Covid-19 Sentry

Contents

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

From Preprints

• Modeling the initial phase of COVID-19 epidemic: The role of age and disease severity in the Basque Country, Spain -

  Declared a pandemic by the World Health Organization (WHO), COVID-19 has spread rapidly around the globe. With eventually substantial global underestimation of infection, by the end of March 2022, more than 470 million cases were confirmed, counting more than 6.1 million deaths worldwide. COVID-19 symptoms range from mild (or no) symptoms to severe illness, with disease severity and death occurring according to a hierarchy of risks, with age and pre-existing health conditions enhancing risks of disease severity. In order to understand the dynamics of disease severity during the initial phase of the pandemic, we propose a modeling framework stratifying the studied population into two groups, older and younger, assuming different risks for severe disease manifestation. The deterministic and the stochastic models are parametrized using epidemiologicaldata for the Basque Country population referring to confirmed cases, hospitalizations and deaths, from February to the end of March 2020. Using similar parameter values, both models were able to describe well the existing data. A detailed sensitivity analysis was performed to identify the key parameters influencing the transmission dynamics of COVID-19 in the population. We observed that the population younger than 60 years old of age would contribute more to the overall force of infection than the older population, as opposed to the already existing age-structured models, opening new ways to understand the effect of population age on disease severity during the COVID-19 pandemic. With mild/asymptomatic cases significantly influencing the disease spreading and control, our findings support the vaccination strategy prioritising the most vulnerable individuals to reduce hospitalization and deaths, as well as the non-pharmaceutical intervention measures to reduce disease transmission.

