+Background Cytokine release syndrome (CRS) is a potentially life-threatening complication of chimeric antigen receptor T (CAR-T) cell therapy. Recent studies indicated critical roles of macrophages and monocytes in CAR-T induced CRS. Here, we report rapid dissipation of CAR-T induced CRS in two patients after receiving Tripterygium glycosides (TG). Effects of triptolide, the major active component of TG, on macrophages and monocytes were examined in animal models. Methods Two patients with CRS after CAR-T cell therapy (for hematological malignancy) received TG (50 mg, p.o.). Flow cytometry analysis and single cell RNA sequencing (scRNAseq) were conducted to examine the effects of TG on immune cells. Potential effects of triptolide were also examined ex vivo using patient-derived monocytes, as well as in mice. Findings Rapid alleviation of fever and cytokine storm was observed within 72 hours after TG treatment. Blood concentration of triptolide ranged from 21 to 154 ng/mL during treatment. Flow cytometry and scRNAseq showed selective depletion of monocytes with minimal impact on CAR-T cells in both patients. In ex vivo experiments with patient-derived monocytes, triptolide dramatically inhibited the synthesis of pro-inflammatory cytokines (e.g., IL-6, IL-10, and IP-10). Triptolide also rapidly and selectively depleted peritoneal concanavalin A activated macrophages and monocytes in mice. Interpretation TG could be a promising treatment for CAR-T induced CRS, as well as other diseases with similar mechanisms, e.g., hemophagocytic lymphohistiocytosis and COVID-19. Our preliminary findings require further verification with properly designed clinical trials. +
++We report a new approach using artificial intelligence to study and classify the severity of COVID-19 using 1208 chest X-rays (CXRs) of 396 COVID-19 patients obtained through the course of disease at Emory Healthcare affiliated hospitals (Atlanta, GA, USA). Using a two-stage transfer learning technique to train a convolutional neural network (CNN), we show that the algorithm is able to classify four classes of disease severity (normal, mild, moderate, and severe) with average area under curve (AUC) of 0.93. In addition, we show that the outputs of different layers of the CNN under dominant filters provide valuable insight about the subtle patterns in the CXRs, which can improve the accuracy in the reading of CXRs by a radiologist. Finally, we show that our approach can be used for studying the disease progression in single patients and its influencing factors. The results suggest that our technique can form the foundation of a more concrete clinical model to predict the evolution of COVID-19 severity and the efficacy of different treatments for each patient through using CXRs and clinical data in early stages. This will be essential in dealing with the upcoming waves of COVID-19 and optimizing resource allocation and treatment. +
++Background: COVID-19 immunity passports could protect the right to free movement but may also 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. +
++Objective To validate and implement an optimized screening method for detection of SARS-CoV-2 RNA combining use of self-collected raw saliva samples, single-step heat-treated virus inactivation and RNA extraction, and direct RT-qPCR. Design Study conducted in three successive phases including: i) method analytical validation against standard RT-qPCR in saliva samples; ii), method diagnostic validation against standard RT-qPCR in nasopharyngeal samples; and iii), method implementation through pilot screening in a reference hospital. Setting Sant Joan de Deu University Hospital (Barcelona, Spain). Participants Phase 2, a prospective cohort of asymptomatic teenagers and young adult players and staff in a youth sports academy followed up during 9 to 12 weeks; Phase 3, asymptomatic health workers, students, aid volunteers, and other staff of the setting. Main outcome measures Method diagnostic sensitivity and specificity. Method performance in a pilot screening. Results Diagnostic validation included 173 participants. At week 0, all saliva and nasopharyngeal samples were negative. In the following weeks, standard RT-qPCR yielded 23 positive results in nasopharyngeal samples. Paired saliva specimens yielded 22 positive and one inconclusive result. Method diagnostic sensitivity and specificity values were 95.7% (95% CI, 79.0-99.2%) and 100.0% (95% CI, 98.6-100.0 %), respectively. A total of 2,709 participants engaged in the pilot screening, with a high rate of participation (83.4% among health workers). Only 17 (0.6%) of saliva samples self-collected by participants in an unsupervised manner were invalid. Saliva was positive in 24 (0.9%) out of 2,692 valid specimens and inconclusive in 27 (1.0%). All 24 saliva-positive and 4 saliva-inconclusive participants were positive by standard RT-PCR in nasopharyngeal samples. Use of a high throughput system allowed fast screening workflow (up to 384 samples in <2 hours). Conclusion Direct RT-qPCT on self-collected raw saliva is a simple, rapid, and accurate method with potential to be scaled up for enhanced SARS-CoV-2 community-wide screening. +
++Objective To estimate the proportion of patients hospitalized with COVID-19 who undergo dialysis, tracheostomy, and extracorporeal membrane oxygenation (ECMO). Design A network cohort study. Setting Six databases from the United States containing routinely-collected patient data: HealthVerity, Premier, IQVIA Open Claims, Optum EHR, Optum SES, and VA-OMOP. Patients Patients hospitalized with a clinical diagnosis or a positive test result for COVID-19. Interventions Dialysis, tracheostomy, and ECMO. Measurements and Main Results 240,392 patients hospitalized with COVID-19 were included (22,887 from HealthVerity, 139,971 from IQVIA Open Claims, 29,061 from Optum EHR, 4,336 from OPTUM SES, 36,019 from Premier, and 8,118 from VA-OMOP). Across the six databases, 9,703 (4.04% [95% CI: 3.96% to 4.11%]) patients received dialysis, 1,681 (0.70% [0.67% to 0.73%]) had a tracheostomy, and 398 (0.17% [95% CI: 0.15% to 0.18%]) patients underwent ECMO over the 30 days following hospitalization. Use of ECMO was generally concentrated among patients who were younger, male, and with fewer comorbidities except for obesity. Tracheostomy was used for a similar proportion of patients regardless of age, sex, or comorbidity. While dialysis was used for a similar proportion among younger and older patients, it was more frequent among male patients and among those with chronic kidney disease. Conclusion Use of dialysis among those hospitalized with COVID-19 is high at around 4%. Although less than one percent of patients undergo tracheostomy and ECMO, the absolute numbers of patients who have undergone these interventions is substantial and can be expected to continue grow given the continuing spread of the COVID-19. +
