Covid-19 Sentry

Contents

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

From Preprints

• The COVID States Project #75: Attitudes toward COVID-19 boosters before and after Omicron -
  Recognizing that the protection conferred by COVID-19 vaccines may wane over time, the US Centers for Disease Control and Prevention (CDC) has encouraged adults in the United States to receive booster shots that can augment their immunity to the virus. While the Biden administration sought to encourage all adults to receive boosters, the CDC initially authorized the shots only for higher-risk individuals. Subsequently, authorization was broadened to all adults, although only higher-risk individuals were encouraged to pursue boosters. Most recently, after substantial criticism, the CDC changed its language to encourage all adults to receive boosters. But regardless of the language, are US adults sufficiently convinced to seek booster shots? Will the same factors that contributed to COVID-19 vaccine hesitancy and vaccine resistance impact booster shots? The answers may have profound public health implications as the US enters the season during which respiratory viruses typically have the greatest impact, and the highly-transmissible Omicron variant rapidly becomes the dominant form of COVID-19, after being labeled a variant of concern by the World Health Organization on November 26th. Between November 3rd and December 3rd, 2021, the COVID States Project asked 22,277 adults in all 50 US states and the District of Columbia about their attitudes and behaviors regarding COVID-19. In particular, we asked about whether people are vaccinated or intend to be vaccinated, and whether they had sought booster shots or intend to seek a booster shot. In this brief report, we examine attitudes toward COVID-19 booster shots, and whether they differ across particular groups of people. Since the survey was ongoing when news about Omicron emerged in the US, we also take an initial look at whether these attitudes have begun to shift along with perceptions of the threat posed by COVID-19 subsequent to the November 26th announcement.
  🖺 Full Text HTML: The COVID States Project #75: Attitudes toward COVID-19 boosters before and after Omicron
• Conjunctival epithelial cells resist productive SARS-CoV-2 infection -
  Although tropism of SARS-CoV-2 for respiratory tract epithelial cells is well established, an open question is whether the conjunctival epithelium is also a target for SARS-CoV-2. Conjunctival epithelial cells, which express viral entry receptors ACE2 and TMPRSS2, constitute the largest exposed epithelium of the ocular surface tissue, and may represent a relevant viral entry route. To address this question, we generated an organotypic air-liquid-interface model of conjunctival epithelium, composed of progenitor, basal and superficial epithelial cells and fibroblasts, which could be maintained successfully up to day 75 of differentiation. Using single-cell RNA Seq, with complementary imaging and virological assays, we observed that while all conjunctival cell types were permissive to SARS-CoV-2 genome expression, a productive infection did not ensue. The early innate immune response to SARS-CoV-2 infection in conjunctival cells was characterised by a robust autocrine and paracrine NF-K{beta} activity, without activation of antiviral interferon signalling. Collectively, these data enrich our understanding of SARS-CoV-2 infection at the human ocular surface, with potential implications for the design of preventive strategies and conjunctival transplants.
  🖺 Full Text HTML: Conjunctival epithelial cells resist productive SARS-CoV-2 infection
• Engineered High-Affinity ACE2 Peptide Mitigates ARDS and Death Induced by Multiple SARS-CoV-2 Variants -
  Vaccine hesitancy and continuing emergence of SARS-CoV-2 variants of concern that may escape vaccine-induced immune responses highlight the urgent need for effective COVID-19 therapeutics. Monoclonal antibodies used in the clinic have varying efficacies against distinct SARS-CoV-2 variants; thus, there is considerable interest in engineered ACE2 peptides with augmented binding affinities for SARS-CoV-2 Spike protein. These could have therapeutic benefit against multiple viral variants. Using machine learning and molecular dynamics simulations, we show how three amino acid substitutions in an engineered soluble ACE2 peptide (sACE22.v2.4-IgG1) markedly increase affinity for the SARS-CoV-2 Spike (S) protein. We demonstrate high binding affinity to S protein of the early SARS-CoV-2 WA-1/2020 isolate and also to multiple variants of concern: B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) SARS-CoV-2 variants. In humanized K18-hACE2 mice, prophylactic and therapeutic administration of sACE22.v2.4-IgG1 peptide prevented acute lung vascular endothelial injury and lung edema (essential features of ARDS) and significantly improved survival after infection by SARS-CoV-2 WA-1/2020 as well as P.1 variant of concern. These studies demonstrate for the first time broad efficacy in vivo of an ACE2 decoy peptide against multiple SARS-CoV-2 variants and point to its therapeutic potential.
  🖺 Full Text HTML: Engineered High-Affinity ACE2 Peptide Mitigates ARDS and Death Induced by Multiple SARS-CoV-2 Variants
• Neutralization against Omicron SARS-CoV-2 from previous non-Omicron infection -
  The explosive spread of the Omicron SARS-CoV-2 variant underscores the importance of analyzing the cross-protection from previous non-Omicron infection. We developed a high-throughput neutralization assay for Omicron SARS-CoV-2 by engineering the Omicron spike gene into an mNeonGreen USA-WA1/2020 SARS-CoV-2 (isolated in January 2020). Using this assay, we determined the neutralization titers of patient sera collected at 1- or 6-months after infection with non- Omicron SARS-CoV-2. From 1- to 6-month post-infection, the neutralization titers against USA-WA1/2020 decreased from 601 to 142 (a 4.2-fold reduction), while the neutralization titers against Omicron-spike SARS-CoV-2 remained low at 38 and 32, respectively. Thus, at 1- and 6-months after non-Omicron SARS-CoV-2 infection, the neutralization titers against Omicron were 15.8- and 4.4-fold lower than those against USA-WA1/2020, respectively. The low cross-neutralization against Omicron from previous non-Omicron infection supports vaccination of formerly infected individuals to mitigate the health impact of the ongoing Omicron surge.
