Covid-19 Sentry

Contents

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

From Preprints

• A Pan-Coronavirus Vaccine Candidate: Nine Amino Acid Substitutions in the ORF1ab Gene Attenuate 99% of 365 Unique Coronaviruses: A Comparative Effectiveness Research Study -
  Background: The COVID-19 pandemic has been a watershed event. Industry and governments have reacted, investing over US$105 billion in vaccine research. The Holy Grail is a universal, pan-coronavirus, vaccine to protect humankind from future SARS-CoV-2 variants and the thousands of similar coronaviruses with pandemic potential. This paper proposes a new vaccine candidate that appears to attenuate the SARS-Cov-2 coronavirus variants to render it safe to use as a vaccine. Moreover, these results indicate it may be efficacious against 99% of 365 coronaviruses. This research model is wet-dry- wet; it originated in genomic sequencing laboratories, evolved to computational modeling, and the candidate result now require validation back in a wet lab. Objectives: This study’s purpose was to test the hypothesis that machine learning applied to sequenced coronaviruses’ genomes could identify which amino acid substitutions likely attenuate the viruses to produce a safe and effective pan-coronavirus vaccine candidate. This candidate is now eligible to be pre-clinically then clinically tested and proven. If validated, it would constitute a traditional attenuated virus vaccine to protect against hundreds of coronaviruses, including the many future variants of SARS-CoV-2 predicted from continuously recombining in unvaccinated populations and spreading by modern mass travel. Methods: Using machine learning, this was an in silico comparative effectiveness research study on trinucleotide functions in nonstructural proteins of 365 novel coronavirus genomes. Sequences of 7,097 codons in the ORF1ab gene were collected from 65 global locations infecting 68 species and reported to the US National Institute of Health. The data were proprietarily transformed twice to enable machine learning ingestion, mapping, and interpretation. The set of 2,590,405 data points was randomly divided into three cohorts: 255 (70%) observations for training; and two cohorts of 55 (15%) observations each for testing. Machine learning models were trained in the statistical programming language R and compared to identify which mixture of the 7.097 x 1023 possible amino-acid-location combinations would attenuate SARS-CoV-2 and other coronaviruses that have infected humans. Results: Contests of machine-learning algorithms identified nine amino-acid point substitutions in the ORF1ab gene that likely attenuate 98.98% of 365 (361) novel coronaviruses. Notably, seven substitutions are for the amino acid alanine. Most of the locations (5 of 9) are in nonstructural proteins (NSPs) 2 and 3. The substitutions are alanine to (1) valine at codon 4273; (2) leucine at codon 5077; (3) phenylalanine at codon 2001; (4) leucine at codon 372; (5) proline at codon 354; (6) phenylalanine at codon 2811; (7) phenylalanine at codon 4703; (8) leucine to serine at codon 2333; and, (9) threonine to alanine at codon 5131. Conclusions: The primary outcome is a new, highly promising, pan-coronavirus vaccine candidate based on nine amino-acid substitutions in the ORF1ab gene. The secondary outcome was evidence that sequences of wet-dry lab collaborations, here machine learning analysis of viral genomes informing codon functions, may discover new broader and more stable vaccines candidates more quickly and inexpensively than traditional methods.
  🖺 Full Text HTML: A Pan-Coronavirus Vaccine Candidate: Nine Amino Acid Substitutions in the ORF1ab Gene Attenuate 99% of 365 Unique Coronaviruses: A Comparative Effectiveness Research Study
• Mortality among healthcare workers in Indonesia during 18 months of COVID-19 -

  Abstract The impact of SARSCoV2 infections upon Indonesian health care workers (HCWs) remains unclear, as mortality data specific to HCWs is not systematically collected or analyzed in this setting. This report describes findings from a systematic collation, abstraction and analysis of HCW fatalities during the first 18 months of COVID19 in Indonesia. HCW who died during the period of March 2020 to July 2021 across Indonesia were identified on Pusara Digital, a community web based digital cemetery database dedicated to HCW. We calculated mortality rates and death risk ratio among HCWs and the general population. Qualitative methods explored concerns regarding mortality among HCWs. The analysis suggests that at least 1,545 HCWs died during the study period. The death of males and females HCWs were almost equally distributed (51% vs. 49%). Most were medical doctors and specialists (535, 35%), nurses (428, 28%), and midwives (359, 23%). Deaths most frequently occurred in the age group of 40 to 59 years old with the median age of 50 years (IQR: 39 to 59). At least 322 (21%) deaths occurred with pre-existing conditions, including 45 who were pregnant. We estimated a minimal HCW mortality rate in Indonesia at 1.707 deaths per 1000 HCW during the first 18 months of COVID19. Provincial HCW mortality rates ranged from 0.136 (West Sulawesi) to 5.32 HCW deaths per 1000 HCWs (East Java). HCW had a significantly higher mortality rate than the general population (RR = 4.92, 95% CI 4.67 to 5.17). The COVID19 event in Indonesia resulted in the loss of many hundreds of HCWs, most of them being senior physicians, nurses, and midwives. The HCW death rate is 5 times higher than everyone else. The sheer sparseness of the workforce requires more protective steps and national systematic surveillance of occupational mortality is urgently needed in this setting.

