Covid-19 Sentry

Contents

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

From Preprints

• Empathy predicts self-isolation behaviour acceptance during coronavirus risk exposure -
  Health risk exposure during the global COVID-19 pandemic has required people to adopt self-isolation. Public authorities have therefore had the difficult task of sustaining such protective but stressful behaviour. Evidence shows that besides egoistic drives, the motivation for self-isolation behaviour could be altruistic. However, the type and role of prosocial motivation in the current pandemic is underestimated and its interaction with risk exposure and psychological distress is largely unknown. Here we show that empathic concern for the most vulnerable predicts acceptance of lockdown measures. In two retrospective studies, one with a general population and one with COVID-19 positive patients, we found that 1) along with health risk exposure, empathic concern is a predictor of acceptance of lockdown measures 2) social covariates and psychological distress have no significant impact. Our results support the need to focus on altruistic behaviours while informing the public instead of on fear-inducing messages.
  🖺 Full Text HTML: Empathy predicts self-isolation behaviour acceptance during coronavirus risk exposure
• Recombination and low-diversity confound homoplasy-based methods to detect the effect of SARS-CoV-2 mutations on viral transmissibility -
  The SARS-CoV-2 variant carrying the Spike protein mutation G614 was first detected in late January 2020 and within a few months became the dominant form globally. In the months that followed, many studies, both in vitro and in animal models, showed that variants carrying this mutation were more infectious and more readily transmitted than the ancestral Wuhan form. Here we investigate why a recently published study by van Dorp et al. failed to detect such higher transmissibility of the G614 variant using homoplasy-based methods. We show that both low diversity and recombination confound the methods utilized by van Dorp et al. and significantly decrease their sensitivity. Furthermore, though they claim no evidence of recombination in their dataset, we and several other studies identify a subset of the sequences as recombinants, possibly enough to affect their statistic adversely.
  🖺 Full Text HTML: Recombination and low-diversity confound homoplasy-based methods to detect the effect of SARS-CoV-2 mutations on viral transmissibility
• Are we ready for COVID-19's Golden Passport? Insights from a Global Physician Survey -

  Background: COVID-19 immunity passports could protect the right to free movement but critics worry about insufficient evidence, privacy, fraud, and discrimination. Objective: To characterize the global physician community9s opinions regarding immunity passports. Design: Cross sectional, random stratified sample of physicians registered with Sermo, a global networking platform open to verified and licensed physicians. Main outcome measures: The survey asked: "Digital immunity passports, based on antibody testing, are being considered to offer proof (e.g. via an app or QR code) that a person has developed lasting immunity to COVID-19 and hence can return to work or travel freely. In your opinion, do we know enough about COVID-19 immunity and it9s duration to offer such immunity passports at the present time?" Possible answers were YES, NO, and UNCERTAIN. Results: The survey was completed by 1004 physicians (67 specialties, 40 countries, 49% frontline specialties) with a mean (SD) age of 49.14 (12) years. Overall, 52% answered NO, 17% were UNCERTAIN, and 31% answered YES (p<0.05). EU physicians were more likely to say YES but even among them it did not exceed 35% approval. US physicians (60%) were more likely to say NO (p<0.05) (Figure). Conclusions: Our findings suggest a current lack of support among physicians for immunity passports. It is hoped that ongoing research and vaccine trials will provide further clarity.

  🖺 Full Text HTML: Are we ready for COVID-19's Golden Passport? Insights from a Global Physician Survey
• COVID-19 Prevention via the Science of Habit Formation -
  The coronavirus disease 2019 (COVID-19) continues to claim lives worldwide. We propose that the science of habit formation offers strategies to increase adherence to COVID-19 prevention behaviors and has potential to be lifesaving, particularly for high risk groups. Eight elements of habit formation are highlighted: addressing incorrect beliefs, setting goals, devising an action plan, establishing contextual cues, adding reinforcement, engaging in repetition, aiming for automaticity and recognizing that change is difficult. In addition, we offer a set of strategies for forming new habits and eliminating existing habits to contain the spread of COVID-19. These strategies are derived from habit formation principles and behavior change techniques and can inform future treatment development research. With the COVID-19 pandemic still raging, there is currently an urgent opportunity to leap knowledge on habit formation processes and interventions forward.
  🖺 Full Text HTML: COVID-19 Prevention via the Science of Habit Formation
• Robotic RNA extraction for SARS-CoV-2 surveillance using saliva samples -

