Covid-19 Sentry

Contents

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

From Preprints

• Houston, we Have a Pandemic: Technical Difficulties, Distractions and Online Student Engagement -
  The COVID-19 pandemic has brought sudden changes to various facets of daily life, including a massive shift to remote education. College students rely on technology to attend class and interact with instructors and peers, while possibly facing technical and situational difficulties at home. Considering the unprecedented situation, the purpose of the present study was to extend online student engagement literature during the COVID-19 pandemic. The survey sample consisted of 78 undergraduate students, recruited online. Participants completed scales on online student engagement, technical difficulties, home distractions and computer self-efficacy, as well as two exploratory open-ended questions on their attitudes towards online classes. Student engagement was negatively correlated with both technical difficulties and home distractions, while computer self-efficacy mediated the relationship between student engagement and technical difficulties. Students reported that what they enjoyed most in e-classes were the exact aspects that interfered with their learning and engagement. The most commonly reported concern in online courses was impaired concentration and technical issues, while flexibility, time efficiency and home comfort were the most prevalent aspects that students enjoyed. The study aims to shed light on engagement in remote learning, as online classes may eventually become an integral component of higher education after the return to a so-called new normality.
  🖺 Full Text HTML: Houston, we Have a Pandemic: Technical Difficulties, Distractions and Online Student Engagement
• The COVID-19 Pandemic in South Asia: A Comprehensive Review of the Genomic Variations, Epidemiological Features, Diagnosis, Treatment and Preventive Schemes -
  Purpose: The purpose of the study was to outline the genomic and epidemiological characteristics of COVID-19 in South Asian countries as well as the diagnosis, treatments, and prevention approaches undertaken by these countries to tackle the COVID-19 pandemic. Design/Methodology/Approach: We searched electronic databases such as Google Scholar, PubMed, and Scopus as well as various national and international COVID-19 websites, WHO databases, and electronic media. Total 63 articles were selected from databases and 34 articles from various other sources. Findings: Scientists observed genomic variations including common mutations in ORF1ab, ORF1a, ORF3a, and S genes, while several unique mutations exist in most isolates from these countries. Demographic analysis showed that the majority of the infected individuals were male and younger adults (20 to 40 years). India had both the highest number of deaths and incidents while Afghanistan had the highest fatality rate (4.37%). Various molecular assay (rRT-PCR), antigen, and antibody-based assays have been developed to facilitate early screening due to the unavailability of any effective treatments. Although every country tried to undertake imperative preventive measures along with vaccination drives, many of them still face grave repercussions due to scarcity of health facilities, under-developed infrastructures, and improvident government policies. Originality/value: To our knowledge, this is the first review appraising various features of the virus and the disease that persists in South Asia, and actions undertaken by authorities of the countries. This review will facilitate timely interventions for future novel outbreaks in the region.
  🖺 Full Text HTML: The COVID-19 Pandemic in South Asia: A Comprehensive Review of the Genomic Variations, Epidemiological Features, Diagnosis, Treatment and Preventive Schemes
• In silico, In vitro Screening of Plant Extracts for Anti-SARS-CoV-2 Activity and Evaluation of Their Acute and Sub- Acute Toxicity -
