Covid-19 Sentry

Contents

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

From Preprints

• Using dialogues to increase positive attitudes towards Covid-19 vaccines in a vaccine-hesitant UK population -
  Recently, Altay et al (2021) showed that five minutes of interaction with a chatbot led to increases in Covid-19 vaccination attitudes and intentions in a French population. Here we replicate this effect in a vaccine-hesitant, UK-based population. We attempt to isolate what made the chatbot condition effective by controlling the amount of information provided, the trustworthiness of the information, and the level of interactivity. Like Altay et al, our experiment allowed participants to navigate a branching dialogue by choosing questions of interest about Covid-19 vaccines. Our control condition used the same questions and answers but removed participant choice by presenting the dialogues at random. Importantly we also targeted those who were either against or neutral towards Covid-19 vaccinations to begin with, screening-out those with already positive attitudes. Replicating Altay et al, we found a similar size increase in positive attitudes towards vaccination, and in intention to get vaccinated. Unlike Altay et al, we found no difference between our two conditions: choosing the questions did not increase vaccine attitudes or intentions any more than our control condition. These results suggest that the attitudes of the vaccine hesitant are modifiable with exposure to in-depth, trustworthy and engaging dialogues.
  🖺 Full Text HTML: Using dialogues to increase positive attitudes towards Covid-19 vaccines in a vaccine-hesitant UK population
• Socio-economic impact of HIV/AIDS and compounding effect of COVID-19 pandemic in sub-Sahara Africa -
  Together with the recent emergence of COVID-19, which is not only directly contributing to high morbidity and mortality but is also destabilizing critical health systems and undermining HIV and other global health initiatives, the spread of HIV/AIDS has adversely impacted all advancements in education, health, standards of living, and life expectancy that Africa has made since the 1950s. However, all nations and regions must work together to find solutions to these global issues, especially sub-Saharan Africa, which has the lowest vaccination rates worldwide and the highest rates of HIV/AIDS infection despite having promising economic possibilities. The goals of this review were to emphasize the effects of HIV and AIDS on socio-economic development in sub-Saharan Africa and to highlight how the COVID-19 pandemic affects this relationship.
  🖺 Full Text HTML: Socio-economic impact of HIV/AIDS and compounding effect of COVID-19 pandemic in sub-Sahara Africa
• An accessible infrastructure for artificial intelligence using a docker-based Jupyterlab in Galaxy -
  Artificial intelligence (AI) programs that train on a large amount of data require powerful compute infrastructure. Jupyterlab notebook provides an excellent framework for developing AI programs but it needs to be hosted on a powerful infrastructure to enable AI programs to train on large data. An open-source, docker-based, and GPU-enabled jupyterlab notebook infrastructure has been developed that runs on the public compute infrastructure of Galaxy Europe for rapid prototyping and developing end-to-end AI projects. Using such a notebook, long-running AI model training programs can be executed remotely. Trained models, represented in a standard open neural network exchange (ONNX) format, and other resulting datasets are created in Galaxy. Other features include GPU support for faster training, git integration for version control, the option of creating and executing pipelines of notebooks, and the availability of multiple dashboards for monitoring compute resources. These features make the jupyterlab notebook highly suitable for creating and managing AI projects. A recent scientific publication that predicts infected regions of COVID-19 CT scan images is reproduced using multiple features of this notebook. In addition, colabfold, a faster implementation of alphafold2, can also be accessed in this notebook to predict the 3D structure of protein sequences. Jupyterlab notebook is accessible in two ways - first as an interactive Galaxy tool and second by running the underlying docker container. In both ways, long-running training can be executed on Galaxy’s compute infrastructure.
  🖺 Full Text HTML: An accessible infrastructure for artificial intelligence using a docker-based Jupyterlab in Galaxy
• Reasons for not getting vaccinated against COVID-19 in German-speaking Switzerland: An online survey among vaccine hesitant 16-60 year olds -
  Background: Several research studies have examined the reasons why people are hesitant to be vaccinated against COVID-19. However, there is no published data to date on Switzerland. Identifying these reasons among the Swiss population who are vaccine hesitant may help inform campaigns to encourage vaccine confidence. Aims: The primary aim of this study is to identify the reasons for not getting vaccinated against COVID-19 among Swiss residents who are vaccine hesitant. The secondary aim is to examine whether reasons differ by age, gender, education, and likelihood of accepting a vaccination to better target campaigns and design interventions. Design: An online survey asked participants to indicate the reasons why they were hesitant to be vaccinated against COVID-19. Setting: German-speaking Swiss Cantons, the survey was administered online between 5 May 2021 and 16 May 2021. Participants: The participants in this analysis were a sample of (N=1191) Swiss residents age 16-60 years old from German-speaking Cantons, who could answer an online survey in German, who had yet not been vaccinated, who had not yet registered for a vaccination appointment, and who did not indicate that they would definitely be vaccinated if offered the chance. Findings: Among people who are vaccine hesitant in Switzerland, the most common reasons for being hesitant were side-effect, safety, and effectiveness concerns. It was also common for people to indicate that they were healthy/at low risk, would decide later, and that they wanted to build immunity naturally. Less common, but still prevalent concerns included wanting more information, thinking COVID-19 was not a real threat, and concerns that the vaccine may serve another purpose. Differences in reasons for being vaccine hesitant were found by age, gender, education, and likelihood of accepting a vaccination if offered. Conclusions: To increase the likelihood of accepting a vaccination, vaccination campaigns should address side-effect, safety, and effectiveness concerns. Campaigns could also consider informing people why it is necessary for people in lower risk groups to be vaccinated, and why vaccination is preferable to infection for building immunity. While campaigns may be effective in reaching some of the population, alternative strategies might be necessary to strengthen the trust relationship with vaccines and vaccine providers in some groups. Less prevalent concerns, such as not liking needles, could be addressed through individual level interventions.
  🖺 Full Text HTML: Reasons for not getting vaccinated against COVID-19 in German-speaking Switzerland: An online survey among vaccine hesitant 16-60 year olds
• Increasing SARS-CoV2 cases, hospitalizations and deaths among the vaccinated elderly populations during the Omicron (B.1.1.529) variant surge in UK. -

