Covid-19 Sentry

Contents

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

From Preprints

• Following the crowd in times of crisis: Descriptive norms predict physical distancing, stockpiling, and prosocial behavior during the COVID-19 pandemic -
  Individuals engage in a variety of behavioral responses to cope with the COVID-19 pandemic, from complying with or transgressing against physical distancing regulations, to stockpiling or prosocial behavior. We predicted that particularly descriptive social norms are important in driving pandemic-related behavior as they offer guidelines in times of insecurity and crisis. To investigate this assumption, we conducted a longitudinal survey with two measurement points (n = 1907) in Germany during spring 2020. Results show that descriptive norms (perceived behavior of close others) positively predicted future transgression against distancing regulations, stockpiling, and prosocial behavior over time. In our analysis, we account for previous behavior as well as other potential predictors (subjective threat, personality). In sum, our findings highlight the power of descriptive norms in increasing compliance with pandemic-related regulations and promoting future prosocial behavior.
  🖺 Full Text HTML: Following the crowd in times of crisis: Descriptive norms predict physical distancing, stockpiling, and prosocial behavior during the COVID-19 pandemic
• Quantifying the effects of fake news on behaviour: Evidence from a study of COVID-19 misinformation. -
  Previous research has argued that fake news may have grave consequences for health behaviour, but surprisingly, no empirical data have been provided to support this assumption. This issue takes on new urgency in the context of the coronavirus pandemic, and the accompanying wave of online misinformation. In this large preregistered study (N = 3746) we investigated the effect of a single exposure to fabricated news stories about COVID-19 on related behavioural intentions. We observed small but measurable effects on some behavioural intentions but not others – for example, participants who read a story about problems with a forthcoming contact-tracing app reported a 5% reduction in willingness to download the app. These data suggest that one-off fake news exposure may have behavioural consequences, though the effects are not large. We also found no effects of providing a general warning about the dangers of online misinformation on response to the fake stories, regardless of the framing of the warning in positive or negative terms. This suggests that generic warnings about online misinformation, such as those used by governments and social media companies, are unlikely to be effective. We conclude with a call for more empirical research on the real-world consequences of fake news.
  🖺 Full Text HTML: Quantifying the effects of fake news on behaviour: Evidence from a study of COVID-19 misinformation.
• Predicting Emerging Themes in Rapidly Expanding COVID-19 Literature with Dynamic Word Embedding Networks and Machine Learning -

  Evidence from peer-reviewed literature is the cornerstone for designing responses to global threats such as COVID-19. The collection of knowledge and interpretation in publications needs to be distilled into evidence by leveraging natural language in ways beyond standard meta-analysis. Several studies have focused on mining evidence from text using natural language processing, and have focused on a handful of diseases. Here we show that new knowledge can be captured, tracked and predicted using the evolution of unsupervised word embeddings and machine learning. Our approach to decipher the flow of latent knowledge in time-varying networks of word-vectors captured thromboembolic complications as an emerging theme in more than 77,000 peer-reviewed publications and more than 11,000 WHO vetted preprints on COVID-19. Furthermore, machine learning based prediction of emerging links in the networks reveals autoimmune diseases, multisystem inflammatory syndrome and neurological complications as a dominant research theme in COVID-19 publications starting March 2021.

  🖺 Full Text HTML: Predicting Emerging Themes in Rapidly Expanding COVID-19 Literature with Dynamic Word Embedding Networks and Machine Learning
• County-Level Estimates of Excess Mortality associated with COVID-19 in the United States -

