Covid-19 Sentry

Contents

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

From Preprints

• The COVID States Project #59: What Americans think about people who are not vaccinated -
  In this report, we evaluate how people feel about those who are vaccinated and those who are not. A common way of measuring these feelings is through feeling thermometers – special survey items aimed at capturing a respondent’s overall level of warmth towards a particular person, group, or idea. Two of the thermometer questions we asked measured feelings towards “People who are vaccinated against COVID-19” and “People who are NOT vaccinated against COVID-19”, with response options ranging from 0 to 100 degrees. These are the two key outcome variables for this report (see the appendix for full question wording). To evaluate the gap between feelings towards those who are vaccinated against COVID-19 and those who are not, we take the difference in scores between the two corresponding thermometer questions. That tells us how much more favorably respondents view one group compared to the other. Our analyses examine how feelings expressed by the respondents are linked to factors such as partisanship, education, gender, age, income, place of residence and personal vaccination status, among others.
  🖺 Full Text HTML: The COVID States Project #59: What Americans think about people who are not vaccinated
• COVID-19 impact on stroke admissions during France′s first epidemic peak: an exhaustive, nationwide, observational study -

  Background and Purpose: The COVID-19 pandemic continues to have great impacts on the care of non-COVID-19 patients. This was especially true during the first epidemic peak in France, which coincided with the national lockdown (17 March 2020 to 10 May 2020). Patients with serious and urgent disease like stroke may have experienced a degradation of care, or may have been hesitant to seek healthcare during this period. The aim of this study was to identify, on a national level, whether a decrease in stroke admissions occurred in spring 2020, by analyzing the evolution of all stroke admissions in France from January 2019 to June 2020. Methods: We conducted a nationwide cohort study using the French national database of hospital admissions (PMSI) to extract exhaustive data on all hospitalizations in France with at least one stroke diagnosis between 1 January 2019 and 30 June 2020. The primary endpoint was the difference in the slope gradients of stroke hospitalizations between pre-epidemic, epidemic peak and post-epidemic periods. Modeling was carried out using Bayesian techniques. Results: Stroke hospitalizations dropped from 10 March 2020 (slope gradient: -11.70), and began to rise again from 22 March (slope gradient: 2.090) to 7 May. In total, there were 23 873 stroke admissions during the period March-April 2020, compared to 29 263 at the same period in 2019, representing a decrease of 18.42%. The percentage change was -15.63%, -25.19%, -18.62% for ischemic strokes, transient ischemic attacks, and hemorrhagic strokes, respectively. In spatial models of French departments, the incidence of COVID-19 explained the ratio of stroke hospitalizations. Conclusions: Stroke hospitalizations in France experienced a decline during the first lockdown period, which cannot be explained by a sudden change in stroke incidence. This decline is therefore likely to be a direct, or indirect, result of the COVID-19 pandemic.

  🖺 Full Text HTML: COVID-19 impact on stroke admissions during France′s first epidemic peak: an exhaustive, nationwide, observational study
• Dynamics of COVID-19 pandemic in India and Pakistan: A metapopulation modelling approach -

  India has been the latest global epicenter for COVID-19, a novel coronavirus disease that emerged in China in late 2019. We present a base mathematical model for the transmission dynamics of COVID-19 in India and its neighbor, Pakistan. The base model, which takes the form of a deterministic system of nonlinear differential equations, is parameterized using cumulative COVID-19 mortality data from each of the two countries. The model was used to assess the population-level impact of the control and mitigation strategies implemented in the two countries (notably community lockdowns, use of face masks, and social-distancing). Numerical simulations of the basic model indicate that, based on the current baseline levels of the control and mitigation strategies implemented, the pandemic trajectory in India is on a downward trend (as characterized by the reproduction number of the disease dynamics in India below, but close to, unity). This downward trend will be reversed, and India will be recording mild outbreaks (i.e., pandemic waves), if the control and mitigation strategies are relaxed from their current levels (e.g., relaxed to the extent that the associated community transmission parameters are increased by 20% or 40% from their current baseline values). Our simulations suggest that India could record up to 460,000 cumulative deaths by early September 2021 under the baseline levels of the control strategies implemented (up to 25,000 of the projected deaths could be averted if the control and mitigation measures are strengthened to the extent that the associated community transmission parameters are reduced by 20% from their baseline values). Our simulations show that the pandemic in Pakistan is much milder, with an estimated projected cumulative mortality of about 24,000 by early September 2021 under the baseline scenario. The basic model was extended to assess the impact of back-and-forth mobility between the two countries. Simulations of the resulting metapopulation model, which uses a Lagrangian mobility framework (based on residence-time spent in each country), shows that the burden of the pandemic in Pakistan increases with increasing values of the average time residents of India spend in Pakistan. In particular, it is shown that the India-to-Pakistan mobility pattern may trigger a significant fourth wave of the pandemic in Pakistan (under certain mobility scenarios and mitigation levels), with daily mortality peaking in mid- August to mid-September of 2021. It is also shown that extending the current travel restrictions by at least three months would significantly enhance the prospect of eliminating the pandemic in both countries. On the other hand, it is shown that, in addition to causing future multiple waves of the pandemic, easing the current levels of control and mitigation measures in the two countries (including travel restrictions) would result in delaying pandemic elimination in India and Pakistan to November and July 2022, respectively.

