Covid-19 Sentry

Contents

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

From Preprints

• Affirming Basic Psychological Needs Promotes Mental Well-Being During the COVID-19 Outbreak -
  We tested if challenges to basic psychological needs (autonomy, competence, relatedness) during the COVID-19 pandemic undermines people’s mental well-being. Furthermore, we tested if an intervention, affirmation of these psychological needs, counteracts this negative impact. Results of Study 1 (N = 153) showed that higher levels of satisfaction of basic psychological needs was related to higher mental well-being during the COVID-19 outbreak. In Study 2 (N = 215) we employed an online intervention enhancing these basic psychological needs. We found increased mental well-being through bolstered relatedness in particular. The intervention also decreased perceived stress. Both studies showed that mental well-being during the COVID-19 pandemic is positively related to the ability to work as usual and the number of people contacted via phone or Internet, but not in person.
  🖺 Full Text HTML: Affirming Basic Psychological Needs Promotes Mental Well-Being During the COVID-19 Outbreak
• Does Chronotype explain Daily Timing of Music Behaviors? -
  We addressed how circadian rhythms influence daily musical activities of performing musicians, who exhibit fine temporal control. Music performances often occur in the evening and late at night; evidence suggests that composing musicians tend to be later chronotypes than non-composing musicians. However, chronotype and daily music-making in performing musicians have yet to be investigated. The current study examined chronotype in actively practicing and/or performing musicians and non-musicians, and whether it was related to the daily timing of music performance. To test influences of daily changes due to the global COVID-19 pandemic, disruptions to musical, athletic, social, and sleep habits were also measured. Performing musicians, active (practicing but non-performing) musicians, inactive musicians, and non-musicians, residing in Canada, completed a 7-day online daily activity and sleep diary in Summer 2020. There were more evening chronotypes than morning chronotypes in the sample. Active/performing musicians tended to be earlier chronotypes than all other groups. Musicians’ chronotype, but not nightly sleep timing, predicted the time of day that musicians made music: Late chronotypes made music later in the day and early chronotypes made music earlier in the day. Music performance and practice amount decreased during the COVID-19 period, but the daily timing of these activities did not change. All participants reported later sleep onset during the COVID-19 period; the amount of social interaction decreased during the COVID-19 period, while exercise increased for some and decreased for others. No changes in the daily timing of exercise, social interaction, or morning wake-up were reported. These findings suggest that performing musicians may be slightly earlier chronotypes than non-performing musicians and non-musicians, despite music performances often occurring in the evening. Chronotype was related to the time of day of music-making independent of nightly sleep timing, suggesting that times of day for making music reflect an individual’s circadian rhythm.
  🖺 Full Text HTML: Does Chronotype explain Daily Timing of Music Behaviors?
• The Behavioral Immune System and Vaccination Intentions During the Coronavirus Pandemic -
  The behavioral immune system is considered to be a psychological adaptation that decreases the risk of infection. Research suggests that, in the current environment, this system can produce attitudes with negative health consequences, such as increased vaccine hesitancy. In three studies, we investigated whether two facets of the behavioral immune system—contamination aversion (i.e., avoiding potential contamination) and perceived infectability (i.e., perceived susceptibility to disease)—predicted intentions to accept COVID-19, influenza, and measles or general childhood vaccinations. Both contamination aversion and perceived infectability were higher during than before the pandemic. In contrast to previous research, those with higher contamination aversion during the pandemic perceived vaccines to be safer and had higher intentions to accept vaccination. Contamination aversion before the pandemic was not associated with perceived vaccine safety or vaccination intentions during the pandemic. Individuals who perceived themselves as more susceptible to diseases were slightly more willing to accept vaccination. We conjecture that high disease threat reverses the relationship between the behavioral immune system response and vaccination. As the associations were weak, individual differences in contamination aversion and perceived infectability are of little practical relevance for vaccine uptake.
  🖺 Full Text HTML: The Behavioral Immune System and Vaccination Intentions During the Coronavirus Pandemic
• Excess Mortality in Suicide caused by COVID-19 in Japan -

  Background: Countermeasures against COVID-19 outbreak such as lockdown and voluntary restrictions against going out adversely affect human stress and economic activity. Particularly, this stress might lead to suicide. Object: We examined excess mortality attributable to suicide caused by COVID-19. Method: We applied the NIID model to suicide deaths from October 2009 through May, 2021 for the whole of Japan by gender. Effects of the great earthquake that struck in eastern Japan on March 11, 2011 were incorporated into the estimation model. Results: Significant excess mortality in suicide was found between July, 2020 and May, 2021 for both genders. It was greater among females than among males. In total, 2950 excess cases of mortality were identified. Discussion and Conclusion: Excess mortality during the four months was more than two times greater than the number of COVID-19 deaths confirmed by PCR testing. Countermeasures against COVID-19 should be chosen carefully in light of suicide effects.