  🖺 Full Text HTML: Neutralization against Omicron SARS- CoV-2 from previous non-Omicron infection
• mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 Omicron variant -
  The BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines generate potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the global emergence of SARS-CoV-2 variants with mutations in the spike protein, the principal antigenic target of these vaccines, has raised concerns over the neutralizing activity of vaccine-induced antibody responses. The Omicron variant, which emerged in November 2021, consists of over 30 mutations within the spike protein. Here, we used an authentic live virus neutralization assay to examine the neutralizing activity of the SARS-CoV-2 Omicron variant against mRNA vaccine-induced antibody responses. Following the 2nd dose, we observed a 30-fold reduction in neutralizing activity against the omicron variant. Through six months after the 2nd dose, none of the sera from naive vaccinated subjects showed neutralizing activity against the Omicron variant. In contrast, recovered vaccinated individuals showed a 22-fold reduction with more than half of the subjects retaining neutralizing antibody responses. Following a booster shot (3rd dose), we observed a 14-fold reduction in neutralizing activity against the omicron variant and over 90% of boosted subjects showed neutralizing activity against the omicron variant. These findings show that a 3rd dose is required to provide robust neutralizing antibody responses against the Omicron variant.
  🖺 Full Text HTML: mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 Omicron variant
• Immune escape of SARS-CoV-2 Omicron variant from mRNA vaccination-elicited RBD-specific memory B cells. -
  Memory B cells (MBCs) represent a second layer of immune protection against SARS-CoV-2. Whether MBCs elicited by mRNA vaccines can recognize the Omicron variant is of major concern. We used bio-layer interferometry to assess the affinity against the receptor-binding-domain (RBD) of Omicron spike of 313 naturally expressed monoclonal IgG that were previously tested for affinity and neutralization against VOC prior to Omicron. We report here that Omicron evades recognition from a larger fraction of these antibodies than any of the previous VOCs. Additionally, whereas 30% of these antibodies retained high affinity against Omicron-RBD, our analysis suggest that Omicron specifically evades antibodies displaying potent neutralizing activity against the D614G and Beta variant viruses. Further studies are warranted to understand the consequences of a lower memory B cell potency on the overall protection associated with current vaccines.
  🖺 Full Text HTML: Immune escape of SARS-CoV-2 Omicron variant from mRNA vaccination-elicited RBD-specific memory B cells.
• Longitudinal characterisation of phagocytic and neutralisation functions of anti-Spike antibodies in plasma of patients after SARS-CoV-2 infection. -
  Phagocytic responses by effector cells to antibody or complement-opsonised viruses have been recognized to play a key role in anti-viral immunity. These include antibody dependent cellular phagocytosis mediated via Fc-receptors, phagocytosis mediated by classically activated complement-fixing IgM or IgG1 antibodies and antibody independent phagocytosis mediated via direct opsonisation of viruses by complement products activated via the mannose-binding lectin pathway. Limited data suggest these phagocytic responses by effector cells may contribute to the immunological and inflammatory responses in SARS-CoV-2 infection, however, their development and clinical significance remain to be fully elucidated. In this cohort of 62 patients, acutely ill individuals were shown to mount phagocytic responses to autologous plasma-opsonised SARS-CoV-2 Spike protein-coated microbeads as early as 10 days post symptom onset. Heat inactivation of the plasma prior to use as an opsonin caused 77-95% abrogation of the phagocytic response, and pre- blocking of Fc-receptors on the effector cells showed only 18-60% inhibition. These results suggest that SARS-CoV-2 can provoke early phagocytosis, which is primarily driven by heat labile components, likely activated complements, with variable contribution from anti-Spike antibodies. During convalescence, phagocytic responses correlated significantly with anti-Spike IgG titers. Older patients and patients with severe disease had significantly higher phagocytosis and neutralisation functions when compared to younger patients or patients with asymptomatic, mild, or moderate disease. A longitudinal study of a subset of these patients over 12 months showed preservation of phagocytic and neutralisation functions in all patients, despite a drop in the endpoint antibody titers by more than 90%. Interestingly, surface plasmon resonance showed a significant increase in the affinity of the anti-Spike antibodies over time correlating with the maintenance of both the phagocytic and neutralisation functions suggesting that improvement in the antibody quality over the 12 months contributed to the retention of effector functions.
  🖺 Full Text HTML: Longitudinal characterisation of phagocytic and neutralisation functions of anti-Spike antibodies in plasma of patients after SARS-CoV-2 infection.
• Blockade of TMPRSS2-mediated priming of SARS-CoV-2 by the N-terminal peptide of lactoferrin -
  In addition to vaccines, there is an urgent need for supplemental antiviral therapeutics to dampen the persistent COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The transmembrane protease serine 2 (TMPRSS2), which is responsible for the proteolytic processing of the SARS-CoV-2 spike protein as virus priming for cell entry, appears as a rational therapeutic target for the clearance of SARS-CoV-2 infection. Accordingly, selective inhibitors of TMPRSS2 represent potential tools for prevention and treatment of COVID-19. Here, we tested the inhibitory capacities of the human milk glycoprotein lactoferrin and its N-terminal peptide pLF1, which we identified as inhibitors of plasminogen, a serine protease homologous to TMPRSS2. In vitro proteolysis assays revealed that, unlike full-length lactoferrin, pLF1 significantly inhibited the proteolytic activity of TMPRSS2. pLF1 inhibited both the proteolytic processing of the SARS-CoV-2 spike protein and the SARS-CoV-2 infection of simian Vero cells. Because lactoferrin is a natural product and several biologically active peptides, such as the N-terminally derived lactoferricins, are produced naturally by pepsin-mediated digestion, natural or synthetic peptides from lactoferrin represent well-achievable candidates for supporting prevention and treatment of COVID-19.