  Saliva is an attractive specimen type for asymptomatic surveillance of COVID-19 in large populations due to its ease of collection and its demonstrated utility for detecting RNA from SARS-CoV-2. Multiple saliva-based viral detection protocols use a direct-to-RT-qPCR approach that eliminates nucleic acid extraction but can reduce viral RNA detection sensitivity. To improve test sensitivity while maintaining speed, we developed a robotic nucleic acid extraction method for detecting SARS-CoV-2 RNA in saliva samples with high throughput. Using this assay, the Free Asymptomatic Saliva Testing (IGI-FAST) research study on the UC Berkeley campus conducted 11,971 tests on supervised self-collected saliva samples and identified rare positive specimens containing SARS-CoV-2 RNA during a time of low infection prevalence. In an attempt to increase testing capacity, we further adapted our robotic extraction assay to process pooled saliva samples. We also benchmarked our assay against the gold standard, nasopharyngeal swab specimens. Finally, we designed and validated a RT-qPCR test suitable for saliva self-collection. These results establish a robotic extraction-based procedure for rapid PCR-based saliva testing that is suitable for samples from both symptomatic and asymptomatic individuals.

  🖺 Full Text HTML: Robotic RNA extraction for SARS-CoV-2 surveillance using saliva samples
• Modeling effectiveness of testing strategies to prevent COVID-19 in nursing homes--United States, 2020 -

  Background: SARS-CoV-2 outbreaks in nursing homes can be large with high case fatality. Identifying asymptomatic individuals early through serial testing is recommended to control COVID-19 in nursing homes, both in response to an outbreak ("outbreak testing" of residents and healthcare personnel) and in facilities without outbreaks ("non-outbreak testing" of healthcare personnel). The effectiveness of outbreak testing and isolation with or without non-outbreak testing was evaluated. Methods: Using published SARS-CoV-2 transmission parameters, the fraction of SARS-CoV-2 transmissions prevented through serial testing (weekly, every three days, or daily) and isolation of asymptomatic persons compared to symptom-based testing and isolation was evaluated through mathematical modeling using a Reed-Frost model to estimate the percentage of cases prevented (i.e., "effectiveness") through either outbreak testing alone or outbreak plus non-outbreak testing. The potential effect of simultaneous decreases (by 10%) in the effectiveness of isolating infected individuals when instituting testing strategies was also evaluated. Results: Modeling suggests that outbreak testing could prevent 54% (weekly testing with 48-hour test turnaround) to 92% (daily testing with immediate results and 50% relative sensitivity) of SARS-CoV-2 infections. Adding non-outbreak testing could prevent up to an additional 8% of SARS-CoV-2 infections (depending on test frequency and turnaround time). However, added benefits of non-outbreak testing were mostly negated if accompanied by decreases in infection control practice. Conclusions: When combined with high-quality infection control practices, outbreak testing could be an effective approach to preventing COVID-19 in nursing homes, particularly if optimized through increased test frequency and use of tests with rapid turnaround.

  🖺 Full Text HTML: Modeling effectiveness of testing strategies to prevent COVID-19 in nursing homes--United States, 2020
• Uncovering clinical risk factors and prediction of severe COVID-19: A machine learning approach based on UK Biobank data -