++Humoral immunity to the Severe Adult Respiratory Syndrome (SARS) Coronavirus (CoV)-2 is not well understood but may be a crucial factor of immune protection. The possibility of antibody cross-reactivity between SARS-CoV-2 and other human coronaviruses (HCoVs) would have important implications for immune protection but also for the development of specific diagnostic ELISA tests. Using peptide microarrays, n=24 patient samples and n=12 control samples were screened for antibodies against the entire SARS-CoV-2 proteome as well as the Spike (S), Nucleocapsid (N), VME1 (V), R1ab, and Protein 3a (AP3A) of the HCoV strains SARS, MERS, UC43 and 229E. While widespread cross-reactivity was revealed across several immune dominant regions of S and N, IgG binding to several SARS-CoV-2-derived peptides provided statistically significant discrimination between COVID-19 patients and controls. Selected target peptides may serve as capture antigens for future, highly COVID-19-specific diagnostic antibody tests. +
++Restrictions on mobility are a key component of infectious disease controls, preventing the spread of infections to as yet unexposed areas, or to regions which have previously eliminated outbreaks. However, even under the most severe restrictions, some travel must inevitably continue, at the very minimum to retain essential services. For COVID-19, most countries imposed severe restrictions on travel at least as soon as it was clear that containment of local outbreaks would not be possible. Such restrictions are known to have had a substantial impact on the economy and other aspects of human health, and so quantifying the impact of such restrictions is an essential part of evaluating the necessity for future implementation of similar measures. In this analysis, we built a simulation model using National statistical data to record patterns of movements to work, and implement levels of mobility recorded in real time via mobile phone apps. This model was fitted to the pattern of deaths due to COVID-19 using approximate Bayesian inference. Our model is able to recapitulate mortality considering the number of deaths and datazones (DZs, which are areas containing approximately 500-1000 residents) with deaths, as measured across 32 individual council areas (CAs) in Scotland. Our model recreates a trajectory consistent with the observed data until 1st of July. According to the model, most transmission was occurring locally (i.e. in the model, 80% of transmission events occurred within spatially defined communities of approximately 100 individuals). We show that the net effect of the various restrictions put into place in March can be captured by a reduction in transmission down to 12% of its pre-lockdown rate effective 28th March. By comparing different approaches to reducing transmission, we show that, while the timing of COVID-19 restrictions influences the role of the transmission rate on the number of COVID-related deaths, early reduction in long distance movements does not reduce death rates significantly. As this movement of individuals from more infected areas to less infected areas has a minimal impact on transmission, this suggests that the fraction of population already immune in infected communities was not a significant factor in these early stages of the national epidemic even when local clustering of infection is taken into account. The best fit model also shows a considerable influence of the health index of deprivation (part of the index of multiple deprivations or iMD) on mortality. The most likely value has the CA with the highest level of health-related deprivation to have on average, a 2.45 times greater mortality rate due to COVID-19 compared to the CA with the lowest, showing the impact of health-related deprivation even in the early stages of the COVID-19 national epidemic. +
++The emergence of the RNA virus SARS-CoV2, the causative agent of COVID-19 and its declaration by the World Health Organization (WHO) as a pandemic has disrupted the delicate balance in health indices globally. Its attendant immune dysregulation and pathobiology is still evolving. Currently, real time PCR is the gold standard diagnostic test, however there are several invalidated antibody-based tests available for possible community screening. With ongoing community transmission in Nigeria, neither the true burden of COVID-19 nor the performance of these kits is presently known. This study therefore, compared the performance of the SARS CoV2 antibody test and the real time Polymerase Chain Reaction (Rt-PCR) in the diagnosis of COVID-19. For the purpose of this evaluation, we used the diagnostic test kit by Innovita® Biological Technology CO., LTD China, a total of 521 venous blood samples were collected from consenting patients for the SARS COVID-19 rapid diagnostic kit and Oral and Nasopharyngeal swabs were collected and analyzed using the real time Polymerase chain reaction technique for nucleic acid detection and quantification. +