  🖺 Full Text HTML: Blockade of TMPRSS2-mediated priming of SARS-CoV-2 by the N-terminal peptide of lactoferrin
• Transportation barriers to care among frequent health care users during the COVID pandemic -
  Objective: To investigate transportation barriers to accessing health care services during the COVID-19 pandemic among high-frequency health care users. Data Sources: Between June 21 and July 23, 2021, primary survey data were collected for a sample of patients in North Carolina. Study Design: The study analyzed the prevalence of arriving late to, delaying, or missing medical care and examined how transportation barriers contributed to negative health care outcomes. Data Collection Methods: A web-based survey was administered to North Carolina residents aged 18 and older in the UNC Health system who were enrolled in Medicaid or Medicare and had at least six outpatient medical appointments in the past year. 323 complete responses were analyzed to investigate the prevalence of reporting transportation barriers that resulted in having arrived late to, delayed, or missed care, as well as relationships between demographic and other independent variables and transportation barriers. Qualitative analyses were performed on text response data to explain transportation barriers. Principal Findings: Approximately 1 in 3 respondents experienced transportation barriers to health care between June 2020 and June 2021. Multivariate logistic regressions indicate individuals aged 18–64 were significantly more likely to encounter transportation barriers. Costs of traveling for medical appointments and a lack of driver or car availability emerged as major transportation barriers; however, respondents explained that barriers were often complex, involving circumstantial problems related to one’s ability to access and pay for transportation as well as to personal health. Conclusions: To address transportation barriers, we recommend more coordination between transportation and health professionals and the implementation of programs that expand access to and improve patient awareness of health care mobility services. We also recommend transportation and health entities direct resources to address transportation barriers equitably, as barriers disproportionately burden younger adults under age 65 enrolled in public insurance programs.
  🖺 Full Text HTML: Transportation barriers to care among frequent health care users during the COVID pandemic
• Patient made Long Covid empowers the patient voice -
  Successful, patient-driven advocacy and research in Long Covid is contributing to change our understanding of SARS- CoV-2 infection, viral-onset diseases, and knowledge building in medicine and beyond. Events and epistemic shifts surrounding the rise of Long Covid represent a massive opportunity for empowering the patient voice. Strategies that have proven key to grassroots Long Covid advocacy in our digital era could be further explored and expanded across different patient communities. It is my hope that patient-centred expertise will be further incorporated into the biomedical community. This would contribute to critical changes in medical awareness of chronic diseases and patient care.
  🖺 Full Text HTML: Patient made Long Covid empowers the patient voice
• It-who-must-not-be-named: Covid-19 misinformation, tactics to profit from it and to evade content moderation on YouTube -
  Brazilian YouTube channels spreading vaccine misinformation also misinform the public about the Covid-19 pandemic. Our analysis shows that content creators developed tactics to evade moderation and to profit both from the YouTube Partner Program and from different products, such as courses, books, supplements, and even isolated land — this last item in a pretext to flee from alleged conspiracies. Through the YouTube Partner Program, 516 brands paid for ads that appeared on videos containing Covid-19 misinformation, including the American CDC.
  🖺 Full Text HTML: It-who-must-not- be-named: Covid-19 misinformation, tactics to profit from it and to evade content moderation on YouTube
• Who engaged in home-based arts activities during the COVID-19 pandemic? A cross-sectional analysis of data from 4,731 adults in the United States -
  Arts engagement is a health-related behavior that may be influenced by social inequalities. While the COVID-19 pandemic provided new opportunities for some people to engage in the arts, it might have created barriers for others. We aimed to examine whether there was social patterning in home-based arts engagement during the pandemic in the United States (US), and whether predictors of engagement differed according to the type of arts activity. We included 4,731 adults who participated in the US COVID-19 Social Study between April and July 2020. Three types of home-based arts engagement were considered: reading for pleasure, arts or crafts activities, and digital arts activities. Using logistic regression models, we tested cross-sectional associations between a broad range of demographic, socioeconomic, psychosocial, and health-related factors as well as adverse events and worries during lockdown and each type of arts engagement. The factors most strongly associated with all three types of arts engagement were social support, social network size, age, race/ethnicity, keyworker status, and experiencing physical or psychological abuse during the pandemic. However, most socioeconomic and health-related factors were not associated with arts engagement, including household income and mental and physical health problems. Overall, our findings indicate that the social gradient in arts engagement was reduced in the first four months of the COVID-19 pandemic in the US. Given the health benefits of arts engagement, the potential diversification of arts audiences during the pandemic is promising for both population- level health and wellbeing and the future of the arts and cultural sector.
  🖺 Full Text HTML: Who engaged in home-based arts activities during the COVID-19 pandemic? A cross-sectional analysis of data from 4,731 adults in the United States
• An in silico analysis of early SARS-CoV-2 variant B.1.1.529 (Omicron) genomic sequences and their epidemiological correlates -

