Covid-19 Sentry

Contents

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

From Preprints

• NRP1 and furin as putative mediators of SARS-CoV-2 entry into human brain cells -
  COVID-19 has prominent neurological manifestations including psychiatric symptoms, indicating significant synaptic pathology. Surprisingly, existing evidence suggests negligible expression of the key SARS-CoV-2 host cell entry mediators ACE2 and TMPRSS2 in human brain, which complicates understanding of the pathomechanisms of the neuropsychiatric manifestations in COVID-19. Recent studies suggested that an alternative host-cell entry receptor, NRP1, can mediate entry of furin cleaved SARS-CoV-2 spike proteins into the host cells. However, the role of NRP1 and furin in mediating SARS-CoV-2 entry in human brain cells has been least explored and remains a lacuna in the literature. We performed an in silico analysis of the transcriptomic and proteomic expressions of SARS-CoV-2 host-cell entry receptors and associated tissue proteases in human brain tissue, using the publically available databases. Based on the expression analysis, SARS-CoV-2 entry in human brain cells is likely to be mediated through NRP1 and furin.
  🖺 Full Text HTML: NRP1 and furin as putative mediators of SARS-CoV-2 entry into human brain cells
• Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the SARS-CoV-2 Spike protein -
  Background: SARS-CoV-2-contributes to sickness and death in COVID-19 patients partly by inducing a hyper- proinflammatory immune response in the host airway. This hyper- proinflammatory state involves activation of signaling by NF{kappa}B and ENaC, and expression of high levels of cytokines and chemokines. Post-infection inflammation may contribute to “Long COVID”, and there are also other long term consequences of acute severe COVID-19, which double or triple the chances of dying from any cause within a year. Enhanced signaling by NF{kappa}B and ENaC also marks the airway of patients suffering from cystic fibrosis, a lethal proinflammatory genetic disease due to inactivating mutations in the CFTR gene. We therefore hypothesized that inflammation in the COVID-19 airway might similarly be due to inhibition of CFTR signaling by SARS-CoV-2 Spike protein. Methods: This hypothesis was tested using the hTERT- transformed BCi-NS1.1 basal stem cell, previously derived from small airway epithelia, which were differentiated into a model of small airway epithelia on an air-liquid-interface (ALI). Cyclic AMP-activated CFTR chloride channel activity was measured using an Ussing Chamber. Cell surface-CFTR was labeled with the impermeant biotin method. Results: Exposure of differentiated airway epithelia to SARS-CoV-2 Spike protein resulted in loss of CFTR protein expression. As hypothesized, TNF/NF{kappa}B signaling was activated, based on increased protein expression of TRADD, the first intracellular adaptor for the TNF/TNFR1 complex, TNFR1, the TNF receptor, phosphorylated I{kappa}B, and the chemokine IL8. ENaC activity was also activated, based on specific changes in molecular weights for and{gamma}ENaC. Exposure of the epithelia to viral Spike protein suppressed cAMP-activated CFTR chloride channel activity. However, addition of 30 nM concentrations of cardiac glycoside drugs ouabain, digitoxin and digoxin, prevented loss of channel activity. ACE2 and CFTR were found to co-immunoprecipitate (co-IP) in both basal cells and epithelia, suggesting that the mechanism for Spike-dependent CFTR loss might involve ACE2 as a bridge between Spike and CFTR. In addition, Spike exposure to the epithelia resulted in failure of endosomal recycling to return CFTR to the plasma membrane, suggesting that failure of CFTR recovery from endosomal recycling might be a mechanism for Spike-dependent loss of CFTR. Conclusion: Based on experiments with this model of small airway epithelia, we predict that inflammation in the COVID-19 airway may be mediated by inhibition of CFTR signaling by SARS-CoV-2 Spike protein, thus inducing a CFTR-null, cystic fibrosis-like clinical phenotype. Descriptions of COVID-19 in CF carriers with only one copy of wildtype CFTR suggest that this model- based conclusion might be consistent with patient-based experience.
  🖺 Full Text HTML: Inflammation in the COVID-19 airway is due to inhibition of CFTR signaling by the SARS-CoV-2 Spike protein
• SARS-CoV-2 Omicron efficiently infects human airway, but not alveolar epithelium -