  🖺 Full Text HTML: Dynamics of COVID-19 pandemic in India and Pakistan: A metapopulation modelling approach
• Sensitive and multiplexed RNA detection with Cas13 droplets and kinetic barcoding -

  Rapid and sensitive quantification of RNA is critical for detecting infectious diseases and identifying disease biomarkers. Recent direct detection assays based on CRISPR-Cas13a avoid reverse transcription and DNA amplification required of gold-standard PCR assays, but these assays have not yet achieved the sensitivity of PCR and are not easily multiplexed to detect multiple viruses or variants. Here we show that Cas13a acting on single target RNAs loaded into droplets exhibits stochastic nuclease activity that can be used to enable sensitive, rapid, and multiplexed virus quantification. Using SARS-CoV-2 RNA as the target and combinations of CRISPR RNA (crRNA) that recognize different parts of the viral genome, we demonstrate that reactions confined to small volumes can rapidly achieve PCR-level sensitivity. By tracking nuclease activity within individual droplets over time, we find that Cas13a exhibits rich kinetic behavior that depends on both the target RNA and crRNA. We demonstrate that these kinetic signatures can be harnessed to differentiate between different human coronavirus species as well as SARS-CoV-2 variants within a single droplet. The combination of high sensitivity, short reaction times, and multiplexing makes this droplet-based Cas13a assay with kinetic barcoding a promising strategy for direct RNA identification and quantification.

  🖺 Full Text HTML: Sensitive and multiplexed RNA detection with Cas13 droplets and kinetic barcoding
• Optical nanoscopy reveals SARS-CoV-2-induced remodeling of human airway cells -
  A better understanding of host cell remodeling by the coronavirus SARS-CoV-2 is urgently needed to understand viral pathogenesis and guide drug development. Expression profiling and electron microscopy have frequently been used to study virus-host interactions, but these techniques do not readily enable spatial, sub-cellular and molecular analysis of specific cellular compartments. Here, we use diffraction-unlimited fluorescence microscopy to analyze how SARS-CoV-2 infection exploits and repurposes the subcellular architecture of primary human airway cells. Using STED nanoscopy, we detect viral entry factors along the motile cilia of ciliated cells and visualize key aspects of the viral life cycle. Using Tenfold Robust Expansion (TREx) microscopy, we analyze the extensively remodeled three-dimensional ultrastructure of SARS-CoV-2-infected ciliated cells and uncover Golgi fragmentation, emergence of large and atypical multivesicular bodies enclosing viral proteins, ciliary clustering, and remodeling of the apical surface. These results demonstrate a broadly applicable strategy to study how viruses reorganize host cells with spatial and molecular specificity and provide new insights into SARS-CoV-2 infection in primary human cell models.
  🖺 Full Text HTML: Optical nanoscopy reveals SARS-CoV-2-induced remodeling of human airway cells
• Elapsed time since BNT162b2 vaccine and risk of SARS-CoV-2 infection in a large cohort -

  Importance: Israel was among the first countries to launch a large-scale COVID-19 vaccination campaign, and quickly vaccinated its population, achieving early control over the spread of the virus. However, the number of COVID-19 cases is now rapidly increasing, which may indicate that vaccine protection decreases over time. Objective: To determine whether time elapsed since the second BNT162b2 messenger RNA (mRNA) vaccine (Pfizer-BioNTech) injection is significantly associated with the risk of post-vaccination COVID-19 infection. Design: This is a retrospective cohort study performed in a large state-mandated health care organization in Israel. Participants: All fully vaccinated adults who have received a RT-PCR test between May 15, 2021 and July 26, 2021, at least two weeks after their second vaccine injection were included. Patients with a history of past COVID-19 infection were excluded. Main Outcome and Measure: Positive result for the RT-PCR test. Results: The cohort included 33,993 fully vaccinated adults, 49% women, with a mean age of 47 years (SD, 17 years), who received an RT-PCR test for SARS-CoV-2 during the study period. The median time between the second dose of the vaccine and the RT-PCR test was 146 days, interquartile range [121-167] days. 608 (1.8%) patients had positive test results. There was a significantly higher rate of positive results among patients who received their second vaccine dose at least 146 days before the RT-PCR test compared to patients who have received their vaccine less than 146 days before: odds ratio for infection was 3.00 for patients aged over 60 (95% CI 1.86-5.11); 2.29 for patients aged between 40 and 59 (95% CI 1.67-3.17); and 1.74 for patients aged between 18 and 39 (95% CI 1.27-2.37); P<0.001 in each age group. Conclusions and Relevance: In this large population study of patients tested for SARS-CoV-2 by RT-PCR following two doses of mRNA BNT162b2 vaccine, we observe a significant increase of the risk of infection in individuals who received their last vaccine dose since at least 146 days ago, particularly among patients older than 60.