  Background: A newly emerged SARS-CoV-2 variant B.1.1.529 has worried health policymakers worldwide due to the presence of a large number of mutations in its genomic sequence, especially in the spike protein region. World Health Organization (WHO) has designated it as a global variant of concern (VOC) and has named as Omicron. A surge in new COVID-19 cases has been reported from certain geographical locations, primarily in South Africa (SA) following the emergence of Omicron. Materials and methods: We performed an in silico analysis of the complete genomic sequences of Omicron available on GISAID (until 2021-12-6) to predict the functional impact of the mutations present in this variant on virus-host interactions in terms of viral transmissibility, virulence/lethality, and immune escape. In addition, we performed a correlation analysis of the relative proportion of the genomic sequences of specific SARS-CoV-2 variants (in the period of 01 Oct-29 Nov 2021) with the current epidemiological data (new COVID-19 cases and deaths) from SA to understand whether the Omicron has an epidemiological advantage over existing variants. Results: Compared to the current list of global VOCs/VOIs (as per WHO) Omicron bears more sequence variation, specifically in the spike protein and host receptor-binding motif (RBM). Omicron showed the closest nucleotide and protein sequence homology with Alpha variant for the complete sequence as well as for RBM. The mutations were found primarily condensed in the spike region (28-48) of the virus. Further, the mutational analysis showed enrichment for the mutations decreasing ACE2-binding affinity and RBD protein expression, in contrast, increasing the propensity of immune escape. An inverse correlation of Omicron with Delta variant was noted (r=-0.99, p< .001, 95% CI: -0.99 to -0.97) in the sequences reported from SA post- emergence of the new variant, later showing a decrease. There has been a steep rise in the new COVID-19 cases in parallel with the increase in the proportion of Omicron since the first case (74-100%), on the contrary, the incidences of new deaths have not been increased (r=-0.04, p>0.05, 95% CI =-0.52 to 0.58). Conclusions: Omicron may have greater immune escape ability than the existing VOCs/VOIs. However, there are no clear indications coming out from the predictive mutational analysis that the Omicron may have higher virulence/lethality than other variants, including Delta. The higher ability for immune escape may be a likely reason for the recent surge in Omicron cases in SA.