  🖺 Full Text HTML: Excess Mortality in Suicide caused by COVID-19 in Japan
• Scaling Up the Discovery of Hesitancy Profiles by Identifying the Framing of Beliefs towards Vaccine Confidence in Twitter Discourse -

  Our study focused on the inference of the framing of confidence in the HPV vaccine throughout a collection of 422,078 tweets as well as the framing of confidence in the COVID-19 vaccines through a collection of 5,865,046 tweets. The vaccine confidence framings were inferred by using a novel Question/Answering framework enabling the derivation of a misinformation taxonomy as well as trust taxonomies for these two vaccines. These taxonomies, along with the analysis of vaccine literacy, the implied moral foundations and the tension between vaccine mandates and civil rights allowed us to discover several profiles of hesitancy for each vaccine across 138,779 Twitter users referring to confidence in HPV vaccine and 665,798 users referring to confidence in COVID-19 vaccines. These hesitancy profiles inform public health messaging approaches to effectively reach Twitter users with promise to shift or bolster vaccine attitudes.

• A Novel Penalized Inverse-Variance Weighted Estimator for Mendelian Randomization with Applications to COVID-19 Outcomes -

  Mendelian randomization (MR) utilizes genetic variants as instrumental variables (IVs) to estimate the causal effect of an exposure variable on an outcome of interest even in the presence of unmeasured confounders. However, the popular inverse-variance weighted (IVW) estimator could be biased in the presence of weak IVs, a common challenge in MR studies. In this article, we develop a novel penalized inverse-variance weighted (pIVW) estimator, which adjusts the original IVW estimator to account for the weak IV issue by using a penalization approach to prevent the denominator of the pIVW estimator from being close to zero. Moreover, we adjust the variance estimation of the pIVW estimator to account for the presence of horizontal pleiotropy. We show that the recently proposed debiased IVW (dIVW) estimator is a special case of our proposed pIVW estimator. We further prove that the pIVW estimator has smaller bias and variance than the dIVW estimator under some regularity conditions. We also conduct extensive simulation studies to demonstrate the performance of the proposed pIVW estimator. Furthermore, we apply the pIVW estimator to estimate the causal effects of five obesity-related exposures on three coronavirus disease 2019 (COVID-19) outcomes. Notably, we find that hypertensive disease is associated with an increased risk of hospitalized COVID-19, and peripheral vascular disease and higher body mass index are associated with increased risks of COVID-19 infection, hospitalized COVID-19 and critically ill COVID-19. The R package for the pIVW method is publicly available at https://github.com/siqixu/mr.pivw.

• Serial interval and transmission dynamics during the SARS-CoV-2 Delta variant predominance in South Korea -

  We estimated mean serial interval and superspreading potential for the predominant Delta variant of SARS-CoV-2. Mean serial intervals were similar with 3.7 and 3.5 days during early and latter periods, respectively. Furthermore, the risk of superspreading events was similar with 23% and 25% of cases seeded 80% of all transmissions.

  🖺 Full Text HTML: Serial interval and transmission dynamics during the SARS-CoV-2 Delta variant predominance in South Korea
• A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program -

  The study aims to determine the shared genetic architecture between COVID-19 severity with existing medical conditions using electronic health record (EHR) data. We conducted a Phenome-Wide Association Study (PheWAS) of genetic variants associated with a critical illness (n=35) or hospitalization (n=42) due to severe COVID-19 using a genome-wide association summary from the Host Genetics Initiative. PheWAS analysis was performed using genotype- phenotype data from the Veterans Affairs Million Veteran Program (MVP). Phenotypes were defined by International Classification of Diseases (ICD) codes mapped to clinically relevant groups using published PheWAS methods. Among 658,582 Veterans, variants associated with severe COVID-19 were tested for association across 1,559 phenotypes. Variants at the ABO locus (rs495828, rs505922) associated with the largest number of phenotypes (nrs495828= 53 and nrs505922=59); strongest association with venous embolism, odds ratio (ORrs495828 1.33 (p=1.32 x 10-199), and thrombosis ORrs505922 1.33, p=2.2 x 10-265. Among 67 respiratory conditions tested, 11 had significant associations including MUC5B locus (rs35705950) with increased risk of idiopathic fibrosing alveolitis OR 2.83, p=4.12 x 10-191; CRHR1 (rs61667602) associated with reduced risk of pulmonary fibrosis, OR 0.84, p=2.26 x 10-12. The TYK2 locus (rs11085727) associated with reduced risk for autoimmune conditions, e.g., psoriasis OR 0.88, p=6.48 x10-23, lupus OR 0.84, p=3.97 x 10-06. PheWAS stratified by genetic ancestry demonstrated differences in genotype-phenotype associations across ancestry. LMNA (rs581342) associated with neutropenia OR 1.29 p=4.1 x 10-13 among Veterans of African ancestry but not European. Overall, we observed a shared genetic architecture between COVID-19 severity and conditions related to underlying risk factors for severe and poor COVID-19 outcomes. Differing associations between genotype-phenotype across ancestries may inform heterogenous outcomes observed with COVID-19. Divergent associations between risk for severe COVID-19 with autoimmune inflammatory conditions both respiratory and non-respiratory highlight the shared pathways and fine balance of immune host response and autoimmunity and caution required when considering treatment targets.