  🖺 Full Text HTML: Elapsed time since BNT162b2 vaccine and risk of SARS-CoV-2 infection in a large cohort
• Temporal Geospatial Analysis of COVID-19 Pre-infection Determinants of Risk in South Carolina -

  Introduction: Disparities and their geospatial patterns exist in coronavirus disease 2019 (COVID-19) morbidity and mortality for people who are engaged with clinical care. However, studies centered on viral infection cases are scarce. It remains unclear with respect to the disparity structure, its geospatial characteristics, and the pre- infection determinants of risk (PIDRs) for people with the infection. This work aimed to assess the geospatial associations between PIDRs and COVID-19 infection at the county level in South Carolina by different timepoints during the pandemic. Method: We used global models including spatial error model (SEM), spatial lag model (SLM), and conditional autoregressive model (CAR), as well as geographically weighted regression model (GWR) as a local model to examine the associations between COVID-19 infection rate and PIDRs. The data were retrieved from multiple sources including USAFacts, US Census Bureau, and Population Estimates Program. Results: The percentage of males and the percentage of the unemployed population were statistically significant (p values < 0.05) with positive coefficients in the three global models (SEM, SLM, CAR) throughout the time. The percentage of white population and obesity rate showed divergent spatial correlations at different times of the pandemic. GWR models consistently have a better model fit than global models, suggesting non-stationary correlations between a region and its neighbors. Conclusion: Characterized by temporal-geospatial patterns, disparities and their PIDRs exist in COVID-19 incidence at the county level in South Carolina. The temporal-geospatial structure of disparities and their PIDRs found in COVID-19 incidence are different from mortality and morbidity for patients who are connected with clinical care. Our findings provided important evidence for prioritizing different populations and developing tailored interventions at different times of the pandemic. These findings provided implications on containing early viral transmission and mitigating consequences of infectious disease outbreaks for possible future pandemics.

  🖺 Full Text HTML: Temporal Geospatial Analysis of COVID-19 Pre-infection Determinants of Risk in South Carolina
• Challenges in Tracking the Risk of COVID-19 in Bangladesh: Evaluation of A Novel Method -

  Identifying actual risk zones in a country where the overall test positive rate (TPR) is higher than 5% is crucial to contain the pandemic. However, TPR-based risk zoning methods are debatable since they do not consider the rate of infection in an area and thus, it has been observed to overestimate the risk. Similarly, the rate of infection in an area has been noticed to underestimate the risk of COVID-19 spreading for the zones with higher TPR. In this article, we discuss the shortcomings of currently available risk zoning methods that are followed in the lower-middle- income countries (LMIC), especially in Bangladesh. We then propose to determine a risk zone by combining the rate of infection with TPR and effective reproduction number, R_t in a distinct manner from existing methods. We evaluate the efficacy of the proposed method with respect to the mass-movement events and show its application to track the evolution of COVID-19 pandemic by identifying the risk zones over time. Demo website for the visualization of the analysis can be found at: http://erdos.dsm.fordham.edu:3000/.