  In late 2021, the highly mutated SARS-CoV-2 Omicron variant emerged, raising concerns about its potential extensive immune evasion, increased transmissibility and pathogenicity. Here, we used organoids of the human airways and alveoli to investigate Omicron’s fitness and replicative potential in comparison with earlier SARS-CoV-2 variants. We report that Omicron replicates more rapidly in the airways and has an increased fitness compared to the early 614G variant and Delta. In contrast, Omicron did not replicate productively in human alveolar type 2 cells. Mechanistically, we show that Omicron does not efficiently use TMPRSS2 for entry or spread through cell-cell fusion. Altogether, our data show that Omicron has an altered tropism and protease usage, potentially explaining its higher transmissibility and decreased pathogenicity.
  🖺 Full Text HTML: SARS-CoV-2 Omicron efficiently infects human airway, but not alveolar epithelium
• Molecular basis of broad neutralization against SARS-CoV-2 variants including Omicron by a human antibody -
  Omicron, a newly emerging SARS-CoV-2 variant, carried a large number of mutations in the spike protein leading to an unprecedented evasion from many neutralizing antibodies (nAbs). Here, we performed a head-to-head comparison of Omicron with other existing highly evasive variants in terms of their reduced sensitivities to antibodies, and found that Omicron variant is significantly more evasive than Beta and Mu variants. Of note, some key mutations occur in the conserved epitopes identified previously, especially in the binding sites of Class 4 nAbs, contributing to the increased Ab evasion. We also reported a broadly nAb (bnAb), VacW-209, which effectively neutralized all tested SARS-CoV-2 variants and even SARS-CoV. Finally, we determined six cryo-electron microscopy structures of VacW-209 complexed with the spike ectodomains of wild-type, Delta, Mu, C.1.2, Omicron, and SARS-CoV, and revealed the molecular basis of the broadly neutralizing activities of VacW-209 against SARS-CoV-2 variants. Overall, Omicron has once again raised the alarm over virus variation with significantly compromised neutralization. BnAbs targeting more conserved epitopes among variants will continue to play a key role in pandemic control and prevention.
  🖺 Full Text HTML: Molecular basis of broad neutralization against SARS-CoV-2 variants including Omicron by a human antibody
• SARS-CoV-2 infection results in lasting and systemic perturbations post recovery -
  SARS-CoV-2 has been found capable of inducing prolonged pathologies collectively referred to as Long-COVID. To better understand this biology, we compared the short- and long-term systemic responses in the golden hamster following either SARS-CoV-2 or influenza A virus (IAV) infection. While SARS-CoV-2 exceeded IAV in its capacity to cause injury to the lung and kidney, the most significant changes were observed in the olfactory bulb (OB) and olfactory epithelium (OE) where inflammation was visible beyond one month post SARS-CoV-2 infection. Despite a lack of detectable virus, OB/OE demonstrated microglial and T cell activation, proinflammatory cytokine production, and interferon responses that correlated with behavioral changes. These findings could be corroborated through sequencing of individuals who recovered from COVID-19, as sustained inflammation in OB/OE tissue remained evident months beyond disease resolution. These data highlight a molecular mechanism for persistent COVID-19 symptomology and characterize a small animal model to develop future therapeutics.
  🖺 Full Text HTML: SARS-CoV-2 infection results in lasting and systemic perturbations post recovery
• A potent alpaca-derived nanobody that neutralizes SARS-CoV-2 variants -
  The spike glycoprotein of SARS-CoV-2 engages with human angiotensin-converting enzyme 2 (ACE2) to facilitate infection. Here, we describe an alpaca-derived heavy chain antibody fragment (VHH), saRBD-1, that disrupts this interaction by competitively binding to the spike protein receptor-binding domain. We further generated an engineered bivalent nanobody construct engineered by a flexible linker, and a dimeric Fc conjugated nanobody construct. Both multivalent nanobodies blocked infection at picomolar concentrations and demonstrated no loss of potency against emerging variants of concern including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Epsilon (B.1.427/429), and Delta (B.1.617.2). saRBD-1 tolerates elevated temperature, freeze-drying, and nebulization, making it an excellent candidate for further development into a therapeutic approach for COVID-19.
  🖺 Full Text HTML: A potent alpaca- derived nanobody that neutralizes SARS-CoV-2 variants
• Long-Term Persistence of IgG Antibodies in recovered COVID-19 individuals at 18 months and the impact of two-dose BNT162b2 (Pfizer-BioNTech) mRNA vaccination on the antibody response -