  BACKGROUND There were increased SARS-CoV2 hospitalizations and deaths noted during Omicron (B.1.1.529) variant surge in UK despite decreased cases, and the reasons are unclear. METHODS In this retrospective observational study, we analyzed reported SARS-CoV2 cases, hospitalizations and deaths during the COVID-19 pandemic in the UK. We also analyzed variables (ethnic, deprivation score vaccination disparities and pre-existing conditions) that can affect the outcomes. The vaccine effectiveness among those ≥18 years of age (August 16, 2021 to March 27, 2022) was analyzed. RESULTS Of the total cases (n= 22,072,550), hospitalizations (n=848,911) and deaths (n=175,070) due to COVID-19 in the UK; 51.3% of cases (n=11,315,793), 28.8% of hospitalizations (n=244,708), and 16.4% of deaths (n=28,659) occurred during the Omicron variant surge. When comparing the period of February 28 - May 1, 2022 with the prior 12-weeks, we observed a significant increase in the case fatality rate (0.19% vs 0.41%; RR 2.11[ 2.06-2.16], p<0.001) and the risk of hospitalizations (1.58% vs 3.72%; RR 2.36[2.34-2.38]; p<0.001). During the same period, we also observed a significant increase in the proportion of cases (23.7% vs 40.3%; RR1.70 [1.70-1.71]; p<0.001) among ≥50 years of age and hospitalizations (39.3% vs 50.3%;RR1.28 [1.27-1.30]; p<0.001) and deaths (67.89% vs 80.07%;RR1.18 [1.16-1.20]; p<0.001) among ≥75 years of age. The vaccine effectiveness (VE) for the third dose was in negative since December 20, 2021, with a significantly increased proportion of SARS-CoV2 cases hospitalizations and deaths among the vaccinated; and a decreased proportion of cases, hospitalizations, and deaths among the unvaccinated. The pre-existing conditions were present in 95.6% of all COVID-19 deaths and we also observed various ethnic, deprivation score and vaccination rate disparities that can adversely affect hospitalization and deaths among the compared groups based on the vaccination status. CONCLUSIONS There is no discernable optimal vaccine effectiveness among ≥18 years of age, vaccinated third dose population since December 20, 2021 during the beginning of the Omicron variant surge. Pre-existing conditions, ethnicity, deprivation score, and vaccination rate disparities data need to be adjusted by the development of validated models for evaluating VE for hospitalizations and deaths. The increased proportion of cases with significantly increased risk of hospitalizations and deaths among the elderly population during the Omicron variant surge underscores the need to prevent infections in the elderly irrespective of vaccination status with uniform screening protocols and protective measures.