  🖺 Full Text HTML: Modeling the initial phase of COVID-19 epidemic: The role of age and disease severity in the Basque Country, Spain
• Prevalence and correlates of depression and anxiety among Chinese international students in US colleges during the COVID-19 pandemic: a cross-sectional study -
  Previous studies showed that the COVID-19 outbreak increased the levels of depression and anxiety in heterogeneous populations. This study examines the prevalence of depression and anxiety among Chinese international students enrolled in US universities during the COVID-19 pandemic and identifies the associated factors, including habits, social and psychological support, sleep quality, and remote learning. Participants were recruited with snowball sampling through 21 Chinese international student associations in US universities. The survey consisted of demographic questions, the Social Support Rating Scale (SSRS), the Insomnia Severity Index (ISI), the Patient Health Questionnaire-9 (PHQ-9), the General Anxiety Disorder-7 (GAD-7), and self-constructed questions on academic performance, financial concerns, use of social media, physical exercise, and psychological support. Cut-off scores of 10 were used for both PHQ-9 and GAD-7 to determine the binary outcomes of depression and anxiety, respectively. Bivariant analyses and multivariable logistic regression analyses were performed to identify the associated factors. Among 1881 participants, we found a prevalence of depression at 24.5% and that of anxiety at 20.7%. Multiple correlates—including recent exposure to traumatic event(s), pandemic-related financial concerns, workload, social support, remote learning, willingness to seek professional help, and sleep quality—were identified. It is critical for future studies to further investigate this student population and for universities to provide more flexible learning options and more access to psychological services.
  🖺 Full Text HTML: Prevalence and correlates of depression and anxiety among Chinese international students in US colleges during the COVID-19 pandemic: a cross-sectional study
• Major Coping-behavior and Risk-perception Factors for the COVID-19 Pandemic and their Psychobehavioral Characteristics -
  Coronavirus disease 2019 (COVID-19) has dramatically changed people’s behavior, to prevent infection and overcome the general adversity caused by the implementation of infection-prevention measures. Here, we investigated the main coping-behavior and risk-perception factors, and the underlying psychological mechanisms (e.g., psychobehavioral characteristics) of coping behavior. We recruited 2,885 Japanese participants (1,524 women, ages 20–91 years). First, we identified four coping-behavior factors (two related to infection and two related to general adversity) and three risk- perception factors (one related to medical aspects and two related to society). Second, we demonstrated that infection prevention was promoted by female sex and etiquette in the Power to Live scale. General-adversity coping behavior was facilitated by shortages of daily necessities. Thus, we identified four parsimonious coping-behavior factors, as well as the risk-perception factors and demographic and psychobehavioral characteristics that influenced them. These results will benefit strategic approaches to optimize the social response to the pandemic.
  🖺 Full Text HTML: Major Coping-behavior and Risk-perception Factors for the COVID-19 Pandemic and their Psychobehavioral Characteristics
• COVID-19 Infection and Transmission Includes Complex Sequence Diversity -
  SARS-CoV-2 whole genome sequencing has played an important role in documenting the emergence of polymorphisms in the viral genome and its continuing evolution during the COVID-19 pandemic. Here we present data from over 360 patients to characterize the complex sequence diversity of individual infections identified during multiple variant surges (e.g., Alpha and Delta; requiring [≥] 80% genome coverage and [≥]100X read depth). Across our survey, we observed significantly increasing SARS-CoV-2 sequence diversity during the pandemic and frequent occurrence of multiple biallelic sequence polymorphisms in all infections. This sequence polymorphism shows that SARS-CoV-2 infections are heterogeneous mixtures. Convention for reporting microbial pathogens guides investigators to report a majority consensus sequence. In our study, we found that this approach would under-report at least 79% of the observed sequence variation. As we find that this sequence heterogeneity is efficiently transmitted from donors to recipients, our findings illustrate that infection complexity must be monitored and reported more completely to understand SARS-CoV-2 infection and transmission dynamics involving both immunocompetent and immunocompromised patients. Many of the nucleotide changes that would not be reported in a majority consensus sequence have now been observed as lineage defining SNPs in Omicron BA.1 and/or BA.2 variants. This suggests that minority alleles in earlier SARS-CoV-2 infections may play an important role in the continuing evolution of new variants of concern.
  🖺 Full Text HTML: COVID-19 Infection and Transmission Includes Complex Sequence Diversity
• Tracking the circulating SARS-CoV-2 variants in Turkey: Complete genome sequencing and molecular characterization of 1000 SARS-CoV-2 samples -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus and has caused a pandemic of acute respiratory disease, named ‘coronavirus disease 2019’ (COVID-19). COVID-19 has a deep impact on public health as one of the most serious pandemics in the last century. Tracking SARS-CoV-2 is important for monitoring and assessing its evolution. This is only possible by detecting all mutations in the viral genome through genomic sequencing. Moreover, accurate detection of SARS-CoV-2 and tracking its mutations is also required for its correct diagnosis. Potential effects of mutations on the prognosis of the disease can be observed. Assignment of epidemiological lineages in an emerging pandemic requires efforts. To address this, we collected 1000 SARS-CoV-2 samples from different geographical regions in Turkey and analyze their genome comprehensively. To track the virus across Turkey we focus on 10 distinct cities in different geographic regions. Each SARS-CoV-2 genome was analyzed and named according to the nomenclature system of Nextclade and Pangolin Lineage. Furthermore, the frequency of the variations observed in 10 months was also determined by region. In this way, we have observed how the virus mutations and what kind of transmission mechanism it has. The effects of age and disease severity on lineage distribution were other considered parameters. The temporal rates of SARS-CoV-2 variants by time in Turkey were close to the global trend. This study is one of the most comprehensive whole genome analyses of SARS-CoV-2 that represents a general picture of the distribution of SARS-CoV-2 variations in Turkey in 2021.
  🖺 Full Text HTML: Tracking the circulating SARS-CoV-2 variants in Turkey: Complete genome sequencing and molecular characterization of 1000 SARS-CoV-2 samples
• Phylogeny and Metadata Network Database for Epidemiologic Surveillance -
  The ongoing SARS-CoV-2 pandemic has highlighted the difficulty in integrating disparate data sources for epidemiologic surveillance. To address this challenge, we have created a graph database to integrate phylogenetic trees, associated metadata, and community surveillance data for phylodynamic inference. As an example use case, we divided 22,713 SARS-CoV-2 samples into 5 groups, generated maximum likelihood trees, and inferred a potential transmission network from a forest of minimum spanning trees built on patristic distances between samples. We then used Cytoscape to visualize the resultant graphs.
  🖺 Full Text HTML: Phylogeny and Metadata Network Database for Epidemiologic Surveillance
• The Spike protein of SARS-CoV-2 impairs lipid metabolism and increases susceptibility to lipotoxicity: implication for a role of Nrf2 -
  Background/objectives Coronavirus disease 2019 (COVID-19) patients exhibit lipid metabolic alterations, but the mechanism remains unknown. In this study, we aimed to investigate whether the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impairs lipid metabolism in host cells. Methods A Spike cell line in HEK293 was generated using the pcDNA vector carrying the Spike gene expression cassette. A control cell line was generated using the empty pcDNA vector. Gene expression profiles related to lipid metabolic, autophagic, and ferroptotic pathways were investigated. Palmitic acid (PA)-overload was used to assess lipotoxicity-induced necrosis. Results As compared with controls, the Spike cells showed a significant increase in lipid depositions on cell membranes as well as dysregulation of expression of a panel of molecules involved lipid metabolism, autophagy, and ferroptosis. The Spike cells showed an upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), a multifunctional transcriptional factor, in response to PA. Furthermore, the Spike cells exhibited increased necrosis in response to PA-induced lipotoxicity compared to control cells in a time- and dose-dependent manner via ferroptosis, which could be attenuated by the Nrf2 inhibitor trigonelline. Conclusions The Spike protein impairs lipid metabolic and autophagic pathways in host cells, leading to increased susceptibility to lipotoxicity via ferroptosis which can be suppressed by a Nrf2 inhibitor. This data also suggests a central role of Nrf2 in Spike-induced lipid metabolic impairments.
  🖺 Full Text HTML: The Spike protein of SARS-CoV-2 impairs lipid metabolism and increases susceptibility to lipotoxicity: implication for a role of Nrf2
• Systematic review of spontaneous reports of myocarditis and pericarditis in transplant recipients and immunocompromised patients following COVID-19 mRNA vaccination -