  This era of emerging variants needs a thorough evaluation of data on the long-term efficacy of immune responses in vaccinated as well as recovered individuals, to understand the overall evolution of the pandemic. In this study, we aimed to assess the dynamics of IgG titers over 18 months in 34 patients from the Umbria region in Italy, who had a documented history of COVID-19 infection in March 2020, and then compared the impact of two-dose BNT162b2 (Pfizer- BioNTech) vaccination on the antibody titers of these patients with the ones who did not receive any dose of vaccine. This is the longest observation (March 2020-September 2021) for the presence of antibodies against SARS-CoV-2 in recovered individuals along with the impact of 2 dose-BNT162b2 vaccination on the titers. Fixed-effect regression models were used for statistical analysis which could be also used to predict future titer trends. At 18 months, 97% participants tested positive for anti-NCP hinting towards the persistence of infection-induced immunity even for the vaccinated individuals. Our study findings demonstrate that while double dose vaccination boosted the IgG titers in recovered individuals 161 times, this boost was relatively short-lived. The unvaccinated recovered individuals, in contrast, continued to show a steady decline but detectable antibody levels. Further studies are required to re-evaluate the timing and dose regimen of vaccines for an adequate immune response in recovered individuals.

  🖺 Full Text HTML: Long-Term Persistence of IgG Antibodies in recovered COVID-19 individuals at 18 months and the impact of two-dose BNT162b2 (Pfizer-BioNTech) mRNA vaccination on the antibody response
• But Is It Okay? The Need to Still Ask Black/African American Mothers About Violence Exposure During The COVID-19 Worldwide Pandemic -
  Black/African American communities endure the double pandemic of COVID-19 and police- and civilian-perpetrated anti-Black violence, with Black/African American mothers at risk for exposure to violence in the home. Questions remain about the potential harm in asking about violence exposure, particularly in the current climate. The purpose of the study is to examine Black/African American mothers’ reactions to participating in violence research during the COVID-19 pandemic in the U.S. Participants (N = 127; Age: M = 32.46 years, SD = 5.61 years) were Black/African American mothers living in an urban, predominantly Black city in the Midwestern U.S. who completed online measures of exposure to violence before, during, and after shelter-in-place orders, as well as their reactions to participating in violence research. We found that the majority of participants did not find participation more distressing than other day to day experiences, with 100% of those with violence histories reporting such research is important. The current study’s findings can promote inclusion of violence measures in research and healthcare settings, with results guiding trauma-informed care for Black/African American mothers.
  🖺 Full Text HTML: But Is It Okay? The Need to Still Ask Black/African American Mothers About Violence Exposure During The COVID-19 Worldwide Pandemic
• ELF5 is a respiratory epithelial cell-specific risk gene for severe COVID-19 -

  Despite two years of intense global research activity, host genetic factors that predispose to a poorer prognosis and severe course of COVID-19 infection remain poorly understood. Here, we identified eight candidate protein mediators of COVID-19 outcomes by establishing a shared genetic architecture at protein-coding loci using large-scale human genetic studies. The transcription factor ELF5 (ELF5) showed robust and directionally consistent associations across different outcome definitions, including a >4-fold higher risk (odds ratio: 4.85; 95%-CI: 2.65-8.89; p-value<3.1x10^-7) for severe COVID-19 per 1 s.d. higher genetically predicted plasma ELF5. We show that ELF5 is specifically expressed in epithelial cells of the respiratory system, such as secretory and alveolar type 2 cells, using single-cell RNA sequencing and immunohistochemistry. These cells are also likely targets of SARS-CoV-2 by colocalisation with key host factors, including ACE2 and TMPRSS2. We also observed a 25% reduced risk of severe COVID-19 per 1 s.d. higher genetically predicted plasma G-CSF, a finding corroborated by a clinical trial of recombinant human G-CSF in COVID-19 patients with lymphopenia reporting a lower number of patients developing critical illness and death. In summary, large-scale human genetic studies together with gene expression at single-cell resolution highlight ELF5 as a novel risk gene for COVID-19 prognosis, supporting a role of epithelial cells of the respiratory system in the adverse host response to SARS-CoV-2.

  🖺 Full Text HTML: ELF5 is a respiratory epithelial cell-specific risk gene for severe COVID-19
• Cross-sectional study to assess the efficacy of SARS-CoV-2 vaccination in patients with monoclonal gammopathies -

  SARS-CoV-2 vaccination is the most effective strategy to protect patients with haematologic malignancies against severe COVID-19, but primary vaccine responses are less effective in this population. Here, we characterized the humoral responses following 3 months after mRNA-based vaccines in patients at different stages of the same plasma cell diseases, including monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and multiple myeloma on first line therapy (MM), compared to a healthy control population matched by sex and age. We observed that plasmas from uninfected MM patients after 3 months post-vaccine have lower SARS-CoV-2 specific IgG and IgA antibodies and decreased neutralization capacity compared with MGUS and SMM individuals, and a group of healthy controls. Importantly, we detected significantly higher plasma neutralization capacity in MM individuals who recovered from COVID-19 compared to their uninfected counterparts, highlighting that hybrid immunity elicit stronger immune responses even in this immunocompromised population. In contrast to MM group, no differences in the vaccine-induced humoral response were observed between uninfected MGUS, SMM and healthy individuals. In conclusion, a booster vaccine dose is recommended in uninfected MM patients to develop an adequate and effective humoral response to SARS-CoV-2 vaccine.

  🖺 Full Text HTML: Cross-sectional study to assess the efficacy of SARS-CoV-2 vaccination in patients with monoclonal gammopathies
• Serum extracellular vesicles trace COVID-19 progression and immune responses -

  Coronavirus disease 2019 (COVID-19) has transformed very quickly into a world pandemic with severe and unexpected consequences on human health. Concerted efforts to generate better diagnostic and prognostic tools have been ongoing. Research, thus far, has primarily focused on the virus itself or the direct immune response to it. Here, we propose extracellular vesicles (EVs) from serum liquid biopsies as a new and unique modality to unify diagnostic and prognostic tools for COVID-19 analyses. EVs are a novel player in intercellular signaling particularly influencing immune responses. We herein show that innate and adaptive immune EVs profiling, together with SARS-CoV-2 Spike S1+ EVs provide a novel signature for COVID-19 infection. It also provides a unique ability to trace the co-existence of viral and host cell signatures to monitor affected tissues and severity of the disease progression. And provide a phenotypic insight into COVID-associated EVs.