  🖺 Full Text HTML: Increasing SARS-CoV2 cases, hospitalizations and deaths among the vaccinated elderly populations during the Omicron (B.1.1.529) variant surge in UK.
• A comparison of four epidemic waves of COVID-19 in Malawi; an observational cohort study -

  Background Compared to the abundance of clinical and genomic information available on patients hospitalised with COVID-19 disease from high-income countries, there is a paucity of data from low-income countries. Our aim was to explore the relationship between viral lineage and patient outcome. Methods We enrolled a prospective observational cohort of adult patients hospitalised with PCR-confirmed COVID-19 disease between July 2020 and March 2022 from Blantyre, Malawi, covering four waves of SARS-CoV-2 infections. Clinical and diagnostic data were collected using an adapted ISARIC clinical characterization protocol for COVID-19. SARS-CoV-2 isolates were sequenced using the MinIONTM in Blantyre. Results We enrolled 314 patients, good quality sequencing data was available for 55 patients. The sequencing data showed that 8 of 11 participants recruited in wave one had B.1 infections, 6/6 in wave two had Beta, 25/26 in wave three had Delta and 11/12 in wave four had Omicron. Patients infected during the Delta and Omicron waves reported fewer underlying chronic conditions and a shorter time to presentation. Significantly fewer patients required oxygen (22.7% [17/75] vs. 58.6% [140/239], p<0.001) and steroids (38.7% [29/75] vs. 70.3% [167/239], p<0.001) in the Omicron wave compared with the other waves. Multivariable logistic-regression demonstrated a trend toward increased mortality in the Delta wave (OR 4.99 [95% CI 1.0-25.0 p=0.05) compared to the first wave of infection. Conclusions Our data show that each wave of patients hospitalised with SARS-CoV-2 was infected with a distinct viral variant. The clinical data suggests that patients with severe COVID-19 disease were more likely to die during the Delta wave.