  🖺 Full Text HTML: Challenges in Tracking the Risk of COVID-19 in Bangladesh: Evaluation of A Novel Method
• Pandemic-Scale Phylogenomics Reveals Elevated Recombination Rates in the SARS-CoV-2 Spike Region -
  Accurate and timely detection of recombinant lineages is crucial for interpreting genetic variation, reconstructing epidemic spread, identifying selection and variants of interest, and accurately performing phylogenetic analyses. During the SARS-CoV-2 pandemic, genomic data generation has exceeded the capacities of existing analysis platforms, thereby crippling real-time analysis of viral recombination. Low SARS-CoV-2 mutation rates make detecting recombination difficult. Here, we develop and apply a novel phylogenomic method to exhaustively search a nearly comprehensive SARS- CoV-2 phylogeny for recombinant lineages. We investigate a 1.6M sample tree, and identify 606 recombination events. Approximately 2.7% of sequenced SARS-CoV-2 genomes have recombinant ancestry. Recombination breakpoints occur disproportionately in the Spike protein region. Our method empowers comprehensive real time tracking of viral recombination during the SARS-CoV-2 pandemic and beyond.
  🖺 Full Text HTML: Pandemic-Scale Phylogenomics Reveals Elevated Recombination Rates in the SARS-CoV-2 Spike Region
• But Mouse, you are not alone: On some severe acute respiratory syndrome coronavirus 2 variants infecting mice -
  In silico predictions combined with in vitro, in vivo and in situ observations collectively suggest that mouse adaptation of the SARS-CoV-2 virus requires an aromatic substitution in position 501 or position 498 (but not both) of the spike protein receptor binding domain. This effect could be enhanced by mutations in positions 417, 484 and 493 (especially K417N, E484K, Q493K and Q493R), and to a lesser extent by mutations in positions 486 and 499 (such as F486L and P499T). Such enhancements due to more favourable binding interactions with residues on the complementary angiotensin-converting enzyme 2 (ACE2) interface, are however, unlikely to sustain mouse infectivity on their own based on theoretical and experimental evidence to date. Our current understanding thus points to the Alpha, Beta and Gamma variants of concern infecting mice, while Delta and Delta Plus lack a similar biomolecular basis to do so. This paper identifies a list of countries where local field surveillance of mice is encouraged because they may have come in contact with humans who had the virus with adaptive mutation(s). It also provides a systematic methodology to analyze the potential for other animal reservoirs and their likely locations.
  🖺 Full Text HTML: But Mouse, you are not alone: On some severe acute respiratory syndrome coronavirus 2 variants infecting mice
• Virucidal activity of CPC-containing oral rinses against SARS-CoV-2 variants and are active in the presence of human saliva -
  The role of human saliva in aerosol-based transmission of SARS-CoV-2 has highlighted the need to understand the potential of oral hygiene products to inactivate the virus. Here we examined the efficacy of mouthwashes containing cetylpyridinium chloride (CPC) or chlorhexidine (CHX) in inactivating SARS-CoV-2. After 30 seconds contact under standard aqueous conditions CPC mouthwashes achieved a [≥]4.0log10 PFU/mL reduction in SARS-CoV-2 (USA-WA1/2020) titres whereas a comparable product containing CHX achieved <2.0log10 PFU/mL reduction. Further testing with CPC mouthwashes demonstrated efficacy against multiple SARS-CoV-2 variants, with inactivation below the limit of detection observed against the Alpha (B.1.1.7), Beta (B.1.35.1) and Gamma (P.1) variants. Virucidal efficacy of CPC mouthwash was also observed in the presence of human saliva with the product delivering [≥]4.0log10 PFU/mL reduction in SARS-CoV-2 titres after 30 seconds providing additional evidence for the virucidal efficacy of CPC mouthwashes under simulated physiological conditions. Together these data suggest CPC-based mouthwashes are effective at inactivating SARS-CoV-2 and further supports the use of mouthwash to mitigate the risk of transmission during density procedures.
  🖺 Full Text HTML: Virucidal activity of CPC-containing oral rinses against SARS-CoV-2 variants and are active in the presence of human saliva
• Rapid assessment of SARS-CoV-2 evolved variants using virus-like particles -
  Newly evolved SARS-CoV-2 variants are driving ongoing outbreaks of COVID-19 around the world. Efforts to determine why these viral variants have improved fitness are limited to mutations in the viral spike (S) protein and viral entry steps using non-SARS-CoV-2 viral particles engineered to display S. Here we show that SARS-CoV-2 virus-like particles can package and deliver exogenous transcripts, enabling analysis of mutations within all structural proteins and rapid dissection of multiple steps in the viral life cycle. Identification of an RNA packaging sequence was critical for engineered transcripts to assemble together with SARS-CoV-2 structural proteins S, nucleocapsid (N), membrane (M) and envelope (E) into non-replicative SARS-CoV-2 virus-like particles (SC2-VLPs) that deliver these transcripts to ACE2- and TMPRSS2-expressing cells. Using SC2-VLPs, we tested the effect of 30 individual mutations within the S and N proteins on particle assembly and entry. While S mutations unexpectedly did not affect these steps, SC2-VLPs bearing any one of four N mutations found universally in more-transmissible viral variants (P199L, S202R, R203M and R203K) showed increased particle production and up to 10-fold more reporter transcript expression in receiver cells. Our study provides a platform for rapid testing of viral variants outside a biosafety level 3 setting and identifies viral N mutations and viral particle assembly as mechanisms to explain the increased spread of current viral variants, including Delta (N:R203M).
