Covid-19 Sentry

Contents

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

From Preprints

• Management of Covid-19 booster mRNA vaccines with Colchicine and NSAIDS -
  An opinion article on the management and prophylaxis of cardiac inflammation during covid19 booster vaccinations in populations at risk.
  🖺 Full Text HTML: Management of Covid-19 booster mRNA vaccines with Colchicine and NSAIDS
• Assessing the potential impact of immunity waning on the dynamics of COVID-19: an endemic model of COVID-19 -

  We developed an endemic model of COVID-19 to assess the impact of vaccination and immunity waning on the dynamics of the disease. Our model exhibits the phenomenon of backward bifurcation and bi-stability, where a stable disease-free equilibrium co-exists with a stable endemic equilibrium. The epidemiological implication of this is that the control reproduction number being less than unity is no longer sufficient to guarantee disease eradication. We showed that this phenomenon could be eliminated by either increasing the vaccine efficacy or by reducing the disease transmission rate (adhering to non-pharmaceutical interventions). Furthermore, we numerically investigated the impacts of vaccination and waning of both vaccine-induced immunity and post-recovery immunity on the disease dynamics. Our simulation results show that the waning of vaccine-induced immunity has more effect on the disease dynamics relative to post-recovery immunity waning, and suggests that more emphasis should be on reducing the waning of vaccine-induced immunity to eradicate COVID-19.

  🖺 Full Text HTML: Assessing the potential impact of immunity waning on the dynamics of COVID-19: an endemic model of COVID-19
• Higher mortality associated with the SARS-CoV-2 Delta variant in the Western Cape, South Africa, using RdRp target delay as a proxy -

  A novel proxy for the Delta variant, RNA-dependent RNA polymerase target delay in the Seegene AllplexTM 2019-nCoV PCR assay, was associated with higher mortality (adjusted Odds Ratio 1.45 [95%CI 1.13-1.86]), compared to presumptive Beta infection, in the Western Cape, South Africa (April-July 2021). Prior diagnosed infection and vaccination were protective.

  🖺 Full Text HTML: Higher mortality associated with the SARS-CoV-2 Delta variant in the Western Cape, South Africa, using RdRp target delay as a proxy
• Predicting willingness to be vaccinated for Covid-19: evidence from New Zealand -

  Governments around the world are seeking to slow the spread of Covid-19 and reduce hospitalisations by encouraging mass vaccinations for Covid-19. The success of this policy depends on most of the population accepting the vaccine and then being vaccinated. Understanding and predicting the motivation of individuals to be vaccinated is, therefore, critical in assessing the likely effectiveness of a mass vaccination programme in slowing the spread of the virus. In this paper we draw on the I3 Response Framework to understand and predict the willingness of New Zealanders to be vaccinated for Covid-19. The Framework differs from most studies predicting willingness to be vaccinated because it is based on the idea that the willingness to adopt a behaviour depends on both involvement (a measure of motivational strength) with the behaviour and attitudes towards the behaviour. We show that predictions of individuals willingness to be vaccinated are improved using involvement and attitudes together, compared to attitudes alone. This result has important implications for the implementation of mass vaccination programmes for Covid-19.

  🖺 Full Text HTML: Predicting willingness to be vaccinated for Covid-19: evidence from New Zealand
• Occupational versus community risk of SARS-CoV-2 infection among employees of a long-term care facility: an observational study -

  Objectives: We investigated the relative contribution of occupational (vs. community) exposure for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among employees of a university-affiliated long-term care facility (LTCF), during the 1st pandemic wave in Switzerland (March to June 2020). Methods: We performed a nested analysis of a seroprevalence study among all volunteering LTCF staff to determine community and nosocomial risk factors for SARS-CoV-2 seropositivity using modified Poison regression. We also combined epidemiological and genetic sequencing data from a coronavirus disease 2019 (COVID-19) outbreak investigation in a LTCF ward to infer transmission dynamics and acquisition routes of SARS-CoV-2, and evaluated strain relatedness using a maximum likelihood phylogenetic tree. Results: Among 285 LTCF employees, 176 participated in the seroprevalence study, of whom 30 (17%) were seropositive for SARS-CoV-2. Most (141/176, 80%) were healthcare workers (HCWs). Risk factors for seropositivity included exposure to a COVID-19 inpatient (adjusted prevalence ratio [aPR] 2.6; 95%CI 0.9-8.1) and community contact with a COVID-19 case (aPR 1.7; 95%CI 0.8-3.5). Among 18 employees included in the outbreak investigation, the outbreak reconstruction suggests 4 likely importation events by HCWs with secondary transmissions to other HCWs and patients. Conclusions: These two complementary epidemiologic and molecular approaches suggest a substantial contribution of both occupational and community exposures to COVID-19 risk among HCWs in LTCFs. These data may help to better assess the importance of occupational health hazards and related legal implications during the COVID-19 pandemic.