  Objectives: To determine whether spontaneous reporting rates of myocarditis and pericarditis differed in immunocompromised patients compared to the whole population overall, and in terms of demographics, vaccine dose, and time-to-onset. Design: Systematic review of spontaneously reported data from the European Union/European Economic Area (EU/EEA), the United States (US) and the United Kingdom (UK). Data Sources: EudraVigilance (EU/EEA), Vaccine Adverse Event Reporting System (VAERS; US) and the Medicines and Healthcare products Regulatory Agency (MRHA, UK) spontaneous reporting databases were searched from date of vaccine launch to 01 December 2021. Eligibility criteria: Publicly available spontaneous reporting data for ″Myocarditis″ and ″Pericarditis″ from EU/EEA and US following COVID-19 mRNA vaccines. Reports with comorbidities or concurrent medication indicative of transplantation, HIV infection, or cancer (″immunocompromised″ population) were compared with each overall database population. Data extraction and synthesis: Two researchers extracted data. Spontaneously reported events of myocarditis and pericarditis were presented for immunocompromised populations for each data source, stratified by age, sex, dose, and time-to-onset (where available). Seriousness of each event was determined according to the ICH E2A definition. Proportional Reporting Ratio (PRR) was calculated. Results: There were 178 reports of myocarditis and pericarditis amongst immunocompromised individuals overall. Seriousness was comparable between the immunocompromised and overall populations in both databases. No trends in age or sex were observed amongst immunocompromised individuals. Most reports followed a second vaccine dose and occurred within 14 days. The frequency of reporting was similar to the wider population (PRR=1.36 [95% CI= 0.89-1.82] for VAERS population). Conclusions: Myocarditis and pericarditis following COVID-19 vaccination are very rare, and benefits of COVID-19 vaccination continue to outweigh any perceived risks. Reporting rates of myocarditis and pericarditis were similar in immunocompromised individuals, however defining characteristics differed compared to the whole population; therefore, continued monitoring of adverse events following vaccination remains vital to understand differences between population subgroups.

  🖺 Full Text HTML: Systematic review of spontaneous reports of myocarditis and pericarditis in transplant recipients and immunocompromised patients following COVID-19 mRNA vaccination
• The impact of COVID-19 restrictions on older adults’ loneliness: Evidence from high-frequency panel data in Austria -

  BACKGROUND: It is unclear how strong and long lasting the effects of (recurring) COVID-19 restrictions are on older adults9 loneliness. METHODS: 469 retired older Austrians (60+) provided 9,732 repeated observations of loneliness across 30 waves of the Austrian Corona Panel Project between March 2020 and March 2022. Ordinal mixed regression models were used to estimate the effect of the strictness of COVID-19 restrictions (stringency index, range=0-100) on older adult9s loneliness. RESULTS: The proportion of older adults who reported to be often lonely correlated (r=0.45) with the stringency index over time: both peaked during lock-downs (stringency index=82, often lonely=10-13%) and were lowest during the summer of 2020 (stringency index=36, often lonely=4-6%). Results from regression models indicate, that when the stringency index increased, loneliness also increased. In turn, as COVID-19 restrictions loosened, levels of loneliness decreased again. Older adults who lived alone were more affected in terms of loneliness by COVID-19 restriction measures compared to those living with others. CONCLUSIONS: More stringent COVID-19 restrictions were associated with an increased in (situational) loneliness among older adults in Austria, and this effect was stronger among those who lived alone. Efforts should be made to enable older adults, in particular those who live alone, to have save in-person contact during periods of strict pandemic restriction measures.

