Covid-19 Sentry

Contents

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

From Preprints

• The best-case heuristic: Relative optimism in a global health pandemic -
  In the first wave of COVID-19, we examined how people evaluate personal risk in a global pandemic. Three experiments identified two kinds of relative optimism (N=2,300 Americans). Consistent with a best-case heuristic, participants made “realistic” predictions of infection risk that were closer to their own best-case scenario than to their worst-case scenario. Infection risk was also rated as lower for oneself than the average person, indicating unrealistic optimism. Both effects were successfully replicated in a high-powered replication (nationally- representative). More generally, infection risk predictions were positively correlated with emotional distress, pro- social intentions, and support of public-health lockdown policies. Although a bipartisan majority supported lockdown, right-leaning conservatives made lower risk predictions and were less supportive than left-leaning liberals. Resistance to early lockdown was also associated with the belief in national superiority. Finally, the best-case heuristic generalized to predicted waiting time for a COVID-19 vaccine and future relationship satisfaction, suggesting a broader pattern.
  🖺 Full Text HTML: The best-case heuristic: Relative optimism in a global health pandemic
• Building a Psychological Ground Truth Dataset with Empathy and Theory-of-Mind During the COVID-19 Pandemic -
  As the mental health crisis deepens with the prolonged COVID-19 pandemic, there is an increasing need for understanding individuals’ emotional experiences. We have built a large-scale Korean text corpus with five self-labeled psychological ground-truths: empathy, loneliness, stress, personality, and emotions. We collected 19,025 documents of daily emotional experiences from 3,805 Korean residents from October to December 2020. We collected 42,128 sentences with different levels of theory-of-mind. Each sentence was annotated by trained psychology students and reviewed by experts. Participants varied in their ages from the early 20s to late 80s and had various social and economic statuses. The pandemic impacted the majority of daily lives, and participants often reported negative emotional experiences. We found the most frequent topics: responses to confirmed cases, health concerns of family members, anger towards people without masks, stress-relief strategies, change of the lifestyle, and preventive practices. We then trained the Word2Vec model to observe specific words that match each topic from the topic model. The current dataset will serve as benchmark data for large-scale and computational methods for identifying mental health levels based on text. This dataset is expected to be used and transformed in many creative ways to mitigate COVID-19-related mental health problems.