  🖺 Full Text HTML: Mortality among healthcare workers in Indonesia during 18 months of COVID-19
• CLINICAL MANIFESTATIONS AND DIAGNOSIS OF CO-INFECTION OF COVID-19, TUBERCULOSIS AND OPPORTUNISTIC PULMONARY INFECTIONS IN LATE-STAGE HIV PATIENTS WITH IMMUNODEFICIENCY -

  Objective. The purpose of the study was to investigate the specific features of clinical manifestations and diagnosis of co-infection of COVID-19, tuberculosis and opportunistic pulmonary infections in late-stage HIV patients. Design. 27 patients with co-infection of COVID-19, tuberculosis, opportunistic pulmonary infections and late-stage HIV infection with immunodeficiency without antiretroviral therapy (group 1) and 27 patients with equivalent parameters but without COVID-19 (group 2) were examined. Results. The patients of the group 1 and group 2 are the persons with social maladjustment and substance addiction. All of them have concomitant viral hepatitis B/C, COPD, opportunistic pulmonary infections and similar clinical and radiological manifestations, which can only be differentiated with microbiological and molecular genetic studies. The patients with co-infection of COVID-19, tuberculosis and HIV pose a high risk of transmission of infection to healthy persons in view of non-adherence to examination and treatment. Conclusion: To prevent the spread of infection among the healthy population, it is necessary to arrange in a mandatory manner an active and regular COVID-19 testing of all patients with tuberculosis/HIV co-infection, especially of late-stage HIV patients without antiretroviral therapy, in the tuberculosis care unit for HIV-infected persons at the tuberculosis dispensary. Key words: comorbidity, coronavirus, TB, AIDS.

