Covid-19 Sentry

Contents

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

From Preprints

• MultiOMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells -
  Despite the availability of vaccines and approved therapeutics, the COVID-19 pandemic continues to rise owing to the emergence of newer variants. Several multi-omics studies have made available extensive evidence on host-pathogen interactions and potential therapeutic targets. Nonetheless, an increased understanding of host signaling networks regulated by post-translational modifications and their ensuing effect on the biochemical and cellular dynamics is critical to expanding the current knowledge on the host response to SARS-CoV-2 infections. Here, employing unbiased global transcriptomics, proteomics, acetylomics, phosphoproteomics, and exometabolome analysis of a lung-derived human cell line, we show that SARS-CoV-2 Norway/Trondheim-S15 strain induces time-dependent alterations in the induction of type I IFN response, activation of DNA damage response, dysregulated Hippo signaling, among others. We provide evidence for the interplay of phosphorylation and acetylation dynamics on host proteins and its effect on the altered release of metabolites, especially organic acids and ketone bodies. Together, our findings serve as a resource of potential targets that can aid in designing novel host-directed therapeutic strategies.
  🖺 Full Text HTML: MultiOMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells
• The Intestinal Microbiome, Dietary Habits, and Physical and Psychological Resilience in Postpartum Women -
  The population of postpartum women suffering from mental illness is increasing steadily, particularly under conditions of the COVID-19 pandemic. Identifying factors that contribute to resilience in postpartum women is urgently needed to decrease risks of poor physical and psychological functioning. Studies have linked variations in the intestinal microbiota to depression in clinical samples, but the impacts in postpartum women in a Japanese population are unknown. We conducted two studies to examine the links between intestinal microbiota, physical condition, and psychological state in nonclinical, postpartum Japanese women. Our results show that decreasing Lachnospira and alpha diversity of microbiome is related to high mental health risk (i.e., parenting stress and/or depression). Psychological resilience and physical conditions were associated with relative abundances of genera Blautia, Clostridium, Eggerthella. This study contributes to further understanding of the gut-brain axis mechanisms and supports proposals for interventions to enhance resilience in postpartum women.
  🖺 Full Text HTML: The Intestinal Microbiome, Dietary Habits, and Physical and Psychological Resilience in Postpartum Women
• A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4+ T cell profile -
  Cellular immune defects associated with suboptimal responses to SARS-CoV-2 mRNA vaccination in people receiving hemodialysis (HD) are poorly understood. We longitudinally analyzed antibody, B cell, CD4+ and CD8+ T cell vaccine responses in 27 HD patients and 26 low-risk control individuals (CI). The first two doses elicit weaker B cell and CD8+ T cell responses in HD than in CI, while CD4+ T cell responses are quantitatively similar. In HD, a third dose robustly boosts B cell responses, leads to convergent CD8+ T cell responses and enhances comparatively more Thelper (TH) immunity. Unsupervised clustering of single-cell features reveals phenotypic and functional shifts over time and between cohorts. The third dose attenuates some features of TH cells in HD (TNF/IL-2 skewing), while others (CCR6, CXCR6, PD-1 and HLA-DR overexpression) persist. Therefore, a third vaccine dose is critical to achieve robust multifaceted immunity in hemodialysis patients, although some distinct TH characteristics endure.
  🖺 Full Text HTML: A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4+ T cell profile
• Future COVID-19 surges prediction based on SARS-CoV-2 mutations surveillance -
  COVID-19 has aptly revealed that airborne viruses such as SARS-CoV-2 with the ability to rapidly mutate, combined with high rates of transmission and fatality can cause a deadly world-wide pandemic in a matter of weeks. Apart from vaccines and post-infection treatment options, strategies for preparedness will be vital in responding to the current and future pandemics. Therefore, there is wide interest in approaches that allow predictions of increase in infections (surges) before they occur. We describe here real time genomic surveillance particularly based on mutation analysis, of viral proteins as a methodology for a priori determination of surge in number of infection cases. The full results are available for SARS-CoV-2 at http://pandemics.okstate.edu/covid19/, and are updated daily as new virus sequences become available. This approach is generic and will also be applicable to other pathogens.
  🖺 Full Text HTML: Future COVID-19 surges prediction based on SARS-CoV-2 mutations surveillance
• Immunogenicity and Protective Efficacy of a SARS-CoV-2 mRNA Vaccine Encoding Secreted Non-Stabilized Spike Protein in Mice -
  Establishment of an mRNA vaccine platform in low- and middle-income countries (LMICs) is important to enhance vaccine accessibility and ensure future pandemic preparedness. Here, we describe the preclinical studies of a SARS-CoV-2 mRNA encoding prefusion-unstabilized ectodomain spike protein encapsulated in lipid nanoparticles (LNP) “ChulaCov19”. In BALB/c mice, ChulaCov19 at 0.2, 1, 10, and 30 g given 2 doses, 21 days apart, elicited robust neutralizing antibody (NAb) and T cells responses in a dose-dependent relationship. The geometric mean titer (GMT) of micro-virus neutralizing (micro-VNT) antibody against wild-type virus was 1,280, 11,762, 54,047, and 62,084, respectively. Higher doses induced better cross-neutralizing antibody against Delta and Omicron variants. This elicited specific immunogenicity was significantly higher than those induced by homologous prime-boost with inactivated (CoronaVac) or viral vector (AZD1222) vaccine. In heterologous prime-boost study, mice primed with either CoronaVac or AZD1222 vaccine and boosted with 5 g ChulaCov19 generated NAb 7-fold higher against wild-type virus (WT) and was also significantly higher against Omicron (BA.1 and BA.4/5) than homologous CoronaVac or AZD1222 vaccination. AZD1222-prime/mRNA-boost had mean spike-specific IFN-{gamma} positive T cells of 3,725 SFC/106 splenocytes, which was significantly higher than all groups except homologous ChulaCov19. Challenge study in human-ACE-2-expressing transgenic mice showed that ChulaCov19 at 1 g or 10 g protected mice from COVID-19 symptoms, prevented SARS-CoV-2 viremia, significantly reduced tissue viral load in nasal turbinate, brain, and lung tissues 99.9-100%, and without anamnestic of Ab response which indicated its protective efficacy. ChulaCov19 is therefore a promising mRNA vaccine candidate either as a primary or a boost vaccination and has entered clinical development.
  🖺 Full Text HTML: Immunogenicity and Protective Efficacy of a SARS-CoV-2 mRNA Vaccine Encoding Secreted Non-Stabilized Spike Protein in Mice
• Correcting COVID-19 Vaccine Misinformation in Ten Countries -
  What can be done to reduce misperceptions about COVID-19 vaccines? We present results from experiments conducted simultaneously on YouGov samples in ten countries (N = 10,600), which reveal that factual corrections consistently reduce false belief about the vaccines. Globally, exposure to corrections increases belief accuracy by .16 on a 4-point scale, while exposure to misinformation decreases belief accuracy by .09 on the same scale. Neither misinformation nor factual corrections affect intent-to-vaccinate or vaccine attitudes. We find modest evidence that the effects of fact-checks endure, with 39% of the original correction effect in the direction of greater accuracy still detectable two weeks after initial exposure. These findings illustrate both the possibilities and limitations of factual corrections. Across ten highly diverse populations, exposure to factual information reliably reduces belief in falsehoods about vaccines, but has minimal influence on subsequent behaviors and attitudes.
  🖺 Full Text HTML: Correcting COVID-19 Vaccine Misinformation in Ten Countries
• Evolution of a globally unique SARS-CoV-2 Spike E484T monoclonal antibody escape mutation in a persistently infected, immunocompromised individual. -

