Covid-19 Sentry

Contents

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

From Preprints

• A large-scale machine learning study of sociodemographic factors contributing to COVID-19 severity -

  Understanding sociodemographic factors behind COVID-19 severity relates to significant methodological difficulties, such as differences in testing policies and epidemics phase, as well as a large number of predictors that can potentially contribute to severity. To account for these difficulties, we assemble 115 predictors for more than 3000 US counties and employ a well-defined COVID-19 severity measure derived from epidemiological dynamics modeling. We then use a number of advanced feature selection techniques from machine learning to determine which of these predictors significantly impact the disease severity. We obtain a surprisingly simple result, where only two variables are clearly and robustly selected - population density and proportion of African Americans. Possible causes behind this result are discussed. We argue that the approach may be useful whenever significant determinants of disease progression over diverse geographic regions should be selected from a large number of potentially important factors.

  🖺 Full Text HTML: A large-scale machine learning study of sociodemographic factors contributing to COVID-19 severity
• Omicron BA.1/BA.2 infections in triple-vaccinated individuals enhance a diverse repertoire of mucosal and blood immune responses -

  Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in large numbers of individuals with hybrid immunity, generated through a combination of vaccination and infection. Based primarily on circulating neutralizing antibody (NAb) data, concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that a history of prior SARS-CoV-2 in particular is associated with profound immune dampening. Taking a broader and comprehensive approach, we characterized mucosal and blood immunity to both spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without a history of previous SARS-CoV-2 infection. We find that the majority of individuals increase BA.1/BA.2/BA.5-specific NAb following infection, but confirm that the magnitude of increase and post-omicron titres are indeed higher in those who were infection-naive. In contrast, significant increases in nasal antibody responses are seen regardless of prior infection history, including neutralizing activity against BA.5 spike. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are still significantly higher in previously-infected individuals, who appear to have maximally induced responses with a CD8+ phenotype of high cytotoxic potential after their 3rd mRNA vaccine dose. Antibody and T cell responses to non-spike antigens also increase significantly regardless of prior infection status, with a boost seen in previously-infected individuals to immunity primed by their first infection. These findings suggest that hybrid immunity induced by omicron breakthrough infections is highly dynamic, complex, and compartmentalised, with significant immune enhancement that can help protect against COVID-19 caused by future omicron variants.

  🖺 Full Text HTML: Omicron BA.1/BA.2 infections in triple-vaccinated individuals enhance a diverse repertoire of mucosal and blood immune responses
• The impact of vaccination frequency on COVID-19 public health outcomes: A model-based analysis -

  While the rapid deployment of SARS-CoV-2 vaccines had a significant impact on the ongoing COVID-19 pandemic, rapid viral immune evasion and waning neutralizing antibody titers have degraded vaccine efficacy. Nevertheless, vaccine manufacturers and public health authorities have a number of levers at their disposal to maximize the benefits of vaccination. Here, we use an agent-based modeling framework coupled with the outputs of a population pharmacokinetic model to examine the impact of boosting frequency and durability of vaccinal response on vaccine efficacy. Our work suggests that repeated dosing at frequent intervals (multiple times a year) may offset the degradation of vaccine efficacy, preserving their utility in managing the ongoing pandemic. Our work relies on assumptions about antibody accumulation and the tolerability of repeated vaccine doses. Given the practical significance of potential improvements in vaccinal utility, clinical research to better understand the effects of repeated vaccination would be highly impactful. These findings are particularly relevant as public health authorities worldwide seek to reduce the frequency of boosters to once a year or less. Our work suggests practical recommendations for vaccine manufacturers and public health authorities and draws attention to the possibility that better outcomes for SARS-CoV-2 public health remain within reach.