  🖺 Full Text HTML: Rapid assessment of SARS-CoV-2 evolved variants using virus-like particles
• Identification of Potent Small Molecule Inhibitors of SARS-CoV-2 Entry -
  The severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 remains a persistent threat to mankind, especially for the immunocompromised and elderly for which the vaccine may have limited effectiveness. Entry of SARS-CoV-2 requires a high affinity interaction of the viral spike protein with the cellular receptor angiotensin- converting enzyme 2. Novel mutations on the spike protein correlate with the high transmissibility of new variants of SARS-CoV-2, highlighting the need for small molecule inhibitors of virus entry into target cells. We report the identification of such inhibitors through a robust high-throughput screen testing 15,000 small molecules from unique libraries. Several leads were validated in a suite of mechanistic assays, including whole cell SARS-CoV-2 infectivity assays. The main lead compound, Calpeptin, was further characterized using SARS-CoV-1 and the novel SARS-CoV-2 variant entry assays, SARS-CoV-2 protease assays and molecular docking. This study reveals Calpeptin as a potent and specific inhibitor of SARS-CoV-2 and some variants.
  🖺 Full Text HTML: Identification of Potent Small Molecule Inhibitors of SARS-CoV-2 Entry
• SARS-CoV-2 variants of concern have acquired mutations associated with an increased spike cleavage -
  For efficient cell entry and membrane fusion, SARS-CoV-2 spike (S) protein needs to be cleaved at two different sites, S1/S2 and S2 by different cellular proteases such as furin and TMPRSS2. Polymorphisms in the S protein can affect cleavage, viral transmission, and pathogenesis. Here, we investigated the role of arising S polymorphisms in vitro and in vivo to understand the emergence of SARS-CoV-2 variants. First, we showed that the S:655Y is selected after in vivo replication in the mink model. This mutation is present in the Gamma Variant Of Concern (VOC) but it also occurred sporadically in early SARS-CoV-2 human isolates. To better understand the impact of this polymorphism, we analyzed the in vitro properties of a panel of SARS-CoV-2 isolates containing S:655Y in different lineage backgrounds. Results demonstrated that this mutation enhances viral replication and spike protein cleavage. Viral competition experiments using hamsters infected with WA1 and WA1-655Y isolates showed that the variant with 655Y became dominant in both direct infected and direct contact animals. Finally, we investigated the cleavage efficiency and fusogenic properties of the spike protein of selected VOCs containing different mutations in their spike proteins. Results showed that all VOCs have evolved to acquire an increased spike cleavage and fusogenic capacity despite having different sets of mutations in the S protein. Our study demonstrates that the S:655Y is an important adaptative mutation that increases viral cell entry, transmission, and host susceptibility. Moreover, SARS-COV-2 VOCs showed a convergent evolution that promotes the S protein processing.
  🖺 Full Text HTML: SARS-CoV-2 variants of concern have acquired mutations associated with an increased spike cleavage
• Immunolocalization studies of vimentin and ACE2 on the surface of cells exposed to SARS-CoV-2 Spike proteins -
  The Spike protein from SARS-CoV-2 mediates docking of the virus onto cells and contributes to viral invasion. Several cellular receptors are involved in SARS-CoV-2 Spike docking at the cell surface, including ACE2 and neuropilin. The intermediate filament protein vimentin has been reported to be present at the surface of certain cells and act as a co-receptor for several viruses; furthermore, its potential involvement in interactions with Spike proteins has been proposed. Here we have explored the binding of Spike protein constructs to several cell types using low-temperature immunofluorescence approaches in live cells, to minimize internalization. Incubation of cells with tagged Spike S or Spike S1 subunit led to discrete dotted patterns at the cell surface, which showed scarce colocalization with a lipid raft marker, but consistent coincidence with ACE2. Under our conditions, vimentin immunoreactivity appeared as spots or patches unevenly distributed at the surface of diverse cell types. Remarkably, several observations including potential antibody internalization and adherence to cells of vimentin-positive structures present in the extracellular medium exposed the complexity of vimentin cell surface immunoreactivity, which requires careful assessment. Notably, overall colocalization of Spike and vimentin signals markedly varied with the cell type and the immunodetection sequence. In turn, vimentin-positive spots moderately colocalized with ACE2; however, a particular enrichment was detected at elongated structures positive for acetylated tubulin, consistent with primary cilia, which also showed Spike binding. Thus, these results suggest that vimentin-ACE2 interaction could occur at selective locations near the cell surface, including ciliated structures, which can act as platforms for SARS-CoV-2 docking.
  🖺 Full Text HTML: Immunolocalization studies of vimentin and ACE2 on the surface of cells exposed to SARS-CoV-2 Spike proteins

