Covid-19 Sentry

Contents

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

From Preprints

• Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda -

  Background: The newly described SARS-CoV-2 lineage C.37 was recently classified as a variant of interest by the WHO (Lambda variant) based on its high circulation rates in South American countries and the presence of critical mutations in the spike protein. The impact of such mutations in infectivity and immune escape from neutralizing antibodies are entirely unknown. Methods: We performed a pseudotyped virus neutralization assay and determined the impact of the Lambda variant on infectivity and immune escape using plasma samples from healthcare workers (HCW) from two centers in Santiago, Chile who received the two-doses scheme of the inactivated virus vaccine CoronaVac. Results: We observed an increased infectivity mediated by the Lambda spike protein that was even higher than that of the D614G (lineage B) or the Alpha and Gamma variants. Compared to the Wild type (lineage A), neutralization was decreased by 3.05-fold for the Lambda variant while it was 2.33-fold for the Gamma variant and 2.03-fold for the Alpha variant. Conclusions: Our results indicate that mutations present in the spike protein of the Lambda variant of interest confer increased infectivity and immune escape from neutralizing antibodies elicited by CoronaVac. These data reinforce the idea that massive vaccination campaigns in countries with high SARS-CoV-2 circulation must be accompanied by strict genomic surveillance allowing the identification of new isolates carrying spike mutations and immunology studies aimed to determine the impact of these mutations in immune escape and vaccines breakthrough.

  🖺 Full Text HTML: Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda
• Post COVID-19 sequelae: A prospective observational study from Northern India -

  Background: Long COVID, or post-COVID-19 sequelae, is being seen in a growing number of patients reporting a constellation of symptoms, both pulmonary and extrapulmonary. Studies on COVID-19 recovered patients are scarce. Thus, there is a need to add granularity to our existing knowledge about the course and long-term effects of the infection. Aim: To describe the clinical details and risk factors of post-COVID sequelae in the North Indian population. Method: This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 to February 2021. Patients aged >18 years with a confirmed COVID-19 disease were recruited after at least two weeks of diagnosis and interviewed for any post-COVID-19 symptoms. Results: Of 1234 patients recruited, who were followed up for a median duration of 91 days (IQR: 45-181 days), 495 (40.11%) patients had symptoms. In 223 (18.1%) patients, the symptoms resolved within four weeks, 150 (12.1%) patients had symptoms till twelve weeks, and 122 (9.9%) patients had symptoms beyond twelve weeks of diagnosis of COVID-19. Most common long COVID-19 symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), disturbed sleep (1.4%), mood disturbances (0.48%) and anxiety (0.6%). The major determinants of developing post-COVID-19 symptoms in the patients were hypothyroidism and the severity of the disease. Conclusion: Most often, patients complain of myalgias, fatigue, dyspnoea, cough and disturbed sleep. Patients who are hypothyroid or have recovered from moderate to severe COVID-19 are at higher risk of developing post-COVID sequelae. Therefore, a multidisciplinary approach is required to diagnose and manage COVID-19 recovered patients.

  🖺 Full Text HTML: Post COVID-19 sequelae: A prospective observational study from Northern India
• Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients -

  Infection with SARS-CoV-2 portends a broad range of outcomes, from a majority of asymptomatic cases or mild clinical courses to a lethal disease. Robust correlates of severe COVID-19 include old age, male sex, poverty and co-morbidities such as obesity, diabetes or cardiovascular disease. A precise knowledge is still lacking of the molecular and biological mechanisms that may explain the association of severe disease with male sex. Here, we show that testosterone trajectories are highly accurate individual predictors (AUC of ROC = 0.928, p < 0.0001) of survival in male COVID-19 patients. Longitudinal determinations of blood levels of luteinizing hormone (LH) and androstenedione suggest an early modest inhibition of the central LH-androgen biosynthesis axis in a majority of patients, followed by either full recovery in survivors or a peripheral failure in lethal cases. Moreover, failure to reinstate physiological testosterone levels was associated with evidence of impaired T helper differentiation and decrease of non-classical monocytes. The strong association of recovery or failure to reinstate testosterone levels with survival or death from COVID-19 in male patients is suggestive of a significant role of testosterone status in the immune responses to COVID-19.

  🖺 Full Text HTML: Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients
• COVID-19 Has Long Term Effects on Chemosensory Functions -