  🖺 Full Text HTML: Occupational versus community risk of SARS-CoV-2 infection among employees of a long-term care facility: an observational study
• Ambivalence and Adherence to Recommendations to Reduce the Spread of COVID-19 -
  Governments worldwide still (Oct. 2021), to some extent, rely on behavioral recommendations to reduce the spread of COVID-19. We examine the role of ambivalence towards both the specific recommendations (micro-ambivalence) and the pandemic as a whole (macro-ambivalence) with regard to compliance. We predict that micro ambivalence relates negatively, whereas macro ambivalence relates positively, to self-reported adherence to recommendations. We present two studies (N = 691) supporting our hypotheses: the more ambivalent people are towards the behavioral recommendations (micro level), the less they report following them. Conversely, the more ambivalent people are about the pandemic as a whole (macro level), the more they report following recommendations. Our findings replicated in a U.S. sample and a representative German sample.
  🖺 Full Text HTML: Ambivalence and Adherence to Recommendations to Reduce the Spread of COVID-19
• Access and quality of sexual and reproductive health (SRH) services in Britain during the early stages of the COVID-19 pandemic: a qualitative interview study of patient experiences -

  Objectives: Access to quality sexual and reproductive health (SRH) services remains imperative, even during a pandemic. Our objective was to understand experiences of delayed or unsuccessful access to SRH services in Britain during the early stages of COVID-19 pandemic. Design: Semi-structured qualitative follow-up interviews were conducted in October-November 2020 (six months after the first UK lockdown) with participants of Natsal-COVID, a quasi- representative web-panel survey of sexual health and behaviour during COVID-19 (n=6654). Inductive thematic analysis was used to identify lessons for future SRH service access and quality. Setting: Telephone interviews with participants from the general population. Participants: 14 women and 6 men (24-47-years-old) reporting unmet need for SRH services and agreeing to recontact (n=311) were selected for interview using socio-demographic quotas. Results: Participant experiences spanned ten different SRH services, including contraception and antenatal/maternity services. At interview, ten participants still experienced unmet need. Participants reported hesitancy and self-censorship of need. Accessing services required tenacity. Challenges included navigating inconsistent information and changing procedures; perceptions of gatekeepers as obstructing access; and inflexible appointment systems. Concerns about reconfigured services included reduced privacy; decreased quality of interactions with professionals; reduced informal support due to lone attendance; and fewer routine physical checks. However, participants also described examples of more streamlined services and staff efforts to compensate for disruptions. Many viewed the blending of telemedicine with in-person care as a positive development. Conclusion: COVID-19 impacted access and quality of SRH services. The accounts of those who struggled to access services revealed self-censorship of need, difficulty navigating shifting service configurations, and perceived reduction in quality due to a socially-distanced service model. Telemedicine offers potential for greater efficiency if blended intelligently with in-person care. We offer some initial data-based recommendations for promoting equitable access and quality in restoration and future adaption of SRH services.

  🖺 Full Text HTML: Access and quality of sexual and reproductive health (SRH) services in Britain during the early stages of the COVID-19 pandemic: a qualitative interview study of patient experiences
• Seroprevalence, prevalence, and genomic surveillance: monitoring the initial phases of the SARS-CoV-2 pandemic in Betim, Brazil -

  The Covid-19 pandemic has created an unprecedented need for epidemiological monitoring using diverse strategies. We conducted a project combining prevalence, seroprevalence, and genomic surveillance approaches to describe the initial pandemic stages in Betim City, Brazil. We collected 3239 subjects in a population-based age-, sex- and neighborhood-stratified, household, prospective; cross-sectional study divided into three surveys 21 days apart sampling the same geographical area. In the first survey, overall prevalence (participants positive in serological or molecular tests) reached 0.46% (90% CI 0.12% - 0.80%), followed by 2.69% (90% CI 1.88% - 3.49%) in the second survey and 6.67% (90% CI 5.42% - 7.92%) in the third. The underreporting reached 11, 19.6, and 20.4 times in each survey, respectively. We observed increased odds to test positive in females compared to males (OR 1.88 95% CI 1.25 - 2.82), while the single best predictor for positivity was ageusia/ anosmia (OR 8.12, 95% CI 4.72 - 13.98). Thirty-five SARS-CoV-2 genomes were sequenced, of which 18 were classified as lineage B.1.1.28, while 17 were B.1.1.33. Multiple independent viral introductions were observed. Integration of multiple epidemiological strategies was able to describe Covid-19 dispersion in the city adequately. Presented results have helped local government authorities to guide pandemic management.