  🖺 Full Text HTML: The impact of COVID-19 restrictions on older adults’ loneliness: Evidence from high-frequency panel data in Austria
• BCG vaccination of Diversity Outbred mice induces cross-reactive antibodies to SARS-CoV-2 spike protein -
  The Bacillus Calmette-Guerin (BCG) vaccine, the only vaccine against tuberculosis, induces cross-protection against pathogens unrelated to Mycobacterium, including viruses. Epidemiological studies have identified potential benefits of BCG vaccination against SARS-CoV-2 infection. While BCG’s heterologous effects have been widely attributable to trained immunity, we hypothesized BCG vaccination could induce cross-reactive antibodies against the spike protein of SARS-CoV-2 Wuhan-Hu-1. The concentration of IgG reactive to SARS-CoV-2 spike protein from the sera of BCG-vaccinated, Diversity Outbred (DO) mice and C57BL/6J inbred mice was measured using ELISA. Sera from 10/15 BCG-vaccinated DO mice possessed more IgG reactive to recombinant spike protein than sera from BCG-vaccinated C57BL/6J mice and unvaccinated DO mice. Amino acid sequences common to BCG cell wall/membrane proteins and SARS-CoV-2 spike protein were identified as potential antigen candidates for future study. These results imply a humoral mechanism, influenced by genotype, by which BCG vaccination could confer immunity to SARS-CoV-2.
  🖺 Full Text HTML: BCG vaccination of Diversity Outbred mice induces cross-reactive antibodies to SARS-CoV-2 spike protein
• Elucidating host cell response pathways and repurposing therapeutics for SARS-CoV-2 and other coronaviruses using gene expression profiles of chemical and genetic perturbations -
  COVID-19 is an ongoing pandemic that has been causing devastation across the globe for over 2 years. Although there are multiple vaccines that can prevent severe symptoms, effective COVID-19 therapeutics are still of importance. Using our proprietary in silico SMarTR engine, we screened more than 22,000 unique compounds represented by over half a million gene expression profiles to uncover compounds that can be repurposed for SARS-CoV-2 and other coronaviruses in a timely and cost-efficient manner. We then tested 13 compounds in vitro and found three with potency against SARS-CoV-2 with reasonable cytotoxicity. Bortezomib and homoharringtonine are some of the most promising hits with IC50 of 1.39 M and 0.16 M, respectively for SARS-CoV-2. Tanespimycin and homoharringtonine were effective against the common cold coronaviruses. In-depth analysis highlighted proteasome, ribosome, and heat shock pathways as key targets in modulating host responses during viral infection. Further studies of these pathways and compounds have provided novel and impactful insights into SARS-CoV-2 biology and host responses that could be further leveraged for COVID-19 therapeutics development.
  🖺 Full Text HTML: Elucidating host cell response pathways and repurposing therapeutics for SARS-CoV-2 and other coronaviruses using gene expression profiles of chemical and genetic perturbations
• An intranasal nanoparticle STING agonist has broad protective immunity against respiratory viruses and variants -
  Respiratory viral infections, especially Influenza (endemic) or SARS-CoV-2 (pandemic since 2020), cause morbidity and mortality worldwide. Despite remarkable progress in the development and deployment of vaccines, they are clearly impacted by the rapid emergence of viral variants. The development of an off-the-shelf, effective, safe, and low-cost drug for prophylaxis against respiratory viral infections is a major unmet medical need. Here, we developed NanoSTING, a liposomally encapsulated formulation of the endogenous STING agonist, cGAMP, to function as an immunoantiviral. NanoSTING rapidly activates the body’s innate immune system to facilitate a broad-spectrum antiviral response against SARS-CoV-2 and influenza variants in hamsters and mice. We demonstrate that a single intranasal dose of NanoSTING can:

1. treat infections throughout the respiratory system and minimize clinical symptoms, (2) protect against highly pathogenic strains of SARS-CoV-2 (alpha and delta), (3) provide durable protection against reinfection from the same strains without the need for retreatment, (4) prevent transmission of the highly infectious SARS-CoV-2 Omicron strain, and (5) provide protection against both oseltamivir-sensitive and resistant strains of influenza. Mechanistically, administration of NanoSTING rapidly upregulated interferon-stimulated and antiviral pathways in both the nasal turbinates and lung. Our results support using NanoSTING as a thermostable, immunoantiviral with broad-spectrum antiviral properties making it appealing as a therapeutic for prophylactic or early post-exposure treatment.
   🖺 Full Text HTML: An intranasal nanoparticle STING agonist has broad protective immunity against respiratory viruses and variants