  🖺 Full Text HTML: The impact of vaccination frequency on COVID-19 public health outcomes: A model-based analysis
• Chimeric chikungunya virus-like particles with surface exposed SARS-CoV-2 RBD elicits potent immunogenic responses in mice. -
  The SARS-CoV-2 pandemic has reinforced efforts for developing effective vaccination strategy for existing and emerging viruses. Currently there are various vaccine technology available for treating viral diseases, however it is imperative to develop and investigate second-generation vaccines such as chimeric virus-like particles (chi-VLPs) vaccine for increased immunogenicity, ease of production and scalability to supplement the worldwide vaccine supply. Intriguingly, chi-VLPs expresses more than one antigenic epitope on its surface, hence it is expected to be a more effective vaccine candidate. Hereby, this study reports, a novel bivalent vaccine design of chimeric alphavirus coronavirus virus-like particles (ChAC-VLPs), displaying fusion glycoproteins of CHIKV and receptor binding domain (RBD) of SARS-CoV-2 on its surface. Uniqueness and versatility of ChAC-VLPs has been demonstrated via a various techniques including Western blot, Immunofluorescence, cryoEM, and dynamic light scattering (DLS). The multimeric epitope display of immunogenic antigens, i.e CHIKV envelop glycoprotein and SARS-CoV-2 RBD was validated by cell-based assays. ChAC-VLP immunized mice has shown substantial neutralization titres for CHIKV (PRNT50 of 1:25) from the serum collected after 2nd booster doses. Similarly, serum antibodies were detected for SARS-CoV2 RBD as observed by antigen specific ELISA and validated using surface plasmon resonance (SPR). SPR binding response was detected to be >200 RU for anti-RBD antibody in post-immunized mice sera. In conclusion, present study proposes ChAC-VLPs as a potential hybrid vaccine candidate for CHIKV and SARS-CoV-2 infection and contributes valuable insights in chi-VLPs domain.
  🖺 Full Text HTML: Chimeric chikungunya virus-like particles with surface exposed SARS-CoV-2 RBD elicits potent immunogenic responses in mice.
• Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals. -
  How infection by a viral variant showing antigenic drift impacts a preformed mature human memory B cell (MBC) repertoire remains an open question. Here, we studied the MBC response up to 6 months after Omicron BA.1 breakthrough infection in individuals previously vaccinated with three doses of mRNA vaccine. Longitudinal analysis, using single-cell multi-omics and functional analysis of monoclonal antibodies from RBD-specific MBCs, revealed that a BA.1 breakthrough infection mostly recruited pre-existing cross-reactive MBCs with limited de novo response against BA.1-restricted epitopes. Reorganization of clonal hierarchy and new rounds of germinal center reaction, however, combined to maintain diversity and induce progressive maturation of the MBC repertoire against common Hu-1 and BA.1, but not BA.5-restricted, SARS-CoV-2 Spike RBD epitopes. Such remodeling was further associated with marked improvement in overall neutralizing breadth and potency. These findings have fundamental implications for the design of future vaccination booster strategies.
  🖺 Full Text HTML: Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals.
• Negative Impact of Daily Screen Use on Inhibitory Control Network in Preadolescence: A Two-Year Follow-Up Study -
  The COVID-19 pandemic has made an unprecedented shift in children’s daily lives. Children are increasingly spending time with screens to learn and connect with others. As the online environment rapidly substitutes in-person experience, understanding children’s neuropsychological trajectories associated with screen experiences is important. Previous findings suggest that excessive screen use can lead children to prefer more immediate rewards over delayed outcomes. We hypothesized that increased screen time delays a child’s development of inhibitory control. By analyzing neuropsychological data from 8,324 children (9-11ys) from the ABCD Study, we found that children who had more screen time showed a higher reward orientation and a weaker inhibitory control system (i.e., fronto-striatal circuitry) in the brain. Importantly, we found that the interaction between screen exposure and reward sensitivity negatively influenced the development of the inhibitory control system in the brain over a two year period. These results indicate possible negative long-term impacts of increased daily screen time on children’s neuropsychological development. The results further demonstrated that screen time influences dorsal striatum connectivity, which suggests that the effect of daily screen use is a habitual seeking behavior. The study provides neural and behavioral evidence on the negative impact of daily screen use on developing children.
  🖺 Full Text HTML: Negative Impact of Daily Screen Use on Inhibitory Control Network in Preadolescence: A Two-Year Follow-Up Study
• SARS-CoV-2 Mpro protease variants of concern display altered viral and host target processing but retain potency towards antivirals -