  Background: In the absence of a specific drug for COVID 19, treatment with plant extracts could be an option worthy of further investigation. Purpose: To screen the phytochemicals for Anti-SARS-CoV-2 in silico and evaluate their safety and efficacy in vitro and in vivo. Method: The phytochemicals for Anti-SARS-CoV-2 were screened in silico using molecular docking. The hits generated from in silico screening were subjected for extraction, isolation and purification. The anti-SARS-CoV-2 activity of plant extracts of Z. piperitum (ATRI-CoV-E1), W. somnifera (ATRI-CoV-E2), C. inophyllum (ATRI-CoV-E3), A. paniculata (ATRI-CoV-E4), and C. Asiatica (ATRI-CoV-E5). The in vitro safety and anti- SARS-CoV-2 activity of plant extracts were performed in VeroE6 cells using Remdesivir as positive control. The acute and sub-acute toxicity study was performed in Wistar male and female rats. Results: The percentage of cell viability for ATRI-COV-E4, ATRI-COV-E5 and ATRI-COV-E2 treated VeroE6 cells were remarkably good on the 24th and 48th hour of treatment. The in vitro anti-SARS-CoV-2 activity of ATRI-COV-E4, ATRI-COV-E5 and ATRI-COV-E2 were significant for both E gene and N gene. The percentage of SARS-CoV-2 inhibition for ATRI-COV-E4 was better than Remdesivir. For E gene and N gene, Remdesivir showed IC50 of 0.15 micromolar and 0.11 micromolar respectively, For E gene and N gene, ATRI-CoV-E4 showed IC50 of 1.18 microgram and 1.16 microgram respectively. Taking the clue from in vitro findings, the plant extracts A. paniculata (ATRI-COV-E4), W. somnifera extract (ATRI-COV-E5) and C. asiatica extract (ATRI-COV-E2) were combined (ATRICOV 452) and evaluated for acute and sub-acute toxicity in Wistar male and female rats. No statistically significant difference in haematological, biochemical and histopathological parameters were noticed. Conclusion: The study demonstrated the Anti-SARS-CoV-2 activity in vitro and safety of plant extracts in both in vitro and in vivo experimental conditions.
  🖺 Full Text HTML: In silico, In vitro Screening of Plant Extracts for Anti-SARS-CoV-2 Activity and Evaluation of Their Acute and Sub-Acute Toxicity
• Cigarette smoke preferentially induces full length ACE2 exposure in primary human airway cells but does not alter susceptibility to SARS-CoV-2 infection -
  Cigarette smoking has multiple serious negative health consequences. However, the epidemiological relationship between cigarette smoking and SARS-CoV-2 infection is controversial; and the interaction between cigarette smoking, airway expression of the ACE2 receptor and the susceptibility of airway cells to infection is unclear. We exposed differentiated air-liquid interface cultures derived from primary human airway stem cells to cigarette smoke extract (CSE) and infected them with SARS-CoV-2. We found that CSE increased expression of full-length ACE2 (flACE2) but did not alter the expression of a Type I-interferon sensitive truncated ACE2 that lacks the capacity to bind SARS-CoV-2 or a panel of interferon-sensitive genes. Importantly, exposure to CSE did not increase viral infectivity despite the increase in flACE2. Our data are consistent with epidemiological data suggesting current smokers are not at excess risk of SARS-CoV-2 infection. This does not detract from public health messaging emphasising the excess risk of severe COVID-19 associated with smoking-related cardiopulmonary disease.
  🖺 Full Text HTML: Cigarette smoke preferentially induces full length ACE2 exposure in primary human airway cells but does not alter susceptibility to SARS-CoV-2 infection
• SARS-CoV-2 mRNA vaccination elicits robust and persistent T follicular helper cell response in humans -
  SARS-CoV-2 mRNA vaccines generate high and persistent levels of circulating anti-spike (S) antibodies and S-specific CD4+ T cells following prime-boost vaccination. It is not yet clear whether vaccine-induced follicular helper CD4+ T (TFH) cell responses in the draining lymph nodes contribute to this outstanding immunogenicity. Using fine needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we show that frequency of TFH correlates with that of S-binding germinal center B cells. Mining of of the responding TFH T cell receptor repertoire revealed a strikingly immunodominant HLA-DPB1*04-restricted response to S167-180 in individuals with this allele, which is itself among the most common HLA alleles in humans. Analysis of paired blood and lymph node specimens show that circulating S-specific TFH cells peak one week after the second immunization while S-specific lymph node TFH persist at nearly constant frequencies for at least six months following mRNA vaccination. Collectively, our results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this very efficacious human vaccine.
  🖺 Full Text HTML: SARS-CoV-2 mRNA vaccination elicits robust and persistent T follicular helper cell response in humans
• SARS-CoV-2 mRNA Vaccination-Associated Myocarditis in Children Ages 12-17: A Stratified National Database Analysis -