  Prolonged infections in immunocompromised individuals may be a source for novel SARS-CoV-2 variants, particularly when both the immune system and antiviral therapy fail to clear the infection, thereby promoting adaptation. Here we describe an approximately 16-month case of SARS-CoV-2 infection in an immunocompromised individual. Following monotherapy with the monoclonal antibody Bamlanivimab, the individual9s virus was resistant to this antibody via a globally unique Spike amino acid variant (E484T) that evolved from E484A earlier in infection. With the emergence and spread of the Omicron Variant of Concern, which also contains Spike E484A, E484T may arise again as an antibody-resistant derivative of E484A.

  🖺 Full Text HTML: Evolution of a globally unique SARS-CoV-2 Spike E484T monoclonal antibody escape mutation in a persistently infected, immunocompromised individual.
• Regional correlations of COVID-19 in Spain -
  This paper analyzes the correlation between confirmed cases of COVID-19 and several geographic, meteorological and socioeconomic variables at the province level in Spain. The results indicate that there is a strong and robust negative relationship between average temperature and the rate of cases of COVID-19. The explanatory power of other geographic and socioeconomic variables is much lower. A parsimonious model including population density and temperature is able to explain 67% of variation in cases of COVID. However, the results are inconclusive regarding the existence of a relationship between changes in temperature and changes in COVID cases, casting doubts on the existence of a negative link between temperature and the spread of the virus.
  🖺 Full Text HTML: Regional correlations of COVID-19 in Spain
• Health System Resilience-enhancing Strategies for Managing Public Health Emergencies of International Concerns (PHEIC): Success and Challenges. A Systematic Review Protocol -

  Introduction Health system resilience is the ability to prepare, manage, and learn from a sudden and unpredictable extreme change which impacts health systems. Health systems globally have recently been affected by a number of catastrophic events, including natural disasters, and infectious disease epidemics. Understanding health system resilience has never been more essential until emerging global pandemics. Therefore, the application of resilience-enhancing strategies with existing frameworks needs to be assessed to identify the management gaps and give valuable recommendations from the lessons learnt from the global pandemic. Methods The systematic review will be reported using the Preferred reporting items for systematic review and meta-analysis protocols guideline (PRISMA-P). Reporting data on health system building blocks and systematic searches on resilience enhancing strategies for the management of Public Health Emergencies of International Concerns (PHEIC) after the establishment of International Health Regulations (IHR) since managing PHEIC after the establishment of IHR in 2007 will be included. The search will be conducted in PubMed, Scopus, Web of Science, and Google Scholar. Discussion Health system resilience is key to coping with catastrophic events, such as the economic crisis and COVID-19 pandemic. The mapping of available literature towards the application of resilience-enhancing strategies with existing frameworks needs to be assessed to identify the management gaps and give valuable recommendations from the lessons learnt from the global pandemic to improve the level of preparedness and response to similar public health emergencies in the future. Conclusion A protocol for a global review of health system resilience for pandemic management is described. This review will add to the body of knowledge about health systems enhancing research and policy formulation.