  The coronavirus disease 2019 (COVID-19) pandemic in the US has been largely monitored on the basis of death certificates containing reference to COVID-19. However, prior analyses reveal that a significant fraction of excess deaths associated with the pandemic were not directly assigned to COVID-19 on the death certificate. The percent of excess deaths not assigned to COVID-19 is also known to vary across US states. However, few studies to date provide information on patterns of excess mortality and excess deaths not assigned to COVID-19 for US counties, despite the importance of this information for health policy and planning. In the present study, we develop and validate a generalized linear model of expected mortality in 2020 based on historical trends in deaths by county of residence between 2011 and 2019. We use the results of the model to generate county estimates of excess mortality and excess deaths not assigned to COVID-19 for each county in the US along with bootstrapped prediction intervals. Overall, in counties that had statistically significant increases in excess mortality, the proportion of excess deaths assigned to COVID-19 was 82%, meaning that 18% of excess deaths were not assigned to COVID-19. The proportion assigned to COVID-19 was lower in the South (77%) and West (78%) as compared to counties in the Midwest (82%) and Northeast (94%). Across US Census Divisions, the proportion was especially low in the East South Central Division (68%). Rural counties across all divisions (68%) reported lower proportions of excess deaths assigned to COVID-19 than urban areas (84%). For instance, in the Pacific Division, less than half of excess deaths were assigned to COVID-19 in nonmetro areas. In contrast, the New England Census Division stood out as the only division where directly assigned COVID-19 deaths actually exceeded excess deaths, meaning there were 1.22 directly assigned COVID-19 deaths for every 1 excess death. However, this finding did not extend to nonmetro areas within New England where less than three-quarters of excess deaths were assigned to COVID-19. The finding that metro areas in New England reported higher direct COVID-19 mortality than excess mortality suggests that reductions in mortality from other causes of death may have occurred in these areas, at least among some populations. Across individual counties, the percentage of excess deaths not assigned to COVID-19 varied substantially, with some counties9 direct COVID-19 tallies capturing only a small fraction of total excess deaths, whereas in other counties the direct COVID-19 death rate far exceeded the number of estimated excess deaths. Taken together, our results suggest that regional inequalities in the mortality burden associated with COVID-19 are not fully revealed by data at the state level and that consideration of excess deaths across US counties is critical for a full accounting of the disparate regional effects of the pandemic on US mortality.

  🖺 Full Text HTML: County-Level Estimates of Excess Mortality associated with COVID-19 in the United States
• SARS-CoV-2 infections in 171 countries and over time -

  Understanding the dynamics of the COVID-19 pandemic, evaluating the efficacy of past and current control measures, and estimating vaccination needs, requires knowledge of the number of infections in the population over time. This number, however, generally differs substantially from the number of confirmed cases due to a large fraction of asymptomatic infections as well as geographically and temporally variable testing effort and strategies. Here I use age-stratified death count statistics, age-dependent infection fatality risks and stochastic modeling to estimate the prevalence and growth of SARS-CoV-2 infections among adults (age >= 20 years) in 171 countries, from early 2020 until April 9, 2021. The accuracy of the approach is confirmed through comparison to previous nationwide general-population seroprevalence surveys in multiple countries. Estimates of infections over time, compared to reported cases, reveal that the fraction of infections that are detected vary widely over time and between countries, and hence comparisons of confirmed cases alone (between countries or time points) often yield a false picture of the pandemic9s dynamics. As of April 9, 2021, the nationwide cumulative SARS-CoV-2 prevalence (past and current infections relative to the population size) is estimated at 61% (95%-CI 42-78) for Peru, 58% (39-83) for Mexico, 57% (31-75) for Brazil, 55% (34-72) for South Africa, 29% (19-48) for the US, 26% (16-49) for the United Kingdom, 19% (12-34) for France, 19% (11-33) for Sweden, 9.6% (6.5-15) for Canada, 11% (7-19) for Germany and 0.67% (0.47-1.1) for Japan. The presented time-resolved estimates expand the possibilities to study the factors that influenced and still influence the pandemic9s progression in 171 countries.