++Background: COVID-19 clinical presentation ranges from asymptomatic to fatal outcome. This variability is due in part to host genome specific mutations. Recently, two families in which COVID-19 segregates like an X-linked recessive monogenic disorder environmentally conditioned by SARS-CoV-2 have been reported leading to identification of loss-of-function variants in TLR7. Objective: We sought to determine whether the two families represent the tip of the iceberg of a subset of COVID-19 male patients. Methods: We compared male subjects with extreme phenotype selected from the Italian GEN-COVID cohort of 1178 SARS-CoV-2-infected subjects (<60y, 79 severe cases versus 77 control cases). We applied the LASSO Logistic Regression analysis, considering only rare variants on the young male subset, picking up TLR7 as the most important susceptibility gene. Results: Rare TLR7 missense variants were predicted to impact on protein function in severely affected males and in none of the asymptomatic subjects. We then investigated a similar white European cohort in Spain, confirming the impact of TRL7 variants. A gene expression profile analysis in peripheral blood mononuclear cells after stimulation with TLR7 agonist demonstrated a reduction of mRNA level of TLR7, IRF7, ISG15, IFN-ɑ and IFN-γ in COVID-19 patients compared with unaffected controls demonstrating an impairment in type I and II INF responses. Conclusion: Young males with TLR7 loss-of-function mutations and severe COVID-19 in the two reported families represent only a fraction of a broader and complex host genome situation. Specifically, missense mutations in the X-linked recessive TLR7 disorder may significantly contribute to disease susceptibility in up to 4% of severe COVID-19. +
++First responders are at increased risk of occupational exposure to SARS-CoV-2 while providing frontline support to communities during the COVID-19 pandemic. In the District of Columbia (DC), first responders were among the first people exposed to and infected with SARS-CoV-2, with over 200 first responders diagnosed with COVID-19 by May 15, 2020. From June-July 2020, DC Health conducted a serologic survey to estimate SARS-CoV-2 seroprevalence and assess risk factors and occupational exposures among a convenience sample of first responders in DC. Of the 310 first responders tested, 3.5% (n = 11) had anti-SARS-CoV-2 antibodies. Seropositivity varied by occupation, with 4.8% (3/62) of firefighters; 3.6% (8/220) of police officers; and no paramedics (0/10) or administration and support staff (0/18) testing positive. Type and consistency of personal protective equipment (PPE) use also varied: all paramedics (n=10) reported wearing a N95 respirator all or most of the time, compared to 83.3% of firefighters, 38.8% of police officers, and 23.5% of administration and support staff (p<0.001). All paramedics reported wearing gloves all or most of the time, compared to 80.0% of firefighters, 27.8% of administration and support staff, and 24.3% of police (p<0.001). The relatively low seroprevalence among first responders highlights the benefits of continuous training on and reinforcement of the proper use of PPE while performing job duties to mitigate potential transmission within and between first responders and the community. +
++The COVID-19 pandemic, within a short time span, has had a significant impact on every aspect of life in almost every country on the planet. As it evolved from a local epidemic isolated to certain regions of China, to the deadliest pandemic since the influenza outbreak of 1918, scientists all over the world have only amplified their efforts to combat it. In that battle, Artificial Intelligence, or AI, with its wide ranging capabilities and versatility, has played a vital role and thus has had a sizable impact. In this review, we present a comprehensive analysis of the use of AI techniques for spatio-temporal modeling and forecasting and impact modeling on diverse populations as it relates to COVID-19. Furthermore, we catalogue the articles in these areas based on spatio-temporal modeling, intrinsic parameters, extrinsic parameters, dynamic parameters and multivariate inputs (to ascertain the penetration of AI usage in each sub area). The manner in which AI is used and the associated techniques utilized vary for each body of work. Majority of articles use deep learning models, compartment models, stochastic methods and numerous statistical methods. We conclude by listing potential paths of research for which AI based techniques can be used for greater impact in tackling the pandemic. +
++Background To limit societal and economic costs of lockdown measures, public health strategies are needed that control the spread of SARS-CoV-2 and simultaneously allow lifting of disruptive measures. Regular universal random screening of large proportions of the population regardless of symptoms has been proposed as a possible control strategy. Methods We developed a mathematical model that includes test sensitivity depending on infectiousness for PCR-based and antigen-based tests, and different levels of onward transmission for testing and non-testing parts of the population. Only testing individuals participate in high-risk transmission events, allowing more transmission in case of unnoticed infection. We calculated the required testing interval and coverage to bring the effective reproduction number due to universal random testing (Rrt) below 1, for different scenarios of risk behavior of testing and non-testing individuals. Findings With R0 = 2.5, lifting all control measures for tested subjects with negative test results would require 100% of the population being tested every three days with a rapid test method with similar sensitivity as PCR-based tests. With remaining measures in place reflecting Re = 1.3, 80% of the population would need to be tested once a week to bring Rrt below 1. With lower proportions tested and with lower test sensitivity, testing frequency should increase further to bring Rrt below 1. With similar Re values for tested and non-tested subjects, and with tested subjects not allowed to engage in higher risk events, at least 80% of the populations needs to tested every five days to bring Rrt below. The impact of the test-sensitivity on the reproduction number is far less than the frequency of testing. Interpretation Regular universal random screening followed by isolation of infectious individuals is not a viable strategy to reopen society after controlling a pandemic wave of SARS-CoV-2. More targeted screening approaches are needed to better use rapid testing such that it can effectively complement other control measures. +