  Main protease of SARS-CoV-2 (Mpro) is the most promising drug target against coronaviruses due to its essential role in virus replication. With newly emerging variants there is a concern that mutations in Mpro may alter structural and functional properties of protease and subsequently the potency of existing and potential antivirals. We explored the effect of 31 mutations belonging to 5 variants of concern (VOC) on catalytic parameters and substrate specificity, which revealed changes in substrate binding and rate of cleavage of a viral peptide. Crystal structures of 11 Mpro mutants provided structural insight into their altered functionality. Additionally, we show Mpro mutations influence proteolysis of an immunomodulatory host protein Galectin-8 (Gal-8) and subsequent significant decrease in cytokine secretion, providing evidence for alterations in escape of host-antiviral mechanisms. Accordingly, mutations associated with the highly virulent Delta VOC resulted in significant increase in Gal-8 cleavage. Importantly, IC50s of nirmatrelvir (Pfizer) and our irreversible inhibitor AVI-8053 demonstrated no changes in potency for both drugs for all mutants, suggesting Mpro will remain a high-priority antiviral drug candidate as SARS-CoV-2 evolves.
  🖺 Full Text HTML: SARS-CoV-2 Mpro protease variants of concern display altered viral and host target processing but retain potency towards antivirals
• Social Isolation Causes Cortical and Trabecular Bone Loss in Adult Male, but not Female, C57BL/6J Mice -
  Social isolation is a potent form of psychosocial stress and is a growing public health concern, particularly among older adults. Even prior to the onset of the COVID-19 pandemic, which has significantly increased the prevalence of isolation and loneliness, researchers have been concerned about a rising “epidemic” of loneliness. Isolation is associated with an increased risk for many physical and mental health disorders and increased overall mortality risk. In addition to social isolation, older adults are also at greater risk for osteoporosis and related fractures. While researchers have investigated the negative effects of other forms of psychosocial stress on bone, including depression and PTSD, the effects of social isolation on bone have not been thoroughly investigated. The aim of this study was to test the hypothesis that social isolation would lead to bone loss in male and female C57BL/6J mice. 16-week-old mice were randomized into social isolation (1 mouse/cage) or grouped housing (4 mice/cage) for four weeks (N=16/group). Social isolation significantly decreased trabecular (BV/TV, BMD, Tb. N., Tb. Th.) and cortical bone (Ct.Th., Ct.Ar., Ct.Ar./Tt.Ar., pMOI, Ct.Por.) parameters in male, but not female mice. Isolated male mice had signs of reduced bone remodeling represented by reduced osteoblast numbers, osteoblast-related gene expression and osteoclast-related gene expression. However, isolated females had increased bone resorption-related gene expression, without any change in bone mass. Overall, our data suggest that social isolation has negative effects on bone in males, but not females, although females showed suggestive effects on bone resorption. These results provide critical insight into the effects of isolation on bone and have key clinical implications as we grapple with the long-term health impacts of the rise in social isolation related to the COVID-19 pandemic.
  🖺 Full Text HTML: Social Isolation Causes Cortical and Trabecular Bone Loss in Adult Male, but not Female, C57BL/6J Mice
• DeepERA: deep learning enables comprehensive identification of drug-target interactions via embedding of heterogeneous data -
  Due to the tremendous combinatorial search space of tremendous drug-protein pairs, deep learning algorithms have been utilized to facilitate the identification of novel drug-target interactions. In this paper, we proposed an end-to-end deep learning model, DeepERA, to identify drug-target interactions based on heterogeneous data. This model assembles three independent feature embedding modules (intrinsic embedding, relational embedding, and annotation embedding) which each represent different attributes of the dataset and jointly contribute to the comprehensive predictions. This is the first work that, to our knowledge, applied deep learning models to learn each intrinsic features, relational features, and annotation features and combine them to predict drug-protein interactions. Our results showed that DeepERA outperformed other deep learning approaches proposed recently. Using our DeepERA framework, we identified 45,603 novel drug-protein interactions for the whole human proteome, including 356 drug-protein interactions for the human proteins targeted by SARS-CoV-2 viral proteins. We also performed computational docking for the selected interactions and conducted a two-way statistical test to “normalize” the docking scores of different proteins/drugs to support our predictions.
  🖺 Full Text HTML: DeepERA: deep learning enables comprehensive identification of drug-target interactions via embedding of heterogeneous data
• Waves in time, but not in space - An analysis of pandemic severity of COVID-19 in Germany based on spatio-temporal clustering -