  🖺 Full Text HTML: Seroprevalence, prevalence, and genomic surveillance: monitoring the initial phases of the SARS-CoV-2 pandemic in Betim, Brazil
• Impact of biologics and small molecules for Inflammatory Bowel Disease on COVID-19 Related Hospitalization: A Systematic Review and Meta-analysis -

  Background The use of biological therapies and small molecules have been a concern for patients with inflammatory bowel disease (IBD) during COVID-19 pandemic. We aim to assess the association between risk of COVID-19 related hospitalization and these agents. Method A systematic review and meta-analysis of all published studies from December 2019 to September 2021 was performed to identify studies that reported COVID-19 related hospitalization in IBD patients receiving biological therapies or tofacitinib. The risk ratio (RR) was calculated to compare the relative risk of COVID-19 related hospitalization in patients receiving these medications to those who were not, at the time of the study. Results 18 studies were included. The relative risk of hospitalization was significantly lower in patients with IBD and COVID-19 who were receiving biologic therapy with RR of 0.47 (95% CI: 0.42-0.52, p < 0.00001). The RR was lower in patients receiving anti-TNFs compared to those who did not [RR= 0.48 (95% CI: 0.41-0.55, p < 0.00001)]. Similar finding was observed in patients taking ustekinumab [RR= 0.55 (95% CI: 0.43-0.72, p < 0.00001)]. Combination therapy of anti-TNF and an immunomodulator did not lower the risk of COVID-19 related hospitalization [RR= 0.98 (95% CI: 0.82-1.18, p =0.84]. The use of vedolizumab [RR= 1.13 (95% CI: 0.75-1.73, p =0.56] and tofacitinib [RR= 0.81 (95% CI: 0.49-1.33, p =0.40] was not associated with lower risk of COVID-19 related hospitalization. Conclusion Regarding COVID-19 related hospitalization in IBD, anti-TNFs and ustekinumab were associated with favorable outcomes. In addition, vedolizumab and tofacitinib were not associated with COVID-19 related hospitalization.

  🖺 Full Text HTML: Impact of biologics and small molecules for Inflammatory Bowel Disease on COVID-19 Related Hospitalization: A Systematic Review and Meta- analysis
• Leaders gender and the fight against COVID-19: investigation, replication, and a possible explanation -

  Objectives To investigate the alleged relationship between leaders gender and COVID-19 related cases and deaths in different countries across the globe. Study design The relationship between leaders gender and percent of women in parliament to COVID-19 cases and death per million was investigated in three time points (10 months) across 180 countries, controlling for possible covariates. Methods Three different types of analyses were run: (1) Six basic t-tests; (2) Two repeated-measure ANOVA tests analyzing change over time; (3) Six stepwise regression analyses for both leaders gender and the percentage of women in parliament. Results Our findings suggest that, contrary to some research and popular media headlines, and in-line with recent academic research, leadership gender is not a significant factor in explaining the variation between countries in the fight against the COVID-19 pandemic. Conclusions We suggest that this alleged relationship may stem from an illusory correlation. We argue that the uncertainty, stress, and anxiety that prevail in these times of global pandemic may be the breeding ground for judgmental biases of this sort.

  🖺 Full Text HTML: Leaders gender and the fight against COVID-19: investigation, replication, and a possible explanation
• A randomized, controlled, feasibility study of RD-X19 in patients with mild-to-moderate COVID-19 in the outpatient setting -

  These studies aimed to further understand the antiviral effects of safe, visible light and demonstrate a therapeutic effect of an investigational treatment device for outpatients with mild to moderate COVID-19. RD-X19 is a handheld medical device precisely engineered to emit blue light through the oral cavity to target the oropharynx and surrounding tissues. At doses that are well-tolerated in an in vitro human epithelial tissue model, the monochromatic visible light delivered by RD-X19 results in light-initiated expression of IL-1α and IL-1β cytokines with corresponding inhibition of SARS-CoV-2 replication. A randomized, double-blind, sham-controlled early feasibility study using the investigational device enrolled 31 subjects with a positive SARS-CoV-2 antigen test and possessing at least two moderate COVID-19 signs and symptoms. Subjects were randomized 2:1 (RD-X19 to sham), treated twice daily for four days, and evaluated over one week. Prespecified outcome measures included assessments of SARS-CoV-2 viral load and clinical assessments of COVID-19. There were no local application site reactions and no device-related adverse events. The time- weighted average change in log viral load throughout the study demonstrated a favorable reduction for RD-X19 compared to sham and at the end of study the mean change in log10 viral load was -3.29 for RD-X19 and -1.81 for sham at Day 8, demonstrating a treatment benefit of -1.48 [95% confidence internal (CI), -2.88 to -0.071]. Among the clinical outcome measures, differences between RD-X19 and sham were also observed, with a 57-hour reduction of median time to sustained resolution of COVID-19 signs and symptoms.