  🖺 Full Text HTML: SARS-CoV-2 infections in 171 countries and over time
• ORAI1 establishes resistance to SARS-CoV-2 infection by regulating tonic type I interferon signaling -
  ORAI1 and STIM1 are the critical mediators of store-operated Ca2+ entry by acting as the pore subunit and an endoplasmic reticulum-resident signaling molecule, respectively. In addition to Ca2+ signaling, STIM1 is also involved in regulation of a cytosolic nucleic acid sensing pathway. Using ORAI1 and STIM1 knockout cells, we examined their contribution to the host response to SARS-CoV-2 infection. STIM1 knockout cells showed strong resistance to SARS-CoV-2 infection due to enhanced type I interferon response. On the contrary, ORAI1 knockout cells showed high susceptibility to SARS-CoV-2 infection as judged by increased expression of viral proteins and a high viral load. Mechanistically, ORAI1 knockout cells showed reduced homeostatic cytoplasmic Ca2+ concentration and severe impairment in tonic interferon signaling. Transcriptome analysis showed downregulation of multiple cellular defense mechanisms, including antiviral signaling pathways in ORAI1 knockout cells, which are likely due to reduced expression of the Ca2+-dependent transcription factors of the activator protein 1 (AP-1) family and MEF2C. Our results identify a novel role of ORAI1-mediated Ca2+ signaling in regulating the baseline type I interferon level, which is a determinant of host resistance to SARS-CoV-2 infection.
  🖺 Full Text HTML: ORAI1 establishes resistance to SARS-CoV-2 infection by regulating tonic type I interferon signaling
• Impaired T-cell and antibody immunity after COVID-19 infection in chronically immunosuppressed transplant recipients -
  Assessment of T-cell immunity to the COVID-19 coronavirus requires reliable assays and is of great interest, given the uncertain longevity of the antibody response. Some recent reports have used immunodominant spike (S) antigenic peptides and anti-CD28 co-stimulation in varying combinations to assess T-cell immunity to SARS-CoV-2. These assays may cause T-cell hyperstimulation and could overestimate antiviral immunity in chronically immunosuppressed transplant recipients, who are predisposed to infections and vaccination failures. Here, we evaluate CD154-expressing T-cells induced by unselected S antigenic peptides in 204 subjects-103 COVID-19 patients and 101 healthy unexposed subjects. Subjects included 72 transplanted and 130 non-transplanted subjects. S-reactive CD154+T-cells co-express and can thus substitute for IFNg (n=3). Assay reproducibility in a variety of conditions was acceptable with coefficient of variation of 2-10.6%. S-reactive CD154+T-cell frequencies were a) higher in 42 healthy unexposed transplant recipients who were sampled pre-pandemic, compared with 59 healthy non-transplanted subjects (p=0.02), b) lower in Tr COVID-19 patients compared with healthy transplant patients (p<0.0001), c) lower in Tr patients with severe COVID-19 (p<0.0001), or COVID-19 requiring hospitalization (p<0.05), compared with healthy Tr recipients. S-reactive T-cells were not significantly different between the various COVID-19 disease categories in NT recipients. Among transplant recipients with COVID-19, cytomegalovirus co-infection occurred in 34%; further, CMV-specific T-cells (p<0.001) and incidence of anti-receptor-binding-domain IgG (p=0.011) were lower compared with non-transplanted COVID-19 patients. Healthy unexposed transplant recipients exhibit pre-existing T-cell immunity to SARS-CoV-2. COVID-19 infection leads to impaired T-cell and antibody responses to SARS-CoV-2 and increased risk of CMV co-infection in transplant recipients.
  🖺 Full Text HTML: Impaired T-cell and antibody immunity after COVID-19 infection in chronically immunosuppressed transplant recipients
• CCR2-dependent monocyte-derived cells restrict SARS-CoV-2 infection -
  SARS-CoV-2 has caused a historic pandemic of respiratory disease (COVID-19) and current evidence suggests severe disease is associated with dysregulated immunity within the respiratory tract. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2-dependent infiltration of monocytes restricts viral burden in the lung. We find that a recently developed mouse-adapted MA-SARS-CoV-2 strain, as well as the emerging B.1.351 variant, trigger an inflammatory response in the lung characterized by expression of pro-inflammatory cytokines and interferon-stimulated genes. scRNA-seq analysis of lung homogenates identified a hyper-inflammatory monocyte profile. Using intravital antibody labeling, we demonstrate that MA-SARS-CoV-2 infection leads to increases in circulating monocytes and an influx of CD45+ cells into the lung parenchyma that is dominated by monocyte-derived cells. We utilize this model to demonstrate that mechanistically, CCR2 signaling promotes infiltration of classical monocytes into the lung and expansion of monocyte-derived cells. Parenchymal monocyte-derived cells appear to play a protective role against MA-SARS-CoV-2, as mice lacking CCR2 showed higher viral loads in the lungs, increased lung viral dissemination, and elevated inflammatory cytokine responses. These studies have identified a CCR2-monocyte axis that is critical for promoting viral control and restricting inflammation within the respiratory tract during SARS-CoV-2 infection.