• Persistent cross-species SARS-CoV-2 variant infectivity predicted via comparative molecular dynamics simulation -
  Widespread human transmission of SARS-CoV-2 highlights the substantial public health, economic, and societal consequences of virus spillover from wildlife and also presents a repeated risk of reverse spillovers back to naive wildlife populations. We employ comparative statistical analyses of a large set of short-term molecular dynamic (MD) simulations to investigate potential human to bat (Rhinolophus macrotis) cross-species infectivity allowed by the binding of SARS-CoV-2 receptor-binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2) across the bat progenitor strain and emerging human strain variants of concern (VOC). We statistically compare the dampening of atom motion during binding across protein sites upon the formation of the RBD-ACE2 binding interface using bat vs. human target receptors (i.e. bACE2 and hACE2). We report that while the bat progenitor viral strain RaTG13 shows some pre-adaption to binding hACE2, it also exhibits stronger overall affinity to bACE2. However, while the early emergent human strains and later VOCs exhibit robust binding to both hACE2 and bACE2, the delta and omicron variants exhibit evolutionary adaption of binding to hACE2. However, we conclude there is a still significant risk of mammalian cross-species infectivity of human VOCs during upcoming waves of infection as COVID-19 transitions from a pandemic to endemic status.
  🖺 Full Text HTML: Persistent cross-species SARS-CoV-2 variant infectivity predicted via comparative molecular dynamics simulation
• Redox regulation of the SARS-CoV-2 main protease provides new opportunities for drug design -
  Besides vaccines, the development of antiviral drugs targeting SARS-CoV-2 is critical for stopping the current COVID-19 pandemic and preventing future outbreaks. The SARS-CoV-2 main protease (Mpro), a cysteine protease with essential functions in viral replication, has been validated as an effective drug target. Here, we show that Mpro is subject to redox regulation and reversibly switches between the enzymatically active dimer and the functionally dormant monomer through redox modifications of cysteine residues. These include sulfenylation, disulfide formation between the catalytic cysteine and a proximal cysteine, and generation of an allosteric lysine-cysteine SONOS bridge that is required for structural stability under oxidative stress conditions, such as those exerted by the innate immune system. We identify homo- and heterobifunctional reagents that mimic the redox switching and possess antiviral activity. The discovered redox switches are conserved in main proteases from other coronaviruses, e.g. MERS and SARS-CoV, indicating their potential as common druggable sites.
  🖺 Full Text HTML: Redox regulation of the SARS-CoV-2 main protease provides new opportunities for drug design
• Mental Health and Clinical Psychological Science in the Time of COVID-19: Challenges, Opportunities, and a Call to Action -
  COVID-19 presents significant social, economic, and medical challenges. Because COVID-19 has already begun to precipitate huge increases in mental health problems, clinical psychological science must assert a leadership role in guiding a national response to this secondary crisis. In this paper, COVID-19 is conceptualized as a unique, compounding, multi-dimensional stressor that will create a vast need for intervention and necessitate new paradigms for mental health service delivery and training. Urgent challenge areas across developmental periods are discussed, followed by a review of psychological symptoms that likely will increase in prevalence and require innovative solutions in both science and practice. Implications for new research directions, clinical approaches, and policy issues are discussed to highlight the opportunities for clinical psychological science to emerge as an updated, contemporary field capable of addressing the burden of mental illness and distress in the wake of COVID-19 and beyond.
  🖺 Full Text HTML: Mental Health and Clinical Psychological Science in the Time of COVID-19: Challenges, Opportunities, and a Call to Action

From Clinical Trials

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

• Functional Capacity in Patients Post Mild COVID-19 - Condition:   COVID-19
  Intervention:   Device: Cardiopulmonary exercise test (CPET)
  Sponsor:   Rambam Health Care Campus
  Recruiting

• Circuit Training Program in Post COVID-19 Patients - Condition:   COVID-19
  Interventions:   Other: Circuit Training Exercise Program;   Other: Aerobic Training Exercise Program
  Sponsor:   Riphah International University
  Recruiting

• The Effect of Home-based Rehabilitation Program After COVID-19 Infection - Condition:   COVID-19
  Interventions:   Behavioral: Add-on telerehabilitation and home-based rehabilitation;   Behavioral: Home-based rehabilitation alone
  Sponsor:  
  National Taiwan University Hospital
  Recruiting

• Efficacy, Safety and Immunogenicity Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition:   COVID-19
  Interventions:   Biological: SARS-CoV-2 protein subunit recombinant vaccine;   Biological: placebo
  Sponsors:   PT Bio Farma;   Faculty of Medicine, Universitas Indonesia, Jakarta;   Faculty of Medicine, Diponegoro University, Semarang;   Faculty of Medicine, Universitas Andalas, Padang;   Faculty of Medicine, Universitas Hassanudin, Makassar
  Recruiting

• A Study to Evaluate the Immunogenicity and Safety of Two Recombinant Protein COVID-19 Vaccines in Population Aged ≥18 Years as Booster Vaccines - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01C;   Biological: SCTV01E;   Biological: Sinopharm inactivated COVID-19 vaccine;   Biological: mRNA-1273
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine in Population Aged ≥18 Years - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Interventions:   Biological: SCTV01E;   Biological: Comirnaty
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