  🖺 Full Text HTML: Serum extracellular vesicles trace COVID-19 progression and immune responses
• Nirmatrelvir, an orally active Mpro inhibitor, is a potent inhibitor of SARS-CoV-2 Variants of Concern -
  New variants of SARS-CoV-2 with potential for enhanced transmission, replication, and immune evasion capabilities continue to emerge causing reduced vaccine efficacy and/or treatment failure. As of January 2021, the WHO has defined five variants of concern (VOC): B.1.1.7 (Alpha, ), B.1.351 (Beta, {beta}), P.1 (Gamma, {gamma}), B.1.617.2 (Delta, {delta}), and B.1.1.529 (Omicron, o). To provide a therapeutic option for the treatment of COVID-19 and variants, Nirmatrelvir, the antiviral component of PAXLOVIDTM, an oral outpatient treatment recently authorized for conditional or emergency use treatment of COVID-19, was developed to inhibit SARS-CoV-2 replication. Nirmatrelvir (PF-07321332) is a specific inhibitor of coronavirus main protease (Mpro, also referred to as 3CLpro), with potent antiviral activity against several human coronaviruses, including SARS-CoV-2, SARS-CoV, and MERS (Owen et al, Science 2021. doi: 10.1126/science.abl4784). Here, we evaluated PF-07321332 against the five SARS-CoV-2 VOC (, {beta}, {gamma}, {delta}, o) and two Variants of Interest or VOI, C.37 ({lambda}) and B.1.621 (), using qRT-PCR in VeroE6 cells lacking the P-glycoprotein (Pgp) multidrug transporter gene (VeroE6 P-gp knockout cells). Nirmatrelvir potently inhibited USA- WA1/2020 strain, and , {beta}, {gamma}, {lambda}, {delta}, , and o variants in VeroE6 P-gp knockout cells with mean EC50 values 38.0 nM, 41.0 nM, 127.2 nM, 24.9 nM, 21.2 nM, 15.9 nM, 25.7 nM and 16.2 nM, respectively. Sequence analysis of the Mpro encoded by the variants showed ~100% identity of active site amino acid sequences, reflecting the essential role of Mpro during viral replication leading to ability of Nirmatrelvir to exhibit potent activity across all the variants.
  🖺 Full Text HTML: Nirmatrelvir, an orally active Mpro inhibitor, is a potent inhibitor of SARS-CoV-2 Variants of Concern
• All-cause excess mortality in the State of Gujarat, India, during the COVID-19 pandemic (March 2020-April 2021) -

  Official COVID-19 mortality statistics are strongly influenced by local diagnostic capacity, strength of the healthcare and vital registration systems, and death certification criteria and capacity, often resulting in significant undercounting of COVID-19 attributable deaths. Excess mortality, which is defined as the increase in observed death counts compared to a baseline expectation, provides an alternate measure of the mortality shock - both direct and indirect - of the COVID-19 pandemic. Here, we use data from civil death registers from a convenience sample of 90 municipalities across the state of Gujarat, India, to estimate the impact of the COVID-19 pandemic on all-cause mortality. Using a model fit to weekly data from January 2019 to February 2020, we estimated excess mortality over the course of the pandemic from March 2020 to April 2021. We estimated 21,300 [95% CI: 20,700, 22,000] excess deaths across these municipalities in this period, representing a 44% [95% CI: 43%, 45%] increase over the expected baseline. The sharpest increase in deaths in our sample was observed in late April 2021, with an estimated 678% [95% CI: 649%, 707%] increase in mortality from expected counts. The 40 to 65 age group experienced the highest increase in mortality relative to the other age groups. We found substantial, yet similar, increases in mortality for males and females. Our excess mortality estimate for these 90 municipalities, representing approximately 5% of the state9s population, exceeds the official COVID-19 death count for the entire state of Gujarat, even before the delta wave of the pandemic in India peaked in May 2021. Prior studies have concluded that true pandemic-related mortality in India greatly exceeds official counts. This study, using data directly from the first point of official death registration data recording, provides incontrovertible evidence of the high excess mortality in Gujarat from March 2020 to April 2021.

  🖺 Full Text HTML: All-cause excess mortality in the State of Gujarat, India, during the COVID-19 pandemic (March 2020-April 2021)
• Structural basis for Nirmatrelvir in vitro efficacy against the Omicron variant of SARS-CoV-2 -
  The COVID-19 pandemic continues to be a public health threat with emerging variants of SARS-CoV-2. Nirmatrelvir (PF-07321332) is a reversible, covalent inhibitor targeting the main protease (Mpro) of SARS-CoV-2 and the active protease inhibitor in PAXLOVID (nirmatrelvir tablets and ritonavir tablets). One of the predominant SARS-CoV-2 variants emerging is the B.1.1.529 Omicron harboring a mutation at amino acid position 132 in the Mpro changing a proline to a histidine (P132H). In vitro biochemical enzymatic assay characterization of the enzyme kinetics of the Omicron Mpro (P132H) demonstrate that it is catalytically comparable to wildtype and that nirmatrelvir has similar potency against both wildtype and Omicron (P132H) Mpro with Ki of 0.933nM (wildtype) and 0.635nM (P132H) each, respectively. This observation is reinforced by our structural determination of nirmatrelvir bound to the omicron Mpro at 1.63[A] resolution. These in vitro data suggest that PAXLOVID has the potential to maintain plasma concentrations of nirmatrelvir many-fold times higher than the amount required tostop the SARS-CoV-2 variant Omicron from replicatingin cells.
  🖺 Full Text HTML: Structural basis for Nirmatrelvir in vitro efficacy against the Omicron variant of SARS-CoV-2
• HAT-field: a very cheap, robust and quantitative point-of-care serological test for Covid-19. -