  Objectives: Establishing the rate of post-vaccination cardiac myocarditis in the 12-15 and 16-17-year-old population in the context of their COVID-19 hospitalization risk is critical for developing a vaccination recommendation framework that balances harms with benefits for this patient demographic. Design, Setting and Participants: Using the Vaccine Adverse Event Reporting System (VAERS), this retrospective epidemiological assessment reviewed reports filed between January 1, 2021, and June 18, 2021, among adolescents ages 12-17 who received mRNA vaccination against COVID-19. Symptom search criteria included the words myocarditis, pericarditis, and myopericarditis to identify children with evidence of cardiac injury. The word troponin was a required element in the laboratory findings. Inclusion criteria were aligned with the CDC working case definition for probable myocarditis. Stratified cardiac adverse event (CAE) rates were reported for age, sex and vaccination dose number. A harm-benefit analysis was conducted using existing literature on COVID-19-related hospitalization risks in this demographic. Main outcome measures: 1) Stratified rates of mRNA vaccine-related myocarditis in adolescents age 12-15 and 16-17; and 2) harm-benefit analysis of vaccine-related CAEs in relation to COVID-19 hospitalization risk. Results: A total of 257 CAEs were identified. Rates per million following dose 2 among males were 162.2 (ages 12-15) and 94.0 (ages 16-17); among females, rates were 13.0 and 13.4 per million, respectively. For boys 12-15 without medical comorbidities receiving their second mRNA vaccination dose, the rate of CAE is 3.7-6.1 times higher than their 120-day COVID-19 hospitalization risk as of August 21, 2021 (7-day hospitalizations 1.5/100k population) and 2.6-4.3-fold higher at times of high weekly hospitalization risk (2.1/100k), such as during January 2021. For boys 16-17 without medical comorbidities, the rate of CAE is currently 2.1-3.5 times higher than their 120-day COVID-19 hospitalization risk, and 1.5-2.5 times higher at times of high weekly COVID-19 hospitalization. Conclusions: Post-vaccination CAE rate was highest in young boys aged 12-15 following dose two. For boys 12-17 without medical comorbidities, the likelihood of post vaccination dose two CAE is 162.2 and 94.0/million respectively. This incidence exceeds their expected 120-day COVID-19 hospitalization rate at both moderate (August 21, 2021 rates) and high COVID-19 hospitalization incidence. Further research into the severity and long-term sequelae of post-vaccination CAE is warranted. Quantification of the benefits of the second vaccination dose and vaccination in addition to natural immunity in this demographic may be indicated to minimize harm.