  🖺 Full Text HTML: Health System Resilience-enhancing Strategies for Managing Public Health Emergencies of International Concerns (PHEIC): Success and Challenges. A Systematic Review Protocol
• Antiporphyrics, antithrombotics and erythropoiesis stimulating agents to treat Covid-19: A living systematic review and meta-analysis -
  Abstract Aims: Covid-19 hematology is hallmarked by porphyrin dysmetabolism, altered hemostasis and erythropoietic distress. We hypothesize that antiporphyrics, antithrombotics and erythropoiesis stimulating agents (ESAs) may prove beneficial in the treatment of severe Covid-19. The objective of the current study was to systematically review and meta-analyse the mortality risk profile of hospitalized Covid-19 patients, when treated with each of the three interventions of interest - versus placebo, standard of care or non-intervention. Methods: Eligible studies were identified from: biorxiv and medrxiv, clinical trials govR4, covid19 trials tracker netR5, DISCOVERR2 (Ebsco), ICTRPR7, PubMedR1 and Google ScholarR3 during search period 27 May-07 June 2022. Risk of bias was assessed with SIGN, NIH and JBI checklists and results quantitatively synthesised for antiporphyrics plus antithrombotics studies. Quantitative synthesis was performed in RevMan 5.4R9 with random effects model meta-analysis. Publication bias was assessed in R by funnel plot, Egger’s regression and trimfill analysis (metafor). Results: Number and type of studies included was 6 RCTs for antiporphyrics, 16 cohort for antithrombotics, and 3 case report/series for ESAs. Both unadjusted and adjusted analyses suggested that hydroxychloroquine treatment was not significantly associated with mortality risk in hospitalised Covid-19 patients (RR 0.95 [0.71, 1.29], P=0.76; aHR 0.78 [0.51, 1.22], P=0.28). Interestingly, the direction of effect shifted further towards favoring intervention when only high quality studies were included in the analysis (unadjusted RR 0.80 [0.42, 1.55]) compared with low quality studies (unadjusted RR 1.59 [0.71, 3.53]) although neither were statistically significant (P=0.51 and P=0.26, respectively). Exposure to antithrombotics was associated with reduced in-hospital mortality risk in adjusted analysis (aOR 0.54 [0.33, 0.86], P=0.01; aHR 0.65 [0.52, 0.82], P=0.0003). Subgroup analysis of adjusted estimates showed that exposure to aspirin (aHR 0.62 [0.50, 0.77], P<0.00001) and heparin (aOR 0.35 [0.14, 0.90], P=0.03) individually were associated with reduced mortality risk. The finding was robust to type of regimen, with pre-admission exposure to antithrombotics (aHR 0.79 [0.67, 0.93], P=0.005) and aspirin (aHR 0.66 [0.52, 0.84], P=0.0009] both showing reduced mortality risk. Additionally, prophylactic dose antithrombotics were associated with reduced mortality (aHR 0.44 [0.32, 0.60], P<0.00001). Publication bias was negative by Egger’s regression test (P=0.95). The direction of effect remained significantly in favor of intervention after trim-and-fill analysis (P=0.0034). Discussion: We make an interim recommendation in favor of antithrombotics, with very low certainty of evidence. We make an interim recommendation in favor of either intervention or non-intervention for both antiporphyrics and ESAs, with low and very low certainty of evidence.
  🖺 Full Text HTML: Antiporphyrics, antithrombotics and erythropoiesis stimulating agents to treat Covid-19: A living systematic review and meta-analysis
• Resistance of SARS-CoV-2 Omicron Subvariant BA.4.6 to Antibody Neutralization -
  SARS-CoV-2 Omicron subvariants BA.4.6, BA.4.7, and BA.5.9 have recently emerged, and BA.4.6 appears to be expanding even in the presence of BA.5 that is globally dominant. Compared to BA.5, these new subvariants harbor a mutation at R346 residue in the spike glycoprotein, raising concerns for further antibody evasion. We compared the viral receptor binding affinity of the new Omicron subvariants with BA.5 by surface plasmon resonance. We also performed VSV-based pseudovirus neutralization assays to evaluate their antigenic properties using sera from individuals who received three doses of a COVID-19 mRNA vaccine (boosted) and patients with BA.1 or BA.2 breakthrough infection, as well as using a panel of 23 monoclonal antibodies (mAbs). Compared to the BA.5 subvariant, BA.4.6, BA.4.7, and