  Background: COVID-19 is a major public health concern. Given the extent of the pandemic, it is urgent to identify risk factors associated with disease severity. Accurate prediction of those at risk of developing severe infections is also of high clinical importance. Methods: Based on the UK Biobank(UKBB data), we built machine learning(ML) models to predict the risk of developing severe or fatal infections, and to evaluate major risk factors involved. We first restricted the analysis to infected subjects(N=7846), then performed analysis at a population level, considering those with no known infection as controls(N for controls=465,728). Hospitalization was used as a proxy for severity. Totally 97 clinical variables(collected prior to COVID-19 outbreak) covering demographic variables, comorbidities, blood measurements(e.g. hematological/liver/renal function/metabolic parameters etc.), anthropometric measures and other risk factors (e.g. smoking/drinking habits) were included as predictors. We also constructed a simplified (lite) prediction model using 27 covariates that can be more easily obtained (demographic and comorbidity data). XGboost (gradient boosted trees) was used for prediction and predictive performance was assessed by cross-validation. Variable importance was quantified by Shapley values and accuracy gain. Shapley dependency and interaction plots were used to evaluate the pattern of relationship between risk factors and outcomes. Results: A total of 2386 severe and 477 fatal cases were identified. For the analysis among infected individuals (N=7846),our prediction model achieved AUCs of 0.723(95% CI:0.711-0.736) and 0.814(CI: 0.791-0.838) for severe and fatal infections respectively. The top five contributing factors for severity were age, number of drugs taken(cnt_tx), cystatin C(reflecting renal function), wait-hip ratio (WHR) and Townsend Deprivation index (TDI). For prediction of mortality, the top features were age, testosterone, cnt_tx, waist circumference(WC) and red cell distribution width (RDW). In analyses involving the whole UKBB population, the corresponding AUCs for severity and fatality were 0.696(CI:0.684-0.708) and 0.802(CI:0.778-0.826) respectively. The same top five risk factors were identified for both outcomes, namely age, cnt_tx, WC, WHR and TDI. Apart from the above features, Type 2 diabetes(T2DM), HbA1c and apolipoprotein A were ranked among the top 10 in at least two (out of four) analyses. Age, cystatin C, TDI and cnt_tx were among the top 10 across all four analyses. As for the lite models, the predictive performances in terms of AUC are broadly similar, with estimated AUCs of 0.716, 0.818, 0.696 and 0.811 respectively. The top-ranked variables were similar to above, including for example age, cnt_tx, WC, male and T2DM. Conclusions: We identified a number of baseline clinical risk factors for severe/fatal infection by an ML approach. For example, age, central obesity, impaired renal function, multi-comorbidities and cardiometabolic abnormalities may predispose to poorer outcomes. The presented prediction models may be useful at a population level to help identify those susceptible to developing severe/fatal infections, hence facilitating targeted prevention strategies. Further replications in independent cohorts are required to verify our findings.