  Importance: A number of studies have revealed either self-reported chemosensory alterations in large groups or objective quantified chemosensory impairments in smaller populations of patients diagnosed with COVID-19. However, due to the great variability in published results regarding COVID-19-induced chemosensory impairments and their follow-up, prognosis for chemosensory functions in patients with such complaints remains unclear. Objective: To describe the various chemosensory alterations associated with COVID-19 and their prevalence and evolution at 3 to 7 months after infection. Design, Setting, and Participants: A follow-up study of 704 health care workers with a RT-PCR confirmed SARS-CoV-2 infection between 28/2/2020 and 14/6/2020 was conducted 3 to 7 months after onset of symptoms. Data were collected with an online questionnaire. Participant had to be ≥18 years old without respiratory illness in the 2 weeks prior to questionnaire completion. Main outcomes and measures: Outcomes included differences in reported chemosensory self-assessment of olfactory, gustatory, and trigeminal functions across time points and Chemosensory Perception Test scores from an easy-to-use at-home self-administered chemosensory test. Results: Among the 704 health care worker participants, 593 (84.2%) were women, the mean (SD) age was 42 (12) years and the questionnaire was answered on average 4.8 (0.8) months after COVID-19. During COVID-19, a decrease in olfactory, gustatory, and trigeminal sensitivities were reported by 81.3%, 81.5% and 48.0% respectively. Three to seven months later, reduced sensitivity was still reported by 52.0%, 41.9% and 23.3% respectively. Chemosensory Perception Test scores indicate that 19.5% of participants had objective olfactory impairment. Conclusions and relevance: A significant proportion of COVID-19 cases have persistent chemosensory impairments at 3 to 7 months after their infection but the majority of those who had completely lost their olfactory, gustatory and trigeminal sensitivity have improved. Given the possible neurological underpinnings of this observation and the important number of individuals infected with SARS-CoV-2, further longitudinal studies are needed to better characterize this phenotype and to report eventual post-COVID-19 neurological sequelae.

  🖺 Full Text HTML: COVID-19 Has Long Term Effects on Chemosensory Functions
• Dimeric IgA is a specific biomarker of recent SARS-CoV-2 infection -

  Current tests for SARS-CoV-2 antibodies (IgG, IgM, IgA) cannot differentiate recent and past infections. We describe a point of care, lateral flow assay for SARS-CoV-2 dIgA based on the highly selective binding of dIgA to a chimeric form of secretory component (CSC), that distinguishes dIgA from monomeric IgA. Detection of specific dIgA uses a complex of biotinylated SARS-CoV-2 receptor binding domain and streptavidin-colloidal gold. SARS-CoV-2-specific dIgA was measured both in 112 cross-sectional samples and a longitudinal panel of 362 plasma samples from 45 patients with PCR-confirmed SARS-CoV-2 infection, and 193 discrete pre-COVID-19 or PCR-negative patient samples. The assay demonstrated 100% sensitivity from 11 days post-symptom onset, and a specificity of 98.2%. With an estimated half-life of 6.3 days, dIgA provides a unique biomarker for the detection of recent SARS-CoV-2 infections with potential to enhance diagnosis and management of COVID-19 at point-of-care.