  🖺 Full Text HTML: A comparison of four epidemic waves of COVID-19 in Malawi; an observational cohort study
• Small Molecule Antiviral Compound Collection (SMACC): a database to support the discovery of broad-spectrum antiviral drug molecules. -
  Diseases caused by new viruses costs thousands if not millions of human lives and trillions of dollars in damage to the global economy. Despite the rapid development of vaccines for SARS-CoV-2, the lack of small molecule antiviral drugs that work against multiple viral families (broad-spectrum antivirals; BSAs) has left the entire world human population vulnerable to the infection between the beginning of the outbreak and the widespread availability of vaccines. Developing BSAs is an attractive, yet challenging, approach that could prevent the next, inevitable, viral outbreak from becoming a global catastrophe. To explore whether historical medicinal chemistry efforts suggest the possibility of discovering novel BSAs, we (i) identified, collected, curated, and integrated all chemical bioactivity data available in ChEMBL for molecules tested in respective assays for 13 emerging viruses that, based on published literature, hold the greatest potential threat to global human health; (ii) identified and solved the challenges related to data annotation accuracy including assay description ambiguity, missing cell or target information, and incorrect BioAssay Ontology (BAO) annotations; (iii) developed a highly curated and thoroughly annotated database of compounds tested in both phenotypic (21,392 entries) and target-based (11,123 entries) assays for these viruses; and (iv) identified a subset of compounds showing BSA activity. For the latter task, we eliminated inconclusive and annotated duplicative entries by checking the concordance between multiple assay results and identified eight compounds active against 3-4 viruses from the phenotypic data, 16 compounds active against two viruses from the target-based data, and 35 compounds active in at least one phenotypic and one target-based assay. The pilot version of our SMACC (Small Molecule Antiviral Compound Collection) database contains over 32,500 entries for 13 viruses. Our analysis indicates that previous research yielded very small number of BSA compounds. We posit that focused and coordinated efforts strategically targeting the discovery of such agents must be established and maintained going forward. The SMACC database publicly available at https://smacc.mml.unc.edu may serve as a reference for virologists and medicinal chemists working on the development of novel BSA agents in preparation for future viral outbreaks.
  🖺 Full Text HTML: Small Molecule Antiviral Compound Collection (SMACC): a database to support the discovery of broad-spectrum antiviral drug molecules.
• Efficient reconciliation of genomic datasets of high similarity -
  We apply Invertible Bloom Lookup Tables (IBLTs) to comparison of k-mer sets originated from large DNA sequence datasets. We show that for similar datasets, IBLTs provide a more space-efficient and, at the same time, more accurate method for estimating Jaccard similarity of underlying k-mer sets, compared to MinHash which is a go-to sketching technique for efficient pairwise similarity estimation. This is achieved by combining IBLTs with k-mer sampling based on syncmers, which constitute a context-independent alternative to minimizers and provide an unbiased estimator of Jaccard similarity. A key property of our method is that involved data structures take space proportional to the difference of k-mer sets and are independent of the size of sets themselves. As another application, we show how our ideas can be applied in order to efficiently compute (an approximation of) k-mers that differ between two datasets, still using a space only proportional to their number. We experimentally illustrate our results on both simulated and real data (SARS-CoV-2 and Streptococcus Pneumoniae genomes).
  🖺 Full Text HTML: Efficient reconciliation of genomic datasets of high similarity
• Responding to the call of the NHS Nightingale, but at what cost?: An auto-ethnography of a volunteer frontline mental health trainer’s experiences during the COVID-19 pandemic. -
  The COVID-19 pandemic has called healthcare workers globally to respond. In the UK, the predicted high demand for extra critical care beds led to the rapid construction of the NHS Nightingale Hospital, London. I volunteered to develop and deliver psychological preparedness training - coined ‘Psychological PPE’ – to over 2300 frontline staff over an eight-week period. Current research has identified broad themes of the impact working on the COVID-19 frontline has on healthcare workers but is yet to capture in-depth accounts of individuals’ experiences. Using autoethnographic enquiry, this research explores my frontline experience at the NHS Nightingale, at the peak of the COVID-19 pandemic, and the personal impact this had on me. Themes identified include the interaction between recognition and sacrifice, emotional lability and fragility, and the impact of transitions. Findings inform personal recovery, as well as future research and policy development pertaining to the sustainable recovery of our NHS people.
  🖺 Full Text HTML: Responding to the call of the NHS Nightingale, but at what cost?: An auto-ethnography of a volunteer frontline mental health trainer’s experiences during the COVID-19 pandemic.
• COVID-19 Causes Ciliary Dysfunction as Demonstrated by Human Intranasal Micro-Optical Coherence Tomography Imaging -
  Severe acute respiratory syndrome coronavirus (SARS-CoV-2), causative agent of coronavirus disease 2019 (COVID-19), binds via ACE2 receptors, highly expressed in ciliated cells of the nasal epithelium. Micro-optical coherence tomography (OCT) is a minimally invasive intranasal imaging technique that can determine cellular and functional dynamics of respiratory epithelia at 1-m resolution, enabling real time visualization and quantification of epithelial anatomy, ciliary motion, and mucus transport. We hypothesized that respiratory epithelial cell dysfunction in COVID-19 will manifest as reduced ciliated cell function and mucociliary abnormalities, features readily visualized by OCT. Symptomatic outpatients with SARS-CoV-2 aged [≥] 18 years were recruited within 14 days of symptom onset. Data was interpreted for subjects with COVID-19 (n=13) in comparison to healthy controls (n=8). Significant reduction in functional cilia, diminished ciliary beat frequency, and abnormal ciliary activity were evident. Other abnormalities included denuded epithelium, presence of mucus rafts, and increased inflammatory cells. Our results indicate that subjects with mild but symptomatic COVID-19 exhibit functional abnormalities of the respiratory mucosa underscoring the importance of mucociliary health in viral illness and disease transmission. Ciliary imaging enables investigation of early pathogenic mechanisms of COVID-19 and may be useful for evaluating disease progression and therapeutic response.
  🖺 Full Text HTML: COVID-19 Causes Ciliary Dysfunction as Demonstrated by Human Intranasal Micro-Optical Coherence Tomography Imaging
• Landscape of infection enhancing antibodies in COVID-19 and healthy donors -
  To assess the frequency of SARS-CoV-2 infection enhancing antibodies in the general population, we searched over 64 million heavy chain antibody sequences from healthy and COVID-19 patient repertoires for sequences similar to 11 previously reported enhancing antibodies. Although the distribution of sequence identities was similar in COVID-19 and healthy repertoires, the COVID-19 hits were significantly more clonally expanded than healthy hits. Furthermore, among the tested hits, 17 out of 94 from COVID-19, compared with 2 out of 96 from healthy, bound to the enhancing epitope. A total of 6 of the 19 epitope-binding antibodies enhanced ACE2 receptor binding to the spike protein. Together, this study revealed that enhancing antibodies are far more frequent in COVID-19 patients than in healthy donors, but a reservoir of potential enhancing antibodies exists in healthy donors that could potentially mature to actual enhancing antibodies upon infection.
  🖺 Full Text HTML: Landscape of infection enhancing antibodies in COVID-19 and healthy donors
• Evolution of SARS-CoV-2 during the first year of the COVID-19 pandemic in Northwestern Argentina -
  Studies about the evolution of SARS-CoV-2 lineages in different backgrounds such as naive populations, are still scarce, especially from South America. The aim of this work was to study the introduction and diversification pattern of SARS-CoV-2 during the first year of the COVID-19 pandemic in the Northwestern Argentina (NWA) region and to analyze the evolutionary dynamics of the main lineages found. In this study, we analyzed a total of 260 SARS-CoV-2 whole-genome sequences from Argentina, belonging to the Provinces of Jujuy, Salta and Tucuman, from March 31st, 2020, to May 22nd, 2021, which covered the full first wave and the early second wave of the COVID-19 pandemic in Argentina. In the first wave, eight lineages were identified: B.1.499 (76.9%), followed by N.5 (10.2%), B.1.1.274 (3.7%), B.1.1.348 (3.7%), B.1 (2.8%), B.1.600 (0.9%), B.1.1.33 (0.9%) and N.3 (0.9%). During the early second wave, the first-wave lineages were displaced by the introduction of variants of concern (VOC) (Alpha, Gamma), or variants of interest (VOI) (Lambda, Zeta, Epsilon) and other lineages with more limited distribution. Phylodynamic analyses of the B.1.499 and N.5, the two most prevalent lineages in NWA, revealed that the substitution rate of lineage N.5 (7.9 x 10-4 substitutions per site per year, s/s/y) was a ~40% faster than that of lineage B.1.499 (5.9 x 10-4 s/s/y), although both are in the same order of magnitude than other non-VOC lineages. No mutations associated with a biological characteristic of importance were observed as signatures markers of the phylogenetic groups established in Northwestern Argentina, however, single sequences in non-VOC lineages did present mutations of biological importance or associated with VOCs as sporadic events, showing that many of these mutations could emerge from circulation in the general population. This study contributed to the knowledge about the evolution of SARS-CoV-2 in a pre-vaccination and without post-exposure immunization period.
  🖺 Full Text HTML: Evolution of SARS-CoV-2 during the first year of the COVID-19 pandemic in Northwestern Argentina
• Modeling infections and deaths averted due to COVID-19 vaccination strategies in Ghana -