  We have recently described a very simple and cheap serological test called HAT to detect antibodies directed against the RBD of the SARS-Cov-2 virus. HAT is based on hemagglutination, triggered by a single reagent (IH4-RBD) comprised of the viral RBD domain fused to a nanobody specific for glycophorin, which is expressed at very high levels at the surface of human red blood cells (RBCs). One of the main initial goals of this study was to devise a test protocol that would be sensitive and reliable, yet require no specialized laboratory equipment such as adjustable pipets, so that it could be performed in the most remote corners of the world by people with minimal levels of training. Because antibody levels against the viral RBD have been found to correlate closely with sero-neutralisation titers, and thus with protection against reinfection, it has become obvious during the course of this study that making this test reliably quantitative would be a further significant advantage. We have found that, in PBN, a buffer which contains BSA and sodium azide, IH4-RBD is stable for over 6 months at room temperature, and that PBN also improves HAT performance compared to using straight PBS. We also show that performing HAT at either 4°C, room temperature or 37°C has minimal influence on the results, and that quantitative evaluation of the levels of antibodies directed against the SARS-CoV-2 RBD can be achieved in a single step using titration of the IH4-RBD reagent. The HAT-field protocol described here requires only very simple disposable equipment and a few microliters of whole blood, such as can be obtained by finger prick. Because it is based on a single soluble reagent, the test can be adapted very simply and rapidly to detect antibodies against variants of the SARS-CoV-2, or conceivably against different pathogens. HAT-field appears well suited to provide quantitative assessments of the serological protection of populations as well as individuals, and given its very low cost, the stability of the IH4-RBD reagent in the adapted buffer, and the simplicity of the procedure, could be deployed pretty much anywhere, including in the poorest countries and the most remote corners of the globe.

From Clinical Trials

• Quantifying Viral Load in Respiratory Particles That Are Generated by Children and Adults With COVID-19 Infection - Condition:   COVID-19
  Intervention:   Device: COVID-19 Aerosol Collection
  Sponsor:  
  Massachusetts General Hospital
  Recruiting

• Evaluation of Safety & Efficacy of MIR 19 ® Inhalation Solution in Patients With Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: MIR 19 ®;   Combination Product: Standard COVID-19 therapy
  Sponsors:   National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia;   St. Petersburg Research Institute of Vaccines and Sera
  Completed

• A Study to Evaluate the Safety and Immunogenicity of Booster With AZD1222, mRNA-1273, or MVC-COV1901 Against COVID-19 - Condition:   COVID-19 Vaccine
  Interventions:   Biological: Half dose of MVC-COV1901;   Biological: Full dose of MVC-COV1901;   Biological: AZD1222;   Biological: Half dose of mRNA-1273
  Sponsors:   Medigen Vaccine Biologics Corp.;   Coalition for Epidemic Preparedness Innovations
  Not yet recruiting

• Efficacy of Breathox Device Inhalation Therapy in the Treatment of Acute Symptoms Associated With COVID-19 and in the Prevention of the Use of Health Resources - Condition:   COVID-19
  Interventions:   Drug: BREATHOX 5 sessions;   Drug: BREATHOX 10 sessions
  Sponsors:   UPECLIN HC FM Botucatu Unesp;   Liita Holdings LTD
  Recruiting

• Plasma Exchange in Covid-19 Patients With Anti-interferon Autoantibodies - Condition:   COVID-19
  Intervention:   Drug: Therapeutic plasma exchange
  Sponsor:  
  Centre Hospitalier St Anne
  Recruiting

• Randomized Multicenter Study on the Efficacy and Safety of Favipiravir for Parenteral Administration Compared to Standard of Care in Hospitalized Patients With COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Favipiravir;   Drug: Remdesivir
  Sponsors:   Promomed, LLC;   Solyur Pharmaceuticals Group
  Completed

• Inhaled Heparin for Hospitalised Patients With Coronavirus Disease 2019 (COVID-19) - Condition:   COVID-19
  Intervention:   Drug: unfractionated Heparin
  Sponsors:  
  Australian National University;   The George Institute;   St George Hospital, Australia;   St Vincent’s Hospital Melbourne;   John Hunter Hospital;   Royal North Shore Hospital
  Not yet recruiting

• A Prospective, Phase II Study to Evaluate Safety of 101-PGC-005 (’005) for Moderate to Severe COVID-19 Disease Along With Standard of Care - Condition:   COVID-19
  Interventions:   Drug: 101-PGC-005 (’005) + SOC;   Drug: Placebo + SOC
  Sponsor:   101 Therapeutics
  Recruiting

• Immunogenicity and Safety Study of a SCB-2019 Vaccine Booster Dose to Adults Who Previously Received Primary Series of Selected COVID-19 Vaccines - Condition:   COVID-19
  Intervention:   Biological: Candidate vaccine, SCB-2019
  Sponsor:   Clover Biopharmaceuticals AUS Pty Ltd
  Not yet recruiting

• Increasing COVID-19 Testing in Chicago’s African American Testing Desserts - Condition:   COVID-19 Pandemic
  Intervention:   Behavioral: COVID-19 Testing
  Sponsor:   Rush University Medical Center
  Recruiting

• The Effect of Telemonitoring on Anxiety and Quality of Life in Patients in COVID 19 Quarantine - Condition:   COVID-19 Pandemic
  Intervention:   Other: tele-monitoring
  Sponsor:  
  Yuksek Ihtisas University
  Completed

• IMPACT OF THERAPEUTIC PLASMA EXCHANGE ON ACQUIRED VACCINAL ANTI-SARS-CoV-2 ANTIBODIES. - Condition:   COVID-19
  Intervention:   Diagnostic Test: Evolution of antibodies titre
  Sponsor:   Cliniques universitaires Saint-Luc- Université Catholique de Louvain
  Recruiting