  🖺 Full Text HTML: Dimeric IgA is a specific biomarker of recent SARS-CoV-2 infection
• Host cellular RNA helicases regulate SARS-CoV-2 infection -
  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has largest RNA genome of approximately 30kb among RNA viruses. The DDX DEAD-box RNA helicase is a multifunctional protein involved in all aspects of RNA metabolism. Therefore, host RNA helicases may regulate and maintain such large viral RNA genome. In this study, I investigated the potential role of several host cellular RNA helicases in SARS-CoV-2 infection. Notably, DDX21 knockdown markedly accumulated intracellular viral RNA and viral production, as well as viral infectivity of SARS-CoV-2, indicating that DDX21 strongly restricts the SARS-CoV-2 infection. As well, MOV10 RNA helicase also suppressed the SARS-CoV-2 infection. In contrast, DDX1, DDX5, and DDX6 RNA helicases were required for SARS-CoV-2 replication. Indeed, SARS-CoV-2 infection dispersed the P-body formation of DDX6 and MOV10 RNA helicases as well as XRN1 exonuclease, while the viral infection did not induce stress granule formation. Accordingly, the SARS-CoV-2 nucleocapsid (N) protein interacted with DDX6, DDX21, and MOV10 and disrupted the P-body formation, suggesting that SARS-CoV-2 N hijacks DDX6 to utilize own viral replication and overcomes their anti-viral effect of DDX21 and MOV10 through as interaction with host cellular RNA helicase. Altogether, host cellular RNA helicases seem to regulate the SARS-CoV-2 infection.
  🖺 Full Text HTML: Host cellular RNA helicases regulate SARS-CoV-2 infection
• Varenicline Prevents SARS-CoV-2 Infection In Vitro and in Rhesus Macaques -
  Background SARS-CoV-2 infections have resulted in a global pandemic, but an antiviral therapy for this novel strain of coronavirus does not currently exist. The objective of our study was to investigate the antiviral potential of the nicotinic acetylcholine receptor (nACHR) agonist varenicline tartrate against SARS-CoV-2. Methods We assessed antiviral activity using in vitro human cell assays and we assessed in vivo efficacy in a rhesus macaque model. Results In vitro studies found that varenicline tartrate, over a range of concentrations, reduced the infectivity of SARS-CoV-2 wildtype, alpha, and beta variants in Calu-3 cells and Caco-2 cells, with maintenance of cell viability. In vivo studies found that varenicline tartrate, administered as a nasal spray to rhesus macaques, reduced SARS-CoV-2 wildtype viral load and inhibited viral replication in the nasal mucosa and upper airway. Conclusion Although the study reported here was exploratory, we have confirmed that the nAChR agonist varenicline has the potential to interact with and inhibit SARS-CoV-2 infection and replication.
  🖺 Full Text HTML: Varenicline Prevents SARS-CoV-2 Infection In Vitro and in Rhesus Macaques
• The SARS-CoV-2 host cell membrane fusion protein TMPRSS2 is a tumor suppressor and its downregulation correlates with increased antitumor immunity and immunotherapy response in lung adenocarcinoma -
  Background TMPRSS2 is a host cell membrane fusion protein for SARS-CoV-2 invading human host cells. It also has an association with cancer, particularly prostate cancer. However, its association with lung cancer remains insufficiently explored. Thus, an in-depth investigation into the association between TMPRSS2 and lung cancer is significant, considering that lung cancer is the leading cause of cancer death and that the lungs are the primary organ SARS-CoV-2 attacks. Methods Using five lung adenocarcinoma (LUAD) genomics datasets, we explored associations between TMPRSS2 expression and immune signatures, cancer-associated pathways, tumor progression phenotypes, and clinical prognosis in LUAD by the bioinformatics approach. Furthermore, we validated the findings from the bioinformatics analysis by performing in vitro experiments with the human LUAD cell line A549 and in vivo experiments with mouse tumor models. We also validated our findings in LUAD patients from Jiangsu Cancer Hospital, China. Results TMPRSS2 expression levels were negatively correlated with the enrichment levels of CD8+ T and NK cells and immune cytolytic activity in LUAD, which represent antitumor immune signatures. Meanwhile, TMPRSS2 expression levels were negatively correlated with the enrichment levels of CD4+ regulatory T cells and myeloid-derived suppressor cells and PD-L1 expression levels in LUAD, which represent antitumor immunosuppressive signatures. However, TMPRSS2 expression levels showed a significant positive correlation with the ratios of immune-stimulatory/immune-inhibitory signatures (CD8+ T cells/PD-L1) in LUAD. It indicated that TMPRSS2 levels had a stronger negative correlation with immune-inhibitory signatures than with immune-stimulatory signatures. TMPRSS2 downregulation correlated with elevated activities of many oncogenic pathways in LUAD, including cell cycle, mismatch repair, p53, and extracellular matrix (ECM) signaling. TMPRSS2 downregulation correlated with increased proliferation, stemness, genomic instability, tumor advancement, and worse survival in LUAD. In vitro and in vivo experiments validated the association of TMPRSS2 deficiency with increased tumor cell proliferation and invasion and antitumor immunity in LUAD. Moreover, in vivo experiments demonstrated that TMPRSS2-knockdown tumors were more sensitive to BMS-1, an inhibitor of PD-1/PD-L1. Conclusions TMPRSS2 is a tumor suppressor, while its downregulation is a positive biomarker of immunotherapy in LUAD. Our data provide a connection between lung cancer and pneumonia caused by SARS-CoV-2 infection.
  🖺 Full Text HTML: The SARS-CoV-2 host cell membrane fusion protein TMPRSS2 is a tumor suppressor and its downregulation correlates with increased antitumor immunity and immunotherapy response in lung adenocarcinoma
• Large scale screening discovers clofoctol as an inhibitor of SARS-CoV-2 replication that reduces COVID-19-like pathology -
  The fastest way to implement a treatment against a new rapidly emerging viral disease consists in screening the potential antiviral activity of drugs approved for human use. This has the advantage of shortening regulatory preclinical development steps. Here, we screened a library of drug compounds, already registered in one or several geographical areas, to identify those exhibiting antiviral activity against SARS-CoV-2 with relevant potency. Of the 1,942 compounds tested, 21 exhibited a substantial antiviral activity in Vero-81 cells. Among them, clofoctol, an antibacterial drug used for the treatment of bacterial respiratory tract infections, was further investigated due to its favorable safety profile and its pharmacokinetic properties. Notably, the peak concentration of clofoctol that can be achieved in human lungs is more than 20 times higher than its IC95 measured against SARS-CoV-2 in human pulmonary cells. Mechanistically, this compound inhibits SARS-CoV-2 at a post-entry step by specifically blocking translation initiation of viral RNA. Lastly, therapeutic treatment of human ACE2 receptor transgenic mice decreased viral load, reduced inflammatory gene expression and improved pulmonary pathology. Altogether, these data strongly support clofoctol as a therapeutic candidate for the treatment of COVID-19 patients.
  🖺 Full Text HTML: Large scale screening discovers clofoctol as an inhibitor of SARS-CoV-2 replication that reduces COVID-19-like pathology
• Flying in the Face of Adversity: A Drosophila-based Virtual CURE Provides Semester-long Authentic Research Opportunity to the Flipped Classroom. -
  A call for the integration of research experiences into all biology curricula has been a major goal for educational reform efforts nationally. Course-Based Undergraduate Research Experiences (CUREs) have been the predominant method of accomplishing this, but their associated costs and complex design can limit their wide adoption. In 2020, the COVID-19 pandemic forced programs to identify unique ways to still provide authentic research experiences while students were virtual. We report here a full guide for the successful implementation of a semester-long virtual CURE that uses Drosophila behavioral assays to explore the connection between pain and addiction with the use of a “lab-in-a-box” sent home to students. Individual components were piloted across three semesters and launched as a 100-level introductory course with 19 students. We found that this course increased science identity and successfully improved key research competencies as per the Undergraduate Research Student Self-Assessment (URSSA) survey. This course is ideal for flipped classrooms ranging from introductory biology to upper-level neuroscience courses and can be integrated directly into the lecture period without the need for building a new course. Given the low cost, recent comfort with virtual learning environments, and the current proliferation of flipped biology classrooms following the 2020 pandemic, this curriculum could serve as an ideal project-based active-learning tool for equitably increasing access to authentic research experiences.