  While pandemic waves are often studied on the national scale, they typically are not distributed evenly within countries. This paper employs a novel approach to analyze the tempo-spatial dynamics of the COVID-19 pandemic in Germany. First, we base the analysis on a composite indicator of pandemic severity to gain a more robust understanding of the temporal dynamics of the pandemic. Second, we subdivide the pandemic during the years 2020 and 2021 into fifteen phases, each with a coherent trend of pandemic severity. Third, we analyze the patterns of spatial association during each phase. Fourth, similar types of trajectories of pandemic severity among all German counties were identified through hierarchical clustering. The results imply that the hotspots and cold spots of the first four waves of the pandemic were relatively stationary in space so that the pandemic moved in time but less in space.

  🖺 Full Text HTML: Waves in time, but not in space - An analysis of pandemic severity of COVID-19 in Germany based on spatio-temporal clustering
• Spatiotemporal transmission of SARS-CoV-2 lineages during 2020-2021 in Pernambuco - Brazil -

  In recent years, the SARS-CoV-2 viruses emerged and spread around the world, leaving a large death toll and long-lasting impact on survivors. As of January 2023, Brazil is still among the countries with the highest number of registered deaths. This continental-size and pluralistic country experienced a heterogenous implementation of non-pharmacological and pharmacological interventions which, associated with large socioeconomic differences between the country regions, has led to distinct virus spread dynamics across the country. Here we investigate the spatiotemporal dispersion of emerging SARS-CoV-2 lineages and its dynamics in distinct epidemiological scenarios in the first two years of the pandemics in the Pernambuco state (Northeast Brazil). We generated a total of 1389 new SARS-CoV-2 genomes from June 2020 to August 2021 covering all major regions of the state. This sampling captured the arrival, communitary transmission and the circulation of the B1.1, B.1.1.28 and B.1.1.33 lineages in the first eight months of the pandemics, the emergence of the former variant of interest P.2 and the emergence and fast replacement of all previous variants by the more transmissible variant of concern P.1 (Gamma) lineage. Based on the incidence and lineage spread pattern we observed that there was an East-to-West to inner state pattern of transmission which is in agreement with the transmission of more populous metropolitan areas to medium and small size country-side cities in the state. Such transmission patterns may be partially explained by the main routes of traffic across municipalities in the state. Nevertheless, inter-state traffic was also another important source of lineage introduction and spread into the state. Our results highlight that the fine grained intrastate analysis of lineages and incidence spread can provide actionable insights for planning future non-pharmacological intervention for air-borne transmissible human pathogens.

  🖺 Full Text HTML: Spatiotemporal transmission of SARS-CoV-2 lineages during 2020-2021 in Pernambuco - Brazil
• Vaccine-elicited B and T cell immunity to SARS-CoV-2 is impaired in chronic lung disease patients -

  The protection afforded by vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to individuals with chronic lung disease is not well established. To understand how chronic lung disease impacts SARS-CoV-2 vaccine-elicited immunity we performed deep immunophenotyping of the humoral and cell mediated SARS-CoV-2 vaccine response in an investigative cohort of vaccinated patients with diverse pulmonary conditions including asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung disease (ILD). Compared to healthy controls, 48% of vaccinated patients with chronic lung diseases had reduced antibody titers to the SARS-CoV-2 vaccine antigen as early as 3-4 months after vaccination, correlating with decreased vaccine-specific memory B cells. Vaccine-specific CD4 and CD8 T cells were also significantly reduced in patients with asthma, COPD, and a subset of ILD patients compared to healthy controls. These findings reveal the complex nature of vaccine-elicited immunity in high-risk patients with chronic lung disease.

  🖺 Full Text HTML: Vaccine-elicited B and T cell immunity to SARS-CoV-2 is impaired in chronic lung disease patients
• COVID-19-related burnout reduces COVID-19 vaccination intention in cardiac patients: a cross-sectional study in Greece -

  Background: New SARS-CoV-2 variants have emerged and COVID-19 is still a public health issue, especially for vulnerable groups such as people with chronic medical conditions. Objective: To investigate the impact of COVID-19-related burnout on COVID-19 vaccination intention in cardiac patients. Moreover, we investigated other possible demographic and psychological predictors of vaccination intention in cardiac patients. Methods: We conducted a cross-sectional study in Greece using a convenience sample. Data collection was performed from 20 November 2022 to 10 January 2023. We measured demographic data, COVID-19-related burnout, anxiety, depression, social support, and resilience. We used the following valid tools: COVID-19 burnout scale, Patient Health Questionnaire-4, Multidimensional Scale of Perceived Social Support, and Brief Resilience Scale. Results: Among patients, 45.8% were willing to accept a COVID-19 booster dose, 25.3% were hesitant, and 28.9% were unwilling. Patients experienced moderate levels of COVID-19-related burnout. After multivariable linear regression analysis, we found that increased age and decreased emotional exhaustion due to COVID-19 were associated with increased vaccination intention. Moreover, patients who have already received a booster dose had also a greater willingness to accept a new booster dose. Conclusions: Identification of factors that influence patients decision to accept a COVID-19 booster dose is crucial to maintain a high vaccination coverage rate among them in order to avoid COVID-19-related outcomes. Since a COVID-19 booster dose on an annual basis seems to be necessary policy makers should develop and implement vaccination programmes tailored for patients.