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

• Non-inferiority Trial on Treatments in Early COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Sotrovimab;   Drug: Tixagevimab Cilgavimab;   Drug: Nirmatrelvir Ritonavir
  Sponsors:   Azienda Ospedaliera Universitaria Integrata Verona;   Agenzia Italiana del Farmaco;   Azienda Sanitaria-Universitaria Integrata di Udine
  Recruiting

• Neutralizing Power of Anti-SARS-CoV-2 (Anti-COVID-19) Serum Antibodies - Conditions:   COVID-19;   SARS CoV 2 Infection
  Intervention:  
  Other: Collection of biological samples
  Sponsor:   Centre Hospitalier Régional d’Orléans
  Not yet recruiting

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

• Immunogenicity，Safety and Cross - Immune Response With the Strains of the Booster Immunization Using an Inactivated COVID-19 Vaccine - Condition:   COVID-19
  Intervention:   Biological: Inactivated COVID-19 Vaccine
  Sponsor:   Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• SARS-CoV-2 Specific Immune Response After COVID-19 Vaccination in Cancer Patients - Conditions:   COVID-19;   Cancer
  Intervention:   Biological: CoronaVac vaccine
  Sponsors:   National Cancer Institute, Thailand;   Mahidol University
  Completed

• Safety and Immunogenicity of Recombinant SARS-CoV-2 Spike Protein Vaccine (CHO Cell) for the Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: ZR-202-CoV;   Other: Placebo
  Sponsors:   Shanghai Zerun Biotechnology Co.,Ltd;   Walvax Biotechnology Co., Ltd.
  Recruiting

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

From PubMed

• Does government intervention affect CO₂ emission reduction effect of producer service agglomeration? Empirical analysis based on spatial Durbin model and dynamic threshold model - Achieving carbon peak and carbon neutrality is an inherent requirement for countries to promote green recovery and transformation of the global economy after the COVID-19 pandemic. As “a smoke-free industry,” producer services agglomeration (PSA) may have significant impacts on CO(2) emission reduction. Therefore, based on the nightlight data to calculate the CO(2) emissions of 268 cities in China from 2005 to 2017, this study deeply explores the impact and transmission mechanism of PSA on CO(2)…

• Famotidine activates the vagus nerve inflammatory reflex to attenuate cytokine storm - Background. Severe COVID-19 is characterized by pro-inflammatory cytokine release syndrome (cytokine storm) which causes high morbidity and mortality. Recent observational and clinical studies suggest famotidine, a histamine 2 receptor (H2R) antagonist widely used to treat gastroesophageal reflux disease , attenuates the clinical course of COVID-19. Because evidence is lacking for a direct antiviral activity of famotidine, a proposed mechanism of action is blocking the effects of histamine…

• Receptor binding domain of SARS-CoV-2 is a functional αv-integrin agonist - Among the novel mutations distinguishing SARS-CoV-2 from similar respiratory coronaviruses is a K403R substitution in the receptor-binding domain (RBD) of the viral spike (S) protein within its S1 region. This amino acid substitution occurs near the angiotensin-converting enzyme 2 (ACE2)-binding interface and gives rise to a canonical RGD adhesion motif that is often found in native extracellular matrix proteins, including fibronectin. In the present study, the ability of recombinant S1-RBD to…

• The Roles of APOBEC-mediated RNA Editing in SARS-CoV-2 Mutations, Replication and Fitness - During COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more infectious or evade vaccines. Viral RNA mutations can arise from misincorporation by RNA-polymerases and modification by host factors. Analysis of SARS-CoV-2 sequence from patients showed a strong bias toward C-to-U mutation, suggesting a potential mutational role by host APOBEC cytosine deaminases that possess broad anti-viral activity. We report the first experimental evidence demonstrating that APOBEC3A,…

• Hippo Signaling Pathway Activation during SARS-CoV-2 Infection Contributes to Host Antiviral Response - SARS-CoV-2, responsible for the COVID-19 pandemic, causes respiratory failure and damage to multiple organ systems. The emergence of viral variants poses a risk of vaccine failures and prolongation of the pandemic. However, our understanding of the molecular basis of SARS-CoV-2 infection and subsequent COVID-19 pathophysiology is limited. In this study, we have uncovered a critical role for the evolutionarily conserved Hippo signaling pathway in COVID-19 pathogenesis. Given the complexity of…

• Different HMGCR-inhibiting statins vary in their association with increased survival in patients with COVID-19 - BACKGROUND: In response to the challenge to rapidly identify treatment options for COVID-19, several studies reported that statins, as a drug class, reduce mortality in these patients. Here we explored the possibility that different statins might differ in their ability to exert protective effects based on computational predictions.