  🖺 Full Text HTML: SARS-CoV-2 mRNA Vaccination-Associated Myocarditis in Children Ages 12-17: A Stratified National Database Analysis
• Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques -
  Advanced age is a key predictor of severe COVID-19. To gain insight into this relationship, particularly with respect to immune responses, we utilized the rhesus macaque model of SARS-CoV-2 infection. Two cohorts of eight older (16-23 years) and eight younger (3-5 years) rhesus macaques were inoculated with SARS-CoV-2. Animals were evaluated using viral RNA quantification, clinical observations, thoracic radiographs, single-cell transcriptomics, multiparameter flow cytometry, multiplex immunohistochemistry, cytokine detection, and lipidomics analysis at pre-defined timepoints in various tissues. Differences in clinical signs, pulmonary infiltrates, and virus replication dynamics were limited between age cohorts. Transcriptional signatures of inflammation-associated genes in cells isolated from bronchoalveolar lavage fluid at 3 dpi revealed efficient mounting of innate immune defenses in both younger and older animals. These findings suggested that age did not substantially skew major facets of acute disease in this model. However, age- specific divergence of immune responses emerged during the post-acute phase of infection (7-21 dpi). Older animals exhibited sustained local inflammatory innate responses while local effector T-cell responses were induced earlier in the younger animals. Circulating lipid mediator and cytokine levels highlighted increased repair-associated signals in the younger animals, in contrast to persistent pro-inflammatory responses in the older animals. In summary, despite similar disease outcomes, multi-omics profiling in SARS-CoV-2-infected rhesus macaques suggests that age may delay or impair the induction of anti-viral cellular immune responses and delay efficient return to immune homeostasis following acute infection.
  🖺 Full Text HTML: Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques
• An anti-SARS-CoV-2 non-neutralizing antibody with Fc-effector function defines a new NTD epitope and delays neuroinvasion and death in K18-hACE2 mice -
  Emerging evidence in animal models indicate that both neutralizing activity and Fc-mediated effector functions of neutralizing antibodies contribute to protection against SARS-CoV-2. It is unclear if antibody effector functions alone could protect against SARS-CoV-2. Here we isolated CV3-13, a non-neutralizing antibody from a convalescent individual with potent Fc-mediated effector functions that targeted the N-terminal domain (NTD) of SARS-CoV-2 Spike. The cryo-EM structure of CV3-13 in complex with SAR-CoV-2 spike revealed that the antibody bound from a distinct angle of approach to a novel NTD epitope that partially overlapped with a frequently mutated NTD supersite in SARS-CoV-2 variants. While CV3-13 did not alter the replication dynamics of SARS-CoV-2 in a K18-hACE2 transgenic mouse model, an Fc-enhanced CV3-13 significantly delayed neuroinvasion and death in prophylactic settings. Thus, we demonstrate that efficient Fc-mediated effector functions can contribute to the in vivo efficacy of anti-SARS-CoV-2 monoclonal antibodies in the absence of neutralization.
  🖺 Full Text HTML: An anti-SARS-CoV-2 non-neutralizing antibody with Fc-effector function defines a new NTD epitope and delays neuroinvasion and death in K18-hACE2 mice
• TET1 controls Cxcl1 induction by DNA demethylation and promotes neutrophil recruitment during acute lung injury -
  Neutrophils are rapidly recruited from the peripheral blood to the inflammatory site to initiate inflammatory response against pathogenic infections. The process to recruit neutrophils must be properly regulated since the abnormal accumulation of neutrophils can cause organ damage and dysfunction. The acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a common cause of respiratory failure that is characterized by the infiltration of neutrophils and epithelial integrity disruption. Indeed, recent studies suggest a pathogenic role of neutrophils in the clinic severity of the coronavirus disease 2019 (COVID-19) ARDS. The chemokine CXCL1, which is rapidly induced by inflammatory stimuli, plays a key role in neutrophil influx during lung inflammation. The molecular basis of Cxcl1 induction is not fully understood. Here we report that TET1, a member of the ten eleven translocation (TET) methylcytosine dioxygenase protein family, displays a striking specificity in the regulation of gene expression in macrophages. RNA sequencing (RNA-seq) analysis showed that Tet1 disruption significantly altered the expression of only 48 genes that include Cxcl1 and several other genes known to be important for cell migration and trafficking in bone marrow derived macrophages (BMDMs) in response to LPS stimulation. TET1 regulates the induction of Cxcl1 by facilitating the DNA demethylation of the Cxcl1 promoter. In Tet1-/- mice, the induction of Cxcl1 was suppressed, resulting in defective neutrophil recruitment to the lung during LPS-induced acute lung injury. Our results identify a novel epigenetic mechanism that selectively controls Cxcl1 induction and neutrophil recruitment during acute lung injury.
  🖺 Full Text HTML: TET1 controls Cxcl1 induction by DNA demethylation and promotes neutrophil recruitment during acute lung injury
• No substantial pre-existing B cell immunity against SARS-CoV-2 in healthy adults -
  Pre-existing immunity against SARS-CoV-2 may have critical implications for our understanding of COVID-19 susceptibility and severity. Various studies recently provided evidence of pre-existing T cell immunity against SARS- CoV-2 in unexposed individuals. In contrast, the presence and clinical relevance of a pre-existing B cell immunity remains to be fully elucidated. Here, we provide a detailed analysis of the B cell response to SARS-CoV-2 in unexposed individuals. To this end, we extensively investigated the memory B cell response to SARS-CoV-2 in 150 adults sampled pre-pandemically. Comprehensive screening of donor plasma and purified IgG samples for binding and neutralization in various functional assays revealed no substantial activity against SARS-CoV-2 but broad reactivity to endemic betacoronaviruses. Moreover, we analyzed antibody sequences of 8,174 putatively SARS-CoV-2-reactive B cells on a single cell level and generated and tested 158 monoclonal antibodies. None of the isolated antibodies displayed relevant binding or neutralizing activity against SARS-CoV-2. Taken together, our results show no evidence of relevant pre- existing antibody and B cell immunity against SARS-CoV-2 in unexposed adults.
  🖺 Full Text HTML: No substantial pre-existing B cell immunity against SARS-CoV-2 in healthy adults
• Reducing air travel related greenhouse gas emissions in academia: An empirical policy overview -
  Demand for air travel must be reduced to align the aviation sector with international climate agreements. In line with this necessity, as well as motivated by the notion that academia has a responsibility to foster sustainable development, some academic institutions have begun reducing greenhouse gas emissions associated with their members’ air travel. Based on an online survey from early 2021, this article summarizes the practices of 35 academic institutions in Western Europe and the US that are committed to achieving such reductions. It aims to facilitate the exchange of knowledge between these institutions, thus creating a basis for informed development of future projects. A new classification of policy measures in this area is applied in this article, which reveals that policy activity focuses on low-coercive measures that encourage substituting air travel with virtual communication technology and ground-based transportation. The findings further indicate that the collection of data on air travel is an essential but challenging precursor to policy action. The discussion shows that these findings are consistent with country-specific analyses of academic institutions’ policy documents. The need for continued action to reduce emissions related to air travel, including ongoing investments in virtual communication, after the COVID-19 pandemic is emphasized. We also discuss potential acceptance of more coercive policy measures and suggest tackling the systemic effects of institutional internationalization strategies by including private travel needs engendered by international recruitment efforts in institutions’ calculations of travel emissions.
  🖺 Full Text HTML: Reducing air travel related greenhouse gas emissions in academia: An empirical policy overview
• SARS-CoV-2 infected cells trigger an acute antiviral response mediated by Plasmacytoid dendritic cells in mild but not severe COVID-19 patients -