• Problems and Needs Analysis of English for Tourism Industry: A Case of Hotel Staff in Phang Nga Province, Thailand -
  Tourism is an important industry that has created a lot of income for many nations, including Thailand; therefore, it is essential to increase its potential as a more sustainable and successful industry, in particular to support a sustainable recovery of nations’ economies after a tough situation like Covid-19. The present study was carried out to investigate tourism staff’s problems and needs for using English at work and to explore their needs for improving English for their work. The participants were 200 hotel staff in Phang Nga Province, Thailand. Data were collected through a 5-point Likert scale questionnaire and a semi-structured interview. Quantitative and qualitative methods were employed for data analysis. The findings showed that in general, the hotel staff’s problem in using English at work was at a moderate level (M=2.76, S.D.=1.11). They had English writing problems the most. They found it very difficult to write letters or e-mails in English. Regarding their needs for using English, it was found that every English skill was rated at a high level (M=3.75, S.D.=1.11), and English speaking was the most necessary. The hotel staff reported that they had to speak English to welcome, greet and say good-bye to foreign guests. Pertaining to their needs for improving English, overall, the hotel staff needed to improve their English skills at a high level (M=3.85, S.D.=0.98). They highly needed to improve their English use in every aspect, especially English listening. Based on the interview information, English courses, handbooks or applications relating to English for hotels are truly needed for their English use improvement.
  🖺 Full Text HTML: Problems and Needs Analysis of English for Tourism Industry: A Case of Hotel Staff in Phang Nga Province, Thailand
• Conversion rate to the secondary conformation state in the binding mode of SARS-CoV-2 spike protein to human ACE2 may predict infectivity efficacy of the underlying virus mutant -
  Since its outbreak in 2019 SARS-CoV-2 has spread with high transmission efficiency across the world, putting health care as well as economic systems under pressure. During the course of the pandemic, the originally identified SARS- CoV-2 variant has been widely replaced by various mutant versions, which showed enhanced fitness due to increased infection and transmission rates. In order to find an explanation, why SARS-CoV-2 and its emerging mutated versions showed enhanced transfection efficiency as compared to SARS-CoV 2002, an improved binding affinity of the spike protein to human ACE has been proposed by crystal structure analysis and was identified in cell culture models. Kinetic analysis of the interaction of various spike protein constructs with the human ACE2 was considered to be best described by a Langmuir based 1:1 stoichiometric interaction. However, we demonstrate in this report that the SARS-CoV-2 spike protein interaction with ACE2 is best described by a two-step interaction, which is defined by an initial binding event followed by a slower secondary rate transition that enhances the stability of the complex by a factor of ~190 with an overall KD of 0.20 nM. In addition, we show that the secondary rate transition is not only present in SARS-CoV-2 wt but is also found in B.1.1.7 where its transition rate is five-fold increased.
  🖺 Full Text HTML: Conversion rate to the secondary conformation state in the binding mode of SARS-CoV-2 spike protein to human ACE2 may predict infectivity efficacy of the underlying virus mutant
• Xeno-nucleic Acid (XNA) 2’-Fluoro-Arabino Nucleic Acid (FANA) Aptamers to the Receptor Binding Domain of SARS-CoV-2 S Protein Block ACE2 Binding -
  The causative agent of COVID-19, SARS-CoV-2, gains access to cells through interactions of the receptor binding domain (RBD) on the viral S protein with angiotensin converting enzyme 2 (ACE2) on the surface of human host cells. Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was used to generate aptamers (nucleic acids selected for high binding affinity to a target) to the RBD made from 2’-fluoroarabinonucleic acid (FANA). The best selected ~ 79 nucleotide aptamers bound the RBD (Arg319-Phe541) and the larger S1 domain (Val16-Arg685) of the 1272 amino acid S protein with equilibrium dissociation constants (KD,app) of ~ 10-20 nM and a binding half-life for the RBD of 53 {+/-} 18 minutes. Aptamers inhibited the binding of the RBD to ACE2 in an ELISA assay. Inhibition, on a per weight basis, was similar to neutralizing antibodies that were specific for RBD. Aptamers demonstrated high specificity, binding with about 10-fold lower affinity to the related S1 domain from the original SARS virus, which also binds to ACE2. Overall, FANA aptamers show affinities comparable to previous DNA aptamers to RBD and S protein and directly block receptor interactions while using an alternative Xeno-nucleic acid (XNA) platform.
  🖺 Full Text HTML: Xeno-nucleic Acid (XNA) 2’-Fluoro-Arabino Nucleic Acid (FANA) Aptamers to the Receptor Binding Domain of SARS-CoV-2 S Protein Block ACE2 Binding
• Repurposing screen highlights broad-spectrum coronavirus antivirals and their host targets -
  Libraries composed of licensed drugs represent a vast repertoire of molecules modulating physiologic processes in humans, thus providing unique opportunities for discovery of host targeting antivirals. We interrogated the ReFRAME repurposing library with 12,993 molecules for broad-spectrum coronavirus antivirals and discovered 134 compounds inhibiting an alphacoronavirus, mapping to 59 molecular target categories. Dominant targets included the 5-hydroxytryptamine receptor and dopamine receptor and cyclin-dependent kinase inhibitors. Counter-screening with SARS- CoV-2 and validation in primary cells identified Phortress, an aryl hydrocarbon receptor (AHR) ligand, Bardoxolone and Omaveloxolone, two nuclear factor, erythroid 2 like 2 (NFE2L2) activators as inhibitors of both alpha- and betacoronaviruses. The landscape of coronavirus targeting molecules provides important information for the development of broad-spectrum antivirals reinforcing pandemic preparedness.
  🖺 Full Text HTML: Repurposing screen highlights broad-spectrum coronavirus antivirals and their host targets
• Water-soluble tocopherol derivatives inhibit SARS-CoV-2 RNA-dependent RNA polymerase -
  The recent emergence of a novel coronavirus, SARS-CoV-2, has led to the global pandemic of the severe disease COVID-19 in humans. While efforts to quickly identify effective antiviral therapies have focused largely on repurposing existing drugs, the current standard of care, remdesivir, remains the only authorized antiviral intervention of COVID-19 and provides only modest clinical benefits. Here we show that water-soluble derivatives of -tocopherol have potent antiviral activity and synergize with remdesivir as inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Through an artificial-intelligence-driven in silico screen and in vitro viral inhibition assay, we identified D– tocopherol polyethylene glycol succinate (TPGS) as an effective antiviral against SARS-CoV-2 and {beta}-coronaviruses more broadly that also displays strong synergy with remdesivir. We subsequently determined that TPGS and other water- soluble derivatives of -tocopherol inhibit the transcriptional activity of purified SARS-CoV-2 RdRp and identified affinity binding sites for these compounds within a conserved, hydrophobic interface between SARS-CoV-2 nonstructural protein 7 and nonstructural protein 8 that is functionally implicated in the assembly of the SARS-CoV-2 RdRp. In summary, we conclude that solubilizing modifications to -tocopherol allow it to interact with the SARS-CoV-2 RdRp, making it an effective antiviral molecule alone and even more so in combination with remdesivir. These findings are significant given that many tocopherol derivatives, including TPGS, are considered safe for humans, orally bioavailable, and dramatically enhance the activity of the only approved antiviral for SARS-CoV-2 infection.
  🖺 Full Text HTML: Water-soluble tocopherol derivatives inhibit SARS-CoV-2 RNA-dependent RNA polymerase
• A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in non-human primates -
  Vaccines against SARS-CoV-2 have been distributed at massive scale in developed countries, and have been effective at preventing COVID-19. Access to vaccines is limited, however, in low- and middle-income countries (LMICs) due to insufficient supply, high costs, and cold storage requirements. New vaccines that can be produced in existing manufacturing facilities in LMICs, can be manufactured at low cost, and use widely available, proven, safe adjuvants like alum, would improve global immunity against SARS-CoV-2. One such protein subunit vaccine is produced by the Serum Institute of India Pvt. Ltd. and is currently in clinical testing. Two protein components, the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen virus-like particles (VLPs), are each produced in yeast, which would enable a low-cost, high-volume manufacturing process. Here, we describe the design and preclinical testing of the RBD-VLP vaccine in cynomolgus macaques. We observed titers of neutralizing antibodies (>104) above the range of protection for other licensed vaccines in non-human primates. Interestingly, addition of a second adjuvant (CpG1018) appeared to improve the cellular response while reducing the humoral response. We challenged animals with SARS-CoV-2, and observed a ~3.4 and ~2.9 log10 reduction in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, compared to sham controls. These results inform the design and formulation of current clinical COVID-19 vaccine candidates like the one described here, and future designs of RBD-based vaccines against variants of SARS-CoV-2 or other betacoronaviruses.
  🖺 Full Text HTML: A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in non-human primates
• Tissue Specific Age Dependence of the Cell Receptors Involved in the SARS-CoV-2 Infection -
  The coronavirus disease 2019 (COVID-19) pandemic has affected tens of millions of individuals and caused hundreds of thousands of deaths worldwide. Due to its rapid surge, there is a shortage of information on viral behavior and host response after SARS-CoV-2 infection. Here we present a comprehensive, multiscale network analysis of the transcriptional response to the virus. We particularly focus on key-regulators, cell-receptors, and host-processes that are hijacked by the virus for its advantage. ACE2-controlled processes involve a key-regulator CD300e (a TYROBP receptor) and the activation of IL-2 pro-inflammatory cytokine signaling. We further investigate the age-dependency of such receptors and identify the adipose and the brain as potentially contributing tissues for the disease’s severity in old patients. In contrast, several other tissues in the young population are more susceptible to SARS-CoV-2 infection. In summary, this present study provides novel insights into the gene regulatory organization during the SARS-CoV-2 infection and the tissue-specific age dependence of the cell receptors involved in COVID-19.
  🖺 Full Text HTML: Tissue Specific Age Dependence of the Cell Receptors Involved in the SARS-CoV-2 Infection
• Adaptation, spread and transmission of SARS-CoV-2 in farmed minks and related humans in the Netherlands -
  In the first wave of the COVID-19 pandemic (April 2020), SARS-CoV-2 was detected in farmed minks and genomic sequencing was performed on mink farms and farm personnel. Here, we describe the outbreak and use sequence data with Bayesian phylodynamic methods to explore SARS-CoV-2 transmission in minks and related humans on farms. High number of farm infections (68/126) in minks and farm related personnel (>50% of farms) were detected, with limited spread to the general human population. Three of five initial introductions of SARS-CoV-2 lead to subsequent spread between mink farms until November 2020. The largest cluster acquired a mutation in the receptor binding domain of the Spike protein (position 486), evolved faster and spread more widely and longer. Movement of people and distance between farms were statistically significant predictors of virus dispersal between farms. Our study provides novel insights into SARS-CoV-2 transmission between mink farms and highlights the importance of combing genetic information with epidemiological information at the animal-human interface.
  🖺 Full Text HTML: Adaptation, spread and transmission of SARS-CoV-2 in farmed minks and related humans in the Netherlands
• hnRNPA1 regulates early translation to replication switch in SARS-CoV-2 life cycle -
  Our study suggests that methylation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is essential for its optimal replication in the target cells. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1, an RNA- binding protein) was shown to mediate deposition of N6-methyladenosine (m6A) in internal SARS-CoV-2 RNA. The levels of hNRNPA1 expression and extent of methylation varied, depending on the course of SARS-CoV-2 life cycle. The recruitment of eIF4E (translational initiation factor) facilitated viral RNA translation at 1 hour post infection (1 hpi). However, at 2 hpi, methylation of internal SARS-CoV-2 RNA recruited hNRNPA1 which facilitated viral RNA transcription but resulted in translational repression, a phenomenon contributing in understanding the early translation to replication switch in the viral life cycle. Besides, the abrogation of methylation also produced a defective 5’ cap of viral RNA which failed to interact with eIF4E, thereby resulting in a decreased synthesis of viral proteins. To conclude, methylation of the internal and 5’ cap of SARS-CoV-2 RNA was shown to regulate transcription and translation of SARS- CoV-2 in a time dependent manner.
  🖺 Full Text HTML: hnRNPA1 regulates early translation to replication switch in SARS-CoV-2 life cycle
• STUDY OF BLOOD GROUP ANALYSIS AND ITS CORRELATION WITH LYMPHOPENIA IN COVID 19 INFECTED CASES OUR EXPERIENCE IN TERITARY CARE HOSPITAL. -