  🖺 Full Text HTML: CLINICAL MANIFESTATIONS AND DIAGNOSIS OF CO-INFECTION OF COVID-19, TUBERCULOSIS AND OPPORTUNISTIC PULMONARY INFECTIONS IN LATE-STAGE HIV PATIENTS WITH IMMUNODEFICIENCY
• Structural and functional characteristics of SARS-CoV-2 Omicron subvariant BA.2 spike -
  The Omicron subvariant BA.2 has become the dominant circulating strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in many countries. We have characterized structural, functional and antigenic properties of the full-length BA.2 spike (S) protein and compared replication of the authentic virus in cell culture and animal model with previously prevalent variants. BA.2 S can fuse membranes more efficiently than Omicron BA.1, mainly due to lack of a BA.1-specific mutation that may retard the receptor engagement, but still less efficiently than other variants. Both BA.1 and BA.2 viruses replicated substantially faster in animal lung than the parental strain in the absence of pre- existing immunity, possibly explaining the heightened transmissibility despite their functionally compromised spikes. As in BA.1, mutations in the BA.2 S remodel its antigenic surfaces leading to strong resistance to neutralizing antibodies. These results suggest that both immune evasion and replicative advantage may contribute to the heightened transmissibility for the Omicron subvariants.
  🖺 Full Text HTML: Structural and functional characteristics of SARS-CoV-2 Omicron subvariant BA.2 spike
• GM-CSF-activated human dendritic cells promote type1 T follicular helper cells (Tfh1) polarization in a CD40-dependent manner -
  T follicular helper (Tfh) cells are specialized CD4+ T cells that regulate humoral immunity by providing B cell help. Tfh1 sub-population was recently identified and associated with severity in infection and autoimmune diseases. The cellular and molecular requirements to induce human Tfh1 differentiation are unknown. Our work investigated the role of human dendritic cells (DC) in promoting Tfh1 differentiation and their physiopathological implication in mycobacterium tuberculosis and mild COVID-19 infection. Activated human blood CD1c+ DC were cocultured with allogeneic naive CD4+ T cells. Single-cell RNA sequencing was then used alongside protein validation to define the induced Tfh lineage. DC signature and correlation with Tfh1 cells in infected patients was established through bioinformatic analysis. Our results show that GM-CSF-activated DC drove the differentiation of Tfh1 cells, displaying typical Tfh molecular features, including 1) high levels of PD-1, CXCR5, and ICOS expression; 2) BCL6 and TBET co- expression; 3) IL-21 and IFN-{gamma} secretion. Mechanistically, GM-CSF triggered the emergence of two distinct DC sub- populations defined by their differential expression of CD40 and ICOS-ligand (ICOS-L), and distinct phenotype, morphology, transcriptomic signature, and function. We showed that Tfh1 differentiation was efficiently and specifically induced by CD40highICOS-Llow DC in a CD40-dependent manner. Tfh1 cells were positively associated with a CD40highICOS- LLow DC signature in patients with latent mycobacterium tuberculosis and mild COVID-19 infection. Our study uncovers a novel CD40-dependent human Tfh1 axis. Immunotherapy modulation of Tfh1 activity might contribute to control diseases where Tfh1 are known to play a key role, such as infections.
  🖺 Full Text HTML: GM-CSF-activated human dendritic cells promote type1 T follicular helper cells (Tfh1) polarization in a CD40-dependent manner
• Removal of Clinically Relevant SARS-CoV-2 Variants by An Affinity Resin Containing Galanthus nivalis Agglutinin -
  The Coronavirus -19 (COVID-19) pandemic due to the SARS-CoV-2 virus has now exceeded two years in duration. The pandemic has been characterized by the development of a succession of variants containing mutations in the spike protein affecting infectiousness, virulence and efficacy of vaccines and monoclonal antibodies. Resistance to vaccination and limitations in the current treatments available require the ongoing development of therapies especially for those with severe disease. The plant lectin Galanthus nivalis binds to mannose structures in the viral envelope. We hypothesized that viral binding should be unaffected by spike protein mutations. Known concentrations of seven clinically relevant SARS-CoV-2 variants were spiked in medium and passed three times over columns containing 1 gm of GNA affinity resin. Percent decrease in viral titer was compared with a control sample. Viral capture efficiency was found to range from 53 to 89% for all variants. Extrapolation indicated that an adult Aethlon Hemopurifier would have more than sufficient binding capacity for viral loads observed in adult patients with severe COVID-19 infection.
  🖺 Full Text HTML: Removal of Clinically Relevant SARS-CoV-2 Variants by An Affinity Resin Containing Galanthus nivalis Agglutinin
• Diet induced obesity and type 2 diabetes drives exacerbated sex-associated disease profiles in K18-hACE2-mice challenged with SARS-CoV-2 -
  SARS-CoV-2 infection results in wide-ranging disease manifestation from asymptomatic to potentially lethal. Infection poses an increased threat of severity to at-risk populations including those with hypertension, diabetes, and obesity. Type 2 Diabetes (T2DM), is characterized, in part, by insulin insensitivity and impaired glucose regulation. T2DM patients have increased disease severity and poorer outcomes with COVID-19. We utilized the diet-induced obesity (DIO) model of Type 2 Diabetes in SARS-CoV-2-susceptible K18-hACE2 transgenic mice to better understand the obesity co- morbidity. Female DIO, but not male DIO mice challenged with SARS-CoV-2 were observed to have shortened time to morbidity compared to normal diet mice. Increase in susceptibility to SARS-CoV2 in female DIO was associated with increased total viral RNA burden compared to male mice. RNAseq analysis was performed on the lungs of non-challenged, challenged, females, males, of either normal diet or DIO cohorts to determine the disease specific transcriptional profiles. DIO female mice had more total activated genes than normal diet mice after challenge; however, male mice experienced a decrease. GO term analysis revealed the DIO condition increased interferon response signatures and interferon gamma production following challenge. Male challenged mice had robust expression of antibody-related genes suggesting antibody producing cell localization in the lung. DIO reduced antibody gene expression in challenged males. Collectively this study establishes a preclinical T2DM/obesity co-morbidity model of COVID-19 in mice where we observed sex and diet specific responses that begin to explain the effects of obesity and diabetes on COVID-19 disease.

• Induction of neutralizing antibodies against SARS-CoV-2 variants by a multivalent mRNA-lipid nanoparticle vaccine encoding SARS-CoV-2/SARS-CoV Spike protein receptor-binding domains -
  To address the need for multivalent vaccines against Coronaviridae that can be rapidly developed and manufactured, we compared antibody responses against SARS-CoV, SARS-CoV-2, and several variants of concern in mice immunized with mRNA-lipid nanoparticle vaccines encoding homodimers or heterodimers of SARS-CoV/SARS-CoV-2 receptor-binding domains. All vaccine constructs induced robust anti-viral antibody responses, and the heterodimeric vaccine elicited an IgG response capable of cross-neutralizing SARS-CoV, SARS-CoV-2 Wuhan-Hu-1, B.1.351 (beta), and B.1.617.2 (delta) variants.
  🖺 Full Text HTML: Induction of neutralizing antibodies against SARS-CoV-2 variants by a multivalent mRNA-lipid nanoparticle vaccine encoding SARS-CoV-2/SARS-CoV Spike protein receptor-binding domains
• The impact of COVID-19 pandemic on bronchiolitis (lower respiratory tract infection) due to respiratory syncytial virus: A systematic review and meta-analysis -

