Covid-19 Sentry

Contents

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

From Preprints

• Nonpharmaceutical Interventions Remain Essential to Reducing COVID-19 Burden Even in a Well-Vaccinated Society: A Modeling Study -

  Vaccination and non-pharmaceutical interventions (NPIs) reduce transmission of SARS-CoV-2 infection, but their effectiveness depends on coverage and adherence levels. We used scenario modeling to evaluate their effects on cases and deaths averted and herd immunity. NPIs and vaccines worked synergistically in different parts of the pandemic to reduce disease burden.

  🖺 Full Text HTML: Nonpharmaceutical Interventions Remain Essential to Reducing COVID-19 Burden Even in a Well-Vaccinated Society: A Modeling Study
• Migration of households from New York City and the Second Peak in Covid-19 cases in New Jersey, Connecticut and New York Counties. -

  The five boroughs of New York City (NYC) were early epicenters of the Covid-19 pandemic in the United States, with over 380,000 cases by May 31. High caseloads were also seen in nearby counties in New Jersey (NJ), Connecticut (CT) and New York (NY). The pandemic started in the area in March with an exponential rise in the number of daily cases, peaked in early April, briefly declined, and then, showed clear signs of a second peak in several counties. We will show that despite control measures such as lockdown and restriction of movement during the exponential rise in daily cases, there was a significant net migration of households from NYC boroughs to the neighboring counties in NJ, CT and NY State. We propose that the second peak in daily cases in these counties around NYC was due, in part, to the movement of people from NYC boroughs to these counties. We estimate the movement of people using “Change of Address” (CoA) data from the US Postal Service, provided under the “Freedom of Information Act” of 1967. To identify the timing of the second peak and the number of cases in it, we use a previously proposed SIR model, which accurately describes the early stages of the coronavirus pandemic in European countries. Subtracting the model fits from the data identified, we establish the timing and the number of cases, NCS, in the second peak. We then related the number of cases in the second peak to the county population density, P, and the excess Change of Address, ECoA, into each county using the simple model N_CS~P^α E_CoA^β which fits the data very well with α = 0.68, β = 0.31 (R^2 = 0.74, p = 1.3e-8). We also find that the time between the first and second peaks was proportional to the distance of the county seat from NY Penn Station, suggesting that this migration of households and disease was a directed flow and not a diffusion process. Our analysis provides a simple method to use change of address data to track the spread of an infectious agent, such as SARS-Cov-2, due to migrations away from epicenters during the initial stages of a pandemic.