BA.5.9 showed similar binding affinities to hACE2 and exhibited similar resistance profiles to boosted and BA.1 breakthrough sera, but BA.4.6 was slightly but significantly more resistant than BA.5 to BA.2 breakthrough sera. Moreover, BA.4.6, BA.4.7, and BA.5.9 showed heightened resistance over to a class of mAbs due to R346T/S/I mutation. Notably, the authorized combination of tixagevimab and cilgavimab completely lost neutralizing activity against these three subvariants. The loss of activity of tixagevimab and cilgavimab against BA.4.6 leaves us with bebtelovimab as the only therapeutic mAb that has retained potent activity against all circulating forms of SARS-CoV-2. As the virus continues to evolve, our arsenal of authorized mAbs may soon be depleted, thereby jeopardizing the wellbeing of millions of immunocompromised persons who cannot robustly respond to COVID-19 vaccines.
  🖺 Full Text HTML: Resistance of SARS-CoV-2 Omicron Subvariant BA.4.6 to Antibody Neutralization
• Omicron-induced interferon signalling prevents influenza A virus infection -
  Recent findings in permanent cell lines suggested that SARS-CoV-2 Omicron BA.1 induces a stronger interferon response than Delta. Here, we show that BA.1 and BA.5 but not Delta induce an antiviral state in air-liquid interface (ALI) cultures of primary human bronchial epithelial (HBE) cells and primary human monocytes. Both Omicron subvariants caused the production of biologically active type I (alpha/beta) and III (lambda) interferons and protected cells from super-infection with influenza A viruses. Notably, abortive Omicron infection of monocytes was sufficient to protect monocytes from influenza A virus infection. Interestingly, while influenza-like illnesses surged during the Delta wave in England, their spread rapidly declined upon the emergence of Omicron. Mechanistically, Omicron-induced interferon signalling was mediated via double-stranded RNA recognition by MDA5, as MDA5 knock-out prevented it. The JAK/ STAT inhibitor baricitinib inhibited the Omicron-mediated antiviral response, suggesting it is caused by MDA5-mediated interferon production, which activates interferon receptors that then trigger JAK/ STAT signalling. In conclusion, our study 1) demonstrates that only Omicron but not Delta induces a substantial interferon response in physiologically relevant models, 2) shows that Omicron infection protects cells from influenza A virus super-infection, and 3) indicates that BA.1 and BA.5 induce comparable antiviral states.
  🖺 Full Text HTML: Omicron-induced interferon signalling prevents influenza A virus infection
• Controllable self-replicating RNA vaccine delivered intradermally elicits predominantly cellular immunity -
  Intradermal delivery of self-replicating RNA (srRNA) is a promising vaccine platform. Considering that human skin temperature is around 33{degrees}C, lower than core body temperature of 37{degrees}C, we have developed an srRNA that functions optimally at skin temperature and is inactivated at or above 37{degrees}C as a safety switch. This temperature-controllable srRNA (c-srRNA), when tested as an intradermal vaccine against SARS-CoV-2, functions when injected naked without lipid nanoparticles. Unlike most currently available vaccines, c-srRNA vaccines predominantly elicit cellular immunity with little or no antibody production. Interestingly, c-srRNA-vaccinated mice produced antigen-specific antibodies upon subsequent stimulation with antigen protein. Antigen-specific antibodies were also produced when B-cell stimulation using antigen protein was followed by c-srRNA booster vaccination. Using c-srRNA, we have designed a pan-coronavirus booster vaccine that incorporates both spike receptor binding domains as viral surface proteins and evolutionarily conserved nucleoproteins as viral non-surface proteins, from both SARS-CoV-2 and MERS-CoV. It can thereby potentially immunize against SARS-CoV-2, SARS-CoV, MERS-CoV, and their variants. c-srRNA may provide a route to activate cellular immunity against a wide variety of pathogens.
  🖺 Full Text HTML: Controllable self-replicating RNA vaccine delivered intradermally elicits predominantly cellular immunity
• A multi-population-based genomic analysis uncovers unique haplotype variants and crucial mutant genes in SARS-CoV-2 -