From Clinical Trials

• ACTIV-5 / Big Effect Trial (BET-C) for the Treatment of COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Danicopan;   Other: Placebo;   Drug: Remdesivir
  Sponsor:   National Institute of Allergy and Infectious Diseases (NIAID)
  Recruiting

• COVID-19 Administration of Single-Dose Subcutaneous or Intramuscular Anti- Spike(s) SARS-CoV-2 Monoclonal Antibodies Casirivimab and Imdevimab in High-Risk Pediatric Participants Under 12 Years of Age - Condition:   COVID-19
  Intervention:   Drug: casirivimab and imdevimab
  Sponsor:  
  Regeneron Pharmaceuticals
  Not yet recruiting

• Phase I/II Study of COVID-19 DNA Vaccine (AG0302-COVID19 High-dose) - Condition:   COVID-19 Lower Respiratory Infection
  Interventions:   Biological: AG0302-COVID19 for Intramuscular Injection;   Biological: AG0302-COVID19 for Intradermal Injection
  Sponsors:   AnGes, Inc.;   Japan Agency for Medical Research and Development
  Not yet recruiting

• Efficacy, Immunogenicity and Safety of COVID-19 Vaccine , Inactivated in Children and Adolescents - Condition:   COVID-19
  Interventions:   Biological: Inactivated COVID-19 Vaccine;   Biological: Controlled vaccine
  Sponsor:   Sinovac Research and Development Co., Ltd.
  Recruiting

• Immunogenicity And Safety of COVID-19 Vaccine , Inactivated Co -Administration With Quadrivalent Influenza Vaccine And 23-valent Pneumococcal Polysaccharide Vaccine - Condition:   COVID-19
  Interventions:   Biological: Experimental Group1;   Biological: Experimental Group 2;   Biological: Experimental Group 3
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• Efficacy of Canrenone as add-on Treatment in Moderate to Severe ARDS in COVID-19 - Condition:   COVID-19 Acute Respiratory Distress Syndrome
  Intervention:  
  Drug: Potassium Canrenoate
  Sponsors:   Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico;   University of Milan;   IRCCS Azienda Ospedaliero-Universitaria di Bologna
  Not yet recruiting

• Study to Evaluate the Immunogenicity and Safety of Heterologous SARS-CoV-2 Vaccine Schemes in an Elderly Population - Condition:   COVID-19 Vaccines
  Intervention:   Drug: Gam-COVID-Vac / Gam-COVID-Vac
  Sponsor:   Ministerio de Salud de Ciudad Autónoma de Buenos Aires
  Recruiting

• Effect of Cyproheptadine on Ventilatory Support-free Days in Critically Ill Patients With COVID-19 - Condition:   COVID-19 Pneumonia
  Intervention:   Drug: Cyproheptadine
  Sponsor:  
  Hospital de Clinicas de Porto Alegre
  Recruiting

• Safety of an Inactivated SARS-CoV-2 Vaccine for Prevention of COVID-19 in Children and Adolescents - Condition:   COVID-19
  Intervention:   Biological: Experimental Group
  Sponsor:  
  Sinovac Research and Development Co., Ltd.
  Not yet recruiting

• Investigating the Efficacy and Safety ICATIBANT For The Treatment of Patients With SARS-CoV-2 (COVID-19) Infection - Condition:   COVID-19 Pneumonia
  Interventions:   Drug: Firazyr;   Other: SoC
  Sponsor:   Sebastian Videla
  Recruiting

• A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy of Lavandula Angustifolia Containing Nasal Spray Medical Device in Preventing Deterioration of COVID-19 in Symptomatic Patients - Condition:   COVID-19 Infection
  Intervention:   Device: Nasal Spray Device
  Sponsors:   The Grasses of Eden Ltd;   Sherutei Briut Clalit
  Not yet recruiting

• Phase 2b Dose-confirmatory Trial to Evaluate the Safety, Immunogenicity and Potential Efficacy of an VSV-ΔG SARS- CoV-2 Vaccine - Condition:   COVID-19
  Interventions:   Drug: IIBR-100;   Drug: Placebo
  Sponsors:  
  NeuroRx, Inc.;   Cromos;   Iqvia Pty Ltd;   Brilife Georgia;   Israel Institute for Biological Research
  Not yet recruiting

• Echinacea Drug for Covid-19 - Condition:   Covid19
  Intervention:   Drug: ECHINACEA ARKOPHARMA
  Sponsors:  
  Jesús R. Requena;   IDIS;   SALUD;   Laboratoires Arkopharma
  Recruiting

• HC-1119 Adjuvant Treatment for Hospitalized COVID-19 Patients - Condition:   COVID-19 Respiratory Infection
  Interventions:   Drug: HC-1119;   Drug: Placebo
  Sponsors:   Applied Biology, Inc.;   Hinova Pharmaceuticals Inc.
  Not yet recruiting

• CRISPR/Cas9-modified Human T Cell ( PD-1 Knockout Engineered T Cells ) for Inducing Long-term Immunity in COVID-19 Patients - Condition:   COVID-19 Respiratory Infection
  Intervention:   Drug: PD-1 Knockout T Cells
  Sponsor:   Mahmoud Ramadan mohamed Elkazzaz
  Not yet recruiting

From PubMed

• Inhibition of elastase enhances the adjuvanticity of alum and promotes anti-SARS-CoV-2 systemic and mucosal immunity - Alum, used as an adjuvant in injected vaccines, promotes T helper 2 (Th2) and serum antibody (Ab) responses. However, it fails to induce secretory immunoglobulin (Ig) A (SIgA) in mucosal tissues and is poor in inducing Th1 and cell-mediated immunity. Alum stimulates interleukin 1 (IL-1) and the recruitment of myeloid cells, including neutrophils. We investigated whether neutrophil elastase regulates the adjuvanticity of alum, and whether a strategy targeting neutrophil elastase could improve…