  Objective This systematic review and meta-analysis aimed to quantitatively evaluate the effect of the COVID-19 pandemic on respiratory syncytial virus (RSV) associated bronchiolitis among hospitalised infants. Methods The study protocol was registered in the PROSPERO database (CRD42022314000) and was designed based on PRISMA guidelines updated in May 2020. The meta-analysis component was modified appropriately to synthesise the pooled proportion of infants having RSV-associated bronchiolitis before the COVID-19 pandemic in 2019 and during the pandemic with 95% confidence interval (CI). Results: The eight qualified studies for the meta-analysis were from Spain, Italy, France and China, including 109,186 symptomatic cases of bronchiolitis before the pandemic in 2019 and 61,982 cases in 2020-2021. The quantitative analysis included laboratory-confirmed RSV infection in 7691 infants with bronchiolitis reported before the pandemic in

2019. Meanwhile, during the pandemic, 4964 cases were associated with RSV infection. The pooled proportion of RSV- associated bronchiolitis cases before the pandemic in 2019 was 16.74% (95% CI 11.73-22.43%). The pooled proportion of confirmed RSV cases during the pandemic in 2020/2021 was 19.20 % (95% CI 12.01-27.59%). Conclusion There was an increase in RSV activity after the relaxation of stringent public health measures during the COVID-19 pandemic.
      🖺 Full Text HTML: The impact of COVID-19 pandemic on bronchiolitis (lower respiratory tract infection) due to respiratory syncytial virus: A systematic review and meta- analysis

• Incorporating Vaccination into Compartment Models for Infectious Diseases -

  The standard way of incorporating vaccination into a compartment model for an infectious disease is as a spontaneous transition process that applies to the entire susceptible class. The large degree of COVID-19 vaccine refusal and initial limitations of supply and distribution require reconsideration of this standard treatment. In this paper, we address these issues for models on endemic and epidemic time scales. On an endemic time scale, we partition the susceptible class into prevaccinated and unprotected subclasses and show that vaccine refusal has a significant impact on endemic behavior, particularly for diseases where immunity is short-lived. On an epidemic time scale, we develop a supply-limited Holling type 3 vaccination model and show that it is an excellent fit to vaccination data. We also extend the Holling model to a COVID-19 scenario in which the population is divided into two risk classes, with the high-risk class being prioritized for vaccination. For both cases with and without stratification by risk, we see significant differences in epidemiological outcomes between the Holling vaccination model and naive models. Finally, we use the new model to explore implications for public health policies in future pandemics.

  🖺 Full Text HTML: Incorporating Vaccination into Compartment Models for Infectious Diseases
• Neuropsychological assessments for dementia research in the COVID-19 era: comparing remote and face-to-face testing -

  Objectives: We explored whether adapting traditional neuropsychological tests for online administration against the backdrop of COVID-19 was feasible for people with diverse forms of dementia and healthy older controls. We compared face-to-face and remote settings to ascertain whether remote administration affected performance. Design: We used a longitudinal design for healthy older controls who completed face-to-face neuropsychological assessments between three and four years before taking part remotely. For patients, we used a cross-sectional design, contrasting a prospective remote cohort with a retrospective face-to-face cohort matched in age, education, and disease duration. Setting: Remote assessments were performed using video-conferencing and online testing platforms, with participants using a personal computer or tablet and situated in a quiet room in their own home. Face-to-face assessments were carried out in dedicated testing rooms in our research centre. Participants: The remote cohort comprised ten healthy older controls (also seen face-to-face 3-4 years previously) and 25 patients (n=8 Alzheimer9s disease (AD); n=3 behavioural variant frontotemporal dementia (bvFTD); n=4 semantic dementia (SD); n=5 progressive nonfluent aphasia (PNFA); n=5 logopenic aphasia (LPA)). The face-to-face patient cohort comprised 64 patients (n=25 AD; n=12 bvFTD; n=9 SD; n=12 PNFA; n=6 LPA). Primary and secondary outcome measures: The outcome measures comprised the strength of evidence under a Bayesian analytic framework for differences in performances between face-to-face and remote testing environments on a general neuropsychological (primary outcomes) and neurolingustic battery (secondary outcomes). Results: There was evidence to suggest comparable performance across testing environments for all participant groups, for a range of neuropsychological tasks across both batteries. Conclusions: Our findings suggest that remote delivery of neuropsychological tests for dementia research is feasible.