  🖺 Full Text HTML: A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program
• SARS-CoV-2 genome sequences from Lucknow, Uttar Pradesh, India by Nanopore Sequencing -
  A new challenge has immerged in the form of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in worldwide. Rapid genome sequencing of SARS-CoV-2 has been a powerful tool to study the pathogenicity of severe acute respiratory syndrome coronavirus 2. During this pandemic situation more genome sequencing of SARS-CoV-2 should be done in order to detect the mutations and genomic modifications across the globe. Here, in this study we have sequenced 23 SARS-CoV-2 positive samples from the state of Uttar Pradesh, India collected during the first pandemic. A range of 2-22 mutations were observed including D614G, L452R, Q613H, Q677H, T1027I in S gene, S194L in N gene, Q57H, L106F, T175I in ORF3a gene as reported previously and also possible novel mutations like P309S in ORF1ab gene, T379I in N gene and L52F, V77I in ORF3a gene were detected. Phylogenetic genome analysis has shown similarity with other SARS-CoV-2 viruses reported in Uttar Pradesh. Mutations in these genes have the potential to affect the severity of the disease. Therefore, identify the mutation is very important to know the pathogenicity of SARS-CoV-2 virus.
  🖺 Full Text HTML: SARS-CoV-2 genome sequences from Lucknow, Uttar Pradesh, India by Nanopore Sequencing
• TREM2+ and interstitial macrophages orchestrate airway inflammation in SARS-CoV-2 infection in rhesus macaques -
  The COVID-19 pandemic remains a global health crisis, yet, the immunopathological mechanisms driving the development of severe disease remain poorly defined. Here, we utilize a rhesus macaque (RM) model of SARS-CoV-2 infection to delineate perturbations in the innate immune system during acute infection using an integrated systems analysis. We found that SARS-CoV-2 initiated a rapid infiltration (two days post infection) of plasmacytoid dendritic cells into the lower airway, commensurate with IFNA production, natural killer cell activation, and induction of interferon-stimulated genes. At this early interval, we also observed a significant increase of blood CD14-CD16+ monocytes. To dissect the contribution of lung myeloid subsets to airway inflammation, we generated a novel compendium of RM-specific lung macrophage gene expression using a combination of sc-RNA-Seq data and bulk RNA-Seq of purified populations under steady state conditions. Using these tools, we generated a longitudinal sc-RNA-seq dataset of airway cells in SARS-CoV-2-infected RMs. We identified that SARS-CoV-2 infection elicited a rapid recruitment of two subsets of macrophages into the airway: a C206+MRC1- population resembling murine interstitial macrophages, and a TREM2+ population consistent with CCR2+ infiltrating monocytes, into the alveolar space. These subsets were the predominant source of inflammatory cytokines, accounting for ~75% of IL6 and TNF production, and >90% of IL10 production, whereas the contribution of CD206+MRC+ alveolar macrophages was significantly lower. Treatment of SARS-CoV-2 infected RMs with baricitinib (Olumiant(R)), a novel JAK1/2 inhibitor that recently received Emergency Use Authorization for the treatment of hospitalized COVID-19 patients, was remarkably effective in eliminating the influx of infiltrating, non-alveolar macrophages in the alveolar space, with a concomitant reduction of inflammatory cytokines. This study has delineated the major subsets of lung macrophages driving inflammatory and anti-inflammatory cytokine production within the alveolar space during SARS-CoV-2 infection.
  🖺 Full Text HTML: TREM2+ and interstitial macrophages orchestrate airway inflammation in SARS-CoV-2 infection in rhesus macaques
• Genetic association of TMPRSS2 rs2070788 polymorphism with COVID-19 Case Fatality Rate among Indian populations -
  SARS-CoV2, the causative agent for COVID-19, an ongoing pandemic, engages the ACE2 receptor to enter the host cell through S protein priming by a serine protease, TMPRSS2. Variation in the TMPRSS2 gene may account for the difference in population disease susceptibility. The haplotype-based genetic sharing and structure of TMPRSS2 among global populations have not been studied so far. Therefore, in the present work, we used this approach with a focus on South Asia to study the haplotypes and their sharing among various populations worldwide. We have used next-generation sequencing data of 393 individuals and analysed the TMPRSS2 gene. Our analysis of genetic relatedness for this gene showed a closer affinity of South Asians with the West Eurasian populations therefore, host disease susceptibility and severity particularly in the context of TMPRSS2 will be more akin to West Eurasian instead of East Eurasian. This is in contrast to our prior study on ACE2 gene which shows South Asian haplotypes have a strong affinity towards West Eurasians. Thus ACE2 and TMPRSS2 have an antagonistic genetic relatedness among South Asians. We have also tested the SNPs frequencies of this gene among various Indian state populations with respect to the case fatality rate. Interestingly, we found a significant positive association between the rs2070788 SNP (G Allele) and the case fatality rate in India. It has been shown that the GG genotype of rs2070788 allele tends to have a higher expression of TMPRSS2 in the lung compared to the AG and AA genotypes, thus it might play a vital part in determining differential disease vulnerability. We trust that this information will be useful in underscoring the role of the TMPRSS2 variant in COVID-19 susceptibility and using it as a biomarker may help to predict populations at risk.
  🖺 Full Text HTML: Genetic association of TMPRSS2 rs2070788 polymorphism with COVID-19 Case Fatality Rate among Indian populations
• Clinical utility of Elecsys Anti-SARS-CoV-2 S assay in COVID-19 vaccination: An exploratory analysis of the mRNA-1273 phase 1 trial -