  🖺 Full Text HTML: Migration of households from New York City and the Second Peak in Covid-19 cases in New Jersey, Connecticut and New York Counties.
• The requisite for acid generation to solubilize insoluble salts may account for surge of glucose levels in some diabetes patients -
  Diabetes is a comorbidity of COVID-19, and the mortality may be pertinent to the wide distribution of insoluble and stiff salts such as calcium oxalate in diabetic sufferers. As an intrinsic self-protective mechanism, tissues in diabetic individuals may build up hydrogen-bonding-capable molecules such as glucose for the generation of acids which can solubilize insoluble and stiff salts or crystals.
  🖺 Full Text HTML: The requisite for acid generation to solubilize insoluble salts may account for surge of glucose levels in some diabetes patients
• A Guilt-Free Strategy Increase Self-Reported Non-Compliance with COVID-19 Preventive Measures: Experimental Evidence from 12 Countries -
  Studies of citizens’ compliance with COVID-19 preventive measures routinely rely on survey data. While essential, public health restrictions provide clear signals of what is socially desirable in this context, creating a potential source of response bias in self-reported measures of compliance. In this research, we examine whether the results of a guilt-free strategy that was used by Daoust et al. (2020) to loosen this constraint are generalizable across twelve countries, and whether the treatment effect varies across subgroups. Our findings show that the guilt-free strategy is a very useful tool in every country included, increasing respondents’ proclivity to report non-compliance by 9 to 16 percentage points. This effect holds for different subgroups based on gender, age and education. We conclude that the inclusion of this strategy should be the new standard for survey research that aims to provide crucial data on the current pandemic.
  🖺 Full Text HTML: A Guilt-Free Strategy Increase Self-Reported Non-Compliance with COVID-19 Preventive Measures: Experimental Evidence from 12 Countries
• Pairing Facts with Imagined Consequences Improves Pandemic-Related Risk Perception -
  The COVID-19 pandemic reached staggering new peaks during an ongoing global resurgence at the end of 2020. Although public health guidelines initially helped to slow the spread of disease, widespread pandemic fatigue and prolonged harm to financial stability and mental wellbeing have contributed to this resurgence. In this late stage of the pandemic, it is clear that new interventions are needed to support long-term behavior change. Here, we examined subjective perceived risk about COVID-19, and the relationship between perceived risk and engagement in risky behaviors. In Study 1 (N = 303), we found that subjective perceived risk is inaccurate but predicts compliance with public health guidelines. In Study 2 (N = 760), we developed a multi-faceted intervention designed to realign perceived risk with actual risk. Participants completed one of three variants of an episodic simulation task; we expected that imagining a COVID-related scenario would increase the salience of risk information and enhance behavior change. Immediately following the episodic simulation, participants completed a risk estimation task with personalized feedback about local risk levels. We found that information prediction error, a measure of surprise, drove beneficial change in perceived risk and willingness to engage in risky activities. Imagining a COVID-related scenario beforehand enhanced the effect of prediction error on learning. Importantly, our intervention produced lasting effects that persisted after a 1-3 week delay. Overall, we describe a fast and feasible online intervention that effectively changed beliefs and intentions about risky behaviors.
  🖺 Full Text HTML: Pairing Facts with Imagined Consequences Improves Pandemic-Related Risk Perception
• Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics -
  Therapeutic mRNAs and vaccines are being developed for a broad range of human diseases, including COVID-19. However, their optimization is hindered by mRNA instability and inefficient protein expression. Here, we describe design principles that overcome these barriers. We develop a new RNA sequencing-based platform called PERSIST-seq to systematically delineate in-cell mRNA stability, ribosome load, as well as in-solution stability of a library of diverse mRNAs. We find that, surprisingly, in-cell stability is a greater driver of protein output than high ribosome load. We further introduce a method called In-line-seq, applied to thousands of diverse RNAs, that reveals sequence and structure-based rules for mitigating hydrolytic degradation. Our findings show that superfolder mRNAs can be designed to improve both stability and expression that are further enhanced through pseudouridine nucleoside modification. Together, our study demonstrates simultaneous improvement of mRNA stability and protein expression and provides a computational-experimental platform for the enhancement of mRNA medicines.
  🖺 Full Text HTML: Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics
• Severity of SARS-CoV-2 infection as a function of the interferon landscape across the respiratory tract of COVID-19 patients. -
  The COVID-19 outbreak driven by SARS-CoV-2 has caused more than 2.5 million deaths globally, with the most severe cases characterized by over-exuberant production of immune-mediators, the nature of which is not fully understood. Interferons of the type I (IFN-I) or type III (IFN-III) families are potent antivirals, but their role in COVID-19 remains debated. Our analysis of gene and protein expression along the respiratory tract shows that IFNs, especially IFN-III, are over-represented in the lower airways of patients with severe COVID-19, while high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity; also, IFN expression varies with abundance of the cell types that produce them. Our data point to a dynamic process of inter- and intra-family production of IFNs in COVID-19, and suggest that IFNs play opposing roles at distinct anatomical sites.
  🖺 Full Text HTML: Severity of SARS-CoV-2 infection as a function of the interferon landscape across the respiratory tract of COVID-19 patients.
• Rapid characterization of spike variants via mammalian cell surface display -
  The SARS-CoV-2 spike (S) protein is a critical component of subunit vaccines and a target for neutralizing antibodies. Spike is also undergoing immunogenic selection with clinical variants that increase infectivity and partially escape convalescent plasma. Here, we describe spike display, a high-throughput platform to rapidly characterize glycosylated spike ectodomains across multiple coronavirus-family proteins. We assayed ~200 variant SARS-CoV-2 spikes for their expression, ACE2 binding, and recognition by thirteen neutralizing antibodies (nAbs). An alanine scan of the N-terminal domain (NTD) highlights a public class of epitopes in the N3 and N5 loops that are recognized by most of the NTD-binding nAbs assayed in this study. Some clinical NTD substitutions abrogate binding to these epitopes but are circulating at low frequencies around the globe. NTD mutations in variants of concern B.1.1.7 (United Kingdom), B.1.351 (South Africa), B.1.1.248 (Brazil), and B.1.427/B.1.429 (California) impact spike expression and escape most NTD-targeting nAbs. However, two classes of NTD nAbs still bind B.1.1.7 spikes and neutralize in pseudoviral assays. B.1.1351 and B.1.1.248 include compensatory mutations that either increase spike expression or increase ACE2 binding affinity. Finally, B.1.351 and B.1.1.248 completely escape a potent ACE2 peptide mimic. We anticipate that spike display will be useful for rapid antigen design, deep scanning mutagenesis, and epitope mapping of antibody interactions for SARS-CoV-2 and other emerging viral threats.
  🖺 Full Text HTML: Rapid characterization of spike variants via mammalian cell surface display
• Sequence analysis of SARS-CoV-2 in nasopharyngeal samples from patients with COVID-19 illustrates population variation and diverse phenotypes, placing the in vitro growth properties of B.1.1.7 and B.1.351 lineage viruses in context. -
  New variants of SARS-CoV-2 are continuing to emerge and dominate the regional and global sequence landscapes. Several variants have been labelled as Variants of Concern (VOCs) because of perceptions or evidence that these may have a transmission advantage, increased risk of morbidly and/or mortality or immune evasion in the context of prior infection or vaccination. Placing the VOCs in context and also the underlying variability of SARS-CoV-2 is essential in understanding virus evolution and selection pressures. Sequences of SARS-CoV-2 in nasopharyngeal swabs from hospitalised patients in the UK were determined and virus isolated. The data indicated the virus existed as a population with a consensus level and non-synonymous changes at a minor variant. For example, viruses containing the nsp12 P323L variation from the Wuhan reference sequence, contained minor variants at the position including P and F and other amino acids. These populations were generally preserved when isolates were amplified in cell culture. In order to place VOCs B.1.1.7 (the UK Kent variant) and B.1.351 (the South African variant) in context their growth was compared to a spread of other clinical isolates. The data indicated that the growth in cell culture of the B.1.1.7 VOC was no different from other variants, suggesting that its apparent transmission advantage was not down to replicating more quickly. Growth of B.1.351 was towards the higher end of the variants. Overall, the study suggested that studying the biology of SARS-CoV-2 is complicated by population dynamics and that these need to be considered with new variants.
  🖺 Full Text HTML: Sequence analysis of SARS-CoV-2 in nasopharyngeal samples from patients with COVID-19 illustrates population variation and diverse phenotypes, placing the in vitro growth properties of B.1.1.7 and B.1.351 lineage viruses in context.
• A recombinant receptor-binding domain in trimeric form generates completely protective immunity against SARS-CoV-2 infection in nonhuman primates -
  Safe and effective vaccination is critical to combatting the COVID-19 pandemic. Here, we developed a trimeric SARS-CoV-2 receptor-binding domain (RBD) subunit vaccine candidate that simulates the natural structure of the spike (S) trimer glycoprotein. Immunization with RBD-trimer induced robust humoral and cellular immune responses and a high level of neutralizing antibodies that were maintained for at least 4 months. Moreover, the antibodies that were produced in response to the vaccine effectively neutralized the SARS-CoV-2 501Y.V2 variant. Of note, when the titers of the antibodies dropped to a sufficiently low level, only one boost quickly activated the anamnestic immune response, resulting in complete protection against the SARS-CoV-2 challenge in rhesus macaques without typical histopathological changes or viral replication in the lungs and other respiratory tissues. Our results indicated that immunization with SARS-CoV-2 RBD-trimer could raise long-term and broad immunity protection in nonhuman primates, thereby offering an optimal vaccination strategy against COVID-19.
  🖺 Full Text HTML: A recombinant receptor-binding domain in trimeric form generates completely protective immunity against SARS-CoV-2 infection in nonhuman primates
• Separable Associations Between Perceived Positive and Negative Online Experiences and Loneliness in Peruvian Adolescents During Physical Isolation in Response to COVID-19 -
  COVID-19 lockdowns around the world have markedly disrupted adolescents’ in-person social networks, putting them at risk for social isolation, loneliness and their detrimental consequences. During lockdown, social media can help adolescents to maintain and develop relationships across distance, particularly with peers. In this longitudinal, observational study following 735 Peruvian adolescents (11-17 years old) from low-to-middle income urban settings, we investigated whether online experiences relate to loneliness during initial stages of lockdown in Perú. We found that loneliness generally did not change between week six and week eleven of lockdown, was higher for females and similar for all grades. Both positive and negative online experiences were more frequent for older students, and females experienced more negative online experiences than males. Loneliness was negatively associated with positive online experiences, with the reverse pattern for negative online experiences, when controlling for family social support and screen time. Our results highlight the association between online experiences and well-being, suggesting that positive online experiences can be an important vehicle for peer relationships in the face of lockdown.
  🖺 Full Text HTML: Separable Associations Between Perceived Positive and Negative Online Experiences and Loneliness in Peruvian Adolescents During Physical Isolation in Response to COVID-19
• A RANDOMIZED TRIAL - INTENSIVE TREATMENT BASED IN IVERMECTIN AND IOTA-CARRAGEENAN AS PRE-EXPOSURE PROPHYLAXIS FOR COVID- 19 IN HEALTHCARE AGENTS -