  🖺 Full Text HTML: Flying in the Face of Adversity: A Drosophila-based Virtual CURE Provides Semester-long Authentic Research Opportunity to the Flipped Classroom.
• Pathology and immunity after SARS-CoV-2 infection in male ferrets is affected by age and inoculation route -
  Improving COVID-19 intervention strategies partly relies on animal models to study SARS-CoV-2 disease and immunity. In our pursuit to establish a model for severe COVID-19, we inoculated young and adult male ferrets intranasally or intratracheally with SARS-CoV-2. Intranasal inoculation established an infection in all ferrets, with viral dissemination into the brain and gut. Upon intratracheal inoculation only adult ferrets became infected. However, neither inoculation route induced observable COVID-19 symptoms. Despite this, a persistent inflammation in the nose was prominent in especially young ferrets and follicular hyperplasia in the bronchi developed 21 days post infection. These effects -if sustained- might resemble long-COVID. Respiratory and systemic cellular responses and antibody responses were induced only in animals with an established infection. We conclude that intranasally-infected ferrets resemble asymptomatic COVID-19 and possibly aspects of long-COVID. Combined with the increasing portfolio to measure adaptive immunity, ferrets are a relevant model for SARS-CoV-2 vaccine research.
  🖺 Full Text HTML: Pathology and immunity after SARS-CoV-2 infection in male ferrets is affected by age and inoculation route
• Classifying COVID-19 variants based on genetic sequences using deep learning models -
  The COrona VIrus Disease (COVID-19) pandemic led to the occurrence of several variants with time. This has led to an increased importance of understanding sequence data related to COVID-19. In this chapter, we propose an alignment-free k-mer based LSTM (Long Short-Term Memory) deep learning model that can classify 20 different variants of COVID-19. We handle the class imbalance problem by sampling a fixed number of sequences for each class label. We handle the vanishing gradient problem in LSTMs arising from long sequences by dividing the sequence into fixed lengths and obtaining results on individual runs. Our results show that one- vs-all classifiers have test accuracies as high as 92.5% with tuned hyperparameters compared to the multi-class classifier model. Our experiments show higher overall accuracies for B.1.1.214, B.1.177.21, B.1.1.7, B.1.526, and P.1 on the one-vs-all classifiers, suggesting the presence of distinct mutations in these variants. Our results show that embedding vector size and batch sizes have insignificant improvement in accuracies, but changing from 2-mers to 3-mers mostly improves accuracies. We also studied individual runs which show that most accuracies improved after the 20th run, indicating that these sequence positions may have more contributions to distinguishing among different COVID-19 variants.
  🖺 Full Text HTML: Classifying COVID-19 variants based on genetic sequences using deep learning models
• Epitope order Matters in multi-epitope-based peptide (MEBP) vaccine design: An in silico study -
  With different countries facing multiple waves, with some SARS-CoV-2 variants more deadly and virulent, the COVID-19 pandemic is becoming more dangerous by the day and the world is facing an even more dreadful extended pandemic with exponential positive cases and increasing death rates. There is an urgent need for more efficient and faster methods of vaccine development against SARS-CoV-2. Compared to experimental protocols, the opportunities to innovate are very high in immunoinformatics/in silico approaches especially with the recent adoption of structural bioinformatics in peptide vaccine design. In recent times, multi-epitope-based peptide vaccine candidates (MEBPVCs) have shown extraordinarily high humoral and cellular responses to immunization. Most of the publications claim that respective reported MEBPVC(s) assembled using a set of in silico predicted epitopes, to be the computationally validated potent vaccine candidate(s) ready for experimental validation. However, in this article, for a given set of predicted epitopes, it is shown that the published MEBPVC is one among the many possible variants and there is high likelihood of finding more potent MEBPVCs than the published candidate. To test the same, a methodology is developed where novel MEBP variants are derived by changing the epitope order of the published MEBPVC. Further, to overcome the limitations of current qualitative methods of assessment of MEBPVC, to enable quantitative comparison, ranking, and the discovery of more potent MEBPVCs, novel predictors, Percent Epitope Accessibility (PEA), Receptor specific MEBP vaccine potency(RMVP), MEBP vaccine potency(MVP) are introduced. The MEBP variants indeed showed varied MVP scores indicating varied immunogenicity. When the MEBP variants were ranked in descending order of their MVP scores, the published MEBPVC had the least MVP score. Further, the MEBP variants with IDs, SPVC_387 and SPVC_206, had the highest MVP scores indicating these variants to be more potent MEBPVCs than the published MEBPVC and hence should be prioritized for experimental testing and validation. Through this method, more vaccine candidates will be available for experimental validation and testing. This study also opens the opportunity to develop new software tools for designing more potent MEBPVCs in less time. The computationally validated top-ranked MEBPVCs must be experimentally tested, validated, and verified. The differences and deviations between experimental results and computational predictions provide an opportunity for improving and developing more efficient algorithms and reliable scoring schemes and software.
  🖺 Full Text HTML: Epitope order Matters in multi-epitope-based peptide (MEBP) vaccine design: An in silico study
• Filthy Animals: Integrating the Behavioral Immune System and Disgust into A Model of Prophylactic Dehumanization -
  The behavioral immune system (BIS) is an evolved psychological mechanism that motivates prophylactic avoidance of disease vectors by eliciting disgust. When felt toward social groups, disgust can dampen empathy and promote dehumanization. Therefore, we investigated whether the BIS facilitates the dehumanization of groups associated with disease by inspiring disgust toward them. An initial content analysis found that Nazi propaganda predominantly dehumanized Jews by portraying them as disease vectors or contaminants. This inspired three correlational studies supporting a Prophylactic Dehumanization Model in which the BIS predicted disgust toward disease-relevant outgroups, and this disgust in turn accounted for the dehumanization of these groups. In a final study, we found this process of prophylactic dehumanization had a downstream effect on increasing anti-immigrant attitudes during the COVID-19 pandemic. However, consistent with the evolutionary logic of a functionally-flexible BIS, this effect only occurred when the threat of COVID-19 was salient. The implications of these results for the study of dehumanization and evolutionary theories of xenophobia are discussed.
  🖺 Full Text HTML: Filthy Animals: Integrating the Behavioral Immune System and Disgust into A Model of Prophylactic Dehumanization
• Highly-Neutralizing COVID-19-Convalescent-Plasmas Potently Block SARS-CoV-2 Replication and Pneumonia in Syrian Hamsters. -
  Despite various attempts to treat SARS-CoV-2-infected patients with COVID-19-convalescent plasmas, neither appropriate approach nor clinical utility has been established. We examined the efficacy of administration of highly-neutralizing COVID-19-convalescent plasma (hn-plasmas) and such plasma-derived IgG administration using the Syrian hamster COVID-19 model. Two hn-plasmas, which were in the best 1% of 340 neutralizing-activity-determined convalescent plasma samples, were intraperitoneally administered to SARS-CoV-2-infected hamsters, resulting in significant reduction of viral titers in lungs by up to 32-fold as compared to the viral titers in hamsters receiving control non-neutralizing plasma, while with two moderately neutralizing plasmas (mn-plasmas) administered, viral titer reduction was by up to 6-fold. IgG fractions purified from the two hn-plasmas also reduced viral titers in lungs than those from the two mn-plasmas. The severity of lung lesions seen in hamsters receiving hn-plasmas was minimal to moderate as assessed using micro-computerized tomography, which histological examination confirmed. Western blotting revealed that all four COVID-19-convalescent-plasmas variably contained antibodies against SARS-CoV-2 components including the receptor-binding domain and S1 domain. The present data strongly suggest that administering potent-neutralizing-activity-confirmed COVID-19-convalescent plasmas would be efficacious in treating patients with COVID-19.
  🖺 Full Text HTML: Highly-Neutralizing COVID-19-Convalescent-Plasmas Potently Block SARS-CoV-2 Replication and Pneumonia in Syrian Hamsters.