  Background The ability to quantify an immune response after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential. This study assessed the clinical utility of the quantitative Roche Elecsys® Anti-SARS-CoV-2 S assay (ACOV2S) using samples from the 2019-nCoV vaccine (mRNA-1273) phase 1 trial (NCT04283461). Methods Samples from 30 healthy participants, aged 18-55 years, who received two injections with mRNA-1273 at a dose of 25 μg (n=15) or 100 μg (n=15), were collected at Days 1 (first vaccination), 15, 29 (second vaccination), 43 and 57. ACOV2S results (shown in U/mL - equivalent to BAU/mL per the first WHO international standard) were compared with results from ELISAs specific to antibodies against the Spike protein (S-2P) and the receptor binding domain (RBD) as well as neutralization tests including nanoluciferase (nLUC80), live-virus (PRNT80), and a pseudovirus neutralizing antibody assay (PsVNA50). Results RBD-specific antibodies were already detectable by ACOV2S at the first time point of assessment (d15 after first vaccination), with seroconversion before in all but 2 participants (25 μg dose group); all had seroconverted by Day 29. Across all post-baseline visits, geometric mean concentration of antibody levels were 3.27-7.48-fold higher in the 100 μg compared with the 25 μg dose group. ACOV2S measurements were highly correlated with those from RBD ELISA (Pearson9s r=0.938; p<0.0001) and S-2P ELISA (r=0.918; p<0.0001). For both ELISAs, heterogeneous baseline results and smaller increases in antibody levels following the second vs first vaccination compared with ACOV2S were observed. ACOV2S showed absence of any baseline noise indicating high specificity detecting vaccine-induced antibody response. Moderate-strong correlations were observed between ACOV2S and neutralization tests (nLUC80 r=0.933; PsVNA50, r=0.771; PRNT80, r=0.672; all p≤0.0001). Conclusion The Elecsys Anti-SARS-CoV-2 S assay (ACOV2S) can be regarded as a highly valuable method to assess and quantify the presence of RBD-directed antibodies against SARS-CoV-2 following vaccination, and may indicate the presence of neutralizing antibodies. As a fully automated and standardized method, ACOV2S could qualify as the method of choice for consistent quantification of vaccine-induced humoral response.

  🖺 Full Text HTML: Clinical utility of Elecsys Anti-SARS-CoV-2 S assay in COVID-19 vaccination: An exploratory analysis of the mRNA-1273 phase 1 trial
• Mental health during the COVID-19 outbreak: the impact of healthy lifestyle behaviors and sociodemographic factors -
  Background: Numerous studies have reported high rates of depressive and anxiety symptoms related to the COVID-19 crisis and the measures implemented to contain the virus spread. Even though restrictive measures, such as mandatory lockdown were not applied in Uruguay, mental health could be affected. Moreover, sociodemographic and lifestyle factors could modulate this impact. We aimed to evaluate the impact of the pandemic on depressive and anxiety symptoms among Uruguayan people and examine the associated factors. Methods: This study was conducted in a non-probabilistic sample of 1051 adults (aged ≥18 years). Depressive (Beck Depression Inventory-II) and anxiety (State-Trait Anxiety Inventory) symptoms were assessed along with isolation conditions, sociodemographic factors, and lifestyle behaviors. Linear models were adjusted to analyze the data. Results: Participants in our sample reported mild-to-moderate depressive symptoms and severe anxiety symptoms. Those who did total isolation reported the highest levels of symptomatology. Also, as days of isolation increased, symptoms increased. Finally, sex, socioeconomic status, age, physical activity, sleeping routines, exposure to light and outdoor activities have an effect on mental health. Conclusions: This study illustrates that the COVID-19 outbreak impacts mental health even in a country with mild-lockdown. Our results highlight the importance of considering sociodemographic and lifestyle factors when developing clinical intervention programs to mitigate the current crisis’s effects.
  🖺 Full Text HTML: Mental health during the COVID-19 outbreak: the impact of healthy lifestyle behaviors and sociodemographic factors
• A high throughput screening assay for inhibitors of SARS-CoV-2 pseudotyped particle entry -
  Effective small molecule therapies to combat the SARS-CoV-2 infection are still lacking as the COVID-19 pandemic continues globally. High throughput screening assays are needed for lead discovery and optimization of small molecule SARS-CoV-2 inhibitors. In this work, we have applied viral pseudotyping to establish a cell-based SARS-CoV-2 entry assay. Here, the pseudotyped particles (PP) contain SARS-CoV-2 spike in a membrane enveloping both the murine leukemia virus (MLV) gag-pol polyprotein and luciferase reporter RNA. Upon addition of PP to HEK293-ACE2 cells, the SARS-CoV-2 spike protein binds to the ACE2 receptor on the cell surface, resulting in priming by host proteases to trigger endocytosis of these particles, and membrane fusion between the particle envelope and the cell membrane. The internalized luciferase reporter gene is then expressed in cells, resulting in a luminescent readout as a surrogate for spike-mediated entry into cells. This SARS-CoV-2 PP entry assay can be executed in a biosafety level 2 containment lab for high throughput screening. From a collection of 5,158 approved drugs and drug candidates, our screening efforts identified 7 active compounds that inhibited the SARS-CoV-2-S PP entry. Of these seven, six compounds were active against live replicating SARS-CoV-2 virus in a cytopathic effect assay. Our results demonstrated the utility of this assay in the discovery and development of SARS-CoV-2 entry inhibitors as well as the mechanistic study of anti-SARS- CoV-2 compounds. Additionally, particles pseudotyped with spike proteins from SARS-CoV-2 B.1.1.7 and B.1.351 variants were prepared and used to evaluate the therapeutic effects of viral entry inhibitors.
  🖺 Full Text HTML: A high throughput screening assay for inhibitors of SARS-CoV-2 pseudotyped particle entry
• Longitudinal characterization of circulating neutrophils uncovers distinct phenotypes associated with disease severity in hospitalized COVID-19 patients -
  Multiple studies have identified an association between neutrophils and COVID-19 disease severity; however, the mechanistic basis of this association remains incompletely understood. Here we collected 781 longitudinal blood samples from 306 hospitalized COVID-19+ patients, 78 COVID-19- acute respiratory distress syndrome patients, and 8 healthy controls, and performed bulk RNA-sequencing of enriched neutrophils, plasma proteomics, cfDNA measurements and high throughput antibody profiling assays to investigate the relationship between neutrophil states and disease severity or death. We identified dynamic switches between six distinct neutrophil subtypes using non-negative matrix factorization (NMF) clustering. At days 3 and 7 post-hospitalization, patients with severe disease had an enrichment of a granulocytic myeloid derived suppressor cell-like state gene expression signature, while non-severe patients with resolved disease were enriched for a progenitor-like immature neutrophil state signature. Severe disease was associated with gene sets related to neutrophil degranulation, neutrophil extracellular trap (NET) signatures, distinct metabolic signatures, and enhanced neutrophil activation and generation of reactive oxygen species (ROS). We found that the majority of patients had a transient interferon-stimulated gene signature upon presentation to the emergency department (ED) defined here as Day 0, regardless of disease severity, which persisted only in patients who subsequently died. Humoral responses were identified as potential drivers of neutrophil effector functions, as enhanced antibody-dependent neutrophil phagocytosis and reduced NETosis was associated with elevated SARS-CoV-2-specific IgG1-to-IgA1 ratios in plasma of severe patients who survived. In vitro experiments confirmed that while patient-derived IgG antibodies mostly drove neutrophil phagocytosis and ROS production in healthy donor neutrophils, patient-derived IgA antibodies induced a predominant NETosis response. Overall, our study demonstrates neutrophil dysregulation in severe COVID-19 and a potential role for IgA-dominant responses in driving neutrophil effector functions in severe disease and mortality.
  🖺 Full Text HTML: Longitudinal characterization of circulating neutrophils uncovers distinct phenotypes associated with disease severity in hospitalized COVID-19 patients