  🖺 Full Text HTML: COVID-19-related burnout reduces COVID-19 vaccination intention in cardiac patients: a cross-sectional study in Greece
• The effects of physiotherapy programs in COVID-19 patients during admission in the hospital -

  Background and aims Several recommendations exist regarding the role of physiotherapy programs (PTPs) in COVID-19 patients. However, none of the studies examines the frequency of bedside PTPs during admission. Thus, this study aimed to compare the different bedside PTPs frequencies on the survival rate, length of hospitalization (LoH), referrals to the intensive care unit (ICU), and in-hospital complications. The safety of patients and the physiotherapist was also investigated. Methods Fifty-two COVID-19 patients were equally assigned into two groups matched on gender and age (1:1 ratio). Experimental group one received 1-2 times of PTPs during hospitalization, and experimental group two received daily PTPs until hospital discharge. The primary outcomes were the survival rate, LoH, referrals to ICU, and in-hospital complications. The secondary outcomes were the adverse events for patients and the number of physiotherapists who contracted with COVID-19. Results Most participants were classified as having mild to moderate COVID-19 with a mean age of 45 years. There were no differences between groups in all primary outcome measures (all p > 0.05). The overall survival rate was 98%. One participant from the Ex-G2 group was referred to the ICU. Two Ex-G1 and four Ex-G2 participants had complications. There were no immediate serious adverse events found after PTPs for both groups. None of the physiotherapists tested positive for COVID-19. Conclusion In COVID-19 patients with mild to moderate conditions, one to two bedside PTPs were enough to achieve the same results as patients who received daily PTPs. PTPs were safe for COVID-19 patients, and physiotherapists.

  🖺 Full Text HTML: The effects of physiotherapy programs in COVID-19 patients during admission in the hospital
• Bioinformatics and system biology approach to identify the influences of COVID-19 on metabolic unhealthy obese patients -

  Objective: The severe acute respiratory syndrome coronavirus 2 has posed a significant challenge to health of individual. Increasing evidence shows that patients with metabolic unhealthy obesity (MUO) and COVID19 have severer complications and higher mortality rate. However, the molecular mechanisms underlying the association between MUO and COVID19 are poorly understood. We sought to implement transcriptomic analysis using bioinformatics and systems biology analysis approaches. Methods: Here, two datasets (GSE196822 and GSE152991) were employed to extract differentially expressed genes (DEGs) to identify common hub genes, shared pathways and candidate drugs and construct a gene disease network. Results: Based on the identified 65 common DEGs, the results revealed hub genes and essential modules. Moreover, common associations between MUO and COVID-19 were found. Transcription factors (TFs) and genes interaction, protein and drug interactions, and DEGs and miRNAs coregulatory network were identified. Furthermore, the gene-disease association were obtained and constructed. Conclusions: The shared pathogenic pathways are noted worth paying attention to. Several genes are highlighted as critical targets for developing treatments for and investigating the complications of COVID19 and MUO. Additionally, multiple genes are identified as promising biomarkers. We think this result of the study may help in selecting and inventing future treatments that can combat COVID-19 and MUO.