  ABSTRACT AIMS AND OBJECTIVES: To study the distribution and frequencies of ABO and Rhesus (Rh) blood groups among confirmed cases of Covid19 infection .We also studied the relation between ABO blood group system and lymphopenia and studied the gender association in COVID19 patients. METHODES A hospital based retrospective study was conducted at Government Medical College Suryapet from1-8-2020 to 30-9-2020. A total of 200 Covid cases were included in the study who came to the hospital with the complaints of Fever, sore throat, body pains, cough, breathlessness, diarrhoea. Patients confirmed Covid infection were tested for blood grouping and RH typing by using forward blood grouping with the help of commercially available standared monoclonal antisera. CBP was processed in sysmax 5 part Haemotology analyzer. Blood group frequency was tested also assed the gender association , covid patients presents with lymphopenia the relation between the ABO blood group and lymphocyte count was determined. RESULTS: Males were more compared to the females .Middle aged group male patients were more commonly involved. Most predominant blood group was group B 79(39.5%), group O 78(39%),group A 37(18.5%), group AB 6(3%),most of them were 190 (95%)Rh positive, only 10 Rh negative (5%).To assess the Lymphopenia in our study we divided the absolute lymphocyte count into 5 groups. Group 1 cases are more 58 (29%), Group 2 91(45.5%), Group 3 30 (15%), Group 4 16(8%), Group 5 5(2.5%). CONCLUSION: Male patients with blood group B were more compared to other blood groups however more number of studies are necessary to confirm these findings in a larger sample and among individuals of different ethnicities. Keywords : ABO , BLOOD GROUPS, Rhesus(Rh) typing.