  IMPORTANCE: The emergency of COVID-19 requires the implementation of urgent strategies to prevent the spread of the disease, mainly in health personnel, who are the most exposed and has the highest risk of becoming infected with the SARS-COV-2. Drug repurposing is a pragmatic strategy, a faster and cheaper option, compared to the new drug development that has proven successful for many drugs and can be a key tool in emergency situations such as the current one that requires quick action. In addition, considering the limited access to vaccines for developing countries, preventive use of ivermectin can be a palliative that minimizes the risks of infection. OBJECTIVE: To evaluate the protective effect of the combination Ivermectin / Iota- Carrageenan (IVER/IOTACRC), intensive treatment with repeated administration in oral- and nasal-spray, respectively, as a prophylaxis treatment prior to exposure to SARS-CoV-2, in health personnel at Public Healthcare Centers. PARTICIPANTS, DESIGN AND SETTING: Randomized controlled 1-1 clinical trial in Personal Health, n = 234. The subjects were divided into experimental (EG: n=117; 39.6 ± 9.4 years old, 65F) and control groups (CG: n=117; 38.4 ± 7.4 years old, 61F). The EG received Ivermectin orally 2 tablets of 6 mg = 12 mg every 7 days, and Iota-Carrageenan 6 sprays per day for 4 weeks. All participants were evaluated by physical examination COVID-19 diagnosed with negative RT-PCR at the beginning, final, and follow-up of the protocol. Differences between the variables were determined using the Chi-square test. The proportion test almost contagious subject and the contagion risk (Odds Ratio) were calculated using software STATA. The level of statistical significance was reached when p-Value < 0.05. RESULT: The number of subjects who were diagnosed with COVID-19 in EG was lower, only 4 of 117 (3.4%) than subjects in CG: 25 of 117 (21.4%) (P-Value = 1.10-5). Nineteen patients had mild symptoms, 4 were in EG whereas, 15 were in CG (p-Value = 0.001). Seven subjects were moderate, and 3 with severe diagnostics, all them in CG. The probability (Odds Ratio) of becoming ill with COVID-19 was significantly lower in EG with values of 0.13, 95% 0.03 to 0.40; p-Value = 1.10-4, this value (<1) indicates a protective effect of the IVER/IOTACRC in the EG. Logistic regression test demonstrated that treatment was effective to prevent COVID-19 (Odds Ratio 0.11, 95% 0.03 to 0.33; p-Value = 1.10-4). We also found that when increase the age, decrease contagious risk (Odds Ratio 0, 93, 95% 0.88 to 0.98, p-Value= 0, 02). On the other hand, the probability of contracting COVID-19 was dependent on the patient9s preexisting comorbidity (Odds Ratio 5.58, 95% 2.20 to 14.16, p-Value = 1.10-5). The other variables sex and designation were independent. CONCLUSION: The intensive preventive treatment (short-term) with IVER/IOTACRC was able to reduce the number of health workers infected with COVID-19. This treatment had also effect in preventing the severity of the disease, since all patients treated were mild. We propose a new therapeutic alternative for prevention and short-term intervention scheme (intensive) that is of benefit of the health worker in this pandemic accelerated time. This intervention did not produce lack of adherence to treatment or adverse effects.