  🖺 Full Text HTML: Uncovering clinical risk factors and prediction of severe COVID-19: A machine learning approach based on UK Biobank data
• Development of spike receptor-binding domain nanoparticle as a vaccine candidate against SARS-CoV-2 infection in ferrets -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of COVID-19 pandemic, enters host cells via the interaction of its Receptor-Binding Domain (RBD) of Spike protein with host Angiotensin-Converting Enzyme 2 (ACE2). Therefore, RBD is a promising vaccine target to induce protective immunity against SARS-CoV-2 infection. In this study, we report the development of RBD protein-based vaccine candidate against SARS-CoV-2 using self-assembling H. pylori-bullfrog ferritin nanoparticles as an antigen delivery. RBD-ferritin protein purified from mammalian cells efficiently assembled into 24-mer nanoparticles. 16-20 months-old ferrets were vaccinated with RBD-ferritin nanoparticles (RBD-nanoparticles) by intramuscular or intranasal inoculation. All vaccinated ferrets with RBD-nanoparticles produced potent neutralizing antibodies against SARS-CoV-2. Strikingly, vaccinated ferrets demonstrated efficient protection from SARS-CoV-2 challenge, showing no fever, body weight loss and clinical symptoms. Furthermore, vaccinated ferrets showed rapid clearance of infectious viruses in nasal washes and lungs as well as viral RNA in respiratory organs. This study demonstrates the Spike RBD-nanoparticle as an effective protein vaccine candidate against SARS-CoV-2.
  🖺 Full Text HTML: Development of spike receptor-binding domain nanoparticle as a vaccine candidate against SARS-CoV-2 infection in ferrets
• The evolutionary making of SARS-CoV-2 -
  Covid-19 is the most devastating pandemic of the past 100 years. A zoonotic transfer presumably at a wildlife market introduced the causative virus, SARS-CoV-2 (sarbecovirus; beta-coronavirus), to humans in late 2019. Meanwhile, the mechanistic details of the infection process have been largely elucidated, and structural models explain binding of the virial spike to the human cell surface receptor ACE2. Yet, the evolutionary trajectory that gave rise to this pathogen is poorly understood. Here we scan SARS-CoV-2 protein sequences in-silico for innovations along the evolutionary lineage starting with the last common ancestor of coronaviruses. Substantial differences in the sets of proteins encoded by SARS-CoV-2 and viruses outside sarbecovirus, and in their domain architectures, indicate divergent functional demands. By contrast, sarbecoviruses themselves are almost fully conserved at these levels of resolution. However, profiling spike evolution on the sub-domain level using predicted linear epitopes reveals that this protein was gradually reshaped within sarbecovirus. The only epitope that is private to SARS-CoV-2 overlaps with the furin cleavage site. This lends phylogenetic support to the hypothesis that a change in strategy facilitated the zoonotic transfer of SARS-CoV-2 and its success as a human pathogen. Upon furin cleavage, spike switches from a "stealth mode" where immunodominant ACE2 binding epitopes are largely hidden to an "attack mode" where these epitopes are exposed. The resulting reinforcement of ACE2 binding extends the window of opportunity for cell entry. SARS-CoV-2 variants fine-tuning this mode switch will be particularly threatening as they optimize immune evasion.
  🖺 Full Text HTML: The evolutionary making of SARS-CoV-2
• NUCLEIC TRANSFORMER: DEEP LEARNING ONNUCLEIC ACIDS WITH SELF-ATTENTION ANDCONVOLUTIONS -
  Much work has been done to apply machine learning and deep learning to genomics tasks, but these applications usually require extensive domain knowledge and the resulting models provide very limited interpretability. Here we present the Nucleic Transformer, a conceptually simple but effective and interpretable model architecture that excels in a variety of DNA/RNA tasks. The Nucleic Transformer processes nucleic acid sequences with self-attention and convolutions, two deep learning techniques that have proved dominant in the fields of computer vision and natural language processing. We demonstrate that the Nucleic Transformer can be trained in both supervised and unsupervised fashion without much domain knowledge to achieve high performance with limited amounts of data in E. coli promoter classification, viral genome identification, and degradation properties of COVID-19 mRNA vaccine candidates. Additionally, we showcase extraction of promoter motifs from learned attention and how direct visualization of self-attention maps assists informed decision making using deep learning models.
  🖺 Full Text HTML: NUCLEIC TRANSFORMER: DEEP LEARNING ONNUCLEIC ACIDS WITH SELF-ATTENTION ANDCONVOLUTIONS
• Conspiratorial thinking during COVID-19: The roles of paranoia, delusion-proneness, and intolerance of uncertainty -
  The COVID-19 global pandemic has left many feeling a sense of profound uncertainty about their world, safety, and livelihood. Information that can help make sense of this uncertainty is offered by both official health-organizations as well as sources espousing misinformation and conspiracy theories. Individuals high in intolerance of uncertainty (IU) may be particularly impacted by the impoverished epistemic environment and may thus be more drawn to conspiratorial thinking (CT). In the present study we show that endorsement of COVID-19-specific conspiracy theories is associated with higher levels of intolerance of uncertainty as well as anxiety, delusion-proneness, and paranoid ideation. Furthermore, delusion-proneness and paranoia explained the relationship between IU and CT, and emerged as independent partial predictors of CT even when controlling for other facets of schizotypy. In contrast, anxiety did not explain the relationship between IU and CT, suggesting a stronger role of cognitive traits as opposed to affective factors. Overall, our findings highlight the importance of individual differences in IU, delusion proneness and paranoia in the development of CT in the context of the acute uncertainty of a global crisis, in which CT is more prevalent and salient. Informational intervention designs may benefit from leveraging the body of work demonstrating the efficacy of targeting IU to incite meaningful changes in thinking.
  🖺 Full Text HTML: Conspiratorial thinking during COVID-19: The roles of paranoia, delusion-proneness, and intolerance of uncertainty
• The SARS-CoV-2 Y453F mink variant displays a striking increase in ACE-2 affinity but does not challenge antibody neutralization -
  SARS-CoV-2 transmission from humans to animals has been reported for many domesticated species, including cats, dogs and minks. Identification of novel spike gene mutations appearing in minks has raised major concerns about potential immune evasion and challenges for the global vaccine strategy. The genetic variant, known as cluster-five, arose among farmed minks in Denmark and resulted in a complete shutdown of the worlds largest mink production. However, the functional properties of this new variant are not established. Here we present functional data on the Y453F cluster-five receptor-binding domain (RBD) and show that it does not decrease established humoral immunity or affect the neutralizing response in a vaccine model based on wild-type RBD or spike. However, it binds the human ACE-2 receptor with a four-fold higher affinity suggesting an enhanced transmission capacity and a possible challenge for viral control.
  🖺 Full Text HTML: The SARS-CoV-2 Y453F mink variant displays a striking increase in ACE-2 affinity but does not challenge antibody neutralization
• Heterologous vaccination regimens with self-amplifying RNA and Adenoviral COVID vaccines induce superior immune responses than single dose vaccine regimens in mice -
  Several vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two dose heterologous vaccination regimens than single dose regimens, with high titre neutralising antibodies induced. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells which is superior to the response induced in homologous vaccination regimens in mice.
  🖺 Full Text HTML: Heterologous vaccination regimens with self-amplifying RNA and Adenoviral COVID vaccines induce superior immune responses than single dose vaccine regimens in mice
• Development of Parent-Adolescent Relationships During the COVID-19 Pandemic: The Role of Stress and Coping -
  The coronavirus disease 2019 (COVID-19) pandemic and the extensive measures to prevent spread of the virus have had a major impact on the daily life of families. Such changes in family routines might have an impact on the quality of parenting and the parent-adolescent relationship. However, not all families might be affected by the crisis to a similar extent. In particular, parents and adolescents who have high levels of COVID-19-related stress might experience reduced quality of parenting or parent-child relationships. Families who are able to cope actively might experience limited or even positive changes in relationships during the COVID-19 pandemic. The current longitudinal, multi-informant, and pre-registered study used data of 240 Dutch parents and adolescents (Mage 11.4 years). Using Latent Change Score models, we examined how parent-reported parenting and adolescent-reported relationship quality changed over a six month’s period, from the pre-COVID-19 to the COVID-19 period. Moreover, we examined the moderating role of parents’ and adolescents’ COVID-19-related stress, coping, and the interaction between stress and coping on relationship change. Results showed that on average both the amount of warmth and conflict in parent-adolescent relationships decreased. For positive parenting, there was a significant interaction effect of stress and coping, with active coping leading to a mitigated decline in the quality of parenting only in families who experienced low levels of COVID-19-related stress.
  🖺 Full Text HTML: Development of Parent-Adolescent Relationships During the COVID-19 Pandemic: The Role of Stress and Coping
• Uniting to Advance Diversity, Equity, and Inclusion in a Pandemic and Post-Pandemic World -
  This contribution examines the context for the newly-founded Diversity, Equity, and Inclusion (DEI) Committee of the European Association of Geochemistry. The report summarises the work to advance DEI undertaken during 2020 under conditions of the COVID-19 global pandemic, acknowledges the various impacts for community members, and takes a forward view to opportunities of a post-pandemic world.
  🖺 Full Text HTML: Uniting to Advance Diversity, Equity, and Inclusion in a Pandemic and Post-Pandemic World