  Background: COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2, SARS-CoV-2. Rigorous detection and treatment strategies against SARS-CoV-2 have become very challenging due to continuous evolutions to the viral genome. Therefore, careful genomic analysis is sorely needed to understand transmission, the cellular mechanism of pathogenicity, and the development of vaccines or drugs. Objective: In this study, we intended to identify SARS-CoV-2 genome variants that may help understand the cellular and molecular foundation of coronavirus infections required to develop effective intervention strategies. Methods: SARS-CoV-2 genome sequences were downloaded from an open-source public database, processed, and analyzed for variants in target detection sites and genes. Results: We have identified six unique variants, G….AAC, T….AAC….T; AAC….T; C……C; C……..C; and C……..T at the nucleocapsid region and eleven major hotspot mutant genes: nsp3, surface glycoprotein, nucleocapsid phosphoprotein, ORF8, nsp6, nsp2, nsp4, helicase, membrane glycoprotein, 39-59 exonuclease, and 2-O-ribose methyltransferases. In addition, we have identified eleven major mutant genes that may have a crucial role in SARS-CoV-2 pathogenesis. Conclusion: Studying haplotype variants and 11 major mutant genes to understand the mechanism of action of fatal pathogenicity and inter-individual variations in immune responses is inevitable for managing target patient groups with identified variants and developing effective anti-viral drugs and vaccines.