  Type I and III interferons (IFN-I/λ) are key antiviral mediators against SARS-CoV-2 infection. Here, we demonstrate that the plasmacytoid dendritic cells (pDCs) are predominant IFN-I/λ source by sensing SARS-CoV-2-infected cells. We show that sensing of viral RNA by pDCs requires sustained cell adhesion with infected cells. In turn, the pDCs restrict viral spread by a local IFN-I/λ response directed toward SARS-CoV-2-infected cells. This specialized function enables pDCs to efficiently turn-off viral replication, likely by a concentrated flux of antiviral effectors at the contact site with infected cells. Therefore, we propose that pDC activation is essential to locally control SARS- CoV-2-infection. By exploring the pDC response in patients, we further demonstrate that pDC responsiveness correlates with the severity of the disease and in particular that it is impaired in severe COVID-19 patients. Thus, the ability of pDCs to respond to SARS-CoV-2-infected cells could be a key to understand severe cases of COVID-19.

  🖺 Full Text HTML: SARS-CoV-2 infected cells trigger an acute antiviral response mediated by Plasmacytoid dendritic cells in mild but not severe COVID-19 patients
• AZD7442 demonstrates prophylactic and therapeutic efficacy in non-human primates and extended half-life in humans -

  Despite the success of SARS-CoV-2 vaccines, there remains a need for more prevention and treatment options for individuals remaining at risk of COVID-19. Monoclonal antibodies (mAbs) against the viral spike protein have potential to both prevent and treat COVID-19, and reduce the risk of severe disease and death. Here, we describe AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct non- overlapping epitopes on the spike protein receptor binding domain to potently neutralize SARS-CoV-2. Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and abrogate effector functions. The AZD7442 mAbs individually prevent the spike protein from binding to angiotensin-converting enzyme 2 receptor, blocking virus cell entry. Together, these two mAbs create a higher barrier to viral escape and a wider breadth of coverage, neutralizing all known SARS-CoV-2 variants of concern. In a non-human primate model of SARS- CoV-2 infection, prophylactic AZD7442 administration prevented infection, while therapeutic administration accelerated virus clearance from lung. In an ongoing Phase I study in healthy participants (NCT04507256), 300 mg intramuscular AZD7442 provided SARS-CoV-2 serum geometric mean neutralizing titers >10-fold above those of convalescent sera for >=3 months, which remained 3-fold above those of convalescent sera 9 months post-AZD7442 administration. Approximately 1-2% of serum AZD7442 levels were detected in nasal mucosa, a site of SARS-CoV-2 infection. Extrapolation of the time course of serum AZD7442 concentrations suggests AZD7442 may provide up to 12 months of protection and benefit individuals at high-risk of COVID-19.

  🖺 Full Text HTML: AZD7442 demonstrates prophylactic and therapeutic efficacy in non-human primates and extended half-life in humans
• High-Throughput Adaptable SARS-CoV-2 Screening for Rapid Identification of Dominant and Emerging Regional Variants -

  Objectives: Emerging SARS-CoV-2 variant strains can be associated with increased transmissibility, more severe disease, and reduced effectiveness of treatments. To improve the availability of regional variant surveillance, we describe a variant genotyping system that is rapid, accurate, adaptable, and able to detect new low-level variants built with existing hospital infrastructure. Methods: We use a tiered high-throughput SARS-CoV-2 screening program to characterizes variants in a supra-regional health system over 76 days. Combining targeted qPCR and selective sequencing, we screen positive SARS-CoV-2 samples from all hospitals within our health care system for genotyping dominant and emerging variants. Results: The median turnaround for genotyping was two days using the high-throughput qPCR-based screen, allowing us to rapidly characterize the emerging Delta variant. In our population, the Delta variant is associated with a lower CT value, lower age at infection, and increased vaccine breakthrough cases. Detection of low- level and potentially emerging variants highlights the utility of a tiered approach. Conclusions: These findings underscore the need for fast, low-cost, high-throughput monitoring of regional viral sequences as the pandemic unfolds and the emergence of SARS-CoV-2 variants increases. Combing qPCR-based screening with selective sequencing allows for rapid genotyping of variants and dynamic system improvement.

  🖺 Full Text HTML: High-Throughput Adaptable SARS-CoV-2 Screening for Rapid Identification of Dominant and Emerging Regional Variants
• Increasing incidence of parosmia and phantosmia in patients recovering from COVID-19 smell loss -

  Importance: Sudden smell loss is a specific early symptom of COVID-19, with an estimated prevalence of ~40% to 75%. Smell impairment affects physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. Objective: To characterize smell function and recovery up to 11 months post COVID-19 infection. Settings, Participants: This longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial respiratory symptoms, chemosensory function, and COVID-19 diagnosis survey (S1) between April and September 2020 and completed a follow-up survey (S2) between September 2020 and February 2021; 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. Main Outcomes & Measures: Primary outcomes are ratings of smell and taste function on a visual analog scale, and self-report of parosmia (smell distortions) and phantosmia (unexplained smells). Secondary outcomes include a checklist of other COVID-19 symptoms. Results: On follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID. During COVID-19 illness, the ability to smell was slightly lower among those who did not recover their pre-illness ability to smell at S2. Conclusions and Relevance: While smell loss improves for many individuals who lost it due to COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is also associated with wider COVID-19 symptoms and may persist for many months after COVID-19 onset. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long-term sequelae; more research into treatment options is strongly warranted given that conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health.

  🖺 Full Text HTML: Increasing incidence of parosmia and phantosmia in patients recovering from COVID-19 smell loss

From Clinical Trials

• High-dose Intravenous Vitamin C (HDIVC) as Adjuvant Therapy in Critical Patients With Positive COVID-19. A Pilot Randomized Controlled Dose-comparison Trial. - Condition:   Covid19
  Interventions:   Drug: High doses of intravenous vitamin C;   Drug: Dextrose 500 mL
  Sponsor:   Hugo Galindo
  Not yet recruiting

• Developing and Testing a COVID-19 Vaccination Acceptance Intervention - Condition:   COVID-19 Vaccination
  Intervention:   Behavioral: Moving to COVID-19 Vaccine Acceptance Intervention
  Sponsors:   VA Office of Research and Development;   VA Bedford Healthcare System
  Not yet recruiting