From Clinical Trials

• Phase III Study of AZD7442 for Treatment of COVID-19 in Outpatient Adults - Condition:   COVID-19
  Interventions:   Drug: AZD7442;   Drug: Placebo
  Sponsor:   AstraZeneca
  Not yet recruiting

• Fluvoxamine Administration in Moderate SARS-CoV-2 (COVID-19) Infected Patients - Condition:   Covid19
  Interventions:   Drug: Placebo;   Drug: Fluvoxamine
  Sponsor:   SigmaDrugs Research Ltd.
  Recruiting

• TOCILIZUMAB - An Option for Patients With COVID-19 Associated Cytokine Release Syndrome; A Single Center Experience - Condition:   Covid19
  Intervention:   Drug: Tocilizumab
  Sponsor:   FMH College of Medicine and Dentistry
  Completed

• Convalescent Plasma in the Treatment of Covid-19 - Condition:   Covid19
  Interventions:   Biological: Convalescent plasma from COVID-19 donors;   Biological: Placebo
  Sponsors:   Helsinki University Central Hospital;   Finnish Red Cross
  Recruiting

• APT™ T3X on the COVID-19 Contamination Rate - Condition:   COVID-19
  Interventions:   Drug: Tetracycline hydrochloride 3%;   Drug: Placebo
  Sponsors:   University of Nove de Julho;   Santa Casa de Misericórdia de Porto Alegre
  Not yet recruiting

• Efficacy of Nano-Ivermectin Impregnated Masks in Prevention of Covid-19 Among Healthy Contacts and Medical Staff - Condition:   Covid-19
  Intervention:   Other: ivermectin impregnated mask
  Sponsor:   South Valley University
  Recruiting

• An Outpatient Clinical Trial Using Ivermectin and Doxycycline in COVID-19 Positive Patients at High Risk to Prevent COVID-19 Related Hospitalization - Condition:   Covid19
  Interventions:   Drug: Ivermectin Tablets;   Drug: Doxycycline Tablets;   Drug: Placebo
  Sponsor:   Max Health, Subsero Health
  Recruiting

• COVID-19 Immunologic Antiviral Therapy With Omalizumab - Condition:   Covid19
  Interventions:   Biological: Omalizumab;   Other: Placebo
  Sponsor:   McGill University Health Centre/Research Institute of the McGill University Health Centre
  Not yet recruiting

• Safety and Efficacy of Doxycycline and Rivaroxaban in COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Doxycycline Tablets;   Drug: Rivaroxaban 15Mg Tab;   Combination Product: Hydroxychloroquine and Azithromycin
  Sponsor:   Yaounde Central Hospital
  Recruiting