  🖺 Full Text HTML: A multi-population-based genomic analysis uncovers unique haplotype variants and crucial mutant genes in SARS-CoV-2
• Scaling rules for pandemics: Estimating infected fraction from identified cases for the SARS-CoV-2 Pandemic -

  Using a modified form of the SIR model, we show that, under general conditions, all pandemics exhibit certain scaling rules. Using only daily data for symptomatic, confirmed cases, these scaling rules can be used to estimate: (i) r_eff, the effective pandemic R-parameter; (ii) f_tot, the fraction of exposed individuals that were infected (symptomatic and asymptomatic); (iii) L_eff, the effective latency, the average number of days an infected individual is able to infect others in the pool of susceptible individuals; and (iv) alpha, the probability of infection per contact between infected and susceptible individuals. We validate the scaling rules using an example and then apply our method to estimate r_eff, f_tot, L_eff and alpha for the first phase of the SARS-Cov-2, Covid-19 pandemic for thirty-four countries where there was a well separated first peak in identified infected daily cases after the outbreak of this pandemic in early 2020. Our results are general and can be applied to any pandemic.

  🖺 Full Text HTML: Scaling rules for pandemics: Estimating infected fraction from identified cases for the SARS-CoV-2 Pandemic

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

• 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

• 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

• 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

• CArdiac REhabilitation for Building Exertional heArt Rate for Chronotropic Incompetence in Long COVID-19 - Conditions:   Long COVID;   COVID-19
  Intervention:   Behavioral: Cardiac Rehabilitation
  Sponsor:   University of California, San Francisco
  Not yet recruiting

• The Impact of a Web-based Psychoeducation Programme With a Motivational AI Chatbot on Covid-19 Vaccine Hesitancy - Conditions:   Vaccine Hesitancy;   COVID-19
  Interventions:   Behavioral: AI-driven Vaccine Communicator;   Behavioral: Self-learning of COVID-19 vaccine knowledge
  Sponsor:   The Hong Kong Polytechnic University
  Not yet 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

• 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

• HRQOL of Life After ECMO Due to COVID-19. - Conditions:   ARDS;   COVID-19 Pneumonia;   Extracorporeal Membrane Oxygenation
  Intervention:   Other: Phone Interview
  Sponsor:   Medical University of Vienna
  Recruiting

• A Study to Evaluate 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

• 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

• 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

• Addressing Post-COVID-19 Musculoskeletal Symptoms - Conditions:   Telemedicine;   Musculoskeletal Disease;   SARS-CoV-2;   Pain;   COVID-19;   Exercise
  Interventions:   Other: Multicomponent exercise program;   Other: Tele-health primary care rehabilitation program
  Sponsor:   Universidad Europea de Madrid
  Not yet recruiting