• Study on Safety and Clinical Efficacy of AZVUDINE in Initial Stage COVID-19 Patients (SARS-CoV-2 Infected) - Condition:   COVID-19
  Interventions:   Drug: AZVUDINE;   Drug: AZVUDINE placebo
  Sponsors:   HRH Holdngs Limited;   GALZU INSTITUTE OF RESEARCH, TEACHING, APPLIED SCIENCE AND TECHNOLOGY, Brazil;   SANTA CASA DE MISERICORDIA DE CAMPOS HOSPITAL (SCMCH), Brazil;   UNIVERSIDADE ESTADUAL DO NORTE FLUMINENSE (UENF), Brazil
  Not yet recruiting

• COVID-19 Morbidity in Healthcare Workers and Vitamin D Supplementation - Condition:   COVID-19 Respiratory Infection
  Intervention:   Drug: Vitamin D
  Sponsor:   Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
  Completed

• Text Message Nudges for COVID-19 Vaccination - Condition:   Covid19
  Intervention:   Behavioral: Text message
  Sponsor:  
  Ascension South East Michigan
  Not yet recruiting

• Quercetin in the Prevention of Covid-19 Infection - Condition:   Covid19
  Interventions:   Dietary Supplement: Quercetin;   Combination Product: Placebo
  Sponsor:   Azienda di Servizi alla Persona di Pavia
  Completed

• A Study to Evaluate Change in Viral Load After OPN-019 in Adults With COVID-19 - Condition:   Covid19
  Intervention:   Drug: OPN-019
  Sponsor:   Optinose US Inc.
  Recruiting

• Physical Activity and Smell Trainings to Help Individuals With Coronavirus Disease (COVID-19) Recover From Persistent Smell and Taste Impairments - A Pilot Study - Condition:   Covid19
  Interventions:   Behavioral: Physical activity;   Other: Smell training
  Sponsor:   Université de Montréal
  Not yet recruiting

• Evaluation of the Efficacy, Safety and Immunogenicity of Inactivated COVID 19 Vaccine(TURKOVAC) in Healthy Population of 18 and 64 Years of Age (Both Inclusive):a Randomized, Double-blind, Phase IIb Clinical Trial - Condition:   Covid19
  Intervention:   Biological: Triple dose vaccination by inactivated Covid19 vaccine
  Sponsors:   Health Institutes of Turkey;   TC Erciyes University;   Kocak Farma;   Mene Research
  Not yet recruiting

• Cardiopulmonary Rehabilitation in Long COVID-19 Patients With Persistent Breathlessness and Fatigue - Condition:   COVID-19 Respiratory Infection
  Intervention:  
  Other: Cardiopulmonary exercise training
  Sponsor:   Louis Bherer
  Recruiting

• Clinical Trial on Sequential Immunization of Recombinant COVID-19 Vaccine (CHO Cells) and Inactivated COVID-19 Vaccine (Vero Cells) in Population Aged 18 Years and Above - Conditions:   COVID-19 Pneumonia;   Coronavirus Infections
  Interventions:   Biological: Recombinant COVID-19 Vaccine (CHO cell);   Biological: COVID-19 vaccine (Vero cells)
  Sponsors:  
  National Vaccine and Serum Institute, China;   China National Biotec Group Company Limited;   Lanzhou Institute of Biological Products Co., Ltd
  Not yet recruiting

• Study to Evaluate the Efficacy and Safety of Colchicine Tablets in Patients With COVID-19 - Conditions:   Covid19;   Colchicine
  Interventions:   Drug: Colchicine Tablets;   Drug: Standard therapy
  Sponsors:   Shanghai Public Health Clinical Center;   Kunming Pharmaceuticals, Inc.
  Not yet recruiting

• Comparison of Detection of SARS-CoV2 (COVID-19) Between Nasopharyngeal Swab Specimens and Those Obtained by Salivary Sputum - Condition:   Covid19
  Intervention:   Diagnostic Test: Salivary test for COVID19
  Sponsor:   Centre Hospitalier de Cayenne
  Active, not recruiting

• Phase 2a MIB-626 vs. Placebo COVID-19 - Conditions:   Covid19;   Stage 1 Acute Kidney Injury
  Interventions:   Drug: MIB-626;   Drug: Placebo;   Other: Home Treatment
  Sponsor:   Metro International Biotech, LLC
  Not yet recruiting

• Clinical Study of the Safety and Immunogenicity of a Recombinant Viral Vector AAV5 (Adeno-Associated Virus Type 5 )-RBD (Receptor Binding Domain)-S Vaccine for the Prevention of Coronavirus Infection (COVID-19) - Conditions:   Coronavirus Infection;   COVID-19
  Interventions:  
  Biological: Low dose BCD-250 injection;   Biological: High dose BCD-250 injection;   Biological: Low dose or high dose BCD-250 injection;   Other: Placebo injection
  Sponsor:   Biocad
  Recruiting