++SARS-CoV-2 pandemic is a health emergency for occupational healthcare workers at COVID19 hospital wards in Italy. The objective of the study was to investigate if U-Earth AIRcel bioreactors were effective in monitoring and improving air quality via detection, capture, and destruction of the SARS-CoV-2 virus, reducing the risk of transmission among healthcare workers. U-Earth AIRcel bioreactors are a demonstrated effective biomonitoring system. We implemented a methodological approach wherein they were placed at various hospitals treating COVID-19 patients in Italy. The detection of the SARS-CoV-2 virus was achieved through rapid biomonitoring testing of the solutes from the AIRcel bioreactors via SARS-CoV-2 rapid test antigen and consecutive reverse transcription-polymerase chain reaction (RT-PCR) analysis with the multiplex platform (XABT) and the Real-Time PCR Rotor-Gene. The marked presence of the SARS-CoV-2 virus was found in multiple water samples via the detection of ORF1ab + N and/or E gene involved in gene expression and cellular signaling of the SARS-CoV virus. The AIRcel bioreactors were able to neutralize the virus effectively as traces of the viruses were no longer found in multiple solute samples after an overnight period. Transmission of COVID-19 via bio-aerosols, transmitted by infected patients, remains a viable threat for health workers. AIRcel bioreactors allow for rapid biomonitoring testing for early virus detection within the environment, reducing the risk of exponential contagion exposure and maintaining good air quality without endangering health workers. This same protocol can also be extended to public spaces as a bio-monitoring tool for hotpots early detection. +
++Humans expel physiological particles continuously through normal respiratory activities such as breathing, talking, coughing and sneezing; a portion of these are aerosol in the size range <5.0 µm. Misconceptions exist on how to best implement face coverings as an effective preventive health measure against potentially infectious respiratory generated aerosol. The aim of this study was to characterise the performance of face coverings against aerosol when worn by individuals, and to quantify the maximum aerosol penetration through the material used in the construction of each mask. The former addresses their use as a means of possible protection against aerosol present in the environment and the latter having relevance to filtration and reducing human generated aerosol from reaching the environment. Face covering performance was assessed by measuring the total inward leakage of aerosol through the mask material and face seal. Aerosol penetration was measured on swatches of material taken from the face covering. An inert polydisperse charge-neutralized NaCl aerosol, with a distribution ranging from 0.023 µm to 5 µm in diameter, was used for the experiments. Total inward leakage tests were completed to assess the protection factor for nine variations of face coverings, including seven reusable cloth masks, of which six were homemade and one was commercially manufactured, and two styles of disposable procedure masks, one with ear loops and one with ties. Our results have shown that face coverings in general provide the wearer only limited protection against aerosol in the environment. All reusable cloth face coverings obtained a practical protection level of less than 2. The performance of the disposable procedure masks varied from 1.7 to 3.6. The mean practical protection level for the nine face coverings was 1.95 with a standard deviation of 0.89. Comparatively, a N95 respirator achieved a protection factor of 166. We have further shown that aerosol readily penetrates through most materials used in face coverings. Aerosol swatch penetration tests were completed on six different fabrics commonly available for reusable homemade face coverings, four different material systems comprised of multiple material types, eight different disposable procedure masks and the filtering material from three different N95 respirators. Maximum aerosol penetration through the six common fabrics varied from 39% to 91%; for systems comprised of multiple types of materials 4% to 23%; for materials used in disposable procedure masks 16% to 80%; and for filtering materials used in N95 respirators 1.0% to 1.9%. We also highlight that with the exception of some of the reusable cloth materials, penetration of particulates at 5 µm diameter, representing the minimum filtration efficiency that could be achieved against droplets, was insignificant; the six common fabrics showed penetration from 1% to 44%; the fabric systems comprised of multiple types of materials <0.9%; the materials used in disposable procedure masks <0.9% to 6%; and the filtering materials used in three different N95 respirators <0.9%. The observations from this study directly demonstrate that face coverings may be optimized by incorporating high filtration efficiency materials in their construction. Face coverings with an enhanced level of filtration would be of benefit in circumstances where SARS-CoV-2 may be present in the aerosol of infected individuals to reduce aerosol emission from respiratory activities penetrating through into the environment. +
++Although the range of immune responses to COVID-19 infection is variable, cytokine storm is observed in many affected individuals. Here we utilize a mutual information algorithm that classifies the information gain for COVID-19 Severity Score (CSS) prediction provided by cytokine expression levels and clinical variables. We found a small number of clinical and cytokine expression variables are predictive of presenting COVID-19 disease severity, raising questions about the mechanism of COVID-19 severe illness. Variables that were most predictive of CSS included clinical variables such as age, abnormal chest x-ray, and cytokines such as macrophage colony-stimulating factor (M-CSF), interferon-inducible protein 10 (IP-10) and Interleukin-1 Receptor Antagonist (IL-1RA). Our results suggest that SARS-CoV-2 infection causes a plethora of changes in cytokine profiles and that particularly in severely ill patients, these changes are consistent with the presence of Macrophage Activation Syndrome and could furthermore be used as a biomarker to predict disease severity. +
+A Study Evaluating the Efficacy and Safety of CKD-314 in Hospitalized Adult Patients Diagnosed With COVID-19 Pneumonia - Condition: COVID-19
Intervention: Drug: Nafamostat Mesilate
Sponsor: Chong Kun Dang Pharmaceutical
Not yet recruiting
Effectiveness and Safety of Rhea Health Tone® as add-on Therapy for COVID-19 in Hospitalized Adults in Indonesia - Condition: Covid19
Intervention: Dietary Supplement: Rhea Health Tone®
Sponsors: Universitas Padjadjaran; PT. Rhea Pharmaceutical Sciences Indonesia; Prodia Diacro Laboratories P.T.