From Clinical Trials

• Prophylaxis of COVID-19 Disease With Ivermectin in COVID-19 Contact Persons [German: Prophylaxe Der COVID-19-Erkrankung Mit Ivermectin Bei COVID-19 Kontaktpersonen] - Condition:   Covid19
  Interventions:   Drug: Ivermectin;   Drug: Placebo
  Sponsors:  
  Infectopharm Arzneimittel GmbH;   GKM Gesellschaft für Therapieforschung mbH
  Not yet recruiting

• Evaluating Safety, Tolerability, and Potential Efficacy of Intranasal AD17002 in Adults With Mild COVID-19 - Condition:   Covid19
  Interventions:   Biological: AD17002;   Biological: Placebo (Formulation buffer)
  Sponsor:   Advagene Biopharma Co. Ltd.
  Not yet recruiting

• Lymphatic Osteopathic Manipulative Medicine to Enhance Coronavirus (COVID-19) Vaccination Efficacy - Condition:   COVID-19
  Interventions:   Other: Lymphatic OMM;   Other: Light Touch
  Sponsor:   Rowan University
  Not yet recruiting

• A Study of AZD1222, a Vaccine for the Prevention of COVID-19 in Immunocompromised Adults - Condition:   COVID-19, SARS-CoV-2
  Intervention:   Biological: AZD1222
  Sponsor:  
  AstraZeneca
  Not yet recruiting

• “Efesovir” (FS-1) for COVID-19, Phase 2 - Condition:   Covid19
  Intervention:   Drug: Efesovir
  Sponsor:   Scientific Center for Anti-infectious Drugs, Kazakhstan
  Not yet recruiting

• SARS-CoV-2 Infection in COVID-19 Vaccinated Patients - Condition:   COVID-19
  Intervention:   Diagnostic Test: COVID-19 vaccinated people
  Sponsor:   Hospices Civils de Lyon
  Recruiting

• The Development of a COVID19 Oral Vaccine Consisting of Bacillus Subtilis Spores - Condition:   COVID-19 Pneumonia
  Intervention:   Biological: Bacillus subtilis
  Sponsor:   DreamTec Research Limited
  Recruiting

• Phase I/II of the Safety and Immunogenicity of SARS-CoV-2 Protein Subunit Recombinant Vaccine in Healthy Populations - Condition:   Covid19
  Interventions:   Biological: SARS-CoV-2 Protein Subunit Recombinant Vaccine;   Biological: SARS-CoV-2 Inactivated Vaccine
  Sponsors:   PT Bio Farma;   Fakultas Kedokteran Universitas Indonesia;   National Institute of Health Research and Development, Ministry of Health Republic of Indonesia
  Not yet recruiting