  🖺 Full Text HTML: Bioinformatics and system biology approach to identify the influences of COVID-19 on metabolic unhealthy obese patients

From Clinical Trials

• Evaluation of Corfluvec Vaccine for the Prevention of COVID-19 in Healthy Volunteers - Condition:   COVID-19
  Interventions:   Biological: Corfluvec component 1 low dose;   Biological: Corfluvec component 2 low dose;   Biological: Corfluvec component 1 high dose;   Biological: Corfluvec component 2 high dose;   Biological: Corfluvec low dose;   Biological: Corfluvec high dose;   Biological: Placebo
  Sponsors:   Tatyana Zubkova;   MDP-CRO, LLC;   St. Petersburg State Pavlov Medical University
  Active, not recruiting

• COVID-19 Self-testing Study - Condition:   COVID-19
  Intervention:   Behavioral: SMARTest mobile app for COVID-19 self-testing
  Sponsor:   Columbia University
  Recruiting

• A Study of Efficacy and Safety of Azvudine vs. Nirmatrelvir-Ritonavir in the Treatment of COVID-19 Infection - Condition:   COVID-19
  Interventions:   Drug: Azvudine;   Drug: Nirmatrelvir-Ritonavir
  Sponsors:   Shandong Provincial Hospital;   Central hospital Affiliated to Shandong First Medical University;   The Second Affiliated Hospital of Shandong First Medical University;   The Affiliated Hospital Of Southwest Medical University;   Gansu Provincial Hospital
  Not yet recruiting

• A Chatbot to Enhance COVID-19 Knowledge - Condition:   COVID-19
  Interventions:   Device: chatbot;   Other: Printed educational booklet
  Sponsor:   Sun Yat-sen University
  Not yet recruiting

• Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia - Condition:   COVID-19 Pneumonia
  Intervention:   Radiation: Low-Dose Radiation Therapy
  Sponsors:   Jiangsu Cancer Institute & Hospital;   Nanjing Chest Hospital;   The Affiliated BenQ Hospital of Nanjing Medical University;   Central South University;   Zhongda Hospital
  Not yet recruiting

• Tetrandrine Tablets Used in Hospitalized Adults With COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Tetrandrine
  Sponsor:   Peking University Third Hospital
  Not yet recruiting

• A Phase 2 Study to Evaluate the Efficacy and Safety of QLS1128 Orally in Symptomatic Participants With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: QLS1128;   Drug: Placebo
  Sponsor:   Qilu Pharmaceutical Co., Ltd.
  Recruiting

• Efficacy of Megadose Vitamin C in Severe and Critical Ill COVID-19 Patients. - Conditions:   Vitamin C;   COVID-19 Pneumonia
  Interventions:   Drug: Vitamin C;   Drug: Placebo
  Sponsor:   Zhujiang Hospital
  Recruiting

• Oropharyngeal Immunoprophylaxis With High Polyphenolic Olive Oil as Clinical Spectrum Mitigating Factor in COVID-19. - Condition:   COVID-19
  Intervention:   Dietary Supplement: High polyphenolic olive oil. (Early harvest olive oil).
  Sponsor:   Hospital General Nuestra Señora del Prado
  Completed

• A Randomized, Phase I Study of DNA Vaccine OC-007 as a Booster Dose of COVID-19 Vaccine - Conditions:   COVID-19 Respiratory Infection;   COVID-19 Vaccine Adverse Reaction
  Interventions:   Biological: DNA vaccine OC-007;   Other: Placebo
  Sponsor:   Matti Sällberg
  Not yet recruiting

• Multicenter Randomized Double-blind Placebo-controlled Study to Investigate Azvudine in Symptomatic Adults With COVID-19 at Increased Risk of Progressing to Severe Illness - Condition:   COVID-19 Respiratory Infection
  Interventions:   Drug: Azvudine;   Drug: Placebo
  Sponsor:   Peking Union Medical College Hospital
  Not yet recruiting

• UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients With Refractory Hypoxia - Conditions:   Mesenchymal Stem Cell;   COVID-19 Pneumonia
  Intervention:   Biological: UC-MSCs treatment
  Sponsors:   Shanghai East Hospital;   Sir Run Run Shaw Hospital
  Recruiting

• Safety and Efficacy of the Therapy With BREINMAX® for the Treatment of Patients With Asthenia After COVID-19 - Conditions:   Asthenia;   COVID-19
  Interventions:   Drug: Ethyl methyl hydroxypyridine succinate + Meldonium;   Drug: Placebo
  Sponsor:   Promomed, LLC
  Completed

• Aerosolized Versus Intravenous Colistin-based Antimicrobial Regimens in Hospitalized COVID-19 Patients With Bacterial Coinfection: A Randomized Controlled Trial - Condition:   Secondary Bacterial Infection in COVID-19 Patients
  Intervention:   Drug: Colistin
  Sponsor:   Beni-Suef University
  Completed