Not yet recruiting
Ivermectin for Severe COVID-19 Management - Condition: COVID-19
Intervention: Drug: Ivermectin
Sponsors: Afyonkarahisar Health Sciences University; NeuTec Pharma
Completed
Fase I Clinical Trial on NK Cells for COVID-19 - Conditions: Covid19; Sars-cov 2
Intervention: Biological: Natural Killer Cells infusion
Sponsor: Hospital de Clinicas de Porto Alegre
Not yet recruiting
A Phase Ⅱ Clinical Trial of Recombinant Corona Virus Disease-19 (COVID-19) Vaccine (Sf9 Cells) - Condition: COVID-19
Interventions: Biological: Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Two dose regimen; Biological: Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Three dose regimen; Biological: High-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Two dose regimen; Biological: High-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Three dose regimen; Biological: Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Two dose regimen; Biological: Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Three dose regimen; Biological: High-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Two dose regimen; Biological: High-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Three dose regimen; Biological: Low-dose placebo (18-59 years) & Two dose regimen; Biological: Low-dose placebo (18-59 years) & Three dose regimen; Biological: High-dose placebo (18-59 years) & Two dose regimen; Biological: High-dose placebo (18-59 years) & Three dose regimen; Biological: Low-dose placebo (60-85 years) & Two dose regimen; Biological: Low-dose placebo (60-85 years) & Three dose regimen; Biological: High-dose placebo (60-85 years) & Two dose regimen; Biological: High-dose placebo (60-85 years) & Three dose regimen
Sponsors: Jiangsu Province Centers for Disease Control and Prevention; West China Hospital
Recruiting
Hydrogen Therapy in Patients With Moderate Covid-19 - Condition: Covid-19
Intervention: Drug: Mixture 3,6% H2 in N2 (96.4%)
Sponsor: University Hospital, Grenoble
Not yet recruiting
Prevention With Chloroquine in Health Personnel Exposed to Infection With Coronavirus Disease 2019 (COVID-19) (TS-COVID) - Condition: Covid19
Intervention: Drug: Chloroquine
Sponsor: Fundacion Clinica Valle del Lili
Active, not recruiting
Adaptive COVID-19 Treatment Trial 4 (ACTT-4) - Condition: COVID-19
Interventions: Drug: Baricitinib; Drug: Dexamethasone; Other: Placebo; Drug: Remdesivir
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Recruiting
Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India - Condition: COVID-19
Interventions: Dietary Supplement: Vitamin D3 (cholecalciferol); Dietary Supplement: Zinc (zinc gluconate); Dietary Supplement: Zinc (zinc gluconate) & Vitamin D (cholecalciferol); Other: Placebo
Sponsors: Harvard School of Public Health; Foundation for Medical Research; University Health Network, Toronto
Not yet recruiting
Organization of Pulmonary Rehabilitation of Post-COVID-19 Patient With Sequelae (REHABCOVID) - Condition: Covid19
Interventions: Other: Respiratory rehabilitation program (RR).; Other: Respiratory tele-rehabilitation program (TRR).
Sponsor: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
Not yet recruiting
Inhaled Heparin for Hospitalised COVID-19 Patients - Condition: Covid19
Intervention: Drug: Unfractionated heparin
Sponsors: Australian National University; Helwan University; Clinica San Camilo, Argentina
Recruiting
Effect of Vitamin D on Hospitalized Adults With COVID-19 Infection - Condition: Covid19
Interventions: Drug: Cholecalciferol; Other: Placebo
Sponsors: University of Liege; Laboratoires SMB S.A.
Recruiting
Efficacy and Safety of Ovotransferrin in COVID-19 Patients - Condition: Covid19
Intervention: Dietary Supplement: Ovotransferrin
Sponsor: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
Not yet recruiting
Study To antagOnize Plasminogen Activator Inhibitor-1 in Severe COVID-19 - Condition: Covid19
Interventions: Drug: TM5614; Other: Placebo
Sponsor: Northwestern University
Recruiting
Using Travelan to Boost Immune Response in Vitro to COVID-19 - Condition: Covid19
Intervention: Other: Travelan OTC
Sponsor: Hadassah Medical Organization
Active, not recruiting
JAK-STAT pathway inhibition and their implications in COVID-19 therapy - As the incidence of COVID-19 increases with time, more and more efforts are made to pave a way out for the therapeutic strategies to deal with the disease progression. Inflammation being a significant influencer has implicated us to re-look into its signaling cascades drawing attention towards the JAK/STAT pathway. Considered as a major signaling mediator of cytokines and chemokines, the JAK/STAT pathway has significantly contributed to the worsening of COVID-19. JAK phosphorylation mediated by…
A Case-Control Study of the 2019 Influenza Vaccine and Incidence of COVID-19 Among Healthcare Workers - CONCLUSIONS: Significant findings suggest that the 2019 influenza vaccine may have a protective association against COVID-19 among HCW.
HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry - Responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through binding of the viral spike protein (SARS-2-S) to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). Here we show that the high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL…
Analysis of the efficacy of HIV protease inhibitors against SARS-CoV-2’s main protease - CONCLUSION: Targeting of SARS-CoV-2 M^(pro) by some of the HIV PIs might be of limited clinical potential, given the high concentration of the drugs required to achieve significant inhibition. Therefore, given their weak inhibition of the viral protease, any potential beneficial effect of the PIs in COVID-19 context might perhaps be attributed to acting on other molecular target(s), rather than SARS-CoV-2 M^(pro).