  This study assessed the impact of various COVID-19 vaccination strategies on health outcomes in Ghana using an age-stratified compartmental model. The population was stratified into three age groups: <25 years, 25-64 years, and 65+ years. Five vaccination optimization scenarios were explored, assuming that one million persons could be vaccinated in three versus six months. We also performed uncertainty analysis by assuming that the available doses were halved and doubled. The vaccine optimization strategies were assessed for the initial strain, followed by a sensitivity analysis for the delta variant by varying the reproduction number and vaccine efficacy. The results showed that vaccinating individuals <65 years was associated with the lowest cumulative infections when one million persons were vaccinated over three months for both the initial strain and the delta variant. On the contrary, prioritizing the elderly (65+) was associated with the lowest cumulative deaths for both strains.

  🖺 Full Text HTML: Modeling infections and deaths averted due to COVID-19 vaccination strategies in Ghana
• Human Epidemiology and RespOnse to SARS-CoV-2 (HEROS): Objectives, Design and Enrollment Results of a 12-City Remote Observational Surveillance Study of Households with Children using Direct-to-Participant Methods -

  The Human Epidemiology and Response to SARS-CoV-2 (HEROS) is a prospective multi-city 6-month incidence study which was conducted from May 2020-February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other NIH-funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5,598 individuals, including 1,913 principal participants (children), 1,913 primary caregivers, 729 secondary caregivers and 1,043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research.

  🖺 Full Text HTML: Human Epidemiology and RespOnse to SARS-CoV-2 (HEROS): Objectives, Design and Enrollment Results of a 12-City Remote Observational Surveillance Study of Households with Children using Direct-to-Participant Methods
• Examining the Impact of Increasing Vaccine Coverage and Nonpharmaceutical Interventions against Coronavirus Disease 2019 In Ghana using Mathematical Modeling -

  Seroprevalence studies assessing community exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Ghana concluded that population-level immunity remained low as of February 2021. Thus, it is important to demonstrate how increasing vaccine coverage reduces the economic and public health impacts associated with transmission of the novel coronavirus. To that end, this study used a Susceptible-Exposed-Presymptomatic-Symptomatic-Asymptomatic-Recovered-Dead-Vaccinated compartmental model to simulate coronavirus disease 2019 (COVID-19) transmission and the role of public health interventions in Ghana. The impact of increasing vaccination rate and decline in transmission rates due to nonpharmaceutical interventions (NPIs) on cumulative infections and deaths averted was explored under different scenarios. Latin hypercube sampling-partial rank correlation coefficient (LHS-PRCC) was used to investigate uncertainty and sensitivity of the outcomes to the parameters. Simulation results suggest that increasing the vaccination rate to achieve 50% coverage was associated with almost 30,000 deaths and 25 million infections averted. In comparison, a 50% decrease in the transmission coefficient was associated with about 50 million infections and 120,000 deaths averted. The LHS-PRCC results also found that cumulative infections and deaths averted were most sensitive to three model parameters: Transmission rate, vaccination rate, and waning immunity rate from infection. There is a need to increase vaccination coverage by ensuring an increased supply. Adherence to NPIs and increased vaccine uptake would successfully mitigate the impact of COVID-19 in Ghana.