• Virucidal activity and mechanism of action of cetylpyridinium chloride against SARS-CoV-2 - CONCLUSIONS: Our results suggest that CPC inhibits the interaction between S protein and ACE2, and thus, reduces infectivity of SARS-CoV-2 and suppresses viral adsorption.

• Synthesis and biological evaluation of 2-benzylaminoquinazolin-4(3H)-one derivatives as a potential treatment for SARS-CoV-2 - Despite the continuing global crisis caused by coronavirus disease 2019 (COVID-19), there is still no effective treatment. Therefore, we designed and synthesized a novel series of 2-benzylaminoquinazolin-4(3H)-one derivatives and demonstrated that they are effective against SARS-CoV-2. Among the synthesized derivatives, 7-chloro-2-(((4-chlorophenyl)(phenyl)methyl)amino)quinazolin-4(3H)-one (Compound 39) showed highest anti-SARS-CoV-2 activity, with a half-maximal inhibitory concentration value…

• Mitoxantrone modulates a heparan sulfate-spike complex to inhibit SARS-CoV-2 infection - Spike-mediated entry of SARS-CoV-2 into human airway epithelial cells is an attractive therapeutic target for COVID-19. In addition to protein receptors, the SARS-CoV-2 spike (S) protein also interacts with heparan sulfate, a negatively charged glycosaminoglycan (GAG) attached to certain membrane proteins on the cell surface. This interaction facilitates the engagement of spike with a downstream receptor to promote viral entry. Here, we show that Mitoxantrone, an FDA- approved topoisomerase…

• Author Correction: Enoxaparin augments alpha-1-antitrypsin inhibition of TMPRSS2, a promising drug combination against COVID-19 - No abstract

• Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model - Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19), with macrophages as one of the main cell types involved. It is urgent to understand the interactions among permissive cells, macrophages, and the SARS-CoV-2 virus, thereby offering important insights into effective therapeutic strategies. Here, we establish a lung and macrophage co-culture system derived from human pluripotent stem cells (hPSCs), modeling the host-pathogen interaction…

• Flavonols and dihydroflavonols inhibit the main protease activity of SARS-CoV-2 and the replication of human coronavirus 229E - Since December 2019, the deadly novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current COVID-19 pandemic. To date, vaccines are available in the developed countries to prevent the infection of this virus; however, medicines are necessary to help control COVID-19. Human coronavirus 229E (HCoV-229E) causes the common cold. The main protease (M^(pro)) is an essential enzyme required for the multiplication of these two viruses in the host cells, and thus is an…

• Dexamethasone: Insights into Pharmacological Aspects, Therapeutic Mechanisms, and Delivery Systems - Dexamethasone (DEX) has been widely used to treat a variety of diseases, including autoimmune diseases, allergies, ocular disorders, cancer, and, more recently, COVID-19. However, DEX usage is often restricted in the clinic due to its poor water solubility. When administered through a systemic route, it can elicit severe side effects, such as hypertension, peptic ulcers, hyperglycemia, and hydro-electrolytic disorders. There is currently much interest in developing efficient DEX-loaded…

• Potent Inhibition of SARS-CoV-2 nsp14 N7-Methyltransferase by Sulfonamide-Based Bisubstrate Analogues - Enzymes involved in RNA capping of SARS-CoV-2 are essential for the stability of viral RNA, translation of mRNAs, and virus evasion from innate immunity, making them attractive targets for antiviral agents. In this work, we focused on the design and synthesis of nucleoside-derived inhibitors against the SARS-CoV-2 nsp14 (N7-guanine)-methyltransferase (N7-MTase) that catalyzes the transfer of the methyl group from the S-adenosyl-l-methionine (SAM) cofactor to the N7-guanosine cap. Seven compounds…

• Insighting the optoelectronic, charge transfer and biological potential of benzo-thiadiazole and its derivatives - The current investigation applies the dual approach containing quantum chemical and molecular docking techniques to explore the potential of benzothiadiazole (BTz) and its derivatives as efficient electronic and bioactive materials. The charge transport, electronic and optical properties of BTz derivatives are explored by quantum chemical techniques. The density functional theory (DFT) and time dependent DFT (TD-DFT) at B3LYP/6-31G** level of theory utilized to optimize BTz and newly designed…

From Patent Search

• SYSTEM FOR MONITORING COVID-19 PATIENTS USING A VIRTUAL TELEPRESENCE ROBOT - Attached Separately - link

• MASCARA FACIAL PARA LA INHALACION DE SUBSTANCIAS NEBULIZADAS, CON SISTEMA DE ASPIRACION INCORPORADO - - link

• MACHINE LEARNING TECHNIQUE TO ANALYZE THE WORK PRESSURE OF PARAMEDICAL STAFF DURING COVID 19 - Machine learning technique to analyse the work pressure of paramedical staff during covid 19 is the proposed invention that focuses on identifying the stress levels of paramedical staff. The invention focuses on analysing the level of stress that is induced on the paramedical staff especially during pandemic. - link