• Integrated human/SARS-CoV-2 metabolic models present novel treatment strategies against COVID-19 - The coronavirus disease 2019 (COVID-19) pandemic caused by the new coronavirus (SARS-CoV-2) is currently responsible for more than 3 million deaths in 219 countries across the world and with more than 140 million cases. The absence of FDA- approved drugs against SARS-CoV-2 has highlighted an urgent need to design new drugs. We developed an integrated model of the human cell and SARS-CoV-2 to provide insight into the virus’ pathogenic mechanism and support current therapeutic strategies. We show…

• Assessing the potential correlation of polymorphisms in the IL6R with relative IL6 elevation in severely ill COVID-19 patients’ - CONCLUSIONS: While it is unlikely that “cytokine storm” is the norm in severe COVID19, baseline elevations above 150 pg/ml may be associated with worst outcomes and as such may warrant treatment considerations. So far no clinical studies used IL-6 baseline assessment to stratify the patient population participating in clinical studies. We believe that careful examination and interpretation of the IL-6 levels and genetic variants can help to determine a patient population with a potentially very…

• Evaluation of anti-cancer and anti-covid-19 properties of cationic pentapeptide Glu-Gln-Arg-Pro-Arg, from rice bran protein and its d-isomer analogs through molecular docking simulations - Bioactive peptides derived from food proteins are becoming increasingly popular due to the growing awareness of their health-promoting properties. The structure and mechanism of anti-cancer action of pentapeptide Glu-Gln-Arg-Pro-Arg (EQRPR) derived from a rice bran protein are not known. Theoretical and experimental methods were employed to fill this gap. The conformation analysis of the EQRPR pentapeptide was performed first and the obtained lowest energy conformer was optimized. The…

• BTK inhibitors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A systematic review - CONCLUSIONS AND RELEVANCE: BTKinib use was associated with decreased oxygen requirements and decreased hospitalization rates and duration.

• NMPylation and de-NMPylation of SARS-CoV-2 nsp9 by the NiRAN domain - The catalytic subunit of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) contains two active sites that catalyze nucleotidyl-monophosphate transfer (NMPylation). Mechanistic studies and drug discovery have focused on RNA synthesis by the highly conserved RdRp. The second active site, which resides in a Nidovirus RdRp-Associated Nucleotidyl transferase (NiRAN) domain, is poorly characterized, but both catalytic reactions are essential for viral replication. One study showed that NiRAN transfers…

• Aromatic Cadinane Sesquiterpenoids from the Fruiting Bodies of Phellinus pini Block SARS-CoV-2 Spike-ACE2 Interaction - The ongoing COVID-19 global pandemic caused by SARS-CoV-2 inspires the development of effective inhibitors to block the SARS-CoV-2 spike-ACE2 interaction. A chemical investigation on the fruiting bodies of Phellinus pini led to the isolation of five aromatic cadinane sesquiterpenoids including four new ones, named piniterpenoids A-D (1-4), as well as three known lignans. Their structures were determined by extensive spectroscopic analysis including HRMS and 1D and 2D NMR. All of the aromatic…

• SARS-CoV-2 host cell entry: an in silico investigation of potential inhibitory roles of terpenoids - CONCLUSION: The identified terpenoids from this study provides core structure that can be exploited for further lead optimization to design drugs against SARS-CoV-2 cell-mediated entry proteins. They are therefore recommended for further in vitro and in vivo studies towards developing entry inhibitors against the ongoing COVID-19 pandemic.

• Host ADP-ribosylation and the SARS-CoV-2 macrodomain - The COVID-19 pandemic has prompted intense research efforts into elucidating mechanisms of coronavirus pathogenesis and to propose antiviral interventions. The interferon (IFN) response is the main antiviral component of human innate immunity and is actively suppressed by several non-structural SARS-CoV-2 proteins, allowing viral replication within human cells. Differences in IFN signalling efficiency and timing have emerged as central determinants of the variability of COVID-19 disease severity…

• COVID-19 Ocular Prophylaxis: The Potential Role of Ozonated-Oils in Liposome Eyedrop Gel - CONCLUSIONS: SARS-CoV-2 transmission through the ocular surface should not be ignored. Although the prevalence of coronavirus disease 2019 conjunctivitis infection is low, the need for a barrier to prevent possible viral infection is warranted. OED treatment may prevent the risk of SARS-CoV-2 infection after 72 hours of twice-daily applications.

• Remdesivir for the treatment of COVID-19 - BACKGROUND: Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS-CoV-2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID-19. A thorough understanding of the current evidence regarding the effects of remdesivir as a treatment for SARS-CoV-2 infection based on randomised controlled trials (RCTs) is required.