  🖺 Full Text HTML: A randomized, controlled, feasibility study of RD-X19 in patients with mild-to-moderate COVID-19 in the outpatient setting
• Establishing CREATE: Lessons learned in setting up a training environment for early-career researchers in respiratory medicine -
  Background: The purpose of the National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis (CRE-PF) is to improve and extend the lives of patients living with pulmonary fibrosis through the development of a comprehensive and integrated program of basic and clinical research and education across Australia. A key objective of the CRE-PF was establishment of a unique national training scheme, CREATE, for early-career researchers (ECRs) in respiratory research. CREATE ECRs are broadly drawn from two main fields of researchers: clinicians and scientists, where clinicians tend to be involved in part-time translational research and scientists are involved in broad scientific research including laboratory or genetic research, health economics or population research. Methods: We describe the CREATE Program which, with limited budget and the assistance of key organisations, has provided funding opportunities (scholarships, fellowships, prizes, travel and collaboration grants), professional development (mentoring program, symposia, presentation opportunities and on-line training) and fostered a connected, supportive research community for respiratory ECRs. Results: The CREATE program has successfully fostered the development of the supported researchers, contributing substantially to the future of pulmonary fibrosis research in Australia. During the life of the program the CRE-PF has offered 10 PhD scholarships and five postdoctoral fellowships, awarded 13 travel grants and three grants to promote collaboration between ECRs from different institutes. A mentoring program has been established and CREATE Symposia have been held in association with key meetings. During COVID-19 restrictions, a series of virtual research meetings has offered 12 CREATE ECRs from seven universities the opportunity to present their research to a national audience. CREATE research-related achievements are impressive, including over 80 first-author publications by ECRs, and many conference presentations. Contributions to the research community, measured by committee membership, is also strong. Conclusions: In spite of a very limited budget, wide geographic distribution of participants and the multi- disciplinary nature of the cohort, we have succeeded in providing a unique, supportive academic development environment for CREATE ECRs. Lessons learned in the process of developing this program include the importance of leveraging funding, being flexible, building networks and seeking and responding to ECR input.
  🖺 Full Text HTML: Establishing CREATE: Lessons learned in setting up a training environment for early-career researchers in respiratory medicine
• Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury -
  Severe lung damage in COVID-19 involves complex interactions between diverse populations of immune and stromal cells. In this study, we used a spatial transcriptomics approach to delineate the cells, pathways and genes present across the spectrum of histopathological damage in COVID-19 lung tissue. We applied correlation network-based approaches to deconvolve gene expression data from areas of interest within well preserved post-mortem lung samples from three patients. Despite substantial inter-patient heterogeneity we discovered evidence for a common immune cell signaling circuit in areas of severe tissue that involves crosstalk between cytotoxic lymphocytes and pro-inflammatory macrophages. Expression of IFNG by cytotoxic lymphocytes was associated with induction of chemokines including CXCL9, CXCL10 and CXCL11 which are known to promote the recruitment of CXCR3+ immune cells. The tumour necrosis factor (TNF) superfamily members BAFF (TNFSF13B) and TRAIL (TNFSF10) were found to be consistently upregulated in the areas with severe tissue damage. We used published spatial and single cell SARS-CoV-2 datasets to confirm our findings in the lung tissue from additional cohorts of COVID-19 patients. The resulting model of severe COVID-19 immune-mediated tissue pathology may inform future therapeutic strategies.
  🖺 Full Text HTML: Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury
• Massively collaborative crowdsourced research on COVID19 and the chemical senses -
  In March 2020, the Global Consortium of Chemosensory Research (GCCR) was founded by chemosensory researchers to address then emerging reports of unusual smell and taste dysfunction arising from the SARS-CoV-2 pandemic. Over the next year, the GCCR used a highly collaborative model, along with contemporary Open Science practices, to produce multiple high impact publications on chemosensation and COVID19. This invited manuscript describes the founding of the GCCR, the tools and approaches it used, and a summary of findings to date. These findings are contextualized within a summary of some of the broader insights about chemosensation (smell, taste, and chemesthesis) and COVID19 gained over the last 18 months, including potential mechanisms of loss. Also, it includes a detailed discussion of some current Open Science approaches and practices used by the GCCR to increase transparency, rigor, and reproducibility.
  🖺 Full Text HTML: Massively collaborative crowdsourced research on COVID19 and the chemical senses
• Conflicts of interest and physicians’ attitudes towards hydroxychloroquine as a treatment against COVID-19: A replication and extension of Roussel & Raoult (2020) -