  🖺 Full Text HTML: STUDY OF BLOOD GROUP ANALYSIS AND ITS CORRELATION WITH LYMPHOPENIA IN COVID 19 INFECTED CASES OUR EXPERIENCE IN TERITARY CARE HOSPITAL.
• SARS-CoV-2 variants of concern exhibit reduced sensitivity to live-virus neutralization in sera from CoronaVac vaccinees and naturally infected COVID-19 patients -

  Recent surges in SARS-CoV-2 variants of concern (VOCs) call for the need to evaluate levels of vaccine- and infection- induced SARS-CoV-2 neutralizing antibodies (NAbs). CoronaVac (Sinovac Biotech, Beijing, China) is currently being used for mass vaccination in Thailand as well as other low-income countries. Three VOCs currently circulating within Thailand include the B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta) strains. We assessed NAb potency against the prototypic strain containing the original spike sequence (WT) compared to that against the 3 VOCs using sera derived from a cohort of healthcare workers who received a full 2-dose regimen of CoronaVac. Sera from two other cohorts consisting of COVID-19 patients who had been hospitalized in 2020 and 2021 were evaluated for comparison. We found that, despite equally robust production of S1-RBD-binding IgG and 100% seropositivity, sera from both CoronaVac vaccinees and naturally infected individuals had significantly reduced neutralizing capacity against all 3 VOCs compared to WT. Strikingly, NAb titers against Alpha and Beta were comparable, but Delta appears to be significantly more refractory to NAbs in all groups. Our results may help inform on CoronaVac NAb-inducing capacity, which is a proxy for vaccine efficacy, in the context of the WT strain and 3 VOCs. Our results also have critical implications for public health decisionmakers who may need to maintain efficient mitigation strategies amid a potentially high risk for infection with VOCs even in those who have been previously infected.

  🖺 Full Text HTML: SARS- CoV-2 variants of concern exhibit reduced sensitivity to live-virus neutralization in sera from CoronaVac vaccinees and naturally infected COVID-19 patients
• Use of 1-MNA to Improve Exercise Tolerance and Fatigue in Patients After COVID-19 -