• COVID-19 Messaging for Vaccination - Conditions:   Vaccination Refusal;   COVID-19 Pandemic
  Interventions:   Behavioral: Doctor Videos;   Behavioral: Sharing Videos;   Behavioral: Sharing Videos (Influencers);   Behavioral: Vaccine Ambassador;   Behavioral: Video framing;   Behavioral: Video order
  Sponsors:   Massachusetts Institute of Technology;   Facebook, Inc.;   Code3;   Stanford University;   Harvard University;   Yale University;   Johns Hopkins University;   Massachusetts General Hospital;   Ludwig-Maximilians - University of Munich;   National Institutes of Health (NIH)
  Recruiting

• Respiratory Physiotherapy and Neurorehabilitation in Patients With Post-covid19 Sequelae. - Condition:   COVID-19 Pandemic
  Intervention:   Other: respiratory treatment
  Sponsor:   Universidad Católica de Ávila
  Not yet recruiting

• A Phase 1, Open-label Study to Evaluate the Safety, Tolerability, and Reactogenicity of the Baiya SARS-CoV-2 Vax 2 Vaccine in Healthy Adults - Condition:   COVID-19 Vaccine
  Interventions:   Biological: 25 Baiya SARS-CoV-2 Vax 2;   Biological: 50 Baiya SARS-CoV-2 Vax 2
  Sponsors:   Baiya Phytopharm Co., Ltd.;   National Vaccine Institute, Thailand
  Not yet recruiting

From PubMed

• Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review - Colchicine is an ancient herbal drug derived from Colchicum autumnale. It was first used to treat familial Mediterranean fever and gout. Based on its unique efficacy as an anti-inflammatory agent, colchicine has been used in the therapy of cardiovascular diseases including coronary artery disease, atherosclerosis, recurrent pericarditis, vascular restenosis, heart failure, and myocardial infarction. More recently, colchicine has also shown therapeutic efficacy in alleviating cardiovascular…

• Tissue-level alveolar epithelium model for recapitulating SARS-CoV-2 infection and cellular plasticity - Pulmonary sequelae following COVID-19 pneumonia have been emerging as a challenge; however, suitable cell sources for studying COVID-19 mechanisms and therapeutics are currently lacking. In this paper, we present a standardized primary alveolar cell culture method for establishing a human alveolar epithelium model that can recapitulate viral infection and cellular plasticity. The alveolar model is infected with a SARS-CoV-2 pseudovirus, and the clinically relevant features of the viral entry…

• S100A8 and S100A9, biomarkers of SARS-CoV-2-infection and other diseases, suppress HIV replication in primary macrophages - S100A8 and S100A9 are members of the Alarmin family; these proteins are abundantly expressed in neutrophils and form a heterodimer complex and secreted in plasma upon pathogen infection or acute inflammatory diseases. Recently, both proteins were identified as novel biomarkers of SARS-CoV-2 infection and were shown to play key roles in inducing an aggressive inflammatory response by mediating the release of large amounts of pro-inflammatory cytokines, called the “cytokine storm.” Although…

• The cGAS-STING pathway drives type I IFN immunopathology in COVID-19 - Coronavirus disease 2019 (COVID-19), caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS- CoV-2), is characterized by significant lung pathology and extrapulmonary complications^(1,2). Type I interferons (IFNs) play an essential role in the pathogenesis of COVID-19^(3-5). While rapid induction of type I IFNs limits virus propagation, sustained elevation of type I IFNs in the late phase of the infection is associated with aberrant inflammation and poor clinical…

• Biosynthesis of Calipyridone A Represents a Fungal 2-Pyridone Formation without Ring Expansion in Aspergillus californicus - A chemical investigation of the filamentous fungus Aspergillus californicus led to the isolation of a polyketide- nonribosomal peptide hybrid, calipyridone A (1). A putative biosynthetic gene cluster cpd for production of 1 was next identified by genome mining. The role of the cpd cluster in the production of 1 was confirmed by multiple gene deletion experiments in the host strain as well as by heterologous expression of the hybrid gene cpdA inAspergillus oryzae. Moreover, chemical analyses of…

• The intrinsically disordered SARS-CoV-2 nucleoprotein in dynamic complex with its viral partner nsp3a - The processes of genome replication and transcription of SARS-CoV-2 represent important targets for viral inhibition. Betacoronaviral nucleoprotein (N) is a highly dynamic cofactor of the replication-transcription complex (RTC), whose function depends on an essential interaction with the amino-terminal ubiquitin-like domain of nsp3 (Ubl1). Here, we describe this complex (dissociation constant - 30 to 200 nM) at atomic resolution. The interaction implicates two linear motifs in the intrinsically…

• Phytoconstituents from Moringa oleifera fruits target ACE2 and open spike glycoprotein to combat SARS-CoV-2: An integrative phytochemical and computational approach - Therapeutic drugs based on natural products for the treatment of SARS-CoV-2 are currently unavailable. This study was conducted to develop an anti-SARS-CoV-2 herbal medicine to face the urgent need for COVID-19 treatment. The bioactive components from ethanolic extract of Moringa oleifera fruits (MOFs) were determined by gas chromatography-mass spectroscopy (GC-MS). Molecular-docking analyses elucidated the binding effects of identified phytocomponents against SARS-CoV-2 spike glycoprotein (PDB…