  Hydroxychloroquine (HCQ) and its use as a treatment against COVID-19 have been at the center of heated debates. Some claim that the hostility of physicians towards HCQ was partly orchestrated by rival pharmaceutical companies seeking to promote their own treatment. In favor of this hypothesis, Roussel and Raoult (2020) have presented the results of a study in which they find a perfect positive correlation (ρ = 1.00) between French physicians9 attitudes towards HCQ and their conflict of interest with Gilead Sciences - the company that has promoted Remdesivir (REM) as a treatment against COVID-19. However, Roussel and Raoult9s study suffers from serious methodological shortcomings, among which is the fact that the statistical methods they employed might tend to artificially inflate correlations. In this study, we use a similar method and sample, but correct for their study s original shortcomings: we provide a detailed, pre-registered method for collecting and coding data, computer inter-rater agreement and use a wide array of appropriate statistical methods to achieve a more reliable estimate the association between conflicts of interest and physicians attitudes towards HCQ. We conclude that Roussel and Raoult s conclusion was misguided and that financial conflicts of interest were not the main predictors of the attitudes of physicians when compared to other factors, such as academic affiliation. Moreover, compared to other pharmaceutical companies, there was no specific link between attitudes towards HCQ and conflicts of interest with Gilead Sciences.

  🖺 Full Text HTML: Conflicts of interest and physicians’ attitudes towards hydroxychloroquine as a treatment against COVID-19: A replication and extension of Roussel &amp; Raoult (2020)

From Clinical Trials

• Randomized Study to Evaluate Intranasal Dose of STI-2099 (COVI-DROPS™) in Outpatient Adults With Mild COVID-19 Infection - Condition:   COVID-19
  Interventions:   Biological: COVI-DROPS;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Efficacy and Safety of Apixaban in COVID-19 Coagulopathy Patients With Respiratory Severity Under Critical Care - Condition:   COVID-19
  Intervention:   Drug: Apixaban
  Sponsors:  
  Scotmann Pharmaceuticals;   Rawalpindi Medical College
  Not yet recruiting

• Efficacy of Home Inspiratory Muscle Training in Post-covid-19 Patients: a Randomized Clinical Trial - Condition:   Covid19
  Intervention:   Device: Inspiratory muscle training
  Sponsor:  
  Universidade Federal do Rio Grande do Norte
  Recruiting

• COVID-19 Study of Pharmacokinetics, Safety, Tolerability, and Efficacy of Intravenous Anti-Spike(s) SARS-CoV-2 Monoclonal Antibodies (Casirivimab+Imdevimab) for the Treatment of Pediatric Patients Hospitalized Due to COVID-19 - Condition:   COVID-19
  Intervention:   Drug: casirivimab+imdevimab
  Sponsor:  
  Regeneron Pharmaceuticals
  Not yet recruiting

• Immunogenicity and Safety of Heterologous and Homologous Boosting With ChAdOx1-S and CoronaVac or a Formulation of SCB-2019 (COVID-19) - Condition:   Covid19
  Interventions:   Biological: ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford- AstraZeneca);   Biological: CoronaVac (Sinovac Biotech);   Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS- protein Subunit Vaccine (SCB-2019 - Clover)
  Sponsors:   D’Or Institute for Research and Education;   Bill and Melinda Gates Foundation;   Instituto Fernandes Figueira
  Not yet recruiting

• Tocilizumab Versus Baricitinib in Patients With Severe COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Tocilizumab;   Drug: Baricitinib
  Sponsor:   University Hospital of Patras
  Recruiting

• The Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients (Phase3) - Condition:   COVID-19
  Interventions:   Drug: Pyramax;   Drug: Placebo
  Sponsor:  
  Shin Poong Pharmaceutical Co. Ltd.
  Recruiting

• Pulmonary Function in Patients Recovering From COVID19 Infection : a Pilot Study - Condition:   COVID-19
  Intervention:   Diagnostic Test: diaphragm ultrasonography
  Sponsor:   University Hospital, Limoges
  Not yet recruiting

• JINZHEN for Treatment of Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: JINZHEN Granules for Oral Solution;   Drug: Placebo
  Sponsor:   Lianyungang Kanion Group, Ltd.
  Not yet recruiting

• Effectiveness of Using Interactive Consulting System to Enhance Decision Aids of COVID-19 Vaccination - Condition:   COVID-19
  Intervention:   Device: Chatbot
  Sponsor:   Sun Yat- sen University
  Recruiting

• Evaluation of the Efficacy of Probiotics to Reduce the Occurrence of Long COVID - Condition:   COVID-19
  Interventions:   Dietary Supplement: Probiotics;   Dietary Supplement: Placebo
  Sponsors:   Centre de recherche du Centre hospitalier universitaire de Sherbrooke;   Lallemand Health Solutions
  Not yet recruiting

• Impact of Nudges on Downloads of COVID-19 Exposure Notification Smartphone Apps: A Randomized Trial - Condition:   COVID-19
  Interventions:   Behavioral: Self-Benefit/Social Norm;   Behavioral: Self- Benefit/No Social Norm;   Behavioral: Other Benefit/Social Norm;   Behavioral: Other Benefit/No Social Norm
  Sponsors:   University of Pennsylvania;   Pennsylvania Department of Health
  Completed