  Abstract Background: Coronavirus disease 2019 (COVID-19) is a serious respiratory disease that results from infection with a newly discovered coronavirus (SARS-COV-2). Unfortunately, COVID-19 is not only a short-term infection but that patients (pts) recovering from SARS-CoV2 infection complain of persisting symptoms including: fatigue, diffuse myalgia and weakness, which may lead to chronic fatigue syndrome. There is currently no evidence that nutritional supplements and/or physical exercise can assist in the recovery of pts with chronic fatigue syndrome. 1-Methylnicotinamide (1-MNA) is an endogenic substance that is produced in the liver when nicotinic acid is metabolized. 1-MNA demonstrates anti-inflammatory and anti-thrombotic properties. Therefore, we investigated whether 1-MNA supplements could improve exercise tolerance and decrease fatigue among patients recovering from SARS-CoV-2. Methods: The study population was composed of pts after COVID-19, expressing subjective feelings of limited tolerance to exercise. The selected pts were randomized into two groups: GrM0 without supplementation; GrM1 with 1-MNA supplementation. At the beginning of the study (Phase 0), in both groups, a 6-minute walk test (6MWT) was carried out and fa-tigue assessment with Fatigue Severity Scale (FSS) was performed. After 1 month (Phase 1), a follow up FSS and 6MWT once more were performed in both groups. Results: A significant improvement in the mean distance covered in the 6MWT was noted among the pts in GrM1, compared to those in GrM0. We also noted that in GrM1 the 6MWT distance was significantly higher after 1 month of supplementation with 1-MNA, compared to the beginning of the study (515.18 m in Phase 0 vs 557.8m in Phase 1; p = 0.000034). In GrM1, significantly more pts improved their distance in the 6MWT (23 out of 25 pts, equal to 92%), by a mean of 47 meters, compared to GrM0 (15 of 25 pts, equal to 60%) (p = 0.0061). After one month, significantly more patients in the group without 1-MNA had severe fatigue (FSS ≥ 4) compared to the group with supplementation (GrM1 = 5 pts (20%) vs GrM0 = 14pts (56%); p = 0.008). Conclusions: 1-MNA supplementation significantly improved physical performance in a 6-minute walk test and reduced the percentage of patients with severe fatigue after COVID-19. The comprehensive action of 1-MNA, including anti-inflammatory and anticoagulant effects, as well as activation of the SIRT1 enzyme, may be beneficial for the recovery of patients with persistent symptoms of fatigue and low tolerance to exercise after COVID-19. Keywords: COVID-19, MNA, chronic fatigue syndrome, post-COVID syndrome

  🖺 Full Text HTML: Use of 1-MNA to Improve Exercise Tolerance and Fatigue in Patients After COVID-19
• Emergence of immune escape at dominant SARS-CoV-2 killer T-cell epitope -

  The adaptive immune system protects against infection via selection of specific antigen receptors on B-cells and T-cells. We studied the prevalent CD8 killer T-cell response mounted against SARS-CoV-2 Spike_269-277 epitope YLQPRTFLL via the most frequent Human Leukocyte Antigen (HLA) class I worldwide, HLA A02. The widespread Spike P272L mutation has arisen in at least 14 different SARS-CoV-2 lineages to date, including in lineages identified as variants of concern. P272L was common in the B.1.177 lineage associated with establishing the second wave in Europe. The large CD8 T-cell response seen across a cohort of HLA A02+ convalescent patients, comprising of over 120 different TCRs, failed to respond to the P272L. Sizable populations (0.01%-0.2%) of total CD8 T-cells from individuals vaccinated against SARS-CoV-2 stained with HLA A*02-YLQPRTFLL multimers but failed to bind to the P272L reagent. Viral escape at prevalent T-cell epitopes restricted by high frequency HLA may be particularly problematic when vaccine immunity is focussed on a single protein such as SARS-CoV-2 Spike and provides a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlights the urgent need for monitoring T-cell escape in new SARS-CoV-2 variants.

  🖺 Full Text HTML: Emergence of immune escape at dominant SARS-CoV-2 killer T-cell epitope

From Clinical Trials

• COVID-19 Vaccinations With a Sweepstakes - Condition:   Covid19
  Intervention:   Behavioral: Philly Vax Sweepstakes
  Sponsors:  
  University of Pennsylvania;   Philadelphia Department of Public Health
  Active, not recruiting

• A Study of PF-07321332/Ritonavir in Nonhospitalized High Risk Adult Participants With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: PF-07321332;   Drug: Ritonavir;   Drug: Placebo
  Sponsor:   Pfizer
  Not yet recruiting

• Building Resiliency and Vital Equity (BRAVE) Project: Understanding Native Americans’ Perceptions/Beliefs About COVID-19 Testing and Vaccination Study - Condition:   Covid19 Virus Infection
  Intervention:   Behavioral: Protect Your Elders Campaign
  Sponsors:   North Carolina Central University;   Lumbee Tribe of North Carolina;   University of North Carolina at Pembroke
  Recruiting

• A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Adolescents - Condition:   Covid19 Vaccine
  Interventions:   Biological: MVC-COV1901(S protein with adjuvant);   Biological: MVC-COV1901(Saline)
  Sponsor:   Medigen Vaccine Biologics Corp.
  Not yet recruiting

• Study on Sequential Immunization of Inactivated COVID-19 Vaccine and Recombinant COVID-19 Vaccine (Ad5 Vector) - Condition:   COVID-19
  Interventions:   Biological: Recombinant SARS-CoV-2 Ad5 vectored vaccine;   Biological: Inactive SARS-CoV-2 vaccine (Vero cell)
  Sponsors:   Jiangsu Province Centers for Disease Control and Prevention;   CanSino Biologics Inc.
  Not yet recruiting

• Covid-19 Virtual Recovery Study - Condition:   Covid19
  Interventions:   Behavioral: Strength RMT;   Behavioral: Strength RMT and nasal breathing;   Behavioral: Endurance RMT;   Behavioral: Endurance RMT and nasal breathing;   Behavioral: Low dose RMT
  Sponsor:   Mayo Clinic
  Not yet recruiting