• Phase IIb Clinical Trial of Recombinant Novel Coronavirus Pneumonia (COVID-19) Vaccine (Sf9 Cells) - Condition:   COVID-19
  Interventions:   Biological: Recombinant COVID-19 vaccine (Sf9 cells);   Biological: Placebo
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   West China Hospital
  Not yet recruiting

• Famotidine vs Placebo for the Treatment of Non-Hospitalized Adults With COVID-19 - Condition:   Covid-19
  Interventions:   Drug: Famotidine;   Drug: Placebo
  Sponsors:   Northwell Health;   Cold Spring Harbor Laboratory
  Recruiting

• COVID-19 and Pregnancy: Placental and Immunological Impacts - Condition:   Covid19
  Intervention:   Other: Specimens specific for the study
  Sponsor:   Hopital Foch
  Recruiting

• Early Use of Hyperimmune Plasma in COVID-19 - Condition:   Covid19
  Intervention:   Other: hyperimmune plasma
  Sponsors:   Catherine Klersy;   Policlinico San Matteo Pavia Fondazione IRCCS
  Recruiting

• Restoration of Endothelial Integrity in Patients With COVID-19 (RELIC) - Condition:   COVID-19
  Intervention:   Biological: Thawed plasma
  Sponsor:   University of Alabama at Birmingham
  Not yet recruiting

• Safety and Preliminary Efficacy Study of GX-I7 in Patients With COVID-19 - Condition:   Covid19
  Interventions:   Drug: GX-I7;   Drug: GX-I7 vehicle
  Sponsor:   Genexine, Inc.
  Recruiting

From PubMed

• Potential effect of Maxing Shigan decoction against coronavirus disease 2019 (COVID-19) revealed by network pharmacology and experimental verification - CONCLUSION: This work explained the positive characteristics of multi-component, multi-target, and multi-approach intervention with MXSGD in combating COVID-19, and preliminary revealed the antiviral and anti-inflammatory pharmacodynamic substances and mechanism of MXSGD, which might provide insights into the vital role of TCM in the prevention and treatment of COVID-19.

• Cardiovascular protective properties of oxytocin against COVID-19 - SARS-CoV-2 infection or COVID-19 has become a worldwide pandemic; however, effective treatment for COVID-19 remains to be established. Along with acute respiratory distress syndrome (ARDS), new and old cardiovascular injuries are important causes of significant morbidity and mortality in COVID-19. Exploring new approaches managing cardiovascular complications is essential in controlling the disease progression and preventing long-term complications. Oxytocin (OXT), an immune-regulating...

• Selection, Identification, and Characterization of SARS-CoV-2 Monoclonal Antibody Resistant Mutants - The use of monoclonal neutralizing antibodies (mNAbs) is being actively pursued as a viable intervention for the treatment of Severe Acute Respiratory Syndrome CoV-2 (SARS-CoV-2) infection and associated coronavirus disease 2019 (COVID-19). While highly potent mNAbs have great therapeutic potential, the ability of the virus to mutate and escape recognition and neutralization of mNAbs represents a potential problem in their use for the therapeutic management of SARS-CoV-2. Studies investigating...

• How IvIg Can Mitigate Covid-19 Disease: A Symmetrical Immune Network Model - In this report we provide a hypothesis of how intravenous immunoglobulin (IvIg) (pooled therapeutic normal IgG) mitigates the severe disease after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The disease is caused by an overreaction of the innate immune system producing a cytokine storm and inflicting multiple organ damage. Our interpretation of IvIg therapy hinges on a recent analysis of the immune dysregulation in Covid-19 infection.^((1)) Previous...

• Strong Binding of Leupeptin with TMPRSS2 Protease May Be an Alternative to Camostat and Nafamostat for SARS-CoV-2 Repurposed Drug: Evaluation from Molecular Docking and Molecular Dynamics Simulations - The unprecedented coronavirus SARS-CoV-2 outbreak at Wuhan, China, caused acute respiratory infection to humans. There is no precise vaccine/therapeutic agents available to combat the COVID-19 disease. Some repurposed drugs are saving the life of diseased, but the complete cure is relatively less. Several drug targets have been reported to inhibit the SARS-CoV-2 virus infection, in that TMPRSS2 (transmembrane protease serine 2) is one of the potential targets; inhibiting this protease stops the...