From PubMed

• Expression analysis of miRNA hsa-let7b-5p in naso-oropharyngeal swabs of COVID-19 patients supports its role in regulating ACE2 and DPP4 receptors - Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for worldwide coronavirus disease (COVID-19). We previously observed that Angiotensin-converting enzyme 2 (ACE2) and Dipeptidyl peptidase-4 (DPP4) are significantly overexpressed in naso-oropharyngeal swabs (NPS) of COVID-19 patients, suggesting their putative functional role in the disease progression. ACE2 and DPP4 overexpression in COVID-19 patients may be associated to epigenetic mechanism, such…

• The Renshen Chishao Decoction Could Ameliorate the Acute Lung Injury but Could Not Reduce the Neutrophil Extracellular Traps Formation - The acute lung injury (ALI) causes severe pulmonary diseases, leading to a high mortality rate. The Renshen and Chishao have protective and anti-inflammatory effects against the ALI. To explore the protective effects of the Renshen Chishao (RC) decoction against the ALI, we established the lipopolysaccharide-indued ALI model and randomly divided the mice into seven groups: control group, ALI group, high-dose RC group, middle-dose RC group, low-dose RC group, middle-dose RC group + CXCR2…

• In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs…

• Identification of trypsin-degrading commensals in the large intestine - Increased levels of proteases, such as trypsin, in the distal intestine have been implicated in intestinal pathological conditions^(1-3). However, the players and mechanisms that underlie protease regulation in the intestinal lumen have remained unclear. Here we show that Paraprevotella strains isolated from the faecal microbiome of healthy human donors are potent trypsin-degrading commensals. Mechanistically, Paraprevotella recruit trypsin to the bacterial surface through type IX secretion…

• Murine Broadly Reactive Antineuraminidase Monoclonal Antibodies Protect Mice from Recent Influenza B Virus Isolates and Partially Inhibit Virus Transmission in the Guinea Pig Model - Current influenza virus vaccines and antivirals have limitations, some of which disproportionately affect their utilization against influenza B viruses. To inform ongoing efforts to address the considerable global burden of influenza B viruses, we previously described five murine monoclonal antibodies that broadly bind conserved epitopes on the neuraminidase of influenza B viruses and protect against lethal challenge in a mouse model when delivered via intraperitoneal injection. Here, we…

• Mucosal Immunity After Novel COVID-19 Infection - Virus-Induced Immunosuppression: Preliminary Study - In recovered COVID-19 patients, the state of mucosal immunity remains understudied. Cytological, functional, and metabolic characteristics of neutrophils and the interleukin status will help to correctly assess the need for immunorehabilitation measures. The study objective is to assess the state of mucosal immunity after COVID-19. A comprehensive study of mucosal immunity included the assessment of nasal mucosal neutrophils with the monitoring of destructive and apoptotic changes as well as…

• Restoration of vascular endothelial integrity by mesenchymal stromal/stem cells in debilitating virus diseases - Endothelial dysfunction is one of the key cornerstone complications of emerging and re-emerging viruses which lead to vascular leakage and a high mortality rate. The mechanism that regulates the origin of endothelial dysregulation is not completely elucidated. Currently, there are no potential pharmacological treatments and curable management for such diseases. In this sense, mesenchymal stromal/stem cells (MSCs) has been emerging to be a promising therapeutic strategy in restoring endothelial…

• RNA G-quadruplex formed in SARS-CoV-2 used for COVID-19 treatment in animal models - The ongoing COVID-19 pandemic has continued to affect millions of lives worldwide, leading to the urgent need for novel therapeutic strategies. G-quadruplexes (G4s) have been demonstrated to regulate life cycle of multiple viruses. Here, we identify several highly conservative and stable G4s in SARS-CoV-2 and clarify their dual-function of inhibition of the viral replication and translation processes. Furthermore, the cationic porphyrin compound 5,10,15,20-tetrakis-(N-methyl-4-pyridyl)porphine…

