including ACE2, DPP4…

• Development of monoclonal antibody-based blocking ELISA for detecting SARS-CoV-2 exposure in animals - The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to public health. Besides humans, SARS-CoV-2 can infect several animal species. Highly sensitive and specific diagnostic reagents and assays are urgently needed for rapid detection and implementation of strategies for prevention and control of the infection in animals. In this study, we initially developed a panel of monoclonal antibodies (mAbs) against SARS-CoV-2 nucleocapsid protein….

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