• ACE2/Ang-(1-7)/Mas1 axis and the vascular system: vasoprotection to COVID-19-associated vascular disease - The two axes of the renin-angiotensin system include the classical ACE/Ang II/AT1 axis and the counter-regulatory ACE2/Ang-(1-7)/Mas1 axis. ACE2 is a multifunctional monocarboxypeptidase responsible for generating Ang-(1-7) from Ang II. ACE2 is important in the vascular system where it is found in arterial and venous endothelial cells and arterial smooth muscle cells in many vascular beds. Among the best characterized functions of ACE2 is its role in regulating vascular tone. ACE2 through its...

• Early Remdesivir Treatment in Covid-19: Why Wait Another Day? - Antiviral drug efficacy commonly depends on how soon after the onset of the infection is the treatment initiated. For COVID-19 there are no studies available to establish the benefit of early initiation of antivirals on patient outcomes. Remdesivir, an inhibitor of SARS-CoV-2 viral replication, was approved for the treatment of COVID-19 in patients requiring hospitalization. However, studies leading to its approval were conducted in COVID-19 patients with lower respiratory tract infection and/or...

• Degradation of SARS-CoV-2 receptor ACE2 by the E3 ubiquitin ligase Skp2 in lung epithelial cells - An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%-18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung...

• Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying miRNA as a Potential Multi Target Therapy to COVID-19: an In Silico Analysis - In the end of 2019 COVID-19 emerged as a new threat worldwide and this disease present impaired immune system, exacerbated production of inflammatory cytokines, and coagulation disturbs. Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) have emerged as a therapeutic option due to its intrinsic properties to alleviate inflammatory responses, capable to promote the restoring of injured tissue. EVs contain heterogeneous cargo, including active microRNAs, small noncoding sequences...

• A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication - Except remdesivir, no specific antivirals for SARS-CoV-2 infection are currently available. Here, we characterize two small-molecule-compounds, named GRL-1720 and 5h, containing an indoline and indole moiety, respectively, which target the SARS-CoV-2 main protease (M^(pro)). We use VeroE6 cell-based assays with RNA-qPCR, cytopathic assays, and immunocytochemistry and show both compounds to block the infectivity of SARS-CoV-2 with EC(50) values of 15 ± 4 and 4.2 ± 0.7 μM for GRL-1720 and 5h,...

• Anti-inflammatory potential of Quercetin in COVID-19 treatment - SARS-CoV-2 is a betacoronavirus causing severe inflammatory pneumonia, so that excessive inflammation is considered a risk factor for the disease. According to reports, cytokine storm is strongly responsible for death in such patients. Some of the consequences of severe inflammation and cytokine storms include acute respiratory distress syndrome, acute lung injury, and multiple organ dysfunction syndromes. Phylogenetic findings show more similarity of the SARS-CoV-2 virus with bat coronaviruses,...

• Thymosin Alpha 1 Mitigates Cytokine Storm in Blood Cells From Coronavirus Disease 2019 Patients - CONCLUSION: These data suggest the potential role of Tα1 in modulating the immune response homeostasis and the cytokine storm in vivo.

• The direct evidence and mechanism of traditional Chinese medicine treatment of COVID-19 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third coronavirus causing serious human disease to spread across the world in the past 20 years, after SARS and Middle East respiratory syndrome. As of mid-September 2020, more than 200 countries and territories have reported 30 million cases of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, including 950,000 deaths. Supportive treatment remains the mainstay of therapy for COVID-19. The World Health Organization...

• Spontaneous binding of potential COVID-19 drugs (Camostat and Nafamostat) to human serine protease TMPRSS2 - Effective treatment or vaccine is not yet available for combating SARS coronavirus 2 (SARS-CoV-2) that caused the COVID-19 pandemic. Recent studies showed that two drugs, Camostat and Nafamostat, might be repurposed to treat COVID-19 by inhibiting human TMPRSS2 required for proteolytic activation of viral spike (S) glycoprotein. However, their molecular mechanisms of pharmacological action remain unclear. Here, we perform molecular dynamics simulations to investigate their native binding sites...

• Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium - The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how the heterogeneity of this diverse cell population contributes to elements of viral tropism and pathogenesis, antiviral immunity, and treatment response to remdesivir. We found that, while a variety of epithelial cell types are susceptible to infection, ciliated cells are the predominant cell target of SARS-CoV-2. The host protease TMPRSS2 was required...