  🖺 Full Text HTML: A RANDOMIZED TRIAL - INTENSIVE TREATMENT BASED IN IVERMECTIN AND IOTA-CARRAGEENAN AS PRE-EXPOSURE PROPHYLAXIS FOR COVID- 19 IN HEALTHCARE AGENTS
• IVERMECTIN REPROPOSING FOR COVID-19 TREATMENT OUTPATIENTS IN MILD STAGE IN PRIMARY HEALTH CARE CENTERS -

  Background: The emergence of COVID-19 requires alternative treatments based on the reuse of drugs as a strategy to prevent the progression of the disease in patients infected with SARS-COV-2. The goal was to evaluate the use of ivermectin in mild stage outpatients to heal and / or reverse the progression of COVID-19 disease towards the development of moderate or severe stages. Methods: Cluster Assigned Clinical Trial (2:1) in outpatients, n = 234. The subjects were divided into experimental (EG: n = 110) and control groups (CG: n = 62). The EG received ivermectin orally 4 drops of 6 mg = 24 mg every 7 days for 4 weeks. All participants were diagnosed by positive RT-PCR for COVID-19 and were evaluated by clinical examination, at the beginning and the end of protocol. Data analyzed were applied the proportion, bivariate, and logical regression tests with level significance p < 0.05. This study was registered at ClinicalTrials.gov Identifier NCT04784481. Findings: Both groups were similar in age, sex, and comorbidities (EG: 56F, median age= 40.0, range: 18.0 - 75.0; CG: 34F, median age = 37.5, range: 18.0 - 71.0). A significant reduction in the symptom numbers was observed in the EG when the medical examination was performed from 5th to 9th days, after starting treatment (p = 0.0026). Although, medical examination from 10th to 14th day, showed a progressive reduction of the percentage symptom numbers, these were not significative in both groups. A higher proportion of medical release was observed in EG (98.2%) vs CG (87.1%) (p = 0.003). EG showed 8 times more chance of receiving medical release than CG (OR 7.99, 95% CI: 1.64 -38.97, p = 0.003). The treatment effect with ivermectin to obtain medical release was analyzed by the logistic regression model based in the following control variables: sex, age, and comorbidities. Then, the chance to obtain medical release was maintained in EG (OR 10.37, 95% CI: 2.05 - 52.04, p = 0.005). Interpretation: Treatment with ivermectin in outpatients with mild stage COVID-19 disease managed to slightly reduce the symptom numbers. Also, this treatment improved the clinical state to obtain medical release, even in the presence of comorbidities. The treatment with ivermectin could significantly prevent the evolution to serious stages since the EG did not present any patient with referral to critical hospitalization.

  🖺 Full Text HTML: IVERMECTIN REPROPOSING FOR COVID-19 TREATMENT OUTPATIENTS IN MILD STAGE IN PRIMARY HEALTH CARE CENTERS
• Development and validation of the RCOS prognostic index: a bedside multivariable logistic regression model to predict hypoxaemia or death in patients with of SARS-CoV-2 infection -