From Clinical Trials

• Cognitive and Psychological Disorders After Severe COVID-19 Infection - Condition:   COVID 19
  Interventions:   Diagnostic Test: Cognitive assessment;   Diagnostic Test: Imaging;   Diagnostic Test: Routine care;   Other: Psychiatric evaluation
  Sponsors:   Central Hospital, Nancy, France;   Centre Hospitalier Universitaire de Besancon;   University Hospital, Strasbourg, France;   Centre Hospitalier Régional Metz-Thionville;   Centre hospitalier Epinal;   Hopitaux Civils de Colmar
  Not yet recruiting

• Phase 1 Study to Assess Safety, Tolerability, PD, PK, Immunogenicity of IV NTR-441 Solution in Healthy Volunteers and COVID-19 Patients - Condition:   Covid19
  Interventions:   Drug: NTR-441;   Drug: Placebo
  Sponsor:   Neutrolis
  Recruiting

• MP1032 Treatment in Patients With Moderate to Severe COVID-19 - Condition:   COVID-19
  Interventions:   Drug: MP1032;   Drug: Placebo
  Sponsors:   MetrioPharm AG;   Syneos Health, LLC
  Not yet recruiting

• Study of Codivir in Patients With COVID-19 - Condition:   Covid19
  Interventions:   Drug: Covidir injections;   Diagnostic Test: One Step Test;   Diagnostic Test: IgM and IgG dosage;   Diagnostic Test: RT-PCR SARS-CoV-2;   Diagnostic Test: Screening blood test;   Diagnostic Test: ECG;   Diagnostic Test: Medical evaluation;   Diagnostic Test: NEWS-2 score;   Diagnostic Test: WHO score
  Sponsor:   Code Pharma
  Active, not recruiting

• Study to Evaluate the Safety and Concentrations of Monoclonal Antibody Against Virus That Causes COVID-19 Disease. - Condition:   COVID-19 Virus Disease
  Interventions:   Biological: MAD0004J08;   Other: Placebo
  Sponsors:   Toscana Life Sciences Sviluppo s.r.l.;   Cross Research S.A.
  Active, not recruiting