• A Ph 2 Trial With an Oral Tableted COVID-19 Vaccine - Condition:   COVID-19
  Interventions:   Drug: VXA-CoV2-1.1-S;   Other: Placebo Tablets
  Sponsor:   Vaxart
  Recruiting

• Test to Stay in School: COVID-19 Testing Following Exposure in School Communities - Condition:   Covid19
  Intervention:   Other: COVID-19 Testing
  Sponsor:  
  Duke University
  Not yet recruiting

• FLuticasone in cOvid Treatment (FLOT) - Condition:   Covid19
  Intervention:   Drug: Fluticasone Propionate
  Sponsor:  
  University of Medicine and Pharmacy at Ho Chi Minh City
  Recruiting

• Efficacy and Safety of Baricitinib in Patients With Moderate and Severe COVID-19 - Condition:   Covid19
  Interventions:   Drug: Baricitinib;   Drug: Placebo
  Sponsor:  
  Incepta Pharmaceuticals Ltd
  Not yet recruiting

• Randomized Trial of COVID-19 Booster Vaccinations (Cobovax Study) - Condition:   COVID-19 Vaccination
  Interventions:   Biological: BNT162b2;   Biological: CoronaVac
  Sponsor:   The University of Hong Kong
  Not yet recruiting

• RCT on the Efficacy of Dexamethasone Versus Methyl Prednisolone in Covid-19 Infected Patients With High Oxygen Flow - Condition:   COVID-19 Pandemic
  Interventions:   Drug: Dexamethasone;   Drug: Methylprednisolone
  Sponsor:   Cairo University
  Recruiting

• Third Dose of mRNA Vaccination to Boost COVID-19 Immunity - Condition:   COVID 19 Vaccine
  Intervention:   Biological: BNT162b2
  Sponsor:  
  The University of Hong Kong
  Recruiting

From PubMed

• The Importance of the Timing of Tocilizumab Administration in Moderate to Severely Ill COVID-19: Single Centered Experience Case series - One of the main causes of death in COVID-19 is the dysregulation of the host’s immune system which leads to cytokine storm, a potentially fatal systemic inflammatory syndrome. Interleukin 6 (IL-6) is a pro-inflammatory cytokine that is produced in response to infections and tissue injuries and is believed to play a pivotal role in the event of a cytokine storm, as signified by its increase in the process. Considering the role of IL-6 as a pro-inflammatory cytokine in the process of cytokine…

• Remdesivir induces persistent mitochondrial and structural damage in human induced pluripotent stem cell derived cardiomyocytes - CONCLUSIONS: Using an in vitro model, we demonstrated that remdesivir can induce cardiotoxicity in hiPSC-CMs at clinically relevant concentrations. These results reveal previously unknown potential side-effects of remdesivir and highlight the importance of further investigations with in vivo animal models and active clinical monitoring to prevent lasting cardiac damage to patients.

• Bhimamycin J, a rare benzo[f]isoindole-dione alkaloid from the marine-derived actinomycete Streptomyces sp. MS180069 - Chemical investigation on a Streptomyces sp. strain MS180069 isolated from a sediment sample collected from the South China Sea, yielded the new benzo[f]isoindole-dione alkaloid, bhimamycin J ( 1 ). The structure was determined by extensive spectroscopic analysis, including HRMS, 1D, 2D NMR, and X-ray diffraction techniques. A molecular docking study revealed 1 as a new molecular motif that binds with human angiotensin converting enzyme2 (ACE2), recently described as the cell surface receptor…

• An observational study of breakthrough SARS-CoV-2 Delta variant infections among vaccinated healthcare workers in Vietnam - BACKGROUND: Data on breakthrough SARS-CoV-2 Delta variant infections in vaccinated individuals are limited.

• Hybrid In Silico Approach Reveals Novel Inhibitors of Multiple SARS-CoV-2 Variants - The National Center for Advancing Translational Sciences (NCATS) has been actively generating SARS-CoV-2 high-throughput screening data and disseminates it through the OpenData Portal (https://opendata.ncats.nih.gov/covid19/). Here, we provide a hybrid approach that utilizes NCATS screening data from the SARS-CoV-2 cytopathic effect reduction assay to build predictive models, using both machine learning and pharmacophore-based modeling. Optimized models were used to perform two iterative rounds…

• The acid sphingomyelinase/ceramide system in COVID-19 - Acid sphingomyelinase (ASM) cleaves sphingomyelin into the highly lipophilic ceramide, which forms large gel-like rafts/platforms in the plasma membrane. We showed that SARS-CoV-2 uses these platforms for cell entry. Lowering the amount of ceramide or ceramide blockade due to inhibitors of ASM, genetic downregulation of ASM, anti-ceramide antibodies or degradation by neutral ceramidase protected against infection with SARS-CoV-2. The addition of ceramide restored infection with SARS-CoV-2. Many…

• A Combination of Receptor-Binding Domain and N-Terminal Domain Neutralizing Antibodies Limits the Generation of SARS-CoV-2 Spike Neutralization-Escape Mutants - Most known SARS-CoV-2 neutralizing antibodies (nAbs), including those approved by the FDA for emergency use, inhibit viral infection by targeting the receptor-binding domain (RBD) of the spike (S) protein. Variants of concern (VOC) carrying mutations in the RBD or other regions of S reduce the effectiveness of many nAbs and vaccines by evading neutralization. Therefore, therapies that are less susceptible to resistance are urgently needed. Here, we characterized the memory B-cell repertoire of…