• Absorbed plant MIR2911 in honeysuckle decoction inhibits SARS-CoV-2 replication and accelerates the negative conversion of infected patients - No abstract

• Flavan-based phytoconstituents inhibit Mpro, a SARS-COV-2 molecular target, in silico - A well-validated in-silico approach can provide promising drug candidates for the treatment of the ongoing CoVID19 pandemic. In this study, we have screened 32 phytochemical constituents (PCCs) with Mpro binding site (PDB:6W63) based on which we identified three possible candidates that are likely to be effective against CoVID19-viz., licoleafol (binding energy: -8.1 kcal/mol), epicatechin gallate (-8.5 kcal/mol) and silibinin (-8.4 kcal/mol) that result in higher binding affinity than the known…

• Understanding Covid-19 vaccine acceptance in Pakistan: an echo of previous immunizations or prospect of change? - CONCLUSION: Despite a reasonably good response of Pakistanis to vaccination, factors negatively influencing their intention need to be timely addressed to control this pandemic.

• Bruton tyrosine kinase inhibitors as potential therapeutic agents for COVID-19: A review - Coronavirus disease 2019 (COVID-19) is first detected in December 2019 in Wuhan, China which is a new pandemic caused by SARS-COV-2 that has greatly affected the whole world. Bruton tyrosine kinase (BTK) inhibitors are drugs that are used for the management of cancer, and are being repurposed for COVID-19. BTK regulates macrophage and B cell activation, development, survival, and signaling. Inhibition of BTK has revealed an ameliorative effect on lung injury in patients with severe COVID-19….

From Patent Search

• Camellia nitidissima C.W.Chi Caffeine and Chlorogenic acid composition for anti-SARS-CoV-2 and preparation method and application thereof - - link

• A Novel Method COVID -19 infection using Deep Learning Based System - - link

• A SYSTEM AND METHOD FOR COVID- 19 DIAGNOSIS USING DETECTION RESULTS FROM CHEST X- RAY IMAGES - - link

• Advanced Machine Learning System combating COVID-19 virus Detection, Spread, Prevention and Medical Assistance. - - link

• 一种包装重组流感病毒的重组载体和重组流感病毒及其构建方法和应用 - 本发明提供了一种包装重组流感病毒的重组载体和重组流感病毒及其构建方法和应用，涉及生物医药技术领域。本发明利用A型流感病毒八个基因片段为骨架包装出带有新型冠状病毒SARS‑CoV‑2表面刺突蛋白受体结合域（SARS‑CoV‑2_RBD）片段的重组流感病毒，此重组流感病毒可在复制过程中表达具有生物学活性和免疫原性的刺突蛋白受体结合区域RBD。本发明所述重组流感病毒rgH1N1（PR8）‑PA‑RBD可作为重组病毒类药物，用于2019新型冠状病毒肺炎（COVID‑19）的预防；也可作为体外SARS‑COV‑2 RBD等相关抗原表达和体内递呈系统。 - link

• Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients - - link

• 新型冠状病毒B.1.525尼日利亚突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B.1.525尼日利亚突变株RBD的基因及其应用。本发明的新型冠状病毒B.1.525尼日利亚突变株RBD的基因，其核苷酸序列如SEQ ID NO.1或SEQ ID NO.6所示。本发明通过优化野生型新型冠状病毒B.1.525尼日利亚突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B.1.525尼日利亚突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B.1.525尼日利亚突变株RBD的基因可以用于制备新型冠状病毒疫苗。 - link

• 一种新型冠状病毒的mRNA疫苗 - 本发明公开了一种新型冠状病毒的mRNA疫苗。本发明提供的疫苗，其活性成分为mRNA，如序列表的序列6所示。本发明还保护TF‑RBD蛋白，如序列表的序列2所示。本发明的发明人通过一系列序列设计和序列优化得到了特异DNA分子，进一步构建了特异重组质粒，将特异重组质粒进行体外转录，可以得到多聚化TF‑RBD mRNA。进一步的，发明人制备了负载TF‑RBD mRNA的脂质纳米粒。本发明对于新型冠状病毒的防控具有重大的应用推广价值。 - link

• 新型冠状病毒B．1．1．7英国突变株RBD的基因及其应用 - 本发明属于生物技术领域，具体涉及新型冠状病毒B．1．1．7英国突变株RBD的基因及其应用。本发明的新型冠状病毒B．1．1．7英国突变株RBD的基因，其核苷酸序列如SEQ ID NO.1或SEQ ID NO.6所示。本发明通过优化野生型新型冠状病毒B．1．1．7英国突变株RBD的基因序列，并结合筛选确定了相对最佳序列，优化后序列产生的克隆表达效率比野生型新型冠状病毒B．1．1．7英国突变株RBD序列表达效率大幅提高，从而，本发明的新型冠状病毒B．1．1．7英国突变株RBD的基因更有利于用于制备新型冠状病毒疫苗。 - link

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