• Ivermectin in COVID-19 Management: What is the current evidence? - Ivermectin (IVM), an approved anthelminthic drug, has been reported to have antiviral, antibacterial, and anticancer activities. Antiviral activity is due to the inhibition of nuclear cargo importin (IMP) protein. The anti-SARS CoV-2 activity through in vitro study was first reported by an Australian team. Later, many studies were conducted, and most of the study results were available as non-peer reviewed preprints. In this narrative review, literature on the clinical studies conducted with…

• Inhibition of ACE2-Spike interaction by an ACE2 binder suppresses SARS-CoV-2 entry - The emergence of SARS-CoV-2 variants is a significant concern in developing effective therapeutics and vaccines in the middle of the ongoing COVID-19 pandemic. Here, we identified a novel small molecule that inhibited the interactions between SARS-CoV-2 spike RBDs and ACE2 by modulating ACE2 without impairing its enzymatic activity necessary for normal physiological functions. Furthermore, the identified compounds suppressed viral infection in cultured cells by inhibiting the entry of ancestral…

• Remdesivir significantly reduces SARS-CoV-2 viral load on nasopharyngeal swabs in hospitalized patients with COVID-19: a retrospective case-control study - CONCLUSIONS: The present study shows that the administration of remdesivir in hospitalized COVID-19 patients significantly reduces the VL on nasopharyngeal swabs. This article is protected by copyright. All rights reserved.

• Development and utilization of a surrogate SARS-CoV-2 viral neutralization assay to assess mRNA vaccine responses - CONCLUSIONS: A competitive ELISA based on inhibition of RBD-ACE2r attachment correlates well with PRNT, quantifies significantly higher activity among vaccine recipients with prior COVID (vs. those without), and highlights marked declines in surrogate neutralizing activity over a 6 month period post vaccination. The findings raise concern about the duration of vaccine responses and potential need for booster shots.

• RBD conjugate vaccine with a built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern - The coronavirus 2019 (COVID-19) pandemic is causing serious impacts in the world, and safe and effective vaccines and medicines are the best methods to combat the disease. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a key role in interacting with the angiotensin-converting enzyme 2 (ACE2) receptor, and is regarded as an important target of vaccines. Herein, we constructed the adjuvant-protein conjugate Pam(3)CSK(4)-RBD as a vaccine candidate, in which the N-terminal…

• Neutralizing SARS-CoV-2 by dimeric side chain-to-side chain cross-linked ACE2 peptide mimetics - We present the finding of a dimeric ACE2 peptide mimetic designed through side chain cross-linking and covalent dimerization. It has a binding affinity of 16 nM for the SARS-CoV-2 spike RBD, and effectively inhibits the SARS-CoV-2 pseudovirus in Huh7-hACE2 cells with an IC(50) of 190 nM and neutralizes the authentic SARS-CoV-2 in Caco2 cells with an IC(50) of 2.4 μM. Our study should provide a new insight for the optimization of peptide-based anti-SARS-CoV-2 inhibitors.

• Antiinflammatory potential of nano-curcumin as an alternative therapeutic agent for the treatment of mild-to- moderate hospitalized COVID-19 patients in a placebo-controlled clinical trial - The present study conducted a placebo-controlled clinical trial to evaluate the impact of nano-curcumin on the inflammatory cytokines in mild-to-moderate hospitalized COVID-19 patients. A total of 60 COVID-19 patients were randomly divided into nano-curcumin and control groups, and then they received 240 mg/day nano-curcumin for 7 days. The clinical manifestation and laboratory parameters in patients were recorded on days 0 and seven. Also, SYBR Green real-time PCR and ELISA techniques were…

• Metadichol: A Novel Nanolipid Formulation That Inhibits SARS-CoV-2 and a Multitude of Pathological Viruses In Vitro - Increasing outbreaks of new pathogenic viruses have promoted the exploration of novel alternatives to time-consuming vaccines. Thus, it is necessary to develop a universal approach to halt the spread of new and unknown viruses as they are discovered. One such promising approach is to target lipid membranes, which are common to all viruses and bacteria. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has reaffirmed the importance of interactions between the virus…

From Patent Search

• IDENTIFICATION AND ALARM SYSTEM FOR FACIAL CORONA MASK USING CNN BASED IMAGE PROCESSING - tThe covid-19 epidemic is the world’s largest wake-up call for people to pay attention to their own and society’s health. One thing to keep in mind is that there is a segment of the population that has been exposed to the covid-19 virus and has generated antibodies without developing any significant illnesses and is continuing to be healthy. This indicates that a significant section of the population, even excluding the elderly, lacks the necessary bodily immunity to combat a Viral infection. As terrible as covid-19 is on a global scale, developing personal health standards and preventative measures for any pathogenic virus as a community would have spared many lives. In’this work, a camera is combined with an image processing system to recognise facial masks, which may be improved in a variety of ways. First and foremost, this method is meant to identify masks on a single person’s face. While this method is efficient in identifying someone has a mask, it does not ensure that they will wear it all of the time. The most effective update for this task is to install a camera with a wide field of view so that many individuals can be seen in the frame, and the faces of those who aren’t wearing markings can be identified, as well as the number of people and the timing. - link