Can Host Cell Proteins Like ACE2, ADAM17, TMPRSS2, Androgen Receptor be the Efficient Targets in SARS-CoV-2 Infection? - A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused a large disease outbreak in Wuhan, China in December 2019, is currently spreading across world’s many of the countries. Along with binding of the virus spike with the host cell receptor, fusion of the viral envelope with host cell membranes is a critical step in establishing successful infection of SARS-CoV-2. In this entry process, a diversity of host cell proteases and andro-gen receptor play a…
A novel COVID-19 epidemiological model with explicit susceptible and asymptomatic isolation compartments reveals unexpected consequences of timing social distancing - Motivated by the current COVID-19 epidemic, this work introduces an epidemiological model in which separate compartments are used for susceptible and asymptomatic “socially distant” populations. Distancing directives are represented by rates of flow into these compartments, as well as by a reduction in contacts that lessens disease transmission. The dynamical behavior of this system is analyzed, under various different rate control strategies, and the sensitivity of the basic reproduction number…
Translation of Mycobacterium Survival Strategy to Develop a Lipo-peptide based Fusion Inhibitor - The entry of enveloped viruses requires the fusion of viral and host cell membranes. An effective fusion inhibitor aiming at impeding such membrane fusion may emerge as a broad-spectrum antiviral agent against a wide range of viral infections. Mycobacterium survives inside the phagosome by inhibiting phagosome-lysosome fusion with the help of a coat protein coronin 1. Structural analysis of coronin 1 and other WD40-repeat protein suggest that the trp-asp (WD) sequence is placed at distorted…
Repurposing Anti-Cancer Drugs for COVID-19 Treatment - The novel coronavirus disease 2019 (COVID-19) pandemic has caused catastrophic damage to human life across the globe along with social and financial hardships. According to the Johns Hopkins University Coronavirus Resource Center, more than 41.3 million people worldwide have been infected, and more than 1,133,000 people have died as of October 22, 2020. At present, there is no available vaccine and a scarcity of efficacious therapies. However, there is tremendous ongoing effort towards…
Gammacoronavirus Avian Infectious Bronchitis Virus and Alphacoronavirus Porcine Epidemic Diarrhea Virus Exploit a Cell-Survival Strategy via Upregulation of cFOS to Promote Viral Replication - Coronaviruses have evolved a variety of strategies to optimize cellular microenvironment for efficient replication. In this study, we report the induction of AP-1 transcription factors by coronavirus infection based on genome-wide analyses of differentially expressed genes in cells infected with avian coronavirus infectious bronchitis virus (IBV). Most members of the AP-1 transcription factors were subsequently found to be upregulated during the course of IBV and porcine epidemic diarrhea virus…
Hypothesis: Alpha-1-antitrypsin is a promising treatment option for COVID-19 - No definitive treatment for COVID-19 exists although promising results have been reported with remdesivir and glucocorticoids. Short of a truly effective preventive or curative vaccine against SARS-CoV-2, it is becoming increasingly clear that multiple pathophysiologic processes seen with COVID-19 as well as SARS-CoV-2 itself should be targeted. Because alpha-1-antitrypsin (AAT) embraces a panoply of biologic activities that may antagonize several pathophysiologic mechanisms induced by…
Development of a nano-luciferase based assay to measure the binding of SARS-CoV-2 spike receptor binding domain to ACE-2 - To identify drugs that could potentially be used to treat infection with SARS-CoV-2, a high throughput 384-well assay was developed to measure the binding of the receptor binding domain (RBD) of the viral S1 protein to its main receptor, angiotensin converting enzyme 2 (ACE2). The RBD was fused to both a HiBIT tag and an IL6 secretion signal to enable facile collection from the cell culture media. The addition of culture media containing this protein, termed HiBIT-RBD, to cells expressing ACE2…
Decline in SARS-CoV-2 Antibodies After Mild Infection Among Frontline Health Care Personnel in a Multistate Hospital Network - 12 States, April-August 2020 - Most persons infected with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), develop virus-specific antibodies within several weeks, but antibody titers might decline over time. Understanding the timeline of antibody decline is important for interpreting SARS-CoV-2 serology results. Serum specimens were collected from a convenience sample of frontline health care personnel at 13 hospitals and tested for antibodies to SARS-CoV-2 during April 3-June 19, 2020, and again…
Bacillus Calmette-Guerin vaccination Policy and Consumption of Ammonium Chloride-Enriched Confectioneries May Be Factors Reducing COVID-19 Death Rates in Europe - CONCLUSIONS: The results seem to confirm an association between BCG-positive vaccination policy and salmiak consumption, and lower death rates from COVID-19. Implementing BCG vaccination policy and fortification of foods with salmiak (NH4Cl) may have a significant impact on the control of SARS-CoV epidemic.
Dysregulated immunity in SARS-CoV-2 infected pregnant women - CONCLUSIONS AND RELEVANCE: SARS-CoV-2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of COVID-19 therapeutics in pregnancy. The long-term implications of placental inflammation for neonatal health also requires greater consideration.
Novel gene-specific translation mechanism of dysregulated, chronic inflammation reveals promising, multifaceted COVID-19 therapeutics - Hyperinflammation and lymphopenia provoked by SARS-CoV-2-activated macrophages contribute to the high mortality of Coronavirus Disease 2019 (COVID-19) patients. Thus, defining host pathways aberrantly activated in patient macrophages is critical for developing effective therapeutics. We discovered that G9a, a histone methyltransferase that is overexpressed in COVID-19 patients with high viral load, activates translation of specific genes that induce hyperinflammation and impairment of T cell…
AN EFFICIENT METHODOLOGY TO MANAGE THE ADMISSIONS IN HOSPITALS DURING THE PANDEMICS SUCH AS COVID 19 -
SARS-CoV-2 예방을 위한 mRNA기반 항원보강제 혼합물 합성 방법 - 본 발명은 SARS-CoV-2(코로나 바이러스) 예방을 위한 mRNA 항원보강제에 관한 것으로 코로나 바이러스에 대한 백신으로서 상기의 항원에 대한 예방을 목적으로 하고 있다. 아이디어에는 보강제에 해당하는 완전프로인트항원보강제(CFA)와 불완전프로인트항원보강제(IFA), 번역과 안정성의 최적화가 된 mRNA, mRNA 운반체, 양이온성 지질 나노입자(lipid nanoparticles)로 구성되며 기존의 백신에 비해 효율성과 안정성의 측면에서 더 향상된 효과를 가지고 있다.