  🖺 Full Text HTML: CCR2-dependent monocyte-derived cells restrict SARS-CoV-2 infection
• Mouse Adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge -
  The emergence of SARS-CoV-2 has resulted in a worldwide pandemic causing significant damage to public health and the economy. Efforts to understand the mechanisms of COVID-19 disease have been hampered by the lack of robust mouse models. To overcome this barrier, we utilized a reverse genetic system to generate a mouse-adapted strain of SARS-CoV-2. Incorporating key mutations found in SARSCoV-2 variants, this model recapitulates critical elements of human infection including viral replication in the lung, immune cell infiltration, and significant in vivo disease. Importantly, mouse-adaptation of SARS-CoV-2 does not impair replication in human airway cells and maintains antigenicity similar to human SARS-CoV-2 strains. Utilizing this model, we demonstrate that SARS-CoV-2 infected mice are protected from lethal challenge with the original SARS-CoV, suggesting immunity from heterologous CoV strains. Together, the results highlight the utility of this mouse model for further study of SARS CoV-2 infection and disease.
  🖺 Full Text HTML: Mouse Adapted SARS-CoV-2 protects animals from lethal SARS-CoV challenge
• Sex-biased response to and brain cell infection by SARS-CoV-2 in a highly susceptible human ACE2 transgenic model -
  The COVID-19 pandemic is caused by SARS-CoV-2 infection. Human angiotensin-converting enzyme II (hACE2) has been identified as the receptor enabling SARS-CoV-2 host entry. To establish a mouse model for COVID-19, we generated transgenic mouse lines using the (HS4)2-pCAG-hACE2-HA-(HS4)2 transgene cassette, which expresses HA-tagged hACE2 under control of the CAG promoter and is flanked by HS4 insulators. Expression levels of the hACE2 transgene are respectively higher in lung, brain and kidney of our CAG-hACE2 transgenic mice and relatively lower in duodenum, heart and liver. The CAG-hACE2 mice are highly susceptibility to SARS-CoV-2 infection, with 100 PFU of SARS-CoV-2 being sufficient to induce 87.5% mortality at 9 days post-infection and resulting in a sole (female) survivor. Mortality was 100% at the higher titer of 1000 PFU. At lower viral titers, we also found that female mice exposed to SARS-CoV-2 infection suffered much less weight loss than male mice, implying sex-biased responses to SARS-CoV-2 infection. We subjected neuronal cultures to SARS-CoV-2 pseudovirus infection to ascertain the susceptibilities of neurons and astrocytes. Moreover, we observed that expression of SARS-CoV-2 Spike protein alters the synaptic responses of cultured neurons. Our transgenic mice may serve as a model for severe COVID-19 and sex-biased responses to SARS-CoV-2 infection, aiding in the development of vaccines and therapeutic treatments for this disease.
  🖺 Full Text HTML: Sex-biased response to and brain cell infection by SARS-CoV-2 in a highly susceptible human ACE2 transgenic model
• 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
• A novel highly potent inhibitor of TMPRSS2-like proteases blocks SARS-CoV-2 variants of concern and is broadly protective against infection and mortality in mice -
  The COVID-19 pandemic caused by the SARS-CoV-2 virus remains a global public health crisis. Although widespread vaccination campaigns are underway, their efficacy is reduced against emerging variants of concern (VOCs). Development of host-directed therapeutics and prophylactics could limit such resistance and offer urgently needed protection against VOCs. Attractive pharmacological targets to impede viral entry include type-II transmembrane serine proteases (TTSPs), such as TMPRSS2, whose essential role in the virus lifecycle is responsible for the cleavage and priming of the viral spike protein. Here, we identify and characterize a small-molecule compound, N-0385, as the most potent inhibitor of TMPRSS2 reported to date. N-0385 exhibited low nanomolar potency and a selectivity index of > 1 million at inhibiting SARS-CoV-2 infection in human lung cells and in donor-derived colonoids. Importantly, N-0385 acted as a broad-spectrum coronavirus inhibitor of two SARS-CoV-2 VOCs, B.1.1.7 and B.1.351. Strikingly, single daily intranasal administration of N-0385 early in infection significantly improved weight loss and clinical outcomes, and yielded 100% survival in the severe K18-human ACE2 transgenic mouse model of SARS-CoV-2 disease. This demonstrates that TTSP-mediated proteolytic maturation of spike is critical for SARS-CoV-2 infection in vivo and suggests that N-0385 provides a novel effective early treatment option against COVID-19 and emerging SARS-CoV-2 VOCs.