• Efficacy of Amantadine Treatment in COVID-19 Patients - Condition:   Patients With Moderate or Severe COVID-19
  Intervention:   Drug: Amantadine
  Sponsors:   Noblewell;   Medical Research Agency (ABM);   Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice
  Recruiting

• Internet-based Multidisciplinary Rehabilitation for Longterm COVID-19 Syndrome - Condition:   Long COVID-19
  Intervention:   Behavioral: Multidisciplinary Rehabilitation
  Sponsors:   Danderyd Hospital;   St Göran Hospital, Stockholm
  Recruiting

• A Different Use of The Aerosol Box in COVID-19 Patients; Internal Jugular Vein Cannulation - Condition:   COVID-19 Pneumonia
  Intervention:   Procedure: Internal jugular vein cannulation
  Sponsor:   Bakirkoy Dr. Sadi Konuk Research and Training Hospital
  Completed

• Reconditioning Exercise for COVID-19 Patients Experiencing Residual sYmptoms - Condition:   Covid19
  Intervention:   Other: Exercise Therapy
  Sponsor:  
  Wake Forest University Health Sciences
  Not yet recruiting

• Lipid Emulsion Infusion and COVID-19 Patients - Condition:   Covid19
  Interventions:   Drug: SMOFlipid;   Other: 0.9% saline
  Sponsor:   Assiut University
  Recruiting

• Short Term, High Dose Vitamin D Supplementation in Moderate to Severe COVID-19 Disease - Condition:   Covid19
  Intervention:   Drug: cholecalciferol 6 lakh IU
  Sponsor:  
  Postgraduate Institute of Medical Education and Research
  Not yet recruiting

• Immunogenicity and Safety of an Inactivated COVID-19 Vaccine - Condition:   COVID-19
  Interventions:   Biological: Inactivated COVID-19 Vaccine;   Biological: 23-valent pneumococcal polysaccharide vaccine;   Biological: Inactivated Hepatitis A Vaccine
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• Coenzyme Q10 as Treatment for Long Term COVID-19 - Conditions:   Covid19;   Long Term Covid19
  Interventions:   Drug: Coenzyme Q10;   Drug: Placebo
  Sponsors:   Aarhus University Hospital;   University of Aarhus;   Pharma Nord
  Recruiting

• Effect of Tumor Treating Fields (TTFields, 150 kHz) Concomitant With Best Standard of Care for the Treatment of Hospitalized COVID-19 Patients and Continued Treatment Following Discharge - Condition:   COVID-19
  Intervention:   Device: NovoTTF-100L
  Sponsor:   NovoCure GmbH
  Completed

From PubMed

• SARS-CoV-2 disrupts proximal elements in the JAK-STAT pathway - SARS-CoV-2 can infect multiple organs, including lung, intestine, kidney, heart, liver, and brain. The molecular details of how the virus navigates through diverse cellular environments and establishes replication are poorly defined. Here, we generated a panel of phenotypically diverse, SARS-CoV-2-infectable human cell lines representing different body organs and performed longitudinal survey of cellular proteins and pathways broadly affected by the virus. This revealed universal inhibition of…

• Clinical evaluation of a multiplex real-time RT-PCR assay for detection of SARS-CoV-2 in individual and pooled upper respiratory tract samples - The aim of this study was to identify and validate a sensitive, high-throughput, and cost-effective SARS-CoV-2 real-time RT-PCR assay to be used as a surveillance and diagnostic tool for SARS-CoV-2 in a university surveillance program. We conducted a side-by-side clinical evaluation of a newly developed SARS-CoV-2 multiplex assay (EZ-SARS-CoV-2 Real-Time RT-PCR) with the commercial TaqPath COVID-19 Combo Kit, which has an Emergency Use Authorization from the FDA. The EZ- SARS-CoV-2 RT-PCR…

• Chemical design principles of next-generation antiviral surface coatings - The ongoing coronavirus disease 2019 (COVID-19) pandemic has accelerated efforts to develop high-performance antiviral surface coatings while highlighting the need to build a strong mechanistic understanding of the chemical design principles that underpin antiviral surface coatings. Herein, we critically summarize the latest efforts to develop antiviral surface coatings that exhibit virus-inactivating functions through disrupting lipid envelopes or protein capsids. Particular attention is…

• Covalent Antiviral Agents - Nowadays, many viral infections have emerged and are taking a huge toll on human lives globally. Meanwhile, viral resistance to current drugs has drastically increased. Hence, there is a pressing need to design potent broad-spectrum antiviral agents to treat a variety of viral infections and overcome viral resistance. Covalent inhibitors have the potential to achieve both goals owing to their biochemical efficiency, prolonged duration of action, and the capability to inhibit shallow,…