Vorrichtung zum Reinigen und/oder Desinfizieren von Objekten -
++
Vorrichtung (1) zum Desinfizieren von Objekten mit einer Basiseinheit (2), mit einem Aufnahmebehälter (4) für Wasser, welcher an der Basiseinheit (2) montierbar und von der Basiseinheit demontierbar ist, mit einer Objekthalterung (6) zum Halten und/oder Stützen der Objekte (10), wobei diese Objekthalterung (6) in dem Aufnahmebehälter montierbar ist und mit einer elektrisch betriebenen Reinigungseinrichtung (8), welche in dem Wasser befindliche Objekte zumindest mittelbar reinigt oder desinfiziert, wobei diese Reinigungseinrichtung in der Basiseinheit befindliche Erzeugungsmittel zum Erzeugen einer elektrischen Spannung aufweist sowie einen Plasmagenerator und/oder eine Ultraschallerzeugungseinheit.
wherein the ’ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.
++Atemschutz-Baukastensystem, das aufweist:
+Vorrichtung zur Übergabe von mit Krankheitserregern kontaminierten Gegenständen oder Erzeugnissen nach einer Dekontamination, umfassend eine Einrichtung zur Dekontamination der mit Krankheitserregern kontaminierten Gegenstände oder Erzeugnisse mit mindestens einer UV-Strahlungsquelle (24), eine Durchzugseinrichtung mit Ein- und/oder Ausgabebereichen für die kontaminierten bzw. dekontaminierten Gegenstände oder Erzeugnisse, dadurch gekennzeichnet, dass die Durchzugseinrichtung im Eingang bzw. im Ausgang zum Ein- und/oder Ausgabebereich angeordnete sich paarweise gegenüberliegende Walzen (17) und Räder (4) umfasst, die zum Einzug bzw. zur Ausgabe der kontaminierten bzw. dekontaminierten Gegenstände oder Erzeugnisse vorgesehen sind, wobei die Walzen (17) und die Räder (4) durch im Ein- und/oder Ausgabebereich angeordnete Sensoren (23) und einer elektronische Kontrolleinheit (27) in Bewegung bringbar sind, wobei die Gegenstände oder Erzeugnisse in den Bereich der Einrichtung zur Dekontamination förderbar sind, der zwischen den paarweise angeordneten Walzen (17) und Rädern (4) vorgesehen ist, welcher sich gegenüberliegende Platten (25) aus Quarzglas oder einem UV-transparenten Polymermaterial, wie Graphen oder Kunstglas umfasst, über bzw. unter welchen die UV-Strahlungsquelle (24) angeordnet ist, welche als UVC-LED-Leiste und/oder Modul mit mindestens einer LED-Lampe ausgebildet ist.
제2형 중증급성호흡기증후군 코로나바이러스 감염 질환의 예방 또는 치료용 조성물 - 본 발명은 화학식 1로 표시되는 화합물, 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는 제2형 중증급성호흡기증후군 코로나바이러스 감염 질환 예방 또는 치료용 약학적 조성물을 제공한다. [화학식 1] .
+ JPEG
+ 112020094463686-pat00017.jpg
+ 48
+ 135新型冠状病毒中和性抗体滴度检测ELISA试剂盒 - 本发明提供一种新型冠状病毒中和性抗体滴度检测ELISA试剂盒，其中包括：包被有生物素‑链霉亲和素标记的人ACE2蛋白的酶标板、辣根过氧化酶标记的新型冠状病毒RBD蛋白、新型冠状病毒中和性抗体阳性对照、包被液、洗涤液、稀释液、封闭液、显色液和终止液等。该试剂盒具有成本低，操作简单，高灵敏度、高特异性、高准确度的特点，可用于新型冠状病毒中和抗体的批量、快速检测。
Reagenzien und Verwendungen zur Diagnose einer SARS-CoV-2-Infektion -
++
Diagnostisch nützlicher Träger umfassend ein Polypeptid umfassend SEQ ID NO1 oder eine Variante davon, die an einen Antikörper gegen SEQ ID NO1 aus einer Probe von einem Patienten binden kann, der an einer SARS-CoV-2-Infektion leidet, wobei das Polypeptid bevorzugt auf der Festphase des Trägers immobilisiert ist.
+Verwendung eines Polypeptides umfassend SEQ ID NO1 oder eine Variante davon, die an einen Antikörper gegen SED ID NO1 aus einer Probe von einem Patienten binden kann, zur Herstellung eines diagnostischen Kits.
How to Think for Yourself - Comments
I’m Peter Roberts, immigration attorney who does work for YC startups. AMA - Comments
Blackrota, a heavily obfuscated backdoor written in Go - Comments
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Show HN: 1000 GitHub Data Science projects, now executable in 1 click - Comments
Tossing a Bird That Does Not Fly Out of a Plane (2018) - Comments
Digital Tools I Wish Existed - Comments
Connections by James Burke (1978) - Comments
1.5 is the midpoint between 0 and infinity in Ruby - Comments
Trump’s Final Cruelty: Executing Prisoners - Despite losing the election, the Administration plans to put Brandon Bernard and four other federal prisoners to death.
Trump and a Lesson in How Coups Fail - In countries without free elections, fraud and coercion regularly make a difference. But that’s not the country we have, and it’s not the election we had.
Is College Football Making the Pandemic Worse? - The game has a remarkable power to bring people together. Right now, that’s a problem.
Trump’s Battle to Undermine the Vote in Pennsylvania - Republicans in the state have alleged fraud and attempted to audit ballots. “The long-term goal,” a Democratic legislator told me, was to “falsely delegitimize Joe Biden’s victory.”
Our Brains Explain the Season’s Sadness - A pandemic, compounded by simultaneous political, civil, and natural crises, is overwhelming human evolution’s greatest innovation.