  🖺 Full Text HTML: Neuropsychological assessments for dementia research in the COVID-19 era: comparing remote and face-to- face testing
• Correcting the Reproduction Number for Time-Varying Tests: a Proposal and an Application to COVID-19 in France -

  We provide a novel way to correct the effective reproduction number for the time-varying amount of tests, using the acceleration index as a simple measure of viral spread dynamics (Baunez et al., 2021). Not doing so results in the reproduction number being a biased estimate of viral acceleration and we provide a formal decomposition of the resulting bias, involving the useful notions of test and infectivity intensities. When applied to French data for the COVID-19 pandemic (May 13 - November 19, 2020), our decomposition shows that the reproduction number, when considered alone, consistently underestimates the resurgence of the pandemic since the summer of 2020, compared to the acceleration index which accounts for the time-varying volume of tests. Because the acceleration index aggregates all relevant information and captures in real time the sizable time variation featured by viral circulation, it is a more parsimonious indicator to track the dynamics of an infectious disease outbreak in real time, compared to the equivalent alternative which would be to complement the reproduction number with the test and infectivity intensities.

  🖺 Full Text HTML: Correcting the Reproduction Number for Time-Varying Tests: a Proposal and an Application to COVID-19 in France
• High-Dimensional Multinomial Multiclass Severity Scoring of COVID-19 Pneumonia Using CT Radiomics Features and Machine Learning Algorithms -

  We aimed to construct a prediction model based on computed tomography (CT) radiomics features to classify COVID-19 patients into severe-, moderate-, mild-, and non-pneumonic. A total of 1110 patients were studied from a publicly available dataset with 4-class severity scoring performed by a radiologist (based on CT images and clinical features). CT scans were preprocessed with bin discretization and resized, followed by segmentation of the entire lung and extraction of radiomics features. We utilized two feature selection algorithms, namely Bagging Random Forest (BRF) and Multivariate Adaptive Regression Splines (MARS), each coupled to a classifier, namely multinomial logistic regression (MLR), to construct multiclass classification models. Subsequently, 10-fold cross-validation with bootstrapping (n=1000) was performed to validate the classification results. The performance of multi-class models was assessed using precision, recall, F1-score, and accuracy based on the 4 by 4 confusion matrices. In addition, the areas under the receiver operating characteristic (ROC) curve (AUCs) for multi-class classifications were calculated and compared for both models using multiROC and pROC R packages. Using BRF, 19 radiomics features were selected, 9 from first-order, 6 from GLCM, 1 from GLDM, 1 from shape, 1 from NGTDM, and 1 from GLSZM radiomics features. Ten features were selected using the MARS algorithm, namely 2 from first-order, 1 from GLDM, 2 from GLRLM, 2 from GLSZM, and 3 from GLCM features. The Mean Absolute Deviation and Median from first-order, Small Area Emphasis from GLSZM, and Correlation from GLCM features were selected by both BRF and MARS algorithms. Except for the Inverse Variance feature from GLCM, all selected features by BRF or MARS were significantly associated with four-class outcomes as assessed within MLR (All p-values<0.05). BRF+MLR and MARS+MLR resulted in pseudo-R2 prediction performances of 0.295 and 0.256, respectively. Meanwhile, there were no significant differences between the feature selection models when using a likelihood ratio test (p-value =0.319). Based on confusion matrices for BRF+MLR and MARS+MLR algorithms, the precision was 0.861 and 0.825, the recall was 0.844 and 0.793, whereas the accuracy was 0.933 and 0.922, respectively. AUCs (95% CI)) for multi-class classification were 0.823 (0.795-0.852) and 0.816 (0.788-0.844) for BRF+MLR and MARS+MLR algorithms, respectively. Our models based on the utilization of radiomics features, coupled with machine learning, were able to accurately classify patients according to the severity of pneumonia, thus highlighting the potential of this emerging paradigm in the prognostication and management of COVID-19 patients.

  🖺 Full Text HTML: High-Dimensional Multinomial Multiclass Severity Scoring of COVID-19 Pneumonia Using CT Radiomics Features and Machine Learning Algorithms
• Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1 -

  Mutations in the viral genome of SARS-CoV-2 can impact the performance of molecular diagnostic assays. In some cases, such as S gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here we describe partial ORF1ab gene target failure (pOGTF) on the cobas® SARS- CoV-2 assays, defined by a ≥2 thermocycles delay in detection of the ORF1ab gene compared to the E gene. We demonstrate that pOGTF is 97% sensitive and 99% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may impact transmission, infectivity, and/or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities.

  🖺 Full Text HTML: Partial ORF1ab Gene Target Failure with Omicron BA.2.12.1
• Mapping the emergence of SARS-CoV-2 Omicron variants on a university campus -

  Novel variants continue to emerge in the SARS-CoV-2 pandemic. University testing programs may provide timely epidemiologic and genomic surveillance data to inform public health responses. We conducted testing from September 2021 to February 2022 in a university population under vaccination and indoor mask mandates. A total of 3,048 of 24,393 individuals tested positive for SARS-CoV-2 by RT-PCR; whole genome sequencing identified 209 Delta and 1,730 Omicron genomes of the 1,939 total sequenced. Compared to Delta, Omicron had a shorter median serial interval between genetically identical, symptomatic infections within households (2 versus 6 days, P=0.021). Omicron also demonstrated a greater peak reproductive number (2.4 versus 1.8) and a 1.07 (95% confidence interval: 0.58, 1.57; P<0.0001) higher mean cycle threshold value. Despite near universal vaccination and stringent mitigation measures, Omicron rapidly displaced the Delta variant to become the predominant viral strain and led to a surge in cases in a university population.