  Previous COVID-19 prognostic models have been developed in hospital settings, and are not applicable to COVID-19 cases in the general population. There is an urgent need for prognostic scores aimed to identify patients at high risk of complications at the time of COVID-19 diagnosis. The RDT COVID-19 Observational Study (RCOS) collected clinical data from patients with COVID-19 admitted regardless of the severity of their symptoms in a general hospital in India. We aimed to develop and validate a simple bedside prognostic score to predict the risk of hypoxaemia or death. 4035 patients were included in the development cohort and 2046 in the validation cohort. The primary outcome occurred in 961 (23.8%) and 548 (26.8%) patients in the development and validation cohorts, respectively. The final model included 12 variables: age, systolic blood pressure, heart rate, respiratory rate, aspartate transaminase, lactate dehydrogenase, urea, C-reactive protein, sodium, lymphocyte count, neutrophil count and neutrophil/lymphocyte ratio. In the validation cohort, the area under the receiver operating characteristic curve (AUROCC) was 0.907 (95% CI, 0.892-0.922) and the Brier Score was 0.098. The decision curve analysis showed good clinical utility in hypothetical scenarios where admission of patients was decided according to the prognostic index. When the prognostic index was used to predict mortality in the validation cohort, the AUROCC was 0.947 (95% CI, 0.925-0.97) and the Brier score was 0.0188. If our results are validated in other settings, the RCOS prognostic index could help improve the decision making in the current COVID-19 pandemic, especially in resource limited-settings.

  🖺 Full Text HTML: Development and validation of the RCOS prognostic index: a bedside multivariable logistic regression model to predict hypoxaemia or death in patients with of SARS-CoV-2 infection
• Six-month pulmonary impairment after severe COVID-19: a prospective, multicenter follow-up study -

  Background and objective. Long-term pulmonary sequelae following SARS-CoV-2 pneumonia are not yet confirmed, however preliminary observations suggests a possible relevant clinical, functional and radiological impairment. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 6-month follow-up. Methods. In this multicenter, prospective, observational cohort study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support (oxygen only, continuous positive airway pressure (CPAP) and invasive mechanical ventilation (IMV)) and followed up at 6 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 minutes walking test, chest X-ray, physical exam and modified Medical Research Council (mMRC) dyspnoea score were collected. Results. Between March and June 2020, 312 patients were enrolled (83, 27% women; median [IQR] age 61.1 [53.4,69.3] years). The parameters that showed the highest rate of impairment were DLCO and chest-X-ray, in 46% and 25% of patients, respectively. However, only a minority of patients reported dyspnoea (31%), defined as mMRC ≥ 1, or showed a restrictive ventilatory defects (9%). In the logistic regression model, having asthma as comorbidity was associated with DLCO impairment at follow-up, while prophylactic heparin administration during hospitalisation appeared as a protective factor. Need for invasive ventilatory support during hospitalisation was associated with chest imaging abnormalities. Conclusion. DLCO and radiological assessment appear to be the most sensitive tools to monitor patients with COVID-19 during follow-up. Future studies with longer follow-up are warranted to better understand pulmonary sequelae.

  🖺 Full Text HTML: Six-month pulmonary impairment after severe COVID-19: a prospective, multicenter follow-up study

From Clinical Trials

• Study to Evaluate the Viral Load Reduction of a Single Dose of Plitidepsin in Adult Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Plitidepsin;   Drug: Symptomatic Treatment
  Sponsors:   PharmaMar;   Apices Soluciones S.L.
  Not yet recruiting

• ANTIcoagulation in Severe COVID-19 Patients - Condition:   Severe COVID-19 Pneumonia
  Interventions:   Drug: Tinzaparin, Low dose prophylactic anticoagulation;   Drug: Tinzaparin, High dose prophylactic anticoagulation;   Drug: Tinzaparin,Therapeutic anticoagulation
  Sponsor:   Assistance Publique - Hôpitaux de Paris
  Not yet recruiting

• Immunogenicity and Safety of Recombinant COVID-19 Vaccine (CHO Cells) - Condition:   COVID-19
  Interventions:   Biological: a middle-dose recombinant COVID-19 vaccine (CHO Cell) (18-59 years) at the schedule of day 0, 28, 56;   Biological: a high-dose recombinant COVID-19 vaccine (CHO Cell) (18-59 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose recombinant COVID-19 vaccine (CHO Cell) (60-85 years) at the schedule of day 0, 28, 56;   Biological: a high-dose recombinant COVID-19 vaccine (CHO Cell) (60-85 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose placebo (18-59 years) at the schedule of day 0, 28, 56;   Biological: a high-dose placebo (18-59 years) at the schedule of day 0, 28, 56;   Biological: a middle-dose placebo (60-85 years) at the schedule of day 0, 28, 56;   Biological: a high-dose placebo (60-85 years) at the schedule of day 0, 28, 56
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   Academy of Military Medical Sciences，Academy of Military Sciences，PLA ZHONGYIANKE Biotech Co, Ltd. LIAONINGMAOKANGYUAN Biotech Co, Ltd
  Recruiting

• Neuromodulation in COVID-19 Patients - Condition:   COVID-19
  Interventions:   Device: Transcranial direct-current stimulation;   Device: Sham Transcranial direct-current stimulation
  Sponsors:   D’Or Institute for Research and Education;   Rio de Janeiro State Research Supporting Foundation (FAPERJ);   Conselho Nacional de Desenvolvimento Científico e Tecnológico;   Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
  Not yet recruiting