• Acupuncture as an Adjunctive Therapy for Covid-19 Omicron Randomised Controlled Trial in Patients With Moderate/Severe Pneumonia - Conditions:   Acupuncture;   Covid-19 Omicron;   Pulmonary Function
  Intervention:   Other: Acupuncture
  Sponsor:   The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine
  Recruiting

From PubMed

• Broadly neutralizing aptamers to SARS-CoV-2: a diverse panel of modified DNA antiviral agents - Since its discovery COVID-19 has rapidly spread across the globe with a massive toll on human health with infection mortality rates as high as 10% and a crippling impact on the world economy. Despite numerous advances there remains an urgent need for accurate and rapid point-of-care diagnostic tests, and better therapeutic treatment options. To contribute chemically distinct, non-protein-based affinity reagents, we report here the identification of modified DNA-based aptamers that selectively…

• Functional nucleic acids as potent therapeutics against SARS-CoV-2 infection - The COVID-19 pandemic has posed a severe threat to human life and the global economy. Although conventional treatments, including vaccines, antibodies, and small-molecule inhibitors, have been broadly developed, they usually fall behind the constant mutation of SARS-CoV-2, due to the long screening process and high production cost. Functional nucleic acid (FNA)-based therapeutics are a newly emerging promising means against COVID-19, considering their timely adaption to different mutants and…

• Protein post-translational modification in SARS-CoV-2 and host interaction - SARS-CoV-2 can cause lung diseases, such as pneumonia and acute respiratory distress syndrome, and multi-system dysfunction. Post-translational modifications (PTMs) related to SARS-CoV-2 are conservative and pathogenic, and the common PTMs are glycosylation, phosphorylation, and acylation. The glycosylation of SARS-CoV-2 mainly occurs on spike (S) protein, which mediates the entry of the virus into cells through interaction with angiotensin-converting enzyme 2. SARS-CoV-2 utilizes glycans to…

• Inhibitory effect of phytochemicals towards SARS-CoV-2 papain like protease (PLpro) proteolytic and deubiquitinase activity - Recent studies have shown that RNA-dependent RNA polymerase (RdRp), 3-chymotrypsin-like protease (3CLpro), and papain-like protease (PLpro) are necessary for SARS-CoV-2 replication. Among these three enzymes, PLpro exhibits both proteolytic and deubiquitinase (DUB) activity and is responsible for disrupting the host’s innate immune response against SARS-CoV-2. Because of this unique property of PLpro, we investigated the inhibitory effects of phytochemicals on the SARS-CoV-2 PLpro enzyme. Our…

• Quercetin as a possible complementary agent for early-stage COVID-19: Concluding results of a randomized clinical trial - Background: Quercetin, a natural polyphenol with demonstrated broad-spectrum antiviral, anti-inflammatory, and antioxidant properties, has been proposed as an adjuvant for early-stage coronavirus disease 2019 (COVID-19) infection. Objective: To explore the possible therapeutic effect of quercetin in outpatients with early-stage mild to moderate symptoms of COVID-19. Methods: This was an open-label randomized controlled clinical trial conducted at the department of medicine, King Edward Medical…

• A Selective SARS-CoV-2 Host-Directed Antiviral Targeting Stress Response to Reactive Oxygen Species - The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) catalyzed the development of vaccines and antivirals. Clinically approved drugs against SARS-CoV-2 target the virus directly, which makes them susceptible to viral mutations, which in turn can attenuate their antiviral activity. Here we report a host-directed antiviral (HDA), piperlongumine (PL), which exhibits robust antiviral activity as a result of selective induction of reactive oxygen species in infected cells by…

• Robust Covalent Aptamer Strategy Enables Sensitive Detection and Enhanced Inhibition of SARS-CoV-2 Proteins - Aptamer-based detection and therapy have made substantial progress with cost control and easy modification. However, the conformation lability of an aptamer typically causes the dissociation of aptamer-target complexes during harsh washes and other environmental stresses, resulting in only moderate detection sensitivity and a decreasing therapeutic effect. Herein, we report a robust covalent aptamer strategy to sensitively detect nucleocapsid protein and potently neutralize spike protein…