• In silico identification of SARS-CoV-2 cell entry inhibitors from selected natural antivirals - The aim of this study is to identify potential drug-like molecules against SARS-CoV-2 virus among the natural antiviral compounds published in the Encyclopedia of Traditional Chinese Medicine. To test inhibition capability of these compounds first, we docked them with Spike protein, angiotensin-converting enzyme 2 (ACE2) (PDB ID: 6M0J) and neuropilin 1 (NRP1) (PDB ID: 7JJC) receptors, and found significant docking scores with extra precision up to -11 kcal/mol. Then, their stability in the…

• Xuanfei Baidu Decoction protects against macrophages produced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway - CONCLUSIONS: Xuanfei Baidu Decoction protects against macrophages produced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway.

• Computational and in vitro experimental analyses of the Anti-COVID-19 potential of Mortaparib and MortaparibPlus - COVID-19 pandemic caused by SARS-CoV-2 virus has become a global health emergency. Although new vaccines have been generated and being implicated, discovery and application of novel preventive and control measures are warranted. We aimed to identify compound/s that may possess the potential to either block the entry of virus to host cells or attenuate its replication upon infection. Using host cell surface receptor expression (Angiotensin-converting enzyme 2 (ACE2) and Transmembrane protease…

• Higher rates of COVID-19 but less severe infections reported for patients on Dupilumab: a Big Data analysis of the World Health Organization VigiBase - CONCLUSIONS: Dupilumab use seems to reduce COVID-19 related severity. Further studies are needed to better understand the immunological mechanisms and clinical implications of these findings. Remarkably, the heterogenous nature of the reports and the database structure did not allow to establish a cause-effect link, but only an epidemiologically decreased risk in the patients subset treated with dupilumab.

• Targeting cathepsins: A potential link between COVID-19 and associated neurological manifestations - Many studies have shown that the lysosomal cathepsins, especially cathepsins B/L (CTSB/L) are required for SARS-CoV-2 entry into host cells. Lysosomal proteases, cathepsins are indispensable for normal health and are involved in several brain disorders occurring at different development age periods. On the other hand, it has been well known that COVID-19 infection is largely associated with several neurological disorders. Taken together these findings and given the high levels of expression of…

• In Silico Investigation of Phytoconstituents of Medicinal Herb ‘Piper Longum’ Against SARS-CoV-2 by Molecular Docking and Molecular Dynamics Analysis - Unavailability of treatment for the SARS-CoV-2 virus has raised concern among the population worldwide. This has led to many attempts to find alternative options to prevent the infection of the disease, including focusing on vaccines and drugs. The use of natural products and herbal extracts can be a better option in beating the virus and boosting up immunity. In the present paper, we have done a systematic in silico study of papain-like protease of COVID-19 virus with the chemical constituents…

• Dual-Antigen COVID-19 Vaccine Subcutaneous Prime Delivery With Oral Boosts Protects NHP Against SARS-CoV-2 Challenge - We have developed a dual-antigen COVID-19 vaccine incorporating genes for a modified SARS-CoV-2 spike protein (S-Fusion) and the viral nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) to increase the potential for MHC class II responses. The vaccine antigens are delivered by a human adenovirus serotype 5 platform, hAd5 [E1-, E2b-, E3-], previously demonstrated to be effective in the presence of Ad immunity. Vaccination of rhesus macaques with the hAd5 S-Fusion +…

• Immunotherapy Summary for Cytokine Storm in COVID-19 - COVID-19 pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has ravaged the world, resulting in an alarming number of infections and deaths, and the number continues to increase. The pathogenesis caused by the novel coronavirus was found to be a disruption of the pro-inflammatory/anti-inflammatory response. Due to the lack of effective treatments, different strategies and treatment methods are still being researched, with the use of vaccines to make the body immune…

From Patent Search

• 스몰 RNA 검출 방법 - 본 발명은 스몰(small) RNA의 분석 및 검출 방법에 관한 것이다. 특히, 본 발명은 짧은 염기서열의 RNA까지 분석이 가능하면서도 높은 민감도 및 정확도로 정량적 검출까지 가능하여 감염증, 암 등 여러 질환의 진단 용도로도 널리 활용될 수 있다. - link

• 健康智能检测方法、装置、电子设备及可读存储介质 - 本申请公开了一种健康智能检测方法、装置、电子设备及可读存储介质，其方法包括获取音频信号，并对所述音频信号进行预处理，得到检测信号；将所述检测信号转化为矩阵数字矩阵；将得到的矩阵数字矩阵作为检测样本，输入健康智能检测模型中，以获取检测结果；其中，所述健康智能检测模型是采用迁移学习和卷积神经网络对训练样本进行训练得到的。本申请由于卷积神经网络各组件或部分组件基于迁移学习进行了重新训练，显著提升了对人们健康检测的准确度；且本申请中的健康智能检测模型为分类模型，计算量小，可将其部署于人们的移动终端中，使用方便，极大程度上提升了用户的使用感受。 - link