From PubMed

• Interactions of anti-COVID-19 drug candidates with hepatic transporters may cause liver toxicity and affect pharmacokinetics - Transporters in the human liver play a major role in the clearance of endo- and xenobiotics. Apical (canalicular) transporters extrude compounds to the bile, while basolateral hepatocyte transporters promote the uptake of, or expel, various compounds from/into the venous blood stream. In the present work we have examined the in vitro interactions of some key repurposed drugs advocated to treat COVID-19 (lopinavir, ritonavir, ivermectin, remdesivir and favipiravir), with the key drug transporters…

• In vitro efficacy of Artemisia extracts against SARS-CoV-2 - CONCLUSIONS: Some plant extracts show inhibitory activity against FCoV and SARS-CoV-2. However, it remains unclear whether peak plasma concentrations in humans can reach levels needed to inhibit viral infection following consumption of teas or Covid-Organics. Clinical studies are required to evaluate the utility of these drinks for COVID-19 prevention or treatment of patients.

• Physiologically based pharmacokinetic modelling to investigate the impact of the cytokine storm on CYP3A drug pharmacokinetics in COVID-19 patients - COVID-19 patients may experience a cytokine storm with elevated interleukin-6 (IL-6) levels in response to SARS-CoV-2. IL-6 suppresses hepatic enzymes, including CYP3A; however, the effect on drug exposure and drug-drug interaction magnitudes of the cytokine storm and resulting elevated IL-6 levels have not been characterized in COVID-19 patients. We used physiologically based pharmacokinetic (PBPK) modelling to simulate the effect of inflammation on the pharmacokinetics of CYP3A metabolized…

• Screening Anti-inflammatory, Anticoagulant, and Respiratory Agents for SARS-CoV-2 3CL(pro) Inhibition from Chemical Fingerprints Through a Deep Learning Approach - CONCLUSIONS: Those findings point to a possible desirable synergistic effect in the management of patients with COVID-19 and provide potential directions for in vitro and in vivo research, which are indispensable for the validation of their results.

• Cytoplasmic tail truncation of SARS-CoV-2 Spike protein enhances titer of pseudotyped vectors but masks the effect of the D614G mutation - The high pathogenicity of SARS-CoV-2 requires it to be handled under biosafety level 3 conditions. Consequently, Spike protein pseudotyped vectors are a useful tool to study viral entry and its inhibition, with retroviral, lentiviral (LV) and vesicular stomatitis virus (VSV) vectors the most commonly used systems. Methods to increase the titer of such vectors commonly include concentration by ultracentrifugation and truncation of the Spike protein cytoplasmic tail. However, limited studies have…

• The ApoA-I mimetic peptide 4F attenuates in vitro replication of SARS-CoV-2, associated apoptosis, oxidative stress and inflammation in epithelial cells - An oral antiviral against SARS-CoV-2 that also attenuates inflammatory instigators of severe COVID-19 is not available to date. Herein, we show that the apoA-I mimetic peptide 4 F inhibits Spike mediated viral entry and has antiviral activity against SARS-CoV-2 in human lung epithelial Calu3 and Vero-E6 cells. In SARS-CoV-2 infected Calu3 cells, 4 F upregulated inducers of the interferon pathway such as MX-1 and Heme oxygenase 1 (HO-1) and downregulated mitochondrial reactive oxygen species…

• Analysis of the Role of N-Linked Glycosylation in Cell Surface Expression, Function, and Binding Properties of SARS- CoV-2 Receptor ACE2 - Human angiotensin I-converting enzyme 2 (hACE2) is a type I transmembrane glycoprotein that serves as the major cell entry receptor for SARS-CoV and SARS-CoV-2. The viral spike (S) protein is required for the attachment to ACE2 and subsequent virus-host cell membrane fusion. Previous work has demonstrated the presence of N-linked glycans in ACE2. N-glycosylation is implicated in many biological activities, including protein folding, protein activity, and cell surface expression of biomolecules….

• C(60) fullerene against SARS-CoV-2 coronavirus: an in silico insight - Based on WHO reports the new SARS-CoV-2 coronavirus is currently widespread all over the world. So far > 162 million cases have been confirmed, including > 3 million deaths. Because of the pandemic still spreading across the globe the accomplishment of computational methods to find new potential mechanisms of virus inhibitions is necessary. According to the fact that C(60) fullerene (a sphere-shaped molecule consisting of carbon) has shown inhibitory activity against various protein targets,…

• Functional comparison of MERS-coronavirus lineages reveals increased replicative fitness of the recombinant lineage 5 - Middle East respiratory syndrome coronavirus (MERS-CoV) is enzootic in dromedary camels across the Middle East and Africa. Virus-induced pneumonia in humans results from animal contact, with a potential for limited onward transmission. Phenotypic changes have been suspected after a novel recombinant clade (lineage 5) caused large nosocomial outbreaks in Saudi Arabia and South Korea in 2016. However, there has been no functional assessment. Here we perform a comprehensive in vitro and ex vivo…

• Computational Analysis Illustrates the Mechanism of Qingfei Paidu Decoction in Blocking the Transition of COVID-19 Patients from Mild to Severe Stage - CONCLUSION: QFPDD can prevent the deterioration of COVID-19 in the following mechanisms, i.e. inhibiting SARS-CoV-2 invasion and replication, anti-inflammatory and immune regulation, and repairing body damage. These results will be helpful for the prevention and treatment of COVID-19.