  🖺 Full Text HTML: Examining the Impact of Increasing Vaccine Coverage and Nonpharmaceutical Interventions against Coronavirus Disease 2019 In Ghana using Mathematical Modeling

From Clinical Trials

• A Study to Learn About the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With COVID-19 Who Are Immunocompromised - Condition:   COVID-19
  Interventions:   Drug: Nirmatrelvir;   Drug: Ritonavir;   Drug: Placebo for nirmatrelvir;   Drug: Placebo for ritonavir
  Sponsor:   Pfizer
  Not yet recruiting

• A Randomized Controlled Trial of a Digital, Self-testing Strategy for COVID-19 Infection in South Africa. - Condition:   COVID-19
  Interventions:   Device: Abbott Panbio rapid antigen self-tests;   Other: COVIDSmart CARE! app
  Sponsors:   McGill University Health Centre/Research Institute of the McGill University Health Centre;   University of Cape Town Lung Institute
  Not yet recruiting

• Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients - Condition:   Severe COVID-19
  Interventions:   Biological: Coronavirus-2-specific T cells;   Other: standard of care (SOC)
  Sponsors:   George Papanicolaou Hospital;   General Hospital Of Thessaloniki Ippokratio
  Recruiting

• Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study) - Condition:   COVID-19
  Interventions:   Drug: FB2001;   Drug: FB2001 placebo
  Sponsor:   Frontier Biotechnologies Inc.
  Not yet recruiting

• Engaging Staff to Improve COVID-19 Vaccination Response at Long-Term Care Facilities - Condition:   COVID-19
  Interventions:   Behavioral: Full Intervention;   Other: Enhanced Usual Care
  Sponsors:   Kaiser Permanente;   Patient-Centered Outcomes Research Institute;   Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)
  Recruiting

• A Study to Evaluate the Efficacy of PanCytoVir™ for the Treatment of Non-Hospitalized Patients With COVID-19 Infection - Condition:   COVID-19
  Interventions:   Drug: PanCytoVir™ (probenecid);   Drug: Placebo
  Sponsor:   TrippBio, Inc.
  Not yet recruiting

• Value of Montelukast as a Potential Treatment of Post COVID-19 Persistent Cough - Condition:   Post COVID-19
  Intervention:   Drug: Montelukast Sodium Tablets
  Sponsor:   Assiut University
  Completed

• Topical Antibacterial Agents for Prevention of COVID-19 - Conditions:   COVID-19;   SARS-CoV2 Infection
  Interventions:   Drug: Neosporin;   Other: Vaseline
  Sponsors:   Yale University;   Bill and Melinda Gates Foundation
  Not yet recruiting

• **NanoMn®_COVID-19 A Prospective, Multicenter, Randomized, Placebo-controlled, Parallel-group, Double-blind Trial to Evaluate the Clinical Efficacy of NanoManganese® on Top of Standard of Care, in Adult Patients With Moderate to Severe Coronavirus Disease 2019 (COVID-19)** - Condition:   COVID-19 Pandemic
  Interventions:   Drug: Placebo;   Drug: Experimental drug
  Sponsor:   Medesis Pharma SA
  Recruiting

• Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study - Condition:   Post-COVID19 Condition
  Interventions:   Combination Product: Plasma Exchange Procedure;   Other: Sham Plasma Exchange Procedure
  Sponsors:   Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia;   IrsiCaixa;   Banc de Sang i Teixits
  Not yet recruiting

• Evaluation of Effectiveness of Proprietary Rehabilitation Program in Patients After COVID-19 Infection - Conditions:   COVID-19;   Rehabilitation
  Interventions:   Other: Respiratory training with the use of resistance set on respiratory muscle trainer;   Other: Respiratory training without resistance set on respiratory muscle trainer
  Sponsor:   Medical University of Bialystok
  Recruiting

• Developing an Integrative, Recovery-Based, Post-Acute COVID-19 Syndrome (PACS) Psychotherapeutic Intervention - Condition:   Post-acute COVID-19 Syndrome
  Intervention:   Behavioral: PACS Coping and Recovery (PACS-CR) Intervention
  Sponsor:   VA Office of Research and Development
  Not yet recruiting