• Clinical Decision Support System Based on Non-invasive Tele-monitoring of COVID-19 Patients - Condition:   COVID-19
  Intervention:   Device: Clinical decision support system based on non-invasive multimodal monitoring
  Sponsors:   Increase-Tech;   Hospital Clínico Universitario de Valladolid;   University of Valladolid;   Sanidad de Castilla y León
  Active, not recruiting

• Evaluation of ADG20 for the Treatment of Mild or Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: ADG20;   Drug: Normal saline
  Sponsor:   Adagio Therapeutics, Inc.
  Recruiting

• A Study to Test BI 767551 in People With Mild to Moderate Symptoms of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: BI 767551 intravenous;   Drug: BI 767551 inhaled;   Drug: Placebo intravenous;   Drug: Placebo inhaled
  Sponsor:   Boehringer Ingelheim
  Not yet recruiting

• Tele-rehabilitation Program After Hospitalization for COVID-19 - Condition:   COVID-19 Pneumonia
  Interventions:   Other: TR;   Other: TSu
  Sponsors:   Istituti Clinici Scientifici Maugeri SpA;   Istituto Auxologico Italiano
  Recruiting

• Pilot Trial of XFBD, a TCM, in Persons With COVID-19 - Condition:   Covid19
  Interventions:   Drug: Xuanfei Baidu Granules;   Other: Placebo
  Sponsor:   Darcy Spicer
  Recruiting

• SERUR: COVID-19 Serological Survey of Staff From the University Reims-Champagne Ardennes - Condition:   Covid19
  Intervention:   Diagnostic Test: Anti-SARS-CoV2 Serology
  Sponsor:   Université de Reims Champagne-Ardenne
  Completed

• Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Lyophilized Formulation of BNT162b2 Against COVID-19 in Healthy Adults - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Intervention:   Biological: BNT162b2
  Sponsors:   BioNTech SE;   Pfizer
  Not yet recruiting

• Safety and Tolerability of Emricasan in Symptomatic Outpatients Diagnosed With Mild-COVID-19 - Condition:   Covid19
  Interventions:   Drug: Emricasan;   Other: Placebo
  Sponsor:   Histogen
  Recruiting

• Efficacy of Reinforcing Standard Therapy in COVID-19 Patients With Repeated Transfusion of Convalescent Plasma - Condition:   Covid19
  Interventions:   Other: Convalescent Plasma with antibody against SARS-CoV-2.;   Other: Standard treatment for COVID-19
  Sponsors:   Hospital Son Llatzer;   Fundació d’investigació Sanitària de les Illes Balears
  Recruiting

• Assessment of the Impact of Oral Intervention With Cetylpyridinium Chloride to Decrease SARS-CoV-2 Viral Load in Patients With COVID-19 - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Other: ORAL INTERVENTION WITH CETYLPYRIDINIUM CHLORIDE;   Other: PLACEBO
  Sponsors:   Rosa Tarrago;   Dentaid SL
  Recruiting

• Study to Evaluate the Safety, Tolerability, and Immunogenicity of an RNA Vaccine Candidate Against COVID-19 in Healthy Children <12 Years of Age - Condition:   SARS-CoV-2 Infection, COVID-19
  Interventions:   Biological: Biological/Vaccine: BNT162b2 10mcg;   Biological: BNT162b2 20mcg;   Biological: BNT162b2 30mcg
  Sponsors:   BioNTech SE;   Pfizer
  Not yet recruiting

From PubMed

• Multidisciplinary Approaches Identify Compounds that Bind to Human ACE2 or SARS-CoV-2 Spike Protein as Candidates to Block SARS-CoV-2-ACE2 Receptor Interactions - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emerged virus that causes coronavirus infectious disease 2019 (COVID-19). SARS-CoV-2 spike protein, like SARS-CoV-1, uses the angiotensin converting enzyme 2 (ACE2) as a cellular receptor to initiate infection. Compounds that interfere with the SARS-CoV-2 spike protein receptor binding domain protein (RBD)-ACE2 receptor interaction may function as entry inhibitors. Here, we used a dual strategy of molecular docking and…

• Therapeutic Potential of Metformin in COVID-19: Reasoning for Its Protective Role - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections present with increased disease severity and poor clinical outcomes in diabetic patients compared with their nondiabetic counterparts. Diabetes/hyperglycemia-triggered endothelial dysfunction and hyperactive inflammatory and immune responses are correlated to twofold to threefold higher intensive care hospitalizations and more than twice the mortality among diabetic coronavirus disease 2019 (COVID-19) patients. While…

• Design and synthesis of novel phe-phe hydroxyethylene derivatives as potential coronavirus main protease inhibitors - In response to the current pandemic caused by the novel SARS-CoV-2, we design new compounds based on Lopinavir structure as an FDA-approved antiviral agent which is currently under more evaluation in clinical trials for COVID-19 patients. This is the first example of the preparation of Lopinavir isosteres from the main core of Lopinavir conducted to various heterocyclic fragments. It is proposed that main protease inhibitors play an important role in the cycle life of coronavirus. Thus, the…