• Potent SARS-CoV-2 mRNA Cap Methyltransferase Inhibitors by Bioisosteric Replacement of Methionine in SAM Cosubstrate - Viral mRNA cap methyltransferases (MTases) are emerging targets for the development of broad-spectrum antiviral agents. In this work, we designed potential SARS-CoV-2 MTase Nsp14 and Nsp16 inhibitors by using bioisosteric substitution of the sulfonium and amino acid substructures of the cosubstrate S-adenosylmethionine (SAM), which serves as the methyl donor in the enzymatic reaction. The synthetically accessible target structures were prioritized using molecular docking. Testing of the…

• A high-throughput cell- and virus-free assay shows reduced neutralization of SARS-CoV-2 variants by COVID-19 convalescent plasma - The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies in the serum of an individual indicates prior infection or vaccination. However, it provides limited insight into the protective nature of this immune response. Neutralizing antibodies recognizing the viral spike protein are more revealing, yet their measurement traditionally requires virus- and cell-based systems that are costly, time-consuming, inflexible, and potentially biohazardous. Here, we…

• Drug repurposing against SARS-CoV-2 receptor binding domain using ensemble-based virtual screening and molecular dynamics simulations - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused worldwide pandemic and is responsible for millions of worldwide deaths due to -a respiratory disease known as COVID-19. In the search for a cure of COVID-19, drug repurposing is a fast and cost-effective approach to identify anti-COVID-19 drugs from existing drugs. The receptor binding domain (RBD) of the SARS-CoV-2 spike protein has been a main target for drug designs to block spike protein binding to ACE2 proteins. In this…

• Reconfiguration and dedifferentiation of functional networks during cognitive control across the adult lifespan - Healthy aging is accompanied by reduced cognitive control and widespread alterations in the underlying brain networks; but the extent to which large-scale functional networks in older age show reduced specificity across different domains of cognitive control is unclear. Here we use cov-STATIS (a multi-table multivariate technique) to examine similarity of functional connectivity during different domains of cognitive control-inhibition, initiation, shifting, and working memory-across the adult…

• A possible interaction between favipiravir and methotrexate: Drug-induced hepatotoxicity in a patient with osteosarcoma - INTRODUCTION: Favipiravir is an antiviral agent that is recently used for SARS-CoV2 infection. The drug-drug interactions of favipiravir especially with chemotherapeutic agents in a patient with malignancy are not well known.

• Autoimmune- and complement-mediated hematologic condition recrudescence following SARS-CoV-2 vaccination - A variety of autoimmune disorders have been reported after viral illnesses and specific vaccinations. Cases of de novo immune thrombocytopenia (ITP) have been reported after SARS-CoV-2 vaccination, although its effect on preexisting ITP has not been well characterized. In addition, although COVID-19 has been associated with complement dysregulation, the effect of SARS-CoV-2 vaccination on preexisting complementopathies is poorly understood. We sought to better understand SARS-CoV-2…

• SSRIs: Applications in inflammatory lung disease and implications for COVID-19 - Selective serotonin reuptake inhibitors (SSRIs) have anti-inflammatory properties that may have clinical utility in treating severe pulmonary manifestations of COVID-19. SSRIs exert anti-inflammatory effects at three mechanistic levels:

1. inhibition of proinflammatory transcription factor activity, including NF-κB and STAT3; (b) downregulation of lung tissue damage and proinflammatory cell recruitment via inhibition of cytokines, including IL-6, IL-8, TNF-α, and IL-1β; and (c) direct…

• Cationic Compounds with SARS-CoV-2 Antiviral Activity and their Interaction with OCT/MATE Secretory Transporters - In the wake of the COVID-19 pandemic, drug repurposing has been highlighted for rapid introduction of therapeutics. Proposed drugs with activity against SARS-CoV-2 include compounds with positive charges at physiological pH, making them potential targets for the organic cation (OC) secretory transporters of kidney and liver, i.e., the basolateral Organic Cation Transporters, OCT1 and OCT2; and the apical Multidrug And Toxin Extruders, MATE1 and MATE2-K. We selected several compounds proposed to…

• COVID-19 diagnosis and testing in pediatric heart transplant recipients - Pediatric heart transplant recipients have been expected to be at higher risk of adverse events from developing COVID-19 infection. COVID-19 RNA PCR and antibody testing has been performed in our cohort of patients since March 15, 2020 and outcomes were reviewed. COVID-19 infection in our population of pediatric heart transplant recipients is common (21%), despite recommendations to avoid contact with others. Asymptomatic COVID-19 infection is common as well (55%). Despite the frequency of…

• Determination of camostat and its metabolites in human plasma - preservation of samples and quantification by a validated UHPLC-MS/MS method - CONCLUSIONS: A methodology was developed that preserves camostat and GBPA in plasma samples and provides accurate and sensitive quantification of camostat, GBPA and GBA by UHPLC-MS/MS.