  🖺 Full Text HTML: A novel highly potent inhibitor of TMPRSS2-like proteases blocks SARS-CoV-2 variants of concern and is broadly protective against infection and mortality in mice
• Protective heterologous T cell immunity in COVID-19 induced by MMR and Tdap vaccine antigens -
  T cells are critical for control of viral infection and effective vaccination. We investigated whether prior Measles-Mumps-Rubella (MMR) or Tetanus-Diphtheria-pertussis (Tdap) vaccination elicit cross-reactive T cells that mitigate COVID-19. Using co-cultures of antigen presenting cells (APC) loaded with antigens and autologous T cells, we found a high correlation between responses to SARS-CoV-2 (Spike-S1 and Nucleocapsid) and MMR and Tdap vaccine proteins in both SARS-CoV-2 infected individuals and individuals immunized with mRNA-based SARS-CoV-2 vaccines. The overlapping T cell population contained effector memory T cells (TEMRA) previously implicated in anti-viral immunity and their activation required APC-derived IL-15. TCR- and scRNA-sequencing detected cross-reactive clones with TEMRA features among the cells recognizing SARS-CoV-2, MMR and Tdap epitopes. A propensity-weighted analysis of 73,582 COVID-19 patients revealed that severe disease outcomes (hospitalization and transfer to intensive care unit or death) were reduced in MMR or Tdap vaccinated individuals by 38-32% and 23-20% respectively. In summary, SARS-CoV-2 re-activates memory T cells generated by Tdap and MMR vaccines, which may reduce disease severity.
  🖺 Full Text HTML: Protective heterologous T cell immunity in COVID-19 induced by MMR and Tdap vaccine antigens
• Highly functional Cellular Immunity in SARS-CoV-2 Non-Seroconvertors is associated with immune protection -
  The role of T cells in the control of SARS-CoV-2 infection has been underestimated in favor of neutralizing antibodies. However, cellular immunity is essential for long-term viral control and protection from disease severity. To understand T-cell immunity in the absence of antibody generation we focused on a group of SARS-CoV-2 Non-Seroconvertors (NSC) recovered from infection. We performed an immune comparative analysis of SARS-CoV-2 infected individuals stratified by the absence or presence of seroconversion and disease severity. We report high levels of total naive and low effector CD8+ T cells in NSC. Moreover, polyfunctional Nucleocapsid (NP)-specific CD8+ T-cell responses, as well as reduced levels of T-cell activation monitored by PD-1 and activation-induced markers, were distinctive immunological traits in NSC. Longitudinal data support the stability of the NSC phenotype over three months. Our results implicate highly functional SARS-CoV-2 Spike and NP T-cell responses with low immune activation in protection from disease severity in the absence of seroconversion.
  🖺 Full Text HTML: Highly functional Cellular Immunity in SARS-CoV-2 Non-Seroconvertors is associated with immune protection
• Semi-supervised identification of SARS-CoV-2 molecular targets -
  SARS-CoV-2 genomic sequencing efforts have scaled dramatically to address the current global pandemic and aid public health. In this work, we analyzed a corpus of 66,000 SARS-CoV-2 genome sequences. We developed a novel semi-supervised pipeline for automated gene, protein, and functional domain annotation of SARS-CoV-2 genomes that differentiates itself by not relying on use of a single reference genome and by overcoming atypical genome traits. Using this method, we identified the comprehensive set of known proteins with 98.5% set membership accuracy and 99.1% accuracy in length prediction compared to proteome references including Replicase polyprotein 1ab (with its transcriptional slippage site). Compared to other published tools such as Prokka (base) and VAPiD, we yielded an 6.4- and 1.8-fold increase in protein annotations. Our method generated 13,000,000 molecular target sequences— some conserved across time and geography while others represent emerging variants. We observed 3,362 non-redundant sequences per protein on average within this corpus and describe key D614G and N501Y variants spatiotemporally. For spike glycoprotein domains, we achieved greater than 97.9% sequence identity to references and characterized Receptor Binding Domain variants. Here, we comprehensively present the molecular targets to refine biomedical interventions for SARS-CoV-2 with a scalable high-accuracy method to analyze newly sequenced infections.
  🖺 Full Text HTML: Semi-supervised identification of SARS-CoV-2 molecular targets