• ANTIMICROBIAL SANITIZING FORMULATION - An antimicrobial sanitizing formulation, comprising, i) isopropyl alcohol in the range of 0.1%- 80% w/w, ii) an emollient in the range of 0.1%-15% w/w, iii) hydrogen peroxide in the range of 0.1 0.13% w/w, iv) citric acid in the range of 0.1% to 2.0% w/w, v) silver nitrate in the range of 0.1% to 0.5% w/w, and vi) a fragrance imparting agent in the range of 0.1% to 2.0% w/w. - link

• A HEALTH BAND WITH A BIOMETRIC MODULE AND WORKING METHOD THEREOF - The present invention discloses a health band with a biometric module and method thereof. The assembly includes, but not limited to, a plurality of sensors configured to gather health data associated with a predefined symptom of a medical condition of a user; a memory unit configured to store the data and an interface, which is configured to determine the medical condition using the data;a processing unit configured to execute the application; and a notification facility configured to provide a notification upon receiving from the interface an instruction associated with the notification, wherein the notification is associated with a drug reminder and the like. - link

• RNA 검출 방법 - 본 발명은 RNA의 분석 및 검출 방법에 관한 것이다. 특히, 본 발명은 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

• REUNION OF PHOTOTHERMAL THERAPY WITH MXENE ADSORBED UREMIC TOXINS AND CYTOKINES: A SHILED FOR COVID-19 PATENTS - The COVID-19 pandemic has created havoc throughout the world. The disease has proved to be more fatalfor patients having comorbidities like diabetics, lungs and kidney infections, etc. In the case of COVID-19 patientsI having kidney injury, the. removal of uremic toxins from the blood is hindered and there is a rapid surge in the levelj of cytokine hormone resulting in the death of the patient in a short interval of time. To resolve this issue,iI; researchers have examined that the immediate removal of these toxins can improve the condition of the patient to a |greater extent. Studies have also found the presence of SARS CoV-2 viral RNAs in the blood of COVID-19patients, which risks their life as well as impacts the blood transfusion process, especially in the case ofasymptomatic patients. Hence it is required to control the surge of cytokines and uremic toxins as well as disinfectthe blood of the patient from the virus. MXenes, having a foam-like porous structure and hydrophilic negativesurface functionalization have greater adsorption efficiency as well as superior photothermal activity. Utilizingthese properties of MXenes, the MXene membranes can be used in the dialyzer that can help in the efficient andBiuick removal of the uremic toxins, cytokines, and other impurities from the blood. Along with this the greaterTJAdsorption efficiency of MXenes to amino acids result in the trapping of the SARS CoV-2 viruses on the surface J)3>f the MXene. Many researchers as well as the WHO have proved the efficient reduction of the viral copy numbersjjvith the increase of temperature. Hence, followed by the trapping of the viruses, the implementation of"Zphotothermal Therapy can result in the inactivation and denaturation of the viruses and their respective viral RNAsBJlby the produced heat. The same process can be repeated several times to get better results. This whole process canr>oQ-esult in impurity-free and infection-free blood, that can be returned back to the body of the patient or can be!— I Sitilized for the blood transfusion process without any risk of infection.IM - link

• REDUCING AND STOPPING OXYGEN WASTAGE IN HOSPITAL - In an aspect, the present invention discloses a system (200) for prevention and reduction of oxygen wastage from oxygen mask (202). The system (200) includes the oxygen mask (202) having straps; a tension sensor (204), the tension sensor being sensitive towards tension produced in the straps as the oxygen gets leakage through sides of the mask (202); a processor configured in alignment with the tension sensor (204); and a buzzer (206) in alignment with processor. - link

• 编码SARS-COV-2病毒C.37突变株抗原的DNA分子、DNA疫苗及应用 - 本发明涉及生物技术领域，具体而言，提供了一种编码SARS‑COV‑2病毒C.37突变株抗原的DNA分子、DNA疫苗及应用。本发明提供的SEQ ID NO：1核酸序列在真核表达系统中能够高效转录和表达，而且具有免疫原性，表现在体液免疫和细胞免疫应答中，以此作为活性成分的核酸疫苗同样具有良好的免疫原性。 - link

• SARS-COV-2病毒B.1.617.2突变株DNA疫苗及应用 - 本发明涉及生物技术领域，具体而言，提供了一种编码SARS‑COV‑2病毒B.1.617.2突变株抗原的DNA分子、DNA疫苗及应用。本发明提供的SEQ ID NO：1核酸序列在真核表达系统中能够高效转录和表达，而且具有免疫原性，表现在体液免疫和细胞免疫应答中，以此作为活性成分的核酸疫苗同样具有良好的免疫原性。 - link

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

• A METHOD TO REVEAL MOTIF PATTERNS OF COVID-19 USING MULTIPLE SEQUENCE ALIGNMENT - This present invention consists of different levels of computation and work in a pipeline manner i.e., input of one will be output of another and it is sequential process. Input data given in form of nucleotide sequence (DNA) of different COVID-19 patients (1). Using these nucleotide sequence perform mutation if possible and arrange them in a sequential order (2). Arrange number of nucleotide sequences of different patients in row wise and also compute number of characters in each row. (3). Compute frequency of occurrence of character in column wise and create a matrix having 4 rows and maximum sequence length will be the column size (4). Find the character like A, T, C, and G which one has maximum score and similarly find for each column to produce a final sequence (5). - link