• Efficacy, Safety, and Immunogenicity Study of the Recombinant Two-component COVID-19 Vaccine (CHO Cell) - Condition:   COVID-19
  Interventions:   Biological: Recombinant two-component COVID-19 vaccine (CHO cell);   Biological: Placebo
  Sponsor:   Jiangsu Rec-Biotechnology Co., Ltd.
  Not yet recruiting

• Cardiovascular Assessment in Patient Recovered From COVID-19 and Recovery of Autonomic Nervous System in Association With the Severity of the Disease - Condition:   COVID-19
  Intervention:   Other: Non invasive cardiovascular monitoring with CNAP device of arterial pressure, ECG and respiratory activity
  Sponsor:   IRCCS Policlinico S. Donato
  Recruiting

• Safety and Efficacy of KOVIR (TD0068) in the Combination Regimen With Background Treatment in COVID-19 Patients (KOVIR) - Condition:   COVID-19
  Interventions:   Dietary Supplement: KOVIR (TD0068) oral capsule;   Dietary Supplement: Placebo oral capsule
  Sponsors:   Sunstar Joint Stock Company;   Vietstar Biomedical Research
  Recruiting

From PubMed

• Mechanisms of inhibition of viral RNA replication by nucleotide analogs - Nucleotide analogs are the cornerstone of direct acting antivirals used to control infection by RNA viruses. Here we review what is known about existing nucleotide/nucleoside analogs and the kinetics and mechanisms of RNA and DNA replication, with emphasis on the SARS-CoV-2 RNA dependent RNA polymerase (RdRp) in comparison to HIV reverse transcriptase and Hepatitis C RdRp. We demonstrate how accurate kinetic analysis reveals surprising results to explain the effectiveness of antiviral nucleoside…

• Inhibition of viral RNA-dependent RNA polymerases with clinically relevant nucleotide analogs - The treatment of viral infections remains challenging, in particular in the face of emerging pathogens. Broad-spectrum antiviral drugs could potentially be used as a first line of defense. The RNA-dependent RNA polymerase (RdRp) of RNA viruses serves as a logical target for drug discovery and development efforts. Herein we discuss compounds that target RdRp of poliovirus, hepatitis C virus, influenza viruses, respiratory syncytial virus, and the growing data on coronaviruses. We focus on…

• Effect of Ivermectin and Atorvastatin on Nuclear Localization of Importin Alpha and Drug Target Expression Profiling in Host Cells from Nasopharyngeal Swabs of SARS-CoV-2- Positive Patients - Nuclear transport and vesicle trafficking are key cellular functions involved in the pathogenesis of RNA viruses. Among other pleiotropic effects on virus-infected host cells, ivermectin (IVM) inhibits nuclear transport mechanisms mediated by importins and atorvastatin (ATV) affects actin cytoskeleton-dependent trafficking controlled by Rho GTPases signaling. In this work, we first analyzed the response to infection in nasopharyngeal swabs from SARS-CoV-2-positive and -negative patients by…

• SARS-CoV-2 Spike Impairs DNA Damage Repair and Inhibits V(D)J Recombination In Vitro - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the coronavirus disease 2019 (COVID-19) pandemic, severely affecting public health and the global economy. Adaptive immunity plays a crucial role in fighting against SARS-CoV-2 infection and directly influences the clinical outcomes of patients. Clinical studies have indicated that patients with severe COVID-19 exhibit delayed and weak adaptive immune responses; however, the mechanism by which SARS-CoV-2 impedes adaptive…

• Inhibition of SARS-CoV-2 Replication by a Small Interfering RNA Targeting the Leader Sequence - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected almost 200 million people worldwide and led to approximately 4 million deaths as of August 2021. Despite successful vaccine development, treatment options are limited. A promising strategy to specifically target viral infections is to suppress viral replication through RNA interference (RNAi). Hence, we designed eight small interfering RNAs (siRNAs) targeting the highly conserved 5’-untranslated region (5’-UTR) of…

• Xeno-Nucleic Acid (XNA) 2’-Fluoro-Arabino Nucleic Acid (FANA) Aptamers to the Receptor-Binding Domain of SARS-CoV-2 S Protein Block ACE2 Binding - The causative agent of COVID-19, SARS-CoV-2, gains access to cells through interactions of the receptor-binding domain (RBD) on the viral S protein with angiotensin-converting enzyme 2 (ACE2) on the surface of human host cells. Systematic evolution of ligands by exponential enrichment (SELEX) was used to generate aptamers (nucleic acids selected for high binding affinity to a target) to the RBD made from 2’-fluoro-arabinonucleic acid (FANA). The best selected ~79 nucleotide aptamers bound the…

• Precursors of Viral Proteases as Distinct Drug Targets - Viral proteases are indispensable for successful virion maturation, thus making them a prominent drug target. Their enzyme activity is tightly spatiotemporally regulated by expression in the precursor form with little or no activity, followed by activation via autoprocessing. These cleavage events are frequently triggered upon transportation to a specific compartment inside the host cell. Typically, precursor oligomerization or the presence of a co-factor is needed for activation. A detailed…