  🖺 Full Text HTML: An in silico analysis of early SARS-CoV-2 variant B.1.1.529 (Omicron) genomic sequences and their epidemiological correlates
• Analytical sensitivity of seven SARS-CoV-2 antigen-detecting rapid tests for Omicron variant -

  The emergence of novel SARS-CoV-2 variants of concern (VOCs) requires investigation of a potential impact on diagnostic performance, especially on Antigen-detecting rapid antigenic tests (Ag-RDT). Although anecdotal reports have been circulating that Omicron is in principle detected by several Ag-RDTs, no published data are a yet available for the newly emerged Omicron variant. Here, we have performed an analytical sensitivity testing with cultured virus in seven Ag-RDTs for their sensitivity to Omicron compared to data earlier obtained on VOCs Alpha, Beta Gamma and Delta and a pre-VOC isolate of SARS-CoV-2. Overall, we have found a tendency towards lower sensitivity for Omicron compared to pre- VOC SARS-CoV-2 and the other VOCs across tests. Importantly, while analytical testing with cultured virus may be a proxy for clinical sensitivity, is not a replacement for clinical evaluations which are urgently needed for Ag-RDT performance in Omicron-infected individuals.

  🖺 Full Text HTML: Analytical sensitivity of seven SARS-CoV-2 antigen-detecting rapid tests for Omicron variant
• SARS-CoV-2 variant exposures elicit antibody responses with differential cross-neutralization of established and emerging strains including Delta and Omicron -

  The wide spectrum of SARS-CoV-2 variants with phenotypes impacting transmission and antibody sensitivity necessitates investigation of the immune response to different spike protein versions. Here, we compare the neutralization of variants of concern, including B.1.617.2 (Delta) and B.1.1.529 (Omicron) in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing certain spike mutations with the immunizing exposure. We also observe that exposure to multiple spike variants increases the breadth of variant cross-neutralization. These findings contribute to understanding relationships between exposures and antibody responses and may inform booster vaccination strategies.

  🖺 Full Text HTML: SARS-CoV-2 variant exposures elicit antibody responses with differential cross-neutralization of established and emerging strains including Delta and Omicron

From Clinical Trials

• Trial to Evaluate Nitazoxanide for Treatment of Mild COVID-19 in Subjects Not at High Risk of Severe Illness - Condition:   COVID-19
  Interventions:   Drug: Nitazoxanide;   Drug: Placebo;   Dietary Supplement: Vitamin Super-B Complex
  Sponsor:   Romark Laboratories L.C.
  Not yet recruiting

• Trial to Evaluate Nitazoxanide for Treatment of Mild or Moderate COVID-19 in Subjects at High Risk of Severe Illness - Condition:   COVID-19
  Interventions:   Drug: Nitazoxanide;   Dietary Supplement: Vitamin Super-B Complex;   Drug: Placebo;   Other: Standard of Care
  Sponsor:  
  Romark Laboratories L.C.
  Not yet recruiting

• A Double-blind Randomized Controlled Trial of Ivermectin With Favipiravir in Mild-to-moderate COVID-19 Patients - Condition:   COVID-19
  Interventions:   Drug: Ivermectin Tablets;   Other: Placebo
  Sponsors:   Mahidol University;   Prince of Songkla University
  Not yet recruiting

• A Safety, Tolerability, and Efficacy Study of IBI314 in Ambulatory Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Biological: IBI314;   Other: Placebo
  Sponsor:   Innovent Biologics (Suzhou) Co. Ltd.
  Not yet recruiting

• Adrecizumab (HAM8101) to Improve Prognosis and Outcomes in COVID-19 Trial - Condition:   COVID-19
  Interventions:   Biological: Adrecizumab (HAM 8101);   Drug: Placebo
  Sponsor:   Universitätsklinikum Hamburg-Eppendorf
  Not yet recruiting

• Safety, Tolerability, and Treatment Effect of Belnacasan in Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Belnacasan;   Drug: Placebo
  Sponsor:  
  MedStar Health
  Recruiting

• A Study Evaluating Tocilizumab in Pediatric Patients Hospitalized With COVID-19 - Condition:   COVID-19
  Intervention:   Drug: Tocilizumab
  Sponsor:   Hoffmann- La Roche
  Not yet recruiting

• Immunogenicity Study of the Covid-19 (Recombinante) Vaccine With a 4 or 8 Week Interval Between the First Doses. - Condition:   COVID-19
  Intervention:   Biological: Covid-19 (recombinante) vaccine
  Sponsor:   The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
  Active, not recruiting

• A Study to Evaluate Efficacy and Safety of the Combination of SCTA01 & SCTA01C in Outpatients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: SCTA01 and SCTA01C;   Drug: Placebo
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• Efficacy,Immunogenicity and Safety of COVID-19 Vaccine , Inactivated Booster Dose in Adults Aged 18 Years and Above - Condition:   COVID-19
  Interventions:   Biological: Medium-dosage COVID-19 Vaccine,Inactivated;   Biological: High-dosage COVID-19 Vaccine,Inactivated;   Biological: Placebo-comparator group
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• Safety and Immunogenicity Study of Booster Vaccination in Different Doses of COVID-19 Vaccine (Vero Cell),Inactivated for Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: High-dosage of COVID-19 vaccine (Vero cell), Inactivated;   Biological: Medium-dose COVID-19 Vaccine(Vero Cell),Inactivated
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Active, not recruiting

• Clinical Trial for Oral Formula of Vanillin and Wheat Germ Oil for Treatment of Mild and Moderate COVID-19 Viral Disease - Condition:   Mild-to-moderate COVID-19
  Intervention:   Drug: Oral Capsule
  Sponsors:  
  Alexandria University;   Assoc. Prof. Ayman Baeis;   Dr. Noha Alaa Eldine Hassan Hamdy;   Ph. Hanya Hesham Sweilam
  Recruiting