• Mineralocorticoid Use in COVID-19 Patients - Conditions:   COVID-19;   ARDS
  Intervention:   Drug: Fludrocortisone Acetate 0.1 MG
  Sponsor:   Ain Shams University
  Completed

• A Study to Evaluate Safety, Tolerability, and Immunogenicity of SARS-CoV-2 Variant (COVID-19) mRNA Vaccines - Condition:   COVID-19
  Interventions:   Biological: ABO1009-DP;   Biological: ABO-CoV.617.2;   Other: Placebo
  Sponsor:   Suzhou Abogen Biosciences Co., Ltd.
  Not yet recruiting

• Can Intensive Insulin Therapy Improve Outcomes of COVID-19 Patients - Conditions:   COVID-19;   Dysglycemia
  Interventions:   Drug: Insulin;   Drug: Subcutaneous Insulin
  Sponsor:   Benha University
  Completed

From PubMed

• Rational identification of small molecules derived from 9,10-dihydrophenanthrene as potential inhibitors of 3CL^pro enzyme for COVID-19 therapy: a computer-aided drug design approach - Small molecules such as 9,10-dihydrophenanthrene derivatives have remarkable activity toward inhibition of SARS-CoV-2 3CL^(pro) and COVID-19 proliferation, which show a strong correlation between their structures and bioactivity. Therefore, these small compounds could be suitable for clinical pharmaceutical use against COVID-19. The objective of this study was to remodel the structures of 9,10-dihydrophenanthrene derivatives to achieve a powerful biological activity against 3CL^(pro) and…

• The Pharmacological Mechanism of Xiyanping Injection for the Treatment of Novel Coronavirus Pneumonia (COVID-19): Based on Network Pharmacology Strategy - CONCLUSION: Xiyanping injection may inhibit the release of various inflammatory factors by inhibiting intracellular pathways such as MAPK and TNF. It acts on protein targets such as HSP90AA1 and plays a potential therapeutic role in COVID-19. Thus, compound III may be treated as a potential new drug for the treatment of COVID-19 and the Xiyanping injection may treat patients with COVID-19 infection.

• Comparative Computational Analysis of Dirithromycin and Azithromycin in Search for a Potent Drug against COVID-19 caused by SARS-CoV-2: Evidence from molecular docking and dynamic simulation - Due to the emergency and uncontrolled situation caused by the COVID-19 pandemic that arising in the entire world, it is necessary to choose available drugs that can inhibit or prevent the disease. Therefore, the repurposing of the commercial antibiotic, dirithromycin has been screened for the first time against fifteen receptors and compared to the azithromycin using a molecular docking approach to identify possible SARS-CoV-2 inhibitors. Our docking results showed that dirithromycin fit…

• N-3 polyunsaturated fatty acids block the trimethylamine-N-oxide- ACE2- TMPRSS2 cascade to inhibit the infection of human endothelial progenitor cells by SARS-CoV-2 - Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is a novel coronavirus that infects many types of cells and causes cytokine storms, excessive inflammation, acute respiratory distress to induce failure of respiratory system and other critical organs. In this study, our results showed that trimethylamine-N-oxide (TMAO), a metabolite generated by gut microbiota, acts as a regulatory mediator to enhance the inerleukin-6 (IL-6) cytokine production and the infection of human endothelial…

• Neuromodulation by selective ACE2 inhibitors - Here, neuromodulatory effects of selective ACE2 inhibitors were investigated. Two different types of small molecule ligands for ACE2 inhibition were selected using chemical genetic approach, they were synthesized using developed chemical method and tested using presynaptic rat brain nerve terminals (synaptosomes). EBC-36032 (1 µM) increased in a dose-dependent manner spontaneous and stimulated ROS generation in nerve terminals that was of non-mitochondrial origin. Another inhibitor EBC-36033…

• Prevalence and Mechanisms of Mucus Accumulation in COVID-19 Lung Disease - CONCLUSIONS: SARS-CoV-2 infection is associated with a high prevalence of distal airspace mucus accumulation and increased MUC5B expression in COVID-19 autopsy lungs. HBE culture studies identified roles for EGFR and IL-1R signaling in mucin gene regulation post SARS-CoV-2 infection. These data suggest that time-sensitive mucolytic agents, specific pathway inhibitors, or corticosteroid administration may be therapeutic for COVID-19 lung disease. This article is open access and distributed under…