• Role of Tissue Factor in the Pathogenesis of COVID-19 and the Possible Ways to Inhibit It - COVID-19 (Coronavirus Disease 2019) is a highly contagious infection and associated with high mortality rates, primarily in elderly; patients with heart failure; high blood pressure; diabetes mellitus; and those who are smokers. These conditions are associated to increase in the level of the pulmonary epithelium expression of angiotensin-converting enzyme 2 (ACE-2), which is a recognized receptor of the S protein of the causative agent SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus…

• Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication - SARS-CoV-2 has currently precipitated the COVID-19 global health crisis. We developed a medium-throughput drug-screening system and identified a small-molecule library of 34 of 430 protein kinase inhibitors that were capable of inhibiting the SARS-CoV-2 cytopathic effect in human epithelial cells. These drug inhibitors are in various stages of clinical trials. We detected key proteins involved in cellular signaling pathways mTOR-PI3K-AKT, ABL-BCR/MAPK, and DNA-damage response that are critical…

• A Recombinant Fragment of Human Surfactant Protein D Binds Spike Protein and Inhibits Infectivity and Replication of SARS-CoV-2 in Clinical Samples - COVID -19 is an acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human surfactant protein D (SP-D) is known to interact with spike protein of SARS-CoV, but its immune-surveillance against SARS-CoV-2 is not known. The study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2. The interaction of rfhSP-D with spike protein of SARS-CoV-2 and hACE-2 receptor was…

• Lead Discovery of SARS-CoV-2 Main Protease Inhibitors through Covalent Docking-Based Virtual Screening - During almost all 2020, coronavirus disease 2019 (COVID-19) pandemic has constituted the major risk for the worldwide health and economy, propelling unprecedented efforts to discover drugs for its prevention and cure. At the end of the year, these efforts have culminated with the approval of vaccines by the American Food and Drug Administration (FDA) and the European Medicines Agency (EMA) giving new hope for the future. On the other hand, clinical data underscore the urgent need for effective…

• Inhibition of Human Coronaviruses by Antimalarial Peroxides - As the toll of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues, efforts are ongoing to identify new agents and repurpose safe drugs for its treatment. Antimalarial peroxides have reported antiviral and anticancer activities. Here, we evaluated the in vitro activities of artesunate (AS) and two ozonides (OZ418 and OZ277) against human α-coronavirus NL63 and β-coronaviruses OC43 and SARS-CoV-2 in several cell lines. OZ418 had the best selectivity index (SI) in…

• Interleukin-1 and interleukin-6 inhibition in patients with COVID-19 and hyperinflammation - No abstract

• Interleukin-1 and interleukin-6 inhibition in patients with COVID-19 and hyperinflammation - Authors’ reply - No abstract

• Perspectives on plant flavonoid quercetin-based drugs for novel SARS-CoV-2 - CONCLUSION: The antiviral properties of flavonoid and the molecular mechanisms involved are reviewed. Further, proof for this concept is given by docking of key proteins from SARS-CoV-2 with quercetin.

• BRD4 targeting nanotherapy prevents lipopolysaccharide induced acute respiratory distress syndrome - Acute respiratory distress syndrome (ARDS) is a life threatening respiratory disease associated with pulmonary edema, alveolar dysfunction, hypoxia, and inflammatory cell accumulation. The most contagious form of COVID-19 associated with ARDS caused by SARS-CoV-2. SARS-CoV-2 majorly produces the cytokine storm and severe lung inflammation and ultimately leads to respiratory failure. ARDS is a complex disease and there is no proper therapeutics for effective therapy. Still, there is a huge scope…

• Heparin prevents in vitro glycocalyx shedding induced by plasma from COVID-19 patients - The severe forms and worsened outcomes of COVID-19 (coronavirus disease 19) are closely associated with hypertension and cardiovascular disease. Endothelial cells express Angiotensin-Converting Enzyme 2 (ACE2), which is the entrance door for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The hallmarks of severe illness caused by SARS-CoV-2 infection are increased levels of IL-6, C-reactive protein, D-dimer, ferritin, neutrophilia and lymphopenia, pulmonary intravascular…

• Proteomic Analysis Identifies the RNA Helicase DDX3X as a Host Target Against SARS-CoV-2 Infection - COVID-19 is currently a highly pressing health threat and therapeutic strategies to mitigate the infection impact are urgently needed. Characterization of the SARS-CoV-2 interactome in infected cells may represent a powerful tool to identify cellular proteins hijacked by viruses for their life cycle and develop host-oriented antiviral therapeutics. Here we report the proteomic characterization of host proteins interacting with SARS-CoV-2 Nucleoprotein in infected Vero E6 cells. We identified 24…

• Fever: Could A Cardinal Sign of COVID-19 Infection Reduce Mortality? - With mortality rising from the COVID-19 pandemic, we may be overlooking a key aspect of the immunological response. Fever is a cardinal sign of this rampant infection; however, little attention has been paid towards how a fever may work in our favor in overcoming this disease. Three key aspects of patient care - fever, fluid, and food - can be harmonized to overcome COVID-19 infection. Both animal and human studies have demonstrated that fever suppression during viral infections, either through…