• Safety and Immunogenicity Study of Booster Vaccination With COVID-19 Vaccine (Vero Cell),Inactivated From Different Manufactures for Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: Experimental vaccine 1;   Biological: Experimental vaccine 2;   Biological: Experimental vaccine 3
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• Combination Assessment Trial of COVID-19 Vaccines (COMBAT-COVID) - Condition:   COVID 19 Vaccine
  Interventions:   Biological: BIBP (CNBG, Sinopharm) WIV;   Biological: CanSinoBIO;   Biological: AstraZeneca ChAdOx
  Sponsors:  
  Aga Khan University Hospital, Pakistan;   Coalition for Epidemic Preparedness Innovations;   University of Oxford;   International Vaccine Institute;   Harvard Medical School (HMS and HSDM);   Chughtai Lab;   National Institute of Health, Pakistan
  Not yet recruiting

• Oral Neutralizing Antibody Booster for Post-vaccinated People With COVID19 Vaccine - Condition:   COVID-19 Pandemic
  Intervention:   Dietary Supplement: Bacillus subtilis spore extract
  Sponsors:   DreamTec Research Limited;   Hong Kong Metropolitan University;   DreamTec Cytokine Limited
  Recruiting

From PubMed

• Perspective of HLA-G Induced Immunosuppression in SARS-CoV-2 Infection - COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has threatened public health worldwide. Host antiviral immune responses are essential for viral clearance and disease control, however, remarkably decreased immune cell numbers and exhaustion of host cellular immune responses are commonly observed in patients with COVID-19. This is of concern as it is closely associated with disease severity and poor outcomes. Human leukocyte antigen-G (HLA-G) is a…

• Pre-Steady-State Kinetics of the SARS-CoV-2 Main Protease as a Powerful Tool for Antiviral Drug Discovery - The design of effective target-specific drugs for COVID-19 treatment has become an intriguing challenge for modern science. The SARS-CoV-2 main protease, M^(pro), responsible for the processing of SARS-CoV-2 polyproteins and production of individual components of viral replication machinery, is an attractive candidate target for drug discovery. Specific M^(pro) inhibitors have turned out to be promising anticoronaviral agents. Thus, an effective platform for quantitative screening of…

• Perceptions and Experiences of COVID-19 Vaccine Side-Effects Among Healthcare Workers in Southern Ethiopia: A Cross- Sectional Study - CONCLUSION: While the expectations of most of the healthcare workers regarding the side-effects of the vaccine are parallel to the normal reactions of the vaccine, a significant proportion of the study participants have reported that they perceive COVID-19 vaccine will have life-threatening side-effects. Such fears have also played a role in affecting vaccine uptake. Therefore, the Ministry of Health, and other concerned government bodies should create further awareness on COVID-19 vaccine and…

• Embelin Alleviates Severe Airway Inflammation in OVA-LPS-Induced Rat Model of Allergic Asthma - CONCLUSION: Overall, our findings indicate that embelin can alleviate severe airway inflammation in OVA-LPS-induced model of allergic asthma occurring by suppression of Th2-mediated immune response. Due to its promising anti-asthmatic effect, it is recommended that embelin should be investigated in clinical trials against asthma. It should also be further explored against COVID-19 or COVID-like diseases due to its ameliorative effects on cytokines and immune cell infiltration.

• SARS-CoV-2 spreads through cell-to-cell transmission - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus responsible for the global COVID-19 pandemic. Herein, we provide evidence that SARS-CoV-2 spreads through cell-cell contact in cultures, mediated by the spike glycoprotein. SARS-CoV-2 spike is more efficient in facilitating cell-to-cell transmission than is SARS-CoV spike, which reflects, in part, their differential cell-cell fusion activity. Interestingly, treatment of cocultured cells with…

• Nigellidine (Nigella sativa, black-cumin seed) docking to SARS CoV-2 nsp3 and host inflammatory proteins may inhibit viral replication/transcription and FAS-TNF death signal via TNFR 1/2 blocking - Tissue damage occurs in COVID-19 patients due to nsp3-induced Fas-FasL interaction/TNF-related apoptosis. Presently, possible therapeutic-drug, nigellidine against was screened by bioinformatics studies COVID-19. Atomic-Contact-Energy (ACE) and binding-blocking effects were explored of nigellidine (Nigella sativa L.) in the active/catalytic sites of viral-protein nsp3 and host inflammatory/apoptotic signaling-molecules Fas/TNF receptors TNFR1/TNFR2. A control binding/inhibition of Oseltamivir to…

• Tetrahedron-Based Constitutional Dynamic Network for COVID-19 or Other Coronaviruses Diagnostics and Its Logic Gate Applications - Considering the large-scale outbreak of the coronavirus, it is essential to develop a versatile sensing system for different coronaviruses diagnostics, such as COVID-19, severe acute respiratory syndrome-related coronavirus (SARS-CoV), and bat SARS-like coronavirus (Bat-SL-CoVZC45). In this work, a tetrahedron-based constitutional dynamic network was built as the sensing platform for coronavirus detection. Four different DNA probes were used to construct the tetrahedron structure. DNAzyme and…

• Association of Renin-Angiotensin-Aldosterone System inhibition with Covid-19 hospitalization and all-cause mortality in the UK Biobank - CONCLUSION: Our results suggest protective effects of inhibition of the renin-angiotensin-aldosterone system on Covid-19 hospitalization and mortality, particularly with ACEI, among patients with pharmaceutically treated hypertension. If confirmed by randomized controlled trials, this finding could have high clinical relevance for treating hypertension during the SARS-CoV-2 pandemic.