• Repurposing Halicin as a potent covalent inhibitor for the SARS-CoV-2 main protease - The rapid spread of COVID-19 has caused a worldwide public health crisis. For prompt and effective development of antivirals for SARS-CoV-2, the pathogen of COVID-19, drug repurposing has been broadly conducted by targeting the main protease (M^(Pro)), a key enzyme responsible for the replication of virus inside the host. In this study, we evaluate the inhibition potency of a nitrothiazole-containing drug, halicin, and reveal its reaction and interaction mechanism with M^(Pro). The in vitro…

• Discovery of diminazene as a dual inhibitor of SARS-CoV-2 human host proteases TMPRSS2 and furin using cell-based assays - The proteases TMPRSS2 (transmembrane protease serine 2) and furin are known to play important roles in viral infectivity including systematic COVID-19 infection through priming of the spike protein of SARS-CoV-2 and related viruses. To discover small-molecules capable of inhibiting these host proteases, we established convenient and cost-effective cell-based assays employing Vero cells overexpressing TMPRSS2 and furin. A cell-based proteolytic assay for broad-spectrum protease inhibitors was…

• Profiling Differential Effects of 5 Selective Serotonin Reuptake Inhibitors on TLRs-Dependent and -Independent IL-6 Production in Immune Cells Identifies Fluoxetine as Preferred Anti-Inflammatory Drug Candidate - Excessive proinflammatory cytokine production induced by abnormal activation of Toll-like receptor (TLR) signaling, for example, by SARS-CoV-2 infection, can cause a fatal cytokine storm. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine, used to treat depression, were recently reported to reduce the risk of severe disease in patients with coronavirus disease 2019 (COVID-19), but the mechanisms of the anti-inflammatory effects of SSRIs, and which SSRI would be most…

• Immune response to SARS-CoV-2 in severe disease and long COVID-19 - COVID-19 is mild to moderate in otherwise healthy individuals but may nonetheless cause life-threatening disease and/or a wide range of persistent symptoms. The general determinant of disease severity is age mainly because the immune response declines in aging patients. Here, we developed a mathematical model of the immune response to SARS-CoV-2 and revealed that typical age-related risk factors such as only a several 10 % decrease in innate immune cell activity and inhibition of type-I…

• Novaferon Effectively Inhibits Ancestral SARS-CoV-2 and Omicron Variant in Vitro, 2022 - INTRODUCTION: To identify Novaferon (Nova), a novel recombinant protein of interferon (IFN)-α, antiviral activity against ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Omicron variant in vitro.

• Anti-type I interferon antibodies as a cause of severe COVID-19 - COVID-19 ranges from asymptomatic through to respiratory failure and death. Although specific pre-existing conditions such as age and male sex have been associated with poor outcomes, we remain largely ignorant of the mechanisms predisposing to severe disease. In this study, the authors discovered that approximately 10% of 987 patients with life-threatening COVID-19 harbored neutralizing antibodies to Type I interferons (IFNs)¹. They demonstrated that these antibodies could neutralize high…

• The role of trace N-Oxyl compounds as redox mediator in enhancing antiviral ribavirin elimination in UV/Chlorine process - Ribavirin (RBV) is an antiviral drug used for treating COVID-19 infection. Its release into natural waters would threaten the health of aquatic ecosystem. This study reports an effective approach to degrade RBV by the trace N-oxyl compounds (2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) and N-Hydroxyphthalimide (NHPI)) enhanced UV activated free chlorine (UV/Chlorine) process. The results indicated that TEMPO and NHPI at low concentrations (0.1 μM and 1 μM, respectively) could strongly enhance…

• The Cyclophilin-Dependent Calcineurin Inhibitor Voclosporin Inhibits SARS-CoV-2 Replication in Cell Culture - Kidney transplant recipients (KTRs) are at increased risk for a more severe course of COVID-19, due to their pre-existing comorbidity and immunosuppression. Consensus protocols recommend lowering immunosuppression in KTRs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the optimal combination remains unclear. Calcineurin inhibitors (CNIs) are cornerstone immunosuppressants used in KTRs and some have been reported to possess antiviral activity against RNA viruses,…

• Biological Actions, Implications, and Cautions of Statins Therapy in COVID-19 - The Coronavirus Disease 2019 (COVID-19) showed worse prognosis and higher mortality in individuals with obesity. Dyslipidemia is a major link between obesity and COVID-19 severity. Statins as the most common lipid regulating drugs have shown favorable effects in various pathophysiological states. Importantly, accumulating observational studies have suggested that statin use is associated with reduced risk of progressing to severe illness and in-hospital death in COVID-19 patients. Possible…

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