From Patent Search

• METHOD AND APPARATUS FOR ACQUIRING POWER CONSUMPTION IMPACT BASED ON IMPACT OF COVID-19 EPIDEMIC - - link

• A PHARMACEUTICAL COMPOSITION OF ARTESUNATE AND MEFLOQUINE AND METHOD THEREOF - A pharmaceutical composition for treating Covid-19 virus comprising a therapeutically effective amount of an artesunate or its pharmaceutically acceptable salts thereof and a mefloquine or its pharmaceutically acceptable salts thereof is disclosed. The pharmaceutical composition comprises the artesunate in the ratio of 0.25% to 66% w/v and mefloquine in the ratio of 0.25% to 90% w/v. The composition is found to be effective for the treatment of COVID -19 (SARS-CoV2). The pharmaceutical composition of Artesunate and Mefloquine has been found to be effective and is unexpectedly well tolerated with a low rate of side-effects, and equally high cure-rates than in comparable treatments. The present invention also discloses a method to preparing the pharmaceutical composition comprising of Artesunate and Mefloquine. - link

• Zahnbürstenaufsatz, elektrische Versorgungseinheit einer elektrischen Zahnbürste, elektrische Zahnbürste mit einem Zahnbürstenaufsatz, Zahnbürste sowie Testaufsatz für eine elektrische Zahnbürste -

  Zahnbürstenaufsatz für eine elektrische Zahnbürste (20) umfassend einen Koppelabschnitt (2), über den der Zahnbürstenaufsatz (1) mit einer elektrischen Versorgungseinheit (10) der elektrischen Zahnbürste (20) verbindbar ist und einen Bürstenabschnitt (3), der zur Reinigung der Zähne ausgebildete Reinigungsmittel (3.1) aufweist, dadurch gekennzeichnet, dass an dem Zahnbürstenaufsatz (1) eine Sensoreinheit (4) vorgesehen ist, die dazu ausgebildet ist, selektiv das Vorhandensein eines Virus oder eines Antigen im Speichel eines Nutzers des Zahnbürstenaufsatzes (1) durch Messen zumindest eines virusspezifischen Parameters zu bestimmen.

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• COVID-19 CLASSIFICATION RECOGNITION METHOD BASED ON CT IMAGES OF LUNGS - - link

• Vorrichtung umfassend einen Schutzschirm und einen Filter zum Herausfiltern von Viren aus einem Schall erzeugenden Luftstrom -

  Vorrichtung (10) umfassend einen Schutzschirm (12) und einen Filter (14) zum Herausfiltern von Viren (16) aus einem Schall erzeugenden Luftstrom (18), der von einem Musiker (20) beim Musizieren mit einem Musikinstrument oder beim Singen erzeugt wird, wobei der Schutzschirm (12) zur Verringerung des Risikos einer Infektion mit den Viren (16) dafür vorgesehen ist, wenigstens einen Teil der mit dem Luftstrom transportierten Viren (16) aufzufangen, der Schutzschirm (12) eine erste Seite (22) und eine zweite Seite (24) aufweist, die voneinander abgewandt sind, und der Schutzschirm (12) wenigstens einen sich von der ersten (22) bis zu der zweiten Seite (24) erstreckenden Durchlass (26) aufweist, wobei dieser Durchlass (26) zum Durchströmen mit wenigstens einem Teil des beim Musizieren erzeugten Luftstroms (18) vorgesehen ist und der Filter (14) zum Herausfiltern von Viren (16) aus dem Luftstrom (18) in dem Durchlass (26) des Schutzschirms (12) angeordnet ist.

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• Seil-Haltevorrichtung -

  Seil-Haltevorrichtung (1)

• mit einem Träger (2), und

• mit einer Seil-Klemmeinrichtung (3), die auf dem Träger (2) angeordnet ist.

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• A traditional Chinese medicine composition for COVID-19 and/or influenza and preparation method thereof - - link

• Covid 19 - Chewing Gum - - link

• STOCHASTIC MODEL METHOD TO DETERMINE THE PROBABILITY OF TRANSMISSION OF NOVEL COVID-19 - The present invention is directed to a stochastic model method to assess the risk of spreading the disease and determine the probability of transmission of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). - link

• Fahrzeuglüftungssystem und Verfahren zum Betreiben eines solchen Fahrzeuglüftungssystems -

  Die Erfindung betrifft ein Fahrzeuglüftungssystem (1) zum Belüften einer Fahrgastzelle (2) eines Fahrzeugs (3), mit einem Umluftpfad (5). Die Erfindung ist gekennzeichnet durch eine wenigstens abschnittsweise in einen Umluftansaugbereich (4) des Umluftpads (5) hineinreichende Sterilisationseinrichtung (6), wobei die Sterilisationseinrichtung (6) dazu eingerichtet ist von einem aus der Fahrgastzelle (2) entnommenen Luftstrom getragene Schadstoffe zu inaktivieren und/oder abzutöten.

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