  🖺 Full Text HTML: Mapping the emergence of SARS-CoV-2 Omicron variants on a university campus

From Clinical Trials

• Clinical Performance Evaluation of the Bio-Self™ COVID-19 Antigen Home Test - Condition:   COVID-19
  Interventions:   Device: Bio-Self COVID-19 Antigen Home Test;   Device: Standard of Care COVID-19 Test;   Diagnostic Test: RT-PCR Test
  Sponsors:   BioTeke USA, LLC;   CSSi Life Sciences
  Not yet recruiting

• Immunogenicity and Safety of Fractional Booster Dose of COVID-19 Vaccines Available for Use in Pakistan/Brazil: A Phase 4 Dose-optimizing Trial - Condition:   COVID-19
  Interventions:   Biological: Sinovac;   Biological: AZD1222;   Biological: BNT162b2
  Sponsors:   Albert B. Sabin Vaccine Institute;   Aga Khan University;   Oswaldo Cruz Foundation;   Stanford University
  Not yet recruiting

• A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine as a Booster Dose in Population Aged 12-17 Years - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01E;   Biological: mRNA-1273
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• Evaluate the Safety and Immunogenicity of Ad5 COVID-19 Vaccines for Booster Use in Children Aged 6-17 Years. - Condition:   COVID-19
  Interventions:   Biological: 1 Nebulized inhalation for booster groups;   Biological: 2 Nebulized inhalation for booster groups;   Biological: 3 Nebulized inhalation for booster groups;   Biological: 4 Nebulized inhalation for booster groups;   Biological: 5 Intramuscular injection for booster groups;   Biological: 6 Intramuscular injection for booster groups;   Biological: 7 Intramuscular injection for booster groups;   Biological: 8 Intramuscular injection for booster groups;   Biological: 9 Intramuscular injection for booster groups;   Biological: 10 Intramuscular injection for booster groups;   Biological: 11 Nebulized inhalation for booster groups;   Biological: 12 Nebulized inhalation for booster groups;   Biological: 13 Nebulized inhalation for booster groups;   Biological: 14 Nebulized inhalation for booster groups;   Biological: 15 Intramuscular injection for booster groups;   Biological: 16 Intramuscular injection for booster groups;   Biological: 17 Intramuscular injection for booster groups;   Biological: 18 Intramuscular injection for booster groups;   Biological: 19 Intramuscular injection for booster groups;   Biological: 20 Intramuscular injection for booster groups;   Biological: 21 Nebulized inhalation for primary groups;   Biological: 22 Nebulized inhalation for primary groups;   Biological: 23 Nebulized inhalation for primary groups;   Biological: 24 Nebulized inhalation for primary groups
  Sponsor:  
  Seventh Medical Center of PLA General Hospital
  Not yet recruiting

• A First-In-Human Phase 1b Study of AmnioPul-02 in COVID-19 - Condition:   COVID-19
  Intervention:   Drug: AmnioPul-02
  Sponsor:   Amniotics AB
  Not yet recruiting

• A Study of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Older Adults. - Condition:   COVID-19
  Interventions:   Biological: 20 μg dose of SYS6006;   Biological: 30 μg dose of SYS6006;   Biological: 50 μg dose of SYS6006;   Drug: Placebo
  Sponsor:  
  CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
  Recruiting

• Safety, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine - Condition:   Covid19
  Interventions:   Biological: A Lyophilized COVID-19 mRNA Vaccine;   Biological: Placebo
  Sponsor:   Jiangsu Rec-Biotechnology Co., Ltd.
  Not yet recruiting

• A Study of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Adults Aged 18 -59 Years. - Condition:   COVID-19
  Interventions:   Biological: 20 μg dose of SYS6006;   Biological: 30 μg dose of SYS6006;   Biological: 50 μg dose of SYS6006;   Drug: Placebo
  Sponsor:  
  CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
  Recruiting

• Phase 2b/3 Trial of NuSepin® in COVID-19 Pneumonia Patients - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: NuSepin® 0.2 mg/kg;   Drug: NuSepin® 0.4 mg/kg;   Drug: Placebo
  Sponsor:   Shaperon
  Recruiting

• Aerobic Exercise and Covid-19 Survivors With Post-Intensive Care Syndrome (Pics) - Conditions:   COVID-19;   Post Intensive Care Syndrome
  Interventions:  
  Other: Aerobic Exercise Training;   Other: Home Plan
  Sponsor:   Riphah International University
  Not yet recruiting