• 一种吡咯烷酮中间体的合成方法 - 本发明涉及药物中间体合成技术领域，尤其是一种吡咯烷酮中间体的合成方法，包括以下步骤：化合物1溶液和有机锂试剂溶液泵入连续反应器，反应生成锂氢交换中间体，再泵入卤代乙腈与中间态发生反应生成化合物2；化合物2用固定床反应装置内进行氢化反应，后处理得到化合物3；将化合物3的溶液和氨水溶液泵入连续反应器生成酰胺化合物4；化合物4和脱水剂使用恒流泵泵入连续化反应器，生成化合物5或其氨基上有保护基的中间体；应用串联连续反应技术，将传统釜式数步反应改进为连续化工艺，解决了传统釜式反应的放大效应问题，降低了含金属试剂以及高压氢化等危险反应的安全风险进而避免了超低温反应釜和高压氢化釜等设备，提高了生产效率。 - link

• 一株表达新冠病毒S1蛋白单克隆抗体杂交瘤细胞系及中和活性抗体 - 本发明属于细胞工程与免疫学领域，具体涉及一株表达新冠病毒S1蛋白单克隆抗体杂交瘤细胞系及中和活性抗体。本发明筛选获得一株能高效稳定分泌表达新冠病毒S1蛋白单克隆抗体的杂交瘤细胞系以及其分泌的新冠病毒S1蛋白单克隆抗体；利用普通细胞培养皿培养本发明的重组杂交瘤细胞系，产量可达10mg/L，且纯度能达90%以上；本发明的单抗具有高中和活性，单抗浓度为0.00103μg/mL时即可抑制50％以上新冠假病毒活性，是目前所报告的新冠单抗中和活性最佳的。本发明提供的杂交瘤细胞系或单克隆抗体在新冠病毒的血清学检测、制备新冠病毒感染的试剂或药物及制备新冠病毒抗原或抗体检测的试剂中具有重要的应用价值。 - link

• 基于SARS-CoV-2的S蛋白的疫苗及其用途 - 本公开提供了基于SARS‑CoV‑2的S蛋白的疫苗及其用途，并具体涉及重组SARS‑CoV‑2刺突蛋白(S蛋白)及编码其的mRNA和DNA。本公开还涉及包含编码重组S蛋白的DNA序列的重组质粒。本公开的重组质粒经转录得到mRNA，其包含SEQ ID NO.12所示的序列。本公开进一步涉及包含前述mRNA的mRNA‑载体颗粒例如脂质纳米颗粒(LNP)和组合物例如疫苗组合物。 - link

• CBD Covid 19 Protection - - link

• 一种双价可电离脂质化合物、组合物及其应用 - 本发明涉及核酸药物递送技术领域，特别是关于一种双价可电离脂质化合物、组合物及其应用。本发明提供多种可以递送核酸药物的可电离阳离子脂质，具备较强的可设计性、可生物降解性及高效的体内外转染效率，由其组成的脂质纳米递送系统用于递送mRNA，在细胞水平上，优于目前上市的产品，并且在动物水平也具有良好的递送效率，可以作为核酸药物的递送新的方法，促进核酸药物的发展。 - link

• 一种双价可电离脂质化合物、组合物及其应用 - 本发明涉及核酸药物递送技术领域，特别是关于一种双价可电离脂质化合物、组合物及其应用。本发明提供多种可以递送核酸药物的可电离阳离子脂质，具备较强的可设计性、可生物降解性及高效的体内外转染效率，由其组成的脂质纳米递送系统用于递送mRNA，在细胞水平上，优于目前上市的产品，并且在动物水平也具有良好的递送效率，可以作为核酸药物的递送新的方法，促进核酸药物的发展。 - link

• 新冠肺炎CT图像分割方法及终端设备 - 本发明公开了一种新冠肺炎CT图像分割方法及终端设备，方法包括获取待分割新冠肺炎CT图像；将该图像输入至训练好的分割模型中，得到新冠肺炎病灶区域的图像；其中分割模型包括依次连接的多个下采样模块和下采样模块对应的上采样模块；每个采样模块均包括依次连接的第一提取单元和第二提取单元；上述两个提取单元的卷积模块均为结构重参数化卷积模块。本发明的结构重参数化卷积模块为训练时使用多分支结构，加强模型表达能力，推理时使用单路结构，加快推理速度，快速得出诊断结果。同时，为从不同尺度特征图中学习分层表示，加强模型对图像边缘信息提取，并使梯度更快回流，上采样每一侧输出都连接混合损失函数，实现图像的像素级分割。 - link