• Cell Entry of Animal Coronaviruses - Coronaviruses (CoVs) are a group of enveloped positive-sense RNA viruses and can cause deadly diseases in animals and humans. Cell entry is the first and essential step of successful virus infection and can be divided into two ongoing steps: cell binding and membrane fusion. Over the past two decades, stimulated by the global outbreak of SARS-CoV and pandemic of SARS-CoV-2, numerous efforts have been made in the CoV research. As a result, significant progress has been achieved in our…

• IgG Antibodies Develop to Spike but Not to the Nucleocapsid Viral Protein in Many Asymptomatic and Light COVID-19 Cases - Since SARS-CoV-2 appeared in late 2019, many studies on the immune response to COVID-19 have been conducted, but the asymptomatic or light symptom cases were somewhat understudied as respective individuals often did not seek medical help. Here, we analyze the production of the IgG antibodies to viral nucleocapsid (N) protein and receptor-binding domain (RBD) of the spike protein and assess the serum neutralization capabilities in a cohort of patients with different levels of disease severity. In…

• Potential Molecular Mechanisms of Rare Anti-Tumor Immune Response by SARS-CoV-2 in Isolated Cases of Lymphomas - Recently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS- CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of SARS-CoV-2 and based on a computational approach show that: (i) SARS-CoV-2 Spike-RBD may bind to the extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL and may directly inhibit…

• The Cross-Talk between Thrombosis and Inflammatory Storm in Acute and Long-COVID-19: Therapeutic Targets and Clinical Cases - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a…

• SARS-CoV-2 Neutralizing Antibody Levels Post COVID-19 Vaccination Based on ELISA Method-A Small Real-World Sample Exploration - This study investigated the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies following inoculation with the coronavirus disease (COVID-19) vaccine. From June to July 2021, 127 participants who had completed COVID-19 vaccination (inactivated SARS-CoV-2 vaccine, 64; CoronaVac, 61; CanSino, 2) were recruited and tested using SARS-CoV-2 neutralizing antibody kits. The positive detection rate (inhibition of neutralizing antibodies ≥ 30%) was calculated…

• Longitudinal Humoral Responses after COVID-19 Vaccination in Peritoneal and Hemodialysis Patients over Twelve Weeks - It has been demonstrated that patients on hemo- or peritoneal dialysis are particularly susceptible to SARS-CoV-2 infection and impaired seroconversion compared to healthy controls. Follow-up data on vaccination response in dialysis patients is limited but is greatly needed to individualize and guide (booster) vaccination strategies. In this prospective, multicenter study we measured anti-spike S1 and neutralizing antibodies in 124 hemodialysis patients, 41 peritoneal dialysis patients, and 20…

• Potential Adjuvant Therapeutic Effect of Lactobacillus plantarum Probio-88 Postbiotics against SARS-COV-2 - In response to the ongoing COVID-19 pandemic, the global effort to develop high efficacy countermeasures to control the infection are being conducted at full swing. While the efficacy of vaccines and coronavirus drugs are being tested, the microbiome approach represents an alternative pathophysiology-based approach to prevent the severity of the infection. In the current study, we evaluated the action of a novel probiotic Lactobacillus plantarum Probio-88 against SARS- COV-2 replication and…

• Untimely TGFbeta responses in COVID-19 limit antiviral functions of NK cells - SARS-CoV-2 is a single-stranded RNA virus that causes coronavirus disease 2019 (COVID-19). Given its acute and often self-limiting course, components of the innate immune system are likely central in controlling virus replication thereby determining clinical outcome. Natural killer (NK) cells are innate lymphocytes with notable activity against a broad range of viruses, including RNA viruses^(1,2). NK cell function may be altered during COVID-19 despite increased representation of NK cells with…

From Patent Search

• Anti-SARS-CoV-2 antibodies and uses thereof I - - link

• Anti-SARS-CoV-2 antibodies and uses thereof II - - link

• 휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수물 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 약 90% 이며, 건강한 성인이면, 육각수 물은 약 62% 이며, COVID-19 환자, 사고의 부상, 17만개의 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수 물을 평소보다 많이 흡수 하면서 동반 산소부족 상태가 되며, 육각수물 보충 없이 산소 호흡기를 사용하면 심각한 후유증이 발병 할 수 있다.