• MACHINE LEARNING TECHNIQUE TO ANALYSE THE CONDITION OF COVID-19 PATIENTS BASED ON THEIR SATURATION LEVELS - - link

• 单克隆抗体32C7及其制备方法和用途 - 本发明公开了单克隆抗体32C7及其制备方法和用途。本发明通过制备针对于新冠病毒RBD结构域的中和抗体32C7，在体外通过表面等离子共振检测抗体32C7可以有效地与新冠病毒的S蛋白的RBD结构域结合，通过转基因小鼠感染模型验证了抗体32C7的中和能力，测定了中和抗体32C7对于新冠感染后的肺部病毒滴度和相关炎症因子的抑制效果，结果显示该中和抗体能够明显的抑制病毒在体内的复制并降低炎症因子的产生和肺部炎症浸润。单克隆中和抗体32C7抑制新冠病毒的进入宿主细胞，达到新冠病毒中和抗体的治疗作用，可有效用于治疗或者预防新冠病毒感染引起的呼吸系统损伤。 - link

• 单克隆抗体35B5及其制备方法和用途 - 本发明公开了单克隆抗体35B5及其制备方法和用途。本发明通过制备针对于新冠病毒RBD结构域的中和抗体35B5，在体外通过表面等离子共振检测抗体35B5可以有效地与新冠病毒的S蛋白的RBD结构域结合，通过转基因小鼠感染模型验证了抗体35B5的中和能力，测定了中和抗体35B5对于新冠感染后的肺部病毒滴度和相关炎症因子的抑制效果，结果显示该中和抗体能够明显的抑制病毒在体内的复制并降低炎症因子的产生和肺部炎症浸润。单克隆中和抗体35B5抑制新冠病毒的进入宿主细胞，达到新冠病毒中和抗体的治疗作用，可有效用于治疗或者预防新冠病毒感染引起的呼吸系统损伤。 - link

• A HERB BASED COMPOSITION ANTI VIRAL MEDICINE FOR TREATMENT OF SARS COV 2 AND A METHOD FOR TREATING A PERSON INFECTED BY THE SARS COV 2 VIRUS - A Herbal composition, viz., PONNU MARUNTHU essentially comprising of ALLUIUM CEPA extract. [concentrated to 30%] 75%, SAPINDUS MUKOROSSI - extract [Optimised] 10%, CITRUS X LIMON - extract in its natural form 05 TRACYSPERMUM AMMI (L) – extract 07%,ROSA HYBRIDA - extract 03%, PONNU MARUNTHU solution 50 ml, or as a capsulated PONNU MARUNTHU can be given to SARS cov2 positive Patients, three times a day that is ½ an hour before food; continued for 3 days to 5 days and further taking it for 2 days if need be there; It will completely cure a person. When the SARS cov2 test shows negative this medicine can be discontinued. This indigenous medicine and method for treating a person inflicted with SARS COV 2 viral infection is quite effective in achieving of much needed remedy for the patients and saving precious lives from the pangs of death and ensuring better health of people. - link

• 治疗或预防新冠病毒的靶点 - 本发明提供一种蛋白片段，是如下至少一种：A1)氨基酸酸序列如SEQ ID NO.1所示；A2）氨基酸序列如SEQ ID NO.1第12位‑34位所示；A3）将A1)的蛋白片段的第18、19、28和29位中的任意一个或几个氨基酸残基经过一个或几个氨基酸残基的取代、缺失、添加得到的与A1)所示的蛋白片段具有90％以上的同一性的蛋白片段；A4）氨基酸酸序列如SEQ ID NO.2所示；A5）氨基酸序列如SEQ ID NO.2第32‑41位所示；A6）将A4)的蛋白片段的第35和36位中的任意1个或2个氨基酸残基经过一个或几个氨基酸残基的取代、缺失、添加得到的与A4)所示的蛋白片段具有90％以上的同一性的蛋白片段。 - link

• 以痘苗病毒为载体的新冠疫苗 - 本申请涉及一种基于经过基因工程改造的痘苗病毒为载体的新型冠状病毒南非突变株疫苗。所述疫苗以A46R缺陷的痘苗病毒为载体携带新冠病毒南非突变株S基因核酸序列，所述痘苗病毒载体还可以携带IL‑21，该疫苗在免疫小鼠后可以产生针对新冠病毒南非突变株的抗体。 - link

• 氧化钛负载银单原子的材料在病毒消杀中的应用 - 本发明属于生物医药领域，尤其涉及一种负载银单原子的材料在病毒消杀中的应用，所述氧化钛负载银单原子材料具有以下的结构：银单原子以单分散的形式，稳定地锚定于氧化钛的表面和/或骨架中，键合方式为Ti‑O‑Ag；银单原子的嵌合使Ag单原子和氧化钛的电子结构带隙范围为2.9‑3.2

eV；氧化钛负载银单原子材料具有较银纳米颗粒更加优异的催化活性，具有过氧化物酶活性，利用羟基自由基可高效破坏核酸和蛋白质的原理来实现广谱消杀病毒，银单原子的嵌合使Ag单原子和氧化钛的电子结构带隙变小，对可见光的敏感性更强，可将光照射下的光催化诱导光动力杀伤病毒。 - link

• Anti-Sars-Cov-2 Neutralizing Antibodies - - link