• Targeting an evolutionarily conserved “E-L-L” motif in spike protein to identify a small molecule fusion inhibitor against SARS-CoV-2 - As newer variants of SARS-CoV-2 continue to pose major threats to global human health and economy, identifying novel druggable antiviral targets is the key toward sustenance. Here, we identify an evolutionarily conserved “Ex(3)Lx(6)L” (“E-L-L”) motif present within the HR2 domain of all human and nonhuman coronavirus spike (S) proteins that play a crucial role in stabilizing its postfusion six-helix bundle (6-HB) structure and thus, fusion-mediated viral entry. Mutations within this motif reduce…

• Broad-spectrum antiviral inhibitors targeting pandemic potential RNA viruses - RNA viruses continue to remain a clear and present threat for potential pandemics due to their rapid evolution. To mitigate their impact, we urgently require antiviral agents that can inhibit multiple families of disease-causing viruses, such as arthropod-borne and respiratory pathogens. Potentiating host antiviral pathways can prevent or limit viral infections before escalating into a major outbreak. Therefore, it is critical to identify broad-spectrum antiviral agents. We have tested a small…

• A Systematic Survey of Reversibly Covalent Dipeptidyl Inhibitors of the SARS-CoV-2 Main Protease - SARS-CoV-2 is the coronavirus pathogen of the currently prevailing COVID-19 pandemic. It relies on its main protease (M ^(Pro) ) for replication and pathogenesis. M ^(Pro) is a demonstrated target for the development of antivirals for SARS-CoV-2. Past studies have systematically explored tripeptidyl inhibitors such as nirmatrelvir as M ^(Pro) inhibitors. However, dipeptidyl inhibitors especially those with a spiro residue at their P2 position have not been systematically investigated. In this…

• Extremely potent pan-sarbecovirus neutralizing antibodies generated by immunization of macaques with an AS03-adjuvanted monovalent subunit vaccine against SARS-CoV-2 - The rapid emergence of SARS-CoV-2 variants that evade immunity to vaccination has placed a global health imperative on the development of therapeutic countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent pan-sarbecovirus antibodies from non-human primates vaccinated with an AS03 adjuvanted subunit vaccine against SARS-CoV-2 that recognize conserved epitopes in the receptor binding domain (RBD) with femtomolar affinities….

• Chitosan-Based Formulations Intended as Protective Spray for Mask Surfaces in Prevention of Coronavirus Dissemination - The extraordinary occurrence of COVID-19 by the fast expansion of viral infections has propelled particular interest in developing novel antiviral and virucidal agents to guarantee personal security. The main objective of this work is to propose novel formulations able to optimize the use of personal protection elements. In recent years, chitosan (CH) has attracted attention for being an interesting multifunctional, biodegradable, non-antigenic, non-toxic, and biocompatible natural polymer with…

• Estimating the restraint of SARS-CoV-2 spread using a conventional medical air-cleaning device: Based on an experiment in a typical dental clinical setting - CONCLUSION: The use of OSSM showed the potential to restraint the spread of bioaerosols in clinical settings. Our study demonstrates that OSSM use in dental clinics can reduce the exposure concentrations of bioaerosols for healthcare workers during dental treatment and is beneficial for minimizing the risk of infectious diseases such as COVID-19.

• Density functional modeling, and molecular docking with SARS-CoV-2 spike protein (Wuhan) and omicron S protein (variant) studies of new heterocyclic compounds including a pyrazoline nucleus - Nowadays, different vaccines and antiviral drugs have been developed and their effectiveness has been proven against SARS-CoV-2. Pyrazoline derivatives are biologically active molecules and exhibit broad-spectrum biological activity properties. In this scope, four new molecules (4a-d) including a pyrazoline core were synthesized in order to predict their antiviral properties theoretically. Compounds 4a-d were purified by the crystallization method. The structures of 4a-d were completely…

• Highlights in TMPRSS2 inhibition mechanism with guanidine derivatives approved drugs for COVID-19 treatment - Transmembrane protease serine 2 (TMPRSS2) has been identified as a critical key for the entry of coronaviruses into human cells by cleaving and activating the spike protein of SARS-CoV-2. To block the TMPRSS2 function, 18 approved drugs, containing the guanidine group were tested against TMPRSS2’s ectodomain (7MEQ). Among these drugs, Famotidine, Argatroban, Guanadrel and Guanethidine strongly binds with TMPRSS2 S1 pocket with estimated Fullfitness energies of -1847.12, -1630.87, -1605.81 and…

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