From Patent Search

• 5-(4-TERT-BUTOXY PHENYL)-3-(4N-OCTYLOXYPHENYL)-4,5-DIHYDROISOXAZOLE MOLECULE (C-I): A PROMISING DRUG FOR SARS-COV-2 (TARGET I) AND BLOOD CANCER (TARGET II) - The present invention relates to a method ofmolecular docking of crystalline compound (C-I) with SARS-COV 2 proteins and its repurposing with proteins of blood cancer, comprising the steps of ; employing an algorithmto carry molecular docking calculations of the crystalized compound (C-I); studying the compound computationally to understand the effect of binding groups with the atoms of the amino acids on at least four target proteins of SARS-COV 2; downloading the structure of the proteins; removing water molecules, co enzymes and inhibitors attached to the enzymes; drawing the structure using Chem Sketch software; converting the mol file into a PDB file; using crystalized compound (C-I) for comparative and drug repurposing with two other mutated proteins; docking compound into the groove of the proteins; saving format of docked molecules retrieved; and filtering and docking the best docked results. - link

• USING CLINICAL ONTOLOGIES TO BUILD KNOWLEDGE BASED CLINICAL DECISION SUPPORT SYSTEM FOR NOVEL CORONAVIRUS (COVID-19) WITH THE ADOPTION OF TELECONFERENCING FOR THE PRIMARY HEALTH CENTRES/SATELLITE CLINICS OF ROYAL OMAN POLICE IN SULTANATE OF OMAN - - link

• Peptides and their use in diagnosis of SARS-CoV-2 infection - - link

• A PROCESS FOR SUCCESSFUL MANAGEMENT OF COVID 19 POSITIVE PATIENTS - - link

• IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2 - IN SILICO SCREENING OF ANTIMYCOBACTERIAL NATURAL COMPOUNDS WITH THE POTENTIAL TO DIRECTLY INHIBIT SARS COV 2Insilico screening of antimycobacterial natural compounds with the potential to directly inhibit SARS COV2 relates to the composition for treating SARS-COV-2 comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. The composition also treats treating SARS, Ebola, Hepatitis-B and Hepatitis–C comprising the composition is about 0.1 – 99% and other pharmaceutically acceptable excipients. - link

• Sars-CoV-2 vaccine antigens - - link

• SARS-COV-2 BINDING PROTEINS - - link

• Bildschirmgerät mit verbesserter Wirkung bei der Befestigung von UV-Entkeimungslampen -

  Ein Bildschirmgerät mit verbesserter Wirkung bei der Befestigung von UV-Entkeimungslampen, umfassend: ein Bildschirmgerät, das einen Umfang hat; eine UV-Entkeimungslampe, die sich am Umfang des Bildschirmgeräts befindet; eine Stromquelle, die elektrisch mit der UV-Entkeimungslampe verbunden ist; eine Steuerschaltung, die elektrisch mit der UV-Entkeimungslampe verbunden ist; und eine Befestigungsvorrichtung, durch die die UV-Entkeimungslampe am Umfang des Bildschirmgeräts befestigbar ist, wobei die Befestigungsvorrichtung einen Sitzkörper, eine erste Klemmplatte und eine zweite Klemmplatte aufweist, wobei der Sitzkörper mit der UV-Entkeimungslampe versehen ist, wobei die erste Klemmplatte und die zweite Klemmplatte beabstandet am Sitzkörper gleitbar angeordnet sind, wodurch ein Klemmabstand zwischen der ersten Klemmplatte und der zweiten Klemmplatte besteht, wobei ein elastisches Element zwischen der zweiten Klemmplatte und dem Sitzkörper angeordnet ist, um die zweite Klemmplatte dazu zu zwingen, sich der ersten Klemmplatte zu nähern.

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• Schublade mit antiepidemischer Wirkung -

  Schublade mit antiepidemischer Wirkung, mit einem Schrank (1); mindestens einer Schublade (2), die in dem Schrank (1) angeordnet ist, wobei jede Schublade (2) einen Schubladenraum (25) aufweist; einer UV-Sterilisationsvorrichtung (3), die an der Schublade (2) angeordnet ist; einer Stromquelle (4), die elektrisch mit der UV-Sterilisationsvorrichtung (3) verbunden ist; einer Steuerschaltung (5), die elektrisch mit der Stromquelle (4) und der UV-Sterilisationsvorrichtung (3) verbunden ist; und einem Sensor (6), der elektrisch mit der Steuerschaltung (5) verbunden ist.

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• Gerät zur Unterstützung und Verstärkung natürlicher Lüftung -

  Lüftungssystem für einen mit öffnbaren Fenstern (16) ausgestatteten Gebäuderaum, gekennzeichnet dadurch, dass es ein Gehäuse (18) und einen Ventilator (20) aufweist, wobei durch das Gehäuse eine vom Ventilator erzeugte Luftströmung strömen kann, wobei das Gehäuse dafür eine Einströmöffnung (24) für Luft und eine Ausströmöffnung (22) für Luft enthält, wobei eine der beiden Öffnungen der Form eines Öffnungsspalts (26) zwischen einem Fensterflügel (12) und einem Blendrahmen (14) des Fensters (16) angepasst ist.

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