ATKMB rides on Krishna and Manvir’s strikes in Kolkata Derby - Cashes in on the opportunities to beat SC East Bengal in Kolkata Derby
We had a shot but lost vital wickets: Hardik - ‘When you chase 370-odd, there isn’t much planning; everyone has to play with intent’
Forest Flame for Bangalore 1000 Guineas - Forest Flame, who is in fine fettle as evidenced by her mock race, should be hard to toss in the Bangalore 1000 Guineas (1,600m), the chief event of
Our body language was disappointing, lack of all-round options affecting balance: Kohli - India made a dismal start to their tour of Australia, losing the first ODI by 66 runs here, chasing a mammoth 375-run target after Aaron Finch and Steve Smith smashed hundreds for the hosts.
Spring Grove claims Welcome Trophy - Trainer M.K. Jadhav’s ward Spring Grove, ridden by N.S. Parmar, won the Welcome Trophy, the feature event of the opening day’s races of the Mumbai win
‘State needs ₹563.5 crore from Centre for Mamallapuram beautification’ - Toll rates have been revised to increase the township’s revenue
Mysuru DC vs MLA: War of words continues - H.P. Manjunath, MLA for Hunsur, whose remarks against Deputy Commissioner Rohini Sindhuri had elicited a sharp response from the latter, on Friday so
Parties keep fingers crossed over the choice of intellectuals, employees - LRS, delayed pay revision expected to influence outcome
Hotel converts room into museum - Maradona had stayed in the suite in 2012
Engineer in ACB net for ‘accepting bribe’ - The Anti-Corruption Bureau (ACB) sleuths on Friday arrested a Deputy Executive Engineer identified as Mohan Gandhi of Chitravathi Balancing Reservoir
Coronavirus: Calls in Denmark to dig up millions of dead mink - The hasty mass burial of animals infected with coronavirus was declared illegal.
Belarus protests: Embattled leader Alexander Lukashenko hints he may quit - But opposition leaders dismiss Alexander Lukashenko’s comments as a mere stalling tactic.
Macron ‘shocked’ at beating of black man by Paris police officers - Video of police officers beating a man in Paris left the president visibly upset, an official says.
Italian serenaded by husband outside hospital dies - Carla Sacchi was allowed home days after her husband played his accordion below her hospital window.
Iran diplomat to stand trial in Belgium over ‘France bomb plot’ - Prosecutors in Belgium say he planned an attack on an Iranian opposition rally near Paris in 2018.
Facebook’s Libra currency to launch next year in limited format - Long-awaited project to arrive as soon as January, with just one dollar-backed coin. - link
The best TV deals of Black Friday 2020 - Plus deals on Roku and Fire TV devices, as well as Sonos soundbars. - link
Amazon to pay employee bonus amid threat of Black Friday strikes - One-time payment will be made in January as calls for industrial action grow. - link
The best Apple deals of Black Friday 2020 - Including price drops on new M1 Macs, AirPods Pro, and Apple Watch Series 6. - link
All the best Black Friday 2020 deals we can find (Updated) - We’ve pored over hundreds of Black Friday offers to find the best deals for you. - link
4 types of orgasm… -
+
+Do you know that there are 4 types of orgasm… the Holy Orgasm, The Positive Orgasm, the Negative Orgasm and the Fake Orgasm.
The Holy Orgasm sounds like ‟Oh God, oh god…” The Positive Orgasm goes ‟Yes, yes, oh yes, ” The Negative Orgasm goes ‟no, no, oh no” and the fake orgasm, the fake one goes ‟Oh insert the name of whoever you’re tellng the joke to”
+
submitted by /u/CuttingEpilogue
[link] [comments]
What’s the dirtiest or sexiest joke you have ever heard? -
++
Not the dirtiest but I laughed.
+ ++
Three guys go to a ski lodge, and there are not enough rooms, so they have to share a bed. In the middle of the night, the guy no the right wakes up and says, ‟I had this wild, vivid dream of getting a hand job!” The guy on the left wakes up, and unbelievably, he is had the same dream, too. Then the guy in the middle wakes up and says, ‟That’s funny, I dreamed I was skiing!”
+ + submitted by /u/compactlyExpose735
[link] [comments]
What are the 3 stages of sex after marriage? -
++Tri-weekyl +
++Try Weekly +
++and +
++Try Weakly +
+ submitted by /u/CleftRetreat
[link] [comments]
The deaf Italian Bookkeeper -
++A Mafia Godfather finds out that his bookkeeper of 20 years, Guido, has cheated him out of $10 million.Guido is deaf which is why he got the job in the first place. +
++The Godfather assumed that since Guido could not hear anything, he could never testify in court.When the Godfather goes to confront Guido about his missing $10 million, +
++he takes along his personal lawyer because he knows sign language.The Godfather tells the lawyer, ‟Ask him where the money is!” +
++The lawyer, using sign language, asks Guido, ‟Where‘s the money?” +
++Guido signs back, ‟I do not know what you are talking about.” The lawyer tells the Godfather, ‟He says he doesn‘t know what you are talking about.” +
++The Godfather pulls out a pistol, puts it to Guido‘s head and says, ‟Ask him again or I‘ll kill him!” +
++The lawyer signs to Guido, ‟He will kill you if you do not tell him.” +
++Guido trembles and signs back, ‟OK! You win! The money is in a brown briefcase, buried behind the shed at my cousin Bruno‘s house.” +
++The Godfather asks the lawyer, ‟What did he say?” +
++The lawyer replies, ‟He says you don‘t have the balls to pull the trigger.” +
+ submitted by /u/blufflybelieve
[link] [comments]
I went to the doctor and he said “don’t eat anything fatty.” -
++I asked ‟ no bacon? No burgers?!” +
++To which he replied ‟No fatty, just do not eat anything! ” +
+ submitted by /u/bigHandwash465
[link] [comments]