• Efficacy and Safety of JT001 (VV116) Compared With Paxlovid - Condition:   COVID-19
  Interventions:   Drug: JT001;   Drug: Paxlovid
  Sponsor:  
  Vigonvita Life Sciences
  Recruiting

• Interleukine 6 (IL6) Assay for Predicting Failure of Spontaneous Breathing in Patients With COVID-19 Acute Respiratory Distress Syndrome - Condition:   COVID-19 Acute Respiratory Distress Syndrome
  Interventions:  
  Biological: IL6 assessment;   Biological: CRP and PCT assessment
  Sponsor:  
  Centre Hospitalier Henri Duffaut - Avignon
  Recruiting

• Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial - Condition:   COVID-19 Acute Respiratory Distress Syndrome
  Intervention:   Drug: EXOFLO
  Sponsor:   Direct Biologics, LLC
  Not yet recruiting

• Use of Continuous Glucose Monitors in Coronavirus Disease 2019 ICU and Potential Inpatient Settings - Conditions:   Covid19;   Diabetes Mellitus
  Intervention:   Device: continuous glucose monitoring
  Sponsor:   Tanureet K Arora
  Completed

• Phase Ⅱ Clinical Trial of SARS-CoV-2 mRNA Vaccine - Condition:   SARS-CoV-2
  Interventions:   Biological: SARS-CoV-2 (LVRNA009) 50μg group;   Biological: SARS-CoV-2 (LVRNA009) 100μg group;   Other: Placebo
  Sponsors:   AIM Vaccine Co., Ltd.;   Hunan Provincial Center for Disease Control and Prevention
  Active, not recruiting

From PubMed

• The determination of haemagglutinin influenza antibodies in the Polish population in the epidemic season 2020/2021 during the SARS-CoV-2 pandemic - The aim of the study was to prove the level of antibodies against haemagglutinin in the sera of people from seven age groups in the epidemic season 2020/2021 in Poland to determine the differentiation of the antibody level and the protection rate depending on age. The level of anti-haemagglutinin antibodies was established by haemagglutinin inhibition test (HAI). A total of 700 randomly selected sera from people belonging to 7 different age groups were tested. The results confirmed the presence…

• Harnessing Natural Products by a Pharmacophore-Oriented Semisynthesis Approach for the Discovery of Potential Anti- SARS-CoV-2 Agents - Natural products possessing unique scaffolds may have antiviral activity but their complex structures hinder facile synthesis. A pharmacophore-oriented semisynthesis approach was applied to (-)-maoelactone A ( 1 ) and oridonin ( 2 ) for the discovery of anti-SARS-CoV-2 agents. The Wolff rearrangement/lactonization cascade (WRLC) reaction was developed to construct the unprecedented maoelactone-type scaffold during semisynthesis of 1 . Further mechanistic study suggested a concerted mechanism for…

• Inflammasome activation in infected macrophages drives COVID-19 pathology - Severe COVID-19 is characterized by persistent lung inflammation, inflammatory cytokine production, viral RNA, and sustained interferon (IFN) response all of which are recapitulated and required for pathology in the SARS-CoV-2 infected MISTRG6-hACE2 humanized mouse model of COVID-19 with a human immune system^(1-20). Blocking either viral replication with Remdesivir^(21-23) or the downstream IFN stimulated cascade with anti-IFNAR2 in vivo in the chronic stages of disease attenuated the…

• Recent advances in passive immunotherapies for COVID-19: The Evidence-Based approaches and clinical trials - In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing a global pandemic called COVID-19. Currently, there is no definitive treatment for this emerging disease. Global efforts resulted in developing multiple platforms of COVID-19 vaccines, but their efficacy in humans should be wholly investigated in the long-term clinical and epidemiological follow-ups. Despite the international efforts, COVID-19 vaccination accompanies challenges, including financial and…

• Mutations in the SARS-CoV-2 RNA dependent RNA polymerase confer resistance to remdesivir by distinct mechanisms - The nucleoside analog remdesivir (RDV) is a Food and Drug Administration (FDA)-approved antiviral for treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Thus, it is critical to understand factors that promote or prevent RDV resistance. We passaged SARS-CoV-2 in the presence of increasing concentrations of GS-441524, the parent nucleoside of RDV. After 13 passages, we isolated three viral lineages with phenotypic resistance as defined by increases in…

• A multifunctional colorimetric sensor array for bacterial identification and real-time bacterial elimination to prevent bacterial contamination - Effective identification and real-time inactivation of pathogenic microorganisms is of great importance for preventing their infection and spread in public health, especially considering the huge threat of coronavirus disease 2019 (COVID-19). Herein, a novel multifunctional colorimetric sensor array with 3,3’,5,5’-tetramethylbenzidine (TMB) as a single probe has been constructed. TMB can be efficiently oxidized to generate oxidized TMB (oxTMB) by HAuCl(4), which displays four characteristic…