• Post COVID-19 pandemic: Biofragmentation and soil ecotoxicological effects of microplastics derived from face masks - Because of the COVID-19 pandemic, used face masks have increasingly littered the environment and are causes for concern since they are commonly made of plastics such as polypropylene. Understanding production of microplastics from face masks is essential for predicting the post COVID-19 pandemic impact on the soil ecosystem. We investigated the generation of nanofibers from meltblown face mask filters (MB filters) and their adverse effects on soil species, particularly the earthworm and…

• Triclosan weakens the nitrification process of activated sludge and increases the risk of the spread of antibiotic resistance genes - The usage of triclosan (TCS) may rise rapidly due to the COVID-19 pandemic. TCS usually sinks in the activated sludge. However, the effects of TCS in activated sludge remain largely unknown. The changes in nitrogen cycles and the abundances of antibiotic resistance genes (ARGs) caused by TCS were investigated in this study. The addition of 1000 μg/L TCS significantly inhibited nitrification since the ammonia conversion rate and the abundance of nitrification functional genes decreased by 12.14%….

• Aerosol deposition and airflow dynamics in healthy and asthmatic human airways during inhalation - Inhalation of aerosols such as pharmaceutical aerosols or virus aerosol uptake is of great concern to the human population. To elucidate the underlying aerosol dynamics, the deposition fractions (DFs) of aerosols in healthy and asthmatic human airways of generations 13-15 are predicted. The Navier-stokes equations governing the gaseous phase and the discrete phase model for particles’ motion are solved using numerical methods. The main forces responsible for deposition are inertial impaction…

• Multiscale model of defective interfering particle replication for influenza A virus infection in animal cell culture - Cell culture-derived defective interfering particles (DIPs) are considered for antiviral therapy due to their ability to inhibit influenza A virus (IAV) production. DIPs contain a large internal deletion in one of their eight viral RNAs (vRNAs) rendering them replication-incompetent. However, they can propagate alongside their homologous standard virus (STV) during infection in a competition for cellular and viral resources. So far, experimental and modeling studies for IAV have focused on…

• SARS-CoV-2 Antibody Response to the BNT162b2 mRNA Vaccine in Persons with Past Natural Infection - There are still no agreed guidelines on the vaccination of coronavirus disease 2019 (COVID-19) for previously infected patients. Here, we present two seropositive healthcare workers (HCWs) working in an isolation ward who recovered from COVID-19 in April 2020 and got vaccinated with BNT162b2 vaccine in March 2021. We have assessed the clinical course, vaccine-related adverse events, and antibody response after natural infection and after first and second dose vaccination. One of the two HCWs was…

From Patent Search

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

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

• Expression Vector for Anti-Sars-Cov-2 Neutralizing Antibodies - - link

• DEVELOPMENT OF CNN SCHEME FOR COVID-19 DISEASE DETECTION USING CHEST RADIOGRAPH - - link

• SARS-COV-2 BINDING PROTEINS - - link

• COVID-19胸部CT图像识别方法、装置及电子设备 - 本申请涉及一种COVID‑19胸部CT图像识别方法、装置及电子设备。所述方法获取COVID‑19的胸部CT图像，并针对胸部CT图像的特点，构建新冠肺炎CT识别网络，对该网络进行训练得到COVID‑19胸部CT图像识别模型，并利用该模型对待测CT图像进行分类。采用空洞卷积、深度卷积以及点卷积算子，减少冗余参数；采用并行结构连接方式，实现多尺度特征融合、降低模型复杂度；采用下采样方式，使用最大模糊池化以减少锯齿效应，保持信号的平移不变性；采用通道混洗操作，减少参数量与计算量，提高分类准确率，引入坐标注意力机制，使空间坐标信息与通道信息被关注，抑制不重要的信息，以解决资源匹配问题。 - link

• A PROCESS FOR PREPARING MONTELUKAST SODIUM FOR TREATING COVID 19 PATIENTS - - link

• IDENTIFICATION OF ANTI-COVID 19 AGENT SOMNIFERINE AS INHIBITOR OF MPRO & ACE2-RBD INTERACTION - - link

• 一种脂质化合物及包含其的脂质载体、核酸脂质纳米粒组合物和药物制剂 - 本发明属于基因治疗技术领域，具体涉及一系列脂质化合物及包含其的脂质载体、核酸脂质纳米粒组合物和药物制剂。本发明提供的具有式（I）结构的化合物，可与其它脂质化合物共同制备脂质载体，展现出pH响应性，对核酸药物的包封效率高，大大提升了核酸药物在体内的递送效率；而且，可根据核酸药物需要富集的器官而选用特定结构的脂质化合物作为脂质载体，具有良好的市场应用前景。 - link