From Clinical Trials

• Oestrogen Treatment for COVID-19 Symptoms - Condition:   COVID-19
  Intervention:   Drug: Transdermal estradiol gel
  Sponsors:   Hamad Medical Corporation;   Laboratoires Besins International
  Not yet recruiting

• Standardized Olive Leaf Capsules; as a Co-therapy in the Treatment of COVID-19 Patients - Condition:   Covid19
  Intervention:   Dietary Supplement: Nusapure standardized olive leaves capsule, 750 mg (50% oleuropein)
  Sponsor:   Shimaa M. Abdelgawad
  Not yet recruiting

• Impact of GSE and Xylitol (Xlear) on COVID-19 Symptoms and Time to PCR Negativisation in COVID-19 Patients - Condition:   Covid19
  Intervention:   Drug: GSE and Xylitol
  Sponsor:   Larkin Community Hospital
  Recruiting

• Hydroxychloroquine (HCQ) as Post Exposure Prophylaxis (PEP) for Prevention of COVID-19 - Conditions:   Covid19;   COVID-19 Prevention
  Interventions:   Drug: Hydroxychloroquine (HCQ);   Other: Standard care;   Other: Placebo
  Sponsor:   Postgraduate Institute of Medical Education and Research
  Recruiting

• Study to Evaluate a Single Dose of LTX-109 in Subjects With COVID-19 (Coronavirus Disease 2019) Infection. - Condition:   COVID-19
  Interventions:   Drug: LTX-109 gel, 3%;   Drug: Placebo gel
  Sponsors:   Pharma Holdings AS;   Clinical Trial Consultants AB
  Recruiting

• A Clinical Trial to Evaluate the Recombinant SARS-CoV-2 Vaccine (CHO Cell) for COVID-19 - Condition:   COVID-19
  Interventions:   Biological: low-dose Recombinant SARS-CoV-2 Vaccine (CHO cell);   Biological: high-dose Recombinant SARS-CoV-2 Vaccine (CHO cell);   Biological: placebo
  Sponsors:   National Vaccine and Serum Institute, China;   Lanzhou Institute of Biological Products Co., Ltd;   Beijing Zhong Sheng Heng Yi Pharmaceutical Technology Co., Ltd.;   Zhengzhou University
  Not yet recruiting

• Safety and Efficacy of Niclosamide in Patients With COVID-19 With Gastrointestinal Infection - Condition:   Covid19
  Interventions:   Drug: Niclosamide;   Drug: Placebo
  Sponsor:   AzurRx BioPharma, Inc.
  Recruiting

• A Immunobridging and Immunization Schedules Study of COVID-19 Vaccine (Vero Cell), Inactivated - Condition:   Covid19
  Interventions:   Biological: 3-doses schedule 1 of COVID-19 Vaccine (Vero Cell), Inactivated;   Biological: 3-doses schedule 2 of COVID-19 Vaccine (Vero Cell), Inactivated;   Biological: 3-doses schedule 3 of COVID-19 Vaccine (Vero Cell), Inactivated;   Biological: 2 doses of vaccine
  Sponsors:   China National Biotec Group Company Limited;   Beijing Institute of Biological Products Co Ltd.
  Not yet recruiting

• Convalescent Plasma as Adjunct Therapy for COVID-19 - Condition:   COVID-19
  Intervention:   Biological: Convalescent plasma treatment
  Sponsors:   National Institute of Health Research and Development, Ministry of Health Republic of Indonesia;   Indonesian Red Cross;   Eijkman Institute for Molecular Biology
  Recruiting

• Protecting Our Community: COVID-19 Testing - Conditions:   SARS-CoV-2;   Covid19
  Intervention:   Diagnostic Test: Home-based SARS-CoV-2 test kit
  Sponsors:   Montana State University;   National Institute of General Medical Sciences (NIGMS);   University of Washington;   Fred Hutchinson Cancer Research Center;   Salish Kootenai College
  Recruiting