• Hypoxia inducible factors regulate infectious SARS-CoV-2, epithelial damage and respiratory symptoms in a hamster COVID-19 model - Understanding the host pathways that define susceptibility to Severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) infection and disease are essential for the design of new therapies. Oxygen levels in the microenvironment define the transcriptional landscape, however the influence of hypoxia on virus replication and disease in animal models is not well understood. In this study, we identify a role for the hypoxic inducible factor (HIF) signalling axis to inhibit SARS-CoV-2 infection,…

• Diminished cell proliferation promotes natural killer cell adaptive-like phenotype by limiting FcεRIγ expression - Human adaptive-like natural killer (NK) cells express low levels of FcεRIγ (FcRγ-/low) and are reported to accumulate during COVID-19 infection; however, the mechanism underlying and regulating FcRγ expression in NK cells has yet to be fully defined. We observed lower FcRγ protein expression in NK cell subsets from lung transplant patients during rapamycin treatment, suggesting a link with reduced mTOR activity. Further, FcRγ-/low NK cell subsets from healthy donors displayed reduced mTOR…

• Recent advances in molecular biology of metabolic syndrome pathophysiology: endothelial dysfunction as a potential therapeutic target - Current advances in molecular pathobiology of endotheliocytes dysfunctions are promising in finding the pathogenetic links to the emergence of insulin resistance syndrome. Physiologically, human organism homeostasis is strictly controlled to maintain metabolic processes at the acquainted level. Many factors are involved in maintaining these physiological processes in the organism and any deviation is undoubtedly accompanied by specific pathologies related to the affected process. Fortunately,…

• NETosis and thrombosis in vaccine-induced immune thrombotic thrombocytopenia - Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare yet serious adverse effect of the adenoviral vector vaccines ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Janssen) against COVID-19. The mechanisms involved in clot formation and thrombocytopenia in VITT are yet to be fully determined. Here we show neutrophils undergoing NETosis and confirm expression markers of NETs in VITT patients. VITT antibodies directly stimulate neutrophils to release NETs and induce thrombus formation…

• Beyond the vaccines: a glance at the small molecule and peptide-based anti-COVID19 arsenal - Unprecedented efforts of the researchers have been witnessed in the recent past towards the development of vaccine platforms for the control of the COVID-19 pandemic. Albeit, vaccination stands as a practical strategy to prevent SARS-CoV-2 infection, supplementing the anti-COVID19 arsenal with therapeutic options such as small molecules/peptides and antibodies is being conceived as a prudent strategy to tackle the emerging SARS-CoV-2 variants. Noteworthy to mention that collective efforts from…

• Targeting spike protein-induced TLR/NET axis by COVID-19 therapeutic NRICM102 ameliorates pulmonary embolism and fibrosis - The global COVID-19 pandemic remains a critical public health threat, as existing vaccines and drugs appear insufficient to halt the rapid transmission. During an outbreak from May to August 2021 in Taiwan, patients with severe COVID-19 were administered NRICM102, which was a traditional Chinese medicine (TCM) formula developed based on its predecessor NRICM101 approved for treating mild cases. This study aimed to explore the mechanism of NRICM102 in ameliorating severe COVID-19-related embolic…

• Computational investigation of potent inhibitors against SARS-CoV-2 2’-O-methyltransferase (nsp16): Structure-based pharmacophore modeling, molecular docking, molecular dynamics simulations and binding free energy calculations - The Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has created unprecedented public health and economic crises around the world. SARS-CoV-2 2’-O-methyltransferase (nsp16) adds a “cap” to viral RNA to maintain the stability of viral RNA, and inhibition of nsp16 activity may reduce viral proliferation, making this protein an attractive drug target. Here, we report the identification of several small molecule inhibitors of…

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