육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수 물을 62% ~ 80% 이상, 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link

• 휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 90% 이며, 육각수물은 약 62% 이며, COVID-19, 사고 부상, 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수물을 평소보다 많이 흡수하면서 산소부족 상태가 되며, 육각수 보충 없이 산소호흡기를 사용하면 심각한 후유증이 발병 할 수 있다 육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수물을 62% ~ 80% 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link

• 用于检测新冠病毒的配对抗体及其应用 - 本发明涉及一种用于检测新冠病毒的配对抗体及其应用，其包括第一检测抗体和第二检测抗体；第一检测抗体具有如SEQ ID NO:1~3所示的轻链互补决定区，以及如SEQ ID NO:4~6所示的重链互补决定区，第二检测抗体具有如SEQ ID NO:7~9所示的轻链互补决定区，以及如SEQ ID NO:10~12所示的重链互补决定区。本发明筛选得到具有上述互补决定区序列的配对抗体，其识别N蛋白的不同表位，且由于两种抗体识别的是N蛋白非核酸结合区域，不会受核酸负电荷干扰，对核酸抗原表现出了兼容性，具有较好的稳定性，同时上述配对抗体具有较高的亲和力，病毒N蛋白检测灵敏度高。 - link

• 抗KL-6双特异性抗体及基因、重组载体、药物、试剂盒 - 本发明公开了抗KL‑6双特异性抗体或其变体、或其功能性片段，所述抗KL‑6双特异性抗体或其变体、或其功能性片段包括抗PTS域和抗SEA域，所述抗PTS域的重链可变区的CDR1、CDR2和CDR3分别具有SEQ ID NO.1~3所示的氨基酸序列。本发明还提供了基因、重组载体、药物、试剂盒。本发明的抗KL‑6双特异性抗体或其变体、或其功能性片段用于与KL‑6蛋白特异性结合，基因、重组载体用于抗KL‑6双特异性抗体的制备，药物用于治疗KL‑6蛋白引起的相关疾病，试剂盒用于KL‑6蛋白的定量检测。 - link

• 基于决策树模型与逻辑回归模型组合的感染筛查方法 - 本发明公开了一种基于决策树模型与逻辑回归模型组合的感染筛查方法，其检测操作方便，可提高感染筛查准确性，该方法基于生命体征监护仪实现，生命体征监护仪与远程数据服务平台通信连接，远程数据服务平台依据临床数据进行感染筛查，该方法包括：通过生命体征监护仪检测获取用户临床数据，将临床数据随机划分为训练集、测试集，将训练集均分为两份：训练集A、训练集B，基于训练集A构建决策树模型，同时，对训练集A进行特征选择，将关键特征向量作为已构建的决策树模型的输入，获取新构造特征向量，基于组合特征向量，构造逻辑回归模型，基于决策树模型和逻辑回归模型组合，对测试集进行预测分类，获取分类结果。 - link

• 病毒中和抗体与非中和抗体联合检测方法、检测卡及应用 - 一种病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用，通过病毒受体结合蛋白夹心法原理检测中和抗体，其为通过提前设置病毒受体结合蛋白和能阻断中和抗体与其结合的作为配体的蛋白所形成的复合物，将靶向受体蛋白的非中和抗体提前捕获，保证后续通过夹心法检测中和抗体的特异性。解决了现有技术中中和抗体检测灵敏度低、特异性差以及不能区分中和抗体与非中和抗体的问题，提供了一种简便、快速、灵敏度高、特异性高的病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用。 - link

• 扩增△500-532的SARS-CoV-2 Nsp1基因的引物对及其检测方法 - 本发明公开了一种扩增Δ500‑532的SARS‑CoV‑2 Nsp1基因的引物对及其检测方法。引物对的具体序列如SEQ ID NO.1和SEQ ID NO.2所示，其检测方法为：采用引物对对SARS‑CoV‑2 Nsp1基因进行PCR，对PCR产物进行变性退火后，加入T7EI内切酶孵育，再进行PCR扩增，并判断是否存在Δ500‑532的SARS‑CoV‑2 Nsp1基因。本发明可简便快捷的区分出SARS‑CoV‑2 Nsp1基因突变型和野生型。 - link

• 广谱抗冠状病毒和流感病毒及口腔致病菌复合IgY及其制剂 - 本发明提供一种广谱抗冠状病毒IgY和广谱抗流感病毒IgY以及抗口腔致病菌IgY及其组合抗体和制剂。本发明提供制备广谱抗冠状病毒IgY和广谱抗流感病毒IgY以及抗口腔致病菌IgY及其组合抗体和制剂的方法。广谱抗冠状病毒IgY和广谱抗流感病毒IgY可结合保守的抗原表位，达到广谱中和效果，解决新冠病毒和流感病毒变异的问题。本发明将广谱抗新冠病毒IgY和广谱抗流感病毒IgY以及抗口腔致病菌IgY及其组合抗体制成系列制剂，包括牙膏和口含片以及潄口水和其它日用品、口鼻喷雾剂、消毒剂、洗手液、粉剂、片剂、糖果、滴鼻剂、滴眼剂、口服剂、胶囊剂，应用于防治新冠和流感以及口腔疾病的药物、消毒产品、保健品和医疗器械中。 - link