• Hydrazones and Thiosemicarbazones Targeting Protein-Protein-Interactions of SARS-CoV-2 Papain-like Protease - The papain-like protease (PLpro) of SARS-CoV-2 is essential for viral propagation and, additionally, dysregulation of the host innate immune system. Using a library of 40 potential metal-chelating compounds we performed an X-ray crystallographic screening against PLpro. As outcome we identified six compounds binding to the target protein. Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites of…

• Versisterol, a new endophytic steroid with 3CL protease inhibitory activity from Avicennia marina (Forssk.) Vierh - A new epoxy ergostane sterol, named versisterol, was isolated from Aspergillus versicolor, an endophytic fungus from Avicennia marina. The structure of the isolated compound was deduced by means of one- and two-dimensional NMR and high- resolution mass spectrometry. The absolute stereochemistry was elucidated by NOESY analysis, and experimental and calculated time-dependent density functional theory (TD-DFT) circular dichroism spectroscopy. Versisterol inhibited 3CL protease (3CL^(pro)) with an…

• In silico study of the inhibition of SARS-COV-2 viral cell entry by neem tree extracts - The outbreak of COVID-19, caused by SARS-COV-2, is responsible for higher mortality and morbidity rates across the globe. Until now, there is no specific treatment of the disease and hospitalized patients are treated according to the symptoms they develop. Efforts to identify drugs and/or vaccines are ongoing processes. Natural products have shown great promise in the treatment of many viral related diseases. In this work, using in silico methods, bioactive compounds from the neem tree were…

• Two novel oxetane containing lignans and a new megastigmane from Paronychia arabica and in silico analysis of them as prospective SARS-CoV-2 inhibitors - The chemical characterization of the extract of the aerial parts of Paronychia arabica afforded two oxetane containing lignans, paronychiarabicine A (1) and B (2), and one new megastigmane, paronychiarabicastigmane A (3), alongside a known lignan (4), eight known phenolic compounds (5-12), one known elemene sesquiterpene (13) and one steroid glycoside (14). The chemical structures of the isolated compounds were constructed based upon the HRMS, 1D, and 2D-NMR results. The absolute configurations…

• The interactions of folate with the enzyme furin: a computational study - Entrance of coronavirus into cells happens through the spike proteins on the virus surface, for which the spike protein should be cleaved into S1 and S2 domains. This cleavage is mediated by furin, a member of the proprotein convertases family, which can specifically cleave Arg-X-X-Arg↓ sites of the substrates. Here, folate (folic acid), a water-soluble B vitamin, is introduced for the inhibition of furin activity. Therefore, molecular insight into the prevention of furin activity in the…

• Drug repurposing and computational modeling for discovery of inhibitors of the main protease (M^pro) of SARS-CoV-2 - The main protease (M^(pro) or 3CL^(pro)) is a conserved cysteine protease from the coronaviruses and started to be considered an important drug target for developing antivirals, as it produced a deadly outbreak of COVID-19. Herein, we used a combination of drug reposition and computational modeling approaches including molecular docking, molecular dynamics (MD) simulations, and the calculated binding free energy to evaluate a set of drugs in complex with the M^(pro) enzyme. Particularly, our…

• Natural coumarins as potential anti-SARS-CoV-2 agents supported by docking analysis - COVID-19 is a global pandemic first identified in China, causing severe acute respiratory syndrome. One of the therapeutic strategies for combating viral infections is the search for viral spike proteins as attachment inhibitors among natural compounds using molecular docking. This review aims at shedding light on the antiviral potential of natural products belonging to the natural-products class of coumarins up to 2020. Moreover, all these compounds were filtered based on ADME analysis to…

• Long-term immunological consequences of anti-CD20 therapies on humoral responses to COVID-19 vaccines in multiple sclerosis: an observational study - CONCLUSION: Anti-CD20-induced inhibition of humoral responses to COVID-19 vaccines is transient and antibody production was more pronounced >18 months after anti-CD20 treatment discontinuation. The immunological effect on B-cell counts appears to wane by the same time.

• A VSV-based assay quantifies coronavirus Mpro/3CLpro/Nsp5 main protease activity and chemical inhibition - Protease inhibitors are among the most powerful antiviral drugs. However, for SARS-CoV-2 only a small number of protease inhibitors have been identified thus far and there is still a great need for assays that efficiently report protease activity and inhibition in living cells. Here, we engineer a safe VSV-based system to report both gain- and loss-of- function of coronavirus main protease (M^(pro)/3CLpro/Nsp5) activity in living cells. We use SARS-CoV-2 3CLpro in this system to confirm…

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