• Safety and Immunogenicity of LNP-nCOV saRNA-02 Vaccine Against SARS-CoV-2, the Causative Agent of COVID-19 - Condition:   COVID-19
  Intervention:   Drug: LNP-nCOV saRNA-02 Vaccine
  Sponsor:   MRC/UVRI and LSHTM Uganda Research Unit
  Not yet recruiting

• Efficacy of Inhaled Therapies in the Treatment of Acute Symptoms Associated With COVID-19 - Condition:   Covid19
  Interventions:   Drug: inhaled beclametasone;   Drug: Inahaled beclomethasone / formoterol / glycopyrronium
  Sponsors:   UPECLIN HC FM Botucatu Unesp;   Chiesi Farmaceutici S.p.A.
  Not yet recruiting

• Dapsone Coronavirus SARS-CoV-2 Trial (DAP-CORONA) COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Dapsone 85 mg PO BID;   Drug: Placebo 85 mg PO BID
  Sponsors:   McGill University Health Centre/Research Institute of the McGill University Health Centre;   Pulmonem Inc.
  Not yet recruiting

• Covid-19 Patients Management During Home Isolation - Condition:   Covid19
  Interventions:   Procedure: Oxygen therapy and physical therapy;   Device: Oxygen therapy
  Sponsor:   Cairo University
  Not yet recruiting

• Ivermectin Versus Standard Treatment in Mild COVID-19 - Condition:   Covid19
  Intervention:   Drug: Ivermectin Tablets
  Sponsor:   Assiut University
  Not yet recruiting

• Tolerability,Safety of JS016 in SARS-CoV-2 (COVID-19) - Conditions:   COVID-19;   SARS-CoV-2
  Intervention:   Drug: Combination Product: JS016 (anti-SARS-CoV-2 monoclonal antibody)
  Sponsor:   Peking Union Medical College Hospital
  Recruiting

• SCALE-UP Utah: Community-Academic Partnership to Address COVID-19 Testing Among Utah Community Health Centers - Condition:   Covid19
  Interventions:   Behavioral: Text-Messaging (TM);   Behavioral: Patient Navigation (PN)
  Sponsors:   University of Utah;   Association for Utah Community Health;   Utah Department of Health;   National Institutes of Health (NIH)
  Recruiting

• SCALE-UP Utah: Community-Academic Partnership to Address COVID-19 Vaccination Rates Among Utah Community Health Centers - Condition:   Covid19
  Interventions:   Behavioral: Text-Messaging (TM);   Behavioral: Patient Navigation (PN)
  Sponsors:   University of Utah;   Association for Utah Community Health;   Utah Department of Health;   National Institutes of Health (NIH)
  Recruiting

• Chinese Herbal Formula for COVID-19 - Condition:   Covid19
  Interventions:   Drug: mQFPD;   Drug: organic brown rice
  Sponsor:   University of California, San Diego
  Not yet recruiting

• Remdesivir- Ivermectin Combination Therapy in Severe Covid-19 - Condition:   Covid19
  Intervention:   Drug: Ivermectin
  Sponsor:   Assiut University
  Not yet recruiting

From PubMed

• Probing the SAM Binding Site of SARS-CoV-2 Nsp14 In Vitro Using SAM Competitive Inhibitors Guides Developing Selective Bisubstrate Inhibitors - The COVID-19 pandemic has clearly brought the healthcare systems worldwide to a breaking point, along with devastating socioeconomic consequences. The SARS-CoV-2 virus, which causes the disease, uses RNA capping to evade the human immune system. Nonstructural protein (nsp) 14 is one of the 16 nsps in SARS-CoV-2 and catalyzes the methylation of the viral RNA at N7-guanosine in the cap formation process. To discover small-molecule inhibitors of nsp14 methyltransferase (MTase) activity, we…

• Hydroxychloroquine Inhibits Cardiac Conduction in Aged Patients with Nonmalaria Diseases - CONCLUSION: Age is the most important risk factor of HCQ on cardiac conduction in nonmalaria patients. Electrocardiogram monitoring is suggested in aged patients due to the effects of HCQ on HR, PR, and QTc.

• Multiscale Simulations of SARS-CoV-2 3CL Protease Inhibition with Aldehyde Derivatives. Role of Protein and Inhibitor Conformational Changes in the Reaction Mechanism - We here investigate the mechanism of SARS-CoV-2 3CL protease inhibition by one of the most promising families of inhibitors, those containing an aldehyde group as a warhead. These compounds are covalent inhibitors that inactivate the protease, forming a stable hemithioacetal complex. Inhibitor 11a is a potent inhibitor that has been already tested in vitro and in animals. Using a combination of classical and QM/MM simulations, we determined the binding mode of the inhibitor into the active site…

• Construction of a non-infectious SARS-CoV-2 replicon for antiviral drug testing and gene function studies - The emerging coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread worldwide resulting in global public health emergencies and economic crises. In this study, a non-infectious and biocontainment level-2 compatible SARS-CoV-2 replicon expressing a nano luciferase (nLuc) reporter was constructed in a bacterial artificial chromosomal (BAC) vector by reverse genetics. The nLuc reporter is highly sensitive, easily…

• Anti-Spike Protein Assays to Determine SARS-CoV-2 Antibody Levels: a Head-to-Head Comparison of Five Quantitative Assays - Reliable quantification of the antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly relevant, e.g., for identifying possible vaccine failure and estimating the time of protection. Therefore, we evaluated five different anti-SARS-CoV-2 antibody assays regarding the quantification of anti-spike (S) antibodies. Sera from 69 SARS-CoV-2-naive individuals 21 ± 1 days after vaccination with a single dose of BNT162b2 (Pfizer/BioNTech) were tested using the…

• Pyrimidine biosynthesis inhibitors synergize with nucleoside analogs to block SARS-CoV-2 infection - The ongoing COVID-19 pandemic has highlighted the dearth of approved drugs to treat viral infections, with only ∼90 FDA approved drugs against human viral pathogens. To identify drugs that can block SARS-CoV-2 replication, extensive drug screening to repurpose approved drugs is underway. Here, we screened ∼18,000 drugs for antiviral activity using live virus infection in human respiratory cells. Dose-response studies validate 122 drugs with antiviral activity and selectivity against SARS-CoV-2….

• Efficacy of phytochemicals as immunomodulators in managing COVID-19: a comprehensive view - Throughout history, disease outbreaks have worked havoc upon humanity, sometimes reorienting the history and at times, signaling the end of entire civilizations and the modern pandemic that the world is dealing with, is COVID-19 or SARS-CoV-2. A healthy immunity could be an ideal gear for resisting COVID-19 for neither medicines nor vaccines have been ascertained till date. In view of the present scenario, there is a demanding necessity to analyze innovative and valid techniques for forestalling…

• In vitro antiviral activities of ethanol and aqueous extracts of Vietnamese traditional medicinal plants against Porcine Epidemic Diarrhea virus: a coronavirus family member - Porcine epidemic diarrhea virus (PEDV) causes diarrhea in pigs leading to severe illnesses and high mortality rates. The development of medicinal agents to treat PEDV infection is therefore crucial. In this study, antiviral activities against PEDV of ethanol and aqueous extracts of 17 Vietnamese traditional medicinal plants were evaluated using the cytopathic effect-based assay. The results showed that 14 out of 17 medicinal plants could inhibit the cytopathic effect of PEDV. The ethanol extract…

• Dual inhibition of COVID-19 spike glycoprotein and main protease 3CLpro by Withanone from Withania somnifera - CONCLUSION: The current study reports Withanone as a non-toxic antiviral against SARS-CoV-2 and serve as a potential lead hit for further experimental validation.

• The interaction of the severe acute respiratory syndrome coronavirus 2 spike protein with drug-inhibited angiotensin converting enzyme 2 studied by molecular dynamics simulation - CONCLUSION: We conclude that using ACE2 inhibitors can increase the risk of SARS-CoV-2 infection and worsen COVID-19 disease outcome. We also found that the SARS-CoV-2 can abrogate the function of ACE2 inhibitors and rescue the enzymatic activity of ACE2. Therefore, ACE2 inhibition is not a useful treatment against COVID-19 infection.

• SARS-CoV-2 infection and ACE2 inhibition - No abstract

• Tocilizumab for the treatment of non-critical COVID-19 pneumonia: an overview of the rationale and clinical evidence to date - Introduction: Tocilizumab is one of the main repurposed therapies investigated for COVID-19 pneumonia since the start of the pandemic, but there has been conflicting evidence for its use.Areas covered: This review covers the physiology of interleukin-6 and its role in the pathophysiology of COVID-19. We discuss the use of tocilizumab in other diseases and the rationale for its use in COVID-19. We summarize the design, contrasting results and implications of the clinical trials of tocilizumab in…

• Using body temperature and variables commonly available in the EHR to predict acute infection: a proof-of-concept study showing improved pretest probability estimates for acute COVID-19 infection among discharged emergency department patients - CONCLUSIONS: By incorporating covariates known to affect body temperature, we demonstrated improved pretest probability estimates of acute COVID-19 infection. Future work should be undertaken to further develop and validate our model in a larger, multi-institutional sample.

• Innate immunity, inflammation activation and heat-shock protein in COVID-19 pathogenesis - SARS-CoV-2-induced COVID-19 is a serious pandemic of the 21st century, which has caused a devastating loss of lives and a global economic catastrophe. A successful vaccine against SARS-CoV-2 has suffered a delay due to lack of substantial knowledge about its mechanisms of action. Understanding the innate immune system against SARS-CoV-2 and the role of heat shock proteins’ (HSP) inhibiting and resolution of inflammatory pathways may provide information to the low SARS-CoV-2 mortality rates in…

• A robust SARS-CoV-2 replication model in primary human epithelial cells at the air liquid interface to assess antiviral agents - There are, besides remdesivir, no approved antivirals for the treatment of SARS-CoV-2 infections. To aid in the search for antivirals against this virus, we explored the use of human tracheal airway epithelial cells (HtAEC) and human small airway epithelial cells (HsAEC) grown at the air/liquid interface (ALI). These cultures were infected at the apical side with one of two different SARS-CoV-2 isolates. Each virus was shown to replicate to high titers for extended periods of time (at least 8…

From Patent Search

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

• MEDIDOR DE SATURACION - - link

• 폐마스크 밀봉 회수기 - 본 발명은 마스크 착용 후 버려지는 일회용 폐마스크를 비닐봉지에 넣은 후 밀봉하여 배출함으로써, 2차 감염을 예방하고 일반 생활폐기물과 선별 분리 배출하여 환경오염을 방지하는 데 그 목적이 있다. - link

• 백신 냉각 및 해동 기능을 갖는 백신 보관장치 - 본 발명은 백신 냉각 및 해동 기능을 갖는 백신 보관장치에 관한 것으로, 상, 하부하우징의 제1상, 하부누출방지공간에 냉각물질이 충입된 냉각파이프를 설치하되, 제2상, 하부누출방지공간에 가열물질이 충입된 가열파이프를 설치하여, 구획판부에 의해 구획된 백신냉각공간 및 백신해동공간 각각을 냉각 및 가열하고, 보조도어를 통해 백신냉각공간 내에 수용된 백신을 구획판부의 백신출구도어를 통해 백신해동공간으로 이동시켜, 백신해동공간 내에서 백신을 해동함으로써, 즉시 사용이 가능한 백신을 인출도어를 통해 인출할 수 있다. 본 발명에 따르면, 냉각파이프에 저장된 냉매에 의해 백신냉각공간 내의 온도가 극저온 상태로 변화되고, 극저온 상태를 유지하는 백신냉각공간 내에 백신을 저장하여, 안전하게 보관 할 수 있으며, 백신냉각공간 내의 백신을 백신해동공간 내로 이동시켜, 백신해동공간 내에서 백신을 해동할 수 있고, 이 해동된 백신을 인출도어를 통해 인출한 후 즉시 사용할 수 있어 백신을 해동하는 시간이 단축되며, 보조도어를 통해 백신냉각공간 내의 백신을 백신해동공간으로 이동시켜, 백신이 외기에 노출될 우려가 없으며, 백신냉각공간 내의 백신을 백신해동공간으로 이동시키거나 또는 인출도어를 통해 백신 인출시 정렬장치가 백신을 보조도어 및 인출도어 직하방에 자동 위치시킨다. - link

• 백신 인출용 보조도어를 갖는 백신 저온 보관장치 - 본 발명은 백신정렬 기능을 갖는 백신 저온 보관장치에 관한 것으로, 상, 하부하우징의 이중 격벽 안에 냉매가 충입된 냉매파이프를 설치하여, 이 냉매파이프에 의해 상, 하부하우징의 백신 보관 공간이 극저온 상태를 유지하도록 하고, 하부하우징의 가이드벽 사이에 수용된 백신을 정렬장치로 가압하여, 상부하우징의 보조도어 직하방에 백신이 위치되도록 하되, 이때, 보조도어를 개방하여 하부하우징 내에 수용된 백신을 인출하면, 정렬장치가 가이드벽 사이에 수용된 백신을 보조도어 방향으로 밀어내어, 보조도어 직하방에 백신이 순차적으로 자동 위치된다. 본 발명에 따르면, 상, 하부하우징의 이중 격벽 내에 냉매 파이프가 설치되어, 이 냉매 파이프에 저장된 냉매에 의해 백신 보관공간 내의 온도가 극저온 상태로 변화되고, 이 극저온 상태를 유지하는 백신 보관공간 내에 백신을 저장하여, 안전하게 보관 할 수 있으며, 수분이나 외부 공기 유입이 차단되어 백신을 안전하게 보관되고, 온도계와 압력계를 이용하여 백신 보관공간과 냉매 압력을 실시간으로 감지할 수 있고, 보조도어를 통해 백신 보관공간 내의 백신을 독립적으로 인출할 수 있으며, 보조도어를 통해 백신 인출시 정렬장치가 백신을 보조도어 방향으로 밀어내어, 보조도어 직하방에 백신이 자동 위치되고, 외기 유입 방지로 백신 보관공간 내의 온도가 극저온 상태로 유지된다. - link

• SAFE TOUCH ANTI VIRAL LUGGAGE TROLLEY HANDLE - The invention is directed to a safe-touch, anti-viral luggage trolley handle, comprising PVC plastic with the addition of a silver-based antimicrobial additive. - link

• Mampara plegable portatil - Mampara Plegable Portátil (MPP) diseñada para acoplarse/fijarse al borde de una mesa caracterizada por estar formado por dos mordazas o piezas de sujeción al borde de una mesa donde se ensambla la estructura que porta la pantalla o lámina protectora transparente auto enrollable por mecanismo automático. - link

• METHOD OF IDENTIFYING SEVERE ACUTE RESPIRATORY SYNDROME CORONA VIRUS 2 (SARS-COV-2) RIBONUCLEIC ACID (RNA) - - link

• Erweiterbare Desinfektionsvorrichtung -

  Erweiterbare Desinfektionsvorrichtung, umfassend: einen Hauptkörper, der eine umgekehrt U-förmige Basisplatte aufweist, wobei die umgekehrt U-förmige Basisplatte mit einer Öffnung versehen ist und jeweils eine Seitenplatte sich von zwei Seiten der umgekehrt U-förmigen Basisplatte nach außen erstreckt; und mindestens eine Desinfektionslampe, die in den auf zwei Seiten des Hauptkörpers befindlichen Seitenplatten angeordnet ist und eine Lichtemissionseinheit, eine Erfassungseinheit, eine Steuereinheit und eine Stromversorgungseinheit umfasst.

• link