• Accurate Bulk Quantitation of Droplet Digital Polymerase Chain Reaction - Droplet digital PCR provides superior accuracy for nucleic acid quantitation. The requirement of microfluidics to generate and analyze the emulsions, however, is a barrier to its adoption, particularly in low resource settings or clinical laboratories. Here, we report a novel method to prepare ddPCR droplets by vortexing and readout of the results by bulk analysis of recovered amplicons. We demonstrate the approach by accurately quantitating SARS-CoV-2 sequences using entirely bulk processing…

From Patent Search

• Advanced Machine Learning System combating COVID-19 virus Detection, Spread, Prevention and Medical Assistance. - - link

• Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients - - link

• SARS-CoV-2 anti-viral therapeutic - - link

• 一种基于联邦学习的多用户协同训练人流统计方法及系统 - 本发明提供一种基于联邦学习的多用户协同训练人流统计方法，旨在利用联邦学习框架搭建一个新颖的人群计数模型，达到让多用户多设备同时训练的目的。各个客户端利用图像数据集对图像分类网络进行本地训练以获取本地模型；在各经过至少一次本地训练后，中心服务器从客户端获取本地模型的权值及附加层参数并进行聚合处理；中心服务器利用聚合处理后的权值及附加层参数更新全局模型，并将聚合处理后的权值参数及附加层参数返回给各个客户端；各个客户端利用中心服务器返回的权值以及ground truth值进行贝叶斯估计，计算loss值，并利用返回的权值参数及附加层参数更新本地模型；重复执行直至所有客户端的loss值均收敛，则完成人流统计全局模型和本地模型的训练。 - link

• A POLYHERBAL ALCOHOL FREE FORMULATION FOR ORAL CAVITY - The present invention generally relates to a herbal composition. Specifically, the present invention relates to a polyherbal alcohol free composition comprising of Glycyrrhiza glabra root extract, Ocimum sanctum leaf extract, Elettaria cardamomum fruit extract, Mentha spicata (Spearmint) oil and Tween 80 and method of preparation thereof. The polyherbal alcohol free composition of the present invention possesses excellent antimicrobial properties and useful for oral cavity. - link

• 新型冠状病毒B.1.351南非突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B.1.351南非突变株RBD的基因及其应用。本发明的新型冠状病毒B.1.351南非突变株RBD的基因，其核苷酸序列如SEQIDNO.1或SEQIDNO.6所示。本发明通过优化野生型新型冠状病毒南非B.1.351南非突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B.1.351南非突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B.1.351南非突变株RBD的基因可以用于制备新型冠状病毒疫苗。 - link

• 检测新型冠状病毒中和抗体的试剂盒及其应用 - 本发明涉及生物技术领域，具体而言，提供了一种检测新型冠状病毒中和抗体的试剂盒及其应用。本发明提供的检测新型冠状病毒中和抗体试剂盒，具体包括（a）或（b）两种方案：（a）示踪物标记的RBD三聚体抗原，包被在固体支持物上的ACE2，以及，含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液；（b）示踪物标记的ACE2，包被在固体支持物上的RBD三聚体抗原，以及，含有0.2‑10mg/mL十二烷基二甲基甜菜碱的工作液；其中，RBD三聚体抗原利用二硫键将刺突蛋白的RBD与S2亚基完全交联得到。十二烷基二甲基甜菜碱会显著提高RBD三聚体抗原与新冠中和性抗体结合速度，提升阳性样本平均发光强度，缩短检测时间。 - link

• 一种检测SARS-CoV-2的引物组合物及其应用 - 本发明涉及一种检测SARS‑CoV‑2的引物组合物及其应用。所述引物组合物包括SEQ ID NO:1~SEQ ID NO:12所示的核酸序列。本发明利用所述引物组合物进行逆转录巢式PCR，并结合Sanger测序，能够快速、准确地获取SARS‑CoV‑2基因信息，从而能够实现快速检测SARS‑CoV‑2以及判断SARS‑CoV‑2突变株，且具备良好的准确性、灵敏度、特异性以及重复性。 - link

• 基于多重荧光定量PCR技术的新冠病毒突变序列检测技术及其应用 - 本发明提供一种基于多重荧光定量PCR技术的新冠病毒突变类型检测技术及其应用。本发明主要基于荧光定量PCR技术针对目前S基因重要突变类型，如序列位置23403，序列变化A>G、序列位置23063，序列变化A>T、序列位置22812‑22813，序列变化AG>GA、序列位置23012，序列变化G>A进行单管或多管多重检测。其试剂盒可以很好的鉴别目前流行的D614G、N501Y、K417N、E484K重要突变株且特异性好，对新冠病毒的突变监测具有十分积极的意义。 - link

• 基于荧光定量PCR技术的新冠病毒新型核酸突变检测技术及其应用 - 本发明提供一种基于荧光定量PCR技术的新冠病毒新型核酸突变检测技术及其应用。本发明主要基于荧光定量PCR技术针对目前S基因新突变‑双重变异（E484Q和L452R突变）进行检测。本发明提供的试剂盒可以很好的鉴别E484Q和L452R突变，对新冠病毒的新突变快速监测具有十分积极的意义。 - link