• Immunosuppression in Glomerular Diseases: Implications for SARS-CoV-2 Vaccines and COVID-19 - BACKGROUND: Glomerular diseases (GD) are chronic conditions that often involve immune dysfunction and require immunosuppressive therapy (IST) to control underlying pathogenesis. Unfortunately, such diseases appear to heighten risks of severe outcomes in COVID-19 and predispose to other infections that may be life-threatening. Thus, averting preventable infections is imperative in GD patients.

• Tamoxifen and clomiphene inhibit SARS-CoV-2 infection by suppressing viral entry - No abstract

• The Inhibition of SARS-CoV-2 3CL M(pro) by Graphene and Its Derivatives from Molecular Dynamics Simulations - At present, the most powerful new drugs for COVID-19 are antibody proteins. In addition, there are some star small molecule drugs. However, there are few studies on nanomaterials. Here, we study the intact graphene (IG), defective graphene (DG), and graphene oxide (GO) interacting with COVID-19 protein. We find that they show progressive inhibition of COVID-19 protein. By using molecular dynamics simulations, we study the interactions between SARS-CoV-2 3CL M^(pro) and graphene-related materials…

• Membrane-dependent relief of translation elongation arrest on pseudouridine- and N1-methyl-pseudouridine-modified mRNAs - Expression of therapeutically important proteins has benefited dramatically from the advent of chemically modified mRNAs that feature decreased lability and immunogenicity. This had a momentous effect on the rapid development of COVID-19 mRNA vaccines. Incorporation of the naturally occurring pseudouridine (Ψ) or N1-methyl-pseudouridine (N1mΨ) into in vitro transcribed mRNAs prevents the activation of unwanted immune responses by blocking eIF2α phosphorylation, which inhibits translation. Here,…

• pH Shock-promoted lysozyme corona for efficient pathogenic infections treatment: Effects of surface chemistry of mesoporous silica nanoparticles and loading method - The emergence of antibiotic resistant bacteria because of the antibiotics abusement was the motivation to develop the effective alternatives to traditional antibiotics. Hence, various lysozyme corona were prepared through the physical and covalent attachment of lysozyme molecules onto either the bare or carboxyl-functionalized mesoporous silica particles. The prepared samples were characterized by STEM, TGA/DTA, zeta potential, FTIR, UV-vis and CD spectroscopic methods. All the prepared…

• RBC-hitchhiking chitosan nanoparticles loading methylprednisolone for lung-targeting delivery - Hyper-inflammation associated with cytokine storm syndrome causes high mortality in patients with COVID-19. Glucocorticoids, such as methylprednisolone sodium succinate (MPSS), effectively inhibit this inflammatory response. However, frequent and chronic administration of glucocorticoids at high doses leads to hormone dependence and serious side effects. The aim of the present study was to combine nanoparticles with erythrocytes for the targeted delivery of MPSS to the lungs. Chitosan…

• The seven constitutive respiratory defense barriers against SARS-CoV-2 infection - Before eliciting an adaptive immune response, SARS-CoV-2 must overcome seven constitutive respiratory defense barriers. The first is the mucus covering the respiratory tract’s luminal surface, which entraps inhaled particles, including infectious agents, and eliminates them by mucociliary clearance. The second barrier comprises various components present in the airway lining fluid, the surfactants. Besides providing low surface tension that allows efficient gas exchange at the alveoli,…

From Patent Search

• Hung Thanh Phan COVID-19 NEW SOLUTION - - link

• METHODS OF TREATING SARS-COV-2 INFECTION - - link

• REAL-TIME REST BREAK MANAGEMENT SYSTEM FOR WORKPLACE - The present invention relates to a real-time rest break management system for workplace that comprises of a work desk, wherein first portion is incorporated with a biometric unit 4 for authenticating first user, and a second portion with a telescopic panel 2 associated with a weight sensor 6 and timer unit 7 calculating weight of head/hand manifesting user presence and their resting time period is mounted with an inflated cushion 5, an interactive primary display unit 1 attached over desk enables user to set first/second threshold time for sleeping/taking break, further linked with a tracking interface keeping track of activities and a vibrating unit crafted inside the cushion 5 which is linked to a secondary display unit 8 of second user, giving them access to actuate vibrating unit generating impulses to wake first user when threshold time period is exceeded by the first user. - link

• P2P 네트워크를 이용한 내장된 화상회의 시스템 - 본 발명은 P2P 네트워크를 이용한 내장된 화상회의 시스템에 관한 것으로, 상태표시부(1), 영상송출부(2), 제어부(3), 광고부(4), 입력부(5)를 포함한다. - link

• 小分子化合物肌醇六磷酸酯钠水合物在制备抗SARS-CoV-2药物中的应用 - 本发明公开了小分子化合物肌醇六磷酸酯钠水合物在制备抗严重急性呼吸综合征冠状病毒2(SARS‑CoV‑2)药物中的应用，所述抗SARS‑CoV‑2药物是以肌醇六磷酸酯钠水合物为唯一的活性成份，或包含肌醇六磷酸酯钠水合物的药物组合物，所述抗SARS‑CoV‑2药物是指预防或治疗SARS‑CoV‑2感染的药物。本发明利用SARS‑CoV‑2的易感细胞系，包括非洲绿猴肾细胞Vero

E6以及人肺腺癌细胞Calu‑3，检测肌醇六磷酸酯钠水合物的抗SARS‑CoV‑2活性。实验结果显示，肌醇六磷酸酯钠水合物能有效抑制SARS‑CoV‑2对上述易感细胞的感染，且细胞毒性较小，有希望作为有效抗SARS‑CoV‑2感染的药物，具有应用前景。 - link

• A DOORBELL SYSTEM FOR MONITORING AND RECORDING A PHYSIOLOGICAL DATA OF A PERSON - AbstractTitle: A doorbell system for monitoring and recording a physiological data of a person The present invention provides a doorbell system 500 for monitoring and recording a physiological data of a person. The doorbell system 500 having a transmitter module 100 and a receiving module 200. The transmitter module 100 is having a TOF sensor module 110, an ultrasound detector 120, and an infrared detector 130. Further, a speech recognition system 150, a facial recognition system 160, and a temperature detector 190 are provided for recognizing speech, face, and temperature of the person by comparing pre-stored data. A controlling module 180 is set with a predefined commands for communicating with the transmitter module 100 and receiving module 200. The collected facial and speech data is compared and matched with the pre-stored data then the temperature detector 190 triggers and the door opens when the captured body temperature of the person is matched within the predefined range of temperature.Figure 1 - link

• A study of contemporary trends in investing patterns, household savings, and economic investment. - Because household savings and household investments are intertwined and interdependent, they are discussed briefly in this paper. Household savings account for more than half of a country’s capital formation, which fluctuates due to a variety of economic factors such as inflation and interest rates. Households should gradually shift their savings and investments from physical assets to financial assets to avoid a sudden change in wealth. They should also save and invest using a variety of platforms. Trends in investing and saving will be easier to track and measure this way. This year’s domestic saving rate in India is 2.3 percent lower than last year’s and 1.2 percent lower than the year before. Since 2011, general domestic savings have been steadily declining, with the trend continuing into the following year. According to official data, the GDP in 2020 shrank by 23.9%, the least in previous years and the least since the Covid-19 pandemic in previous years. As a result, the information presented in this paper is drawn from and evaluated from other sources - link

• 靶向刺激体液免疫和细胞免疫的新冠病毒mRNA疫苗 - 本发明公开了一种靶向刺激体液免疫和细胞免疫的新冠病毒mRNA疫苗。本申请的第一方面提供一种分离的DNA分子组合，该DNA分子组合包括第一DNA分子和第二DNA分子和第三DNA分子中的至少一种。通过第一DNA分子以及第二DNA分子和/或第三DNA分子的组合，利用第一DNA分子最终合成的mRNA诱导高滴度的交叉中和抗体，利用第二DNA分子和/或第三DNA分子最终合成的mRNA诱导新冠病毒特异性的细胞毒性T淋巴细胞，从而高效地同时激活相对独立的体液免疫应答和细胞免疫应答，应对新冠病毒在流行传播过程中产生的突变毒株所引发的突破性感染。 - link

• 跨膜丝氨酸蛋白酶2抑制剂在制备治疗和/或预防冠状病毒感染药物中的用途 - 本发明公开了跨膜丝氨酸蛋白酶2抑制剂在制备治疗和/或预防冠状病毒感染药物中的用途。本发明通过亲和垂钓及活性导向分离获得3种化合物，证实该类化合物可以直接地与跨膜丝氨酸蛋白酶2结合，KD<13μM，且能够显著抑制跨膜丝氨酸蛋白酶2的催化活性。在细胞水平上可以有效的抑制新型冠状病毒SARS‑CoV‑2假病毒入侵，表明该类化合物对于制备治疗和/或预防病毒感染药物具有非常积极的作用。化合物1 化合物2 化合物3。 - link

• PROLIPOSOMAL DRY POWDER INHALER OF REMDESIVIR - The present invention is related to Proliposomal Dry Powder Inhaler of Remdesivir and its method thereof for the treatment of viral infections such Coronaviridae (including COVID-19 infection). - link