• Selenium as a Potential Treatment for Moderately-ill, Severely-ill, and Critically-ill COVID-19 Patients. - Condition:   Covid19
  Interventions:   Drug: Selenium (as Selenious Acid);   Other: Placebo
  Sponsors:   CHRISTUS Health;   Pharco Pharmaceuticals
  Not yet recruiting

• Estradiol and Progesterone in Hospitalized COVID-19 Patients - Condition:   Covid19
  Interventions:   Other: Placebo injection and placebo pill;   Drug: Estradiol Cypionate 5 MG/ML;   Drug: Progesterone 200 MG Oral Capsule
  Sponsor:   Tulane University
  Not yet recruiting

• Detection of Covid-19 in Nasopharyngeal Swabs by Using Multi-Spectral Spectrophotometry - Condition:   Covid19
  Intervention:   Diagnostic Test: AP-23
  Sponsor:   Fable Biyoteknoloji San ve Tic A.S
  Recruiting

• COVID-19 Vaccination Take-Up - Conditions:   Covid19;   Vaccination
  Interventions:   Behavioral: Financial incentives;   Behavioral: Convenient scheduling link;   Behavioral: Race concordant;   Behavioral: Gender concordant
  Sponsors:   University of Southern California;   Contra Costa Health Services;   J-PAL North America, State and Local Innovation Initiative;   National Bureau of Economic Research Roybal Center;   National Institute on Aging (NIA)
  Not yet recruiting

• #SafeHandsSafeHearts: An eHealth Intervention for COVID-19 Prevention and Support - Condition:   Covid19
  Intervention:   Behavioral: eHealth for Covid-19 prevention and support
  Sponsor:   University of Toronto
  Recruiting

From PubMed

• The SARS-CoV-2 protein ORF3a inhibits fusion of autophagosomes with lysosomes - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the ongoing coronavirus disease 2019 pandemic. How SARS-CoV-2 regulates cellular responses to escape clearance by host cells is unknown. Autophagy is an intracellular lysosomal degradation pathway for the clearance of various cargoes, including viruses. Here, we systematically screened 28 viral proteins of SARS-CoV-2 and identified that ORF3a strongly inhibited autophagic flux by blocking the fusion of autophagosomes with…

• Galectin-9, a Player in Cytokine Release Syndrome and a Surrogate Diagnostic Biomarker in SARS-CoV-2 Infection - The outbreak of SARS-CoV-2 infection has enormously impacted our lives. Clinical evidence has implicated the emergence of cytokine release syndrome as the prominent cause of mortality in COVID-19 patients. In this study, we observed massive elevation of plasma Galectin-9 (Gal-9) in COVID-19 patients compared to healthy controls (HCs). By using the receiver operating characteristic (ROC) curve, we found that a baseline of 2,042 pg/ml plasma Gal-9 can differentiate SARS-CoV-2-infected from…

• The Non-Specific Antiviral Activity of Polysulfates to Fight SARS-CoV-2, its Mutants and Viruses with Cationic Spikes - Polyanions are negatively charged macromolecules known for several decades as inhibitors of many viruses in vitro, notably AIDS virus. In the case of enveloped viruses, this activity was assigned to the formation of a polyelectrolyte complex between an anionic species, the polyanion, and the spike cationic proteins which are, for polymer chemists, comparable to cationic polyelectrolytes. Unfortunately, in vitro antiviral activity was not confirmed in vivo, possibly because polyanions were…

• In Vitro Inhibitory Analysis of Rationally Designed siRNAs against MERS-CoV Replication in Huh7 Cells - MERS-CoV was identified for the first time in Jeddah, Saudi Arabia in 2012 in a hospitalized patient. This virus subsequently spread to 27 countries with a total of 939 deaths and 2586 confirmed cases and now has become a serious concern globally. Camels are well known for the transmission of the virus to the human population. In this report, we have discussed the prediction, designing, and evaluation of potential siRNA targeting the ORF1ab gene for the inhibition of MERS-CoV replication. The…

• Fast Detection of SARS-CoV-2 RNA Directly from Respiratory Samples Using a Loop-Mediated Isothermal Amplification (LAMP) Test - The availability of simple SARS-CoV-2 detection methods is crucial to contain the COVID-19 pandemic. This study examined whether a commercial LAMP assay can reliably detect SARS-CoV-2 genomes directly in respiratory samples without having to extract nucleic acids (NA) beforehand. Nasopharyngeal swabs (NPS, n = 220) were tested by real-time reverse transcription (RT)-PCR and with the LAMP assay. For RT-PCR, NA were investigated. For LAMP, NA from 26 NPS in viral transport medium (VTM) were…

• Fears Related to COVID-19 among Rural Older People in Japan - Coronavirus disease 2019 (COVID-19) has affected people’s social lives by inhibiting their movement; this seriously impacts the lives of older people in particular. Rural older people may have been particularly affected because they live dispersedly and in isolation. This study explored rural older people’s perceptions of how COVID-19 has impacted their social lives. This qualitative study assessed participants who were 65 years and older and residing in rural Japanese communities. Five focus…

• Remdesivir and Ledipasvir among the FDA-Approved Antiviral Drugs Have Potential to Inhibit SARS-CoV-2 Replication - The rapid spread of the virus, the surge in the number of deaths, and the unavailability of specific SARS-CoV-2 drugs thus far necessitate the identification of drugs with anti-COVID-19 activity. SARS-CoV-2 enters the host cell and assembles a multisubunit RNA-dependent RNA polymerase (RdRp) complex of viral nonstructural proteins that plays a substantial role in the transcription and replication of the viral genome. Therefore, RdRp is among the most suitable targets in RNA viruses. Our aim was…

• Antiviral Properties of the NSAID Drug Naproxen Targeting the Nucleoprotein of SARS-CoV-2 Coronavirus - There is an urgent need for specific antiviral treatments directed against SARS-CoV-2 to prevent the most severe forms of COVID-19. By drug repurposing, affordable therapeutics could be supplied worldwide in the present pandemic context. Targeting the nucleoprotein N of the SARS-CoV-2 coronavirus could be a strategy to impede viral replication and possibly other essential functions associated with viral N. The antiviral properties of naproxen, a non-steroidal anti-inflammatory drug (NSAID) that…

• Structure and function of SARS-CoV-2 polymerase - Coronaviruses use an RNA-dependent RNA polymerase (RdRp) to replicate and express their genome. The RdRp associates with additional non-structural proteins (nsps) to form a replication-transcription complex (RTC) that carries out RNA synthesis, capping and proofreading. However, the structure of the RdRp long remained elusive, thus limiting our understanding of coronavirus genome expression and replication. Recently, the cryo-electron microscopy structure of SARS-CoV-1 RdRp was reported. Driven…

• A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics - The rapid repurposing of antivirals is particularly pressing during pandemics. However, rapid assays for assessing candidate drugs typically involve in vitro screens and cell lines that do not recapitulate human physiology at the tissue and organ levels. Here we show that a microfluidic bronchial-airway-on-a-chip lined by highly differentiated human bronchial-airway epithelium and pulmonary endothelium can model viral infection, strain-dependent virulence, cytokine production and the recruitment…

• The Coronavirus Network Explorer: mining a large-scale knowledge graph for effects of SARS-CoV-2 on host cell function - CONCLUSIONS: The approach presented here can identify biologically plausible hypotheses for COVID-19 pathogenesis, explicitly connected to the immunological, virological and pathological observations seen in SARS-CoV-2 infected patients. The discovery of repurposable drugs is driven by prior knowledge of relevant functional endpoints that reflect known viral biology or clinical observations, therefore suggesting potential mechanisms of action. We believe that the CNE offers relevant insights…

• Complement inhibition in severe COVID-19 - Blocking C5a seems to be key: Author’s reply - No abstract

• Experimental and natural evidence of SARS-CoV-2 infection-induced activation of type I interferon responses - Type I interferons (IFNs) are our first line of defence against virus infection. Recent studies have suggested the ability of SARS-CoV-2 proteins to inhibit IFN responses. Emerging data also suggest that timing and extent of IFN production is associated with manifestation of COVID-19 severity. In spite of progress in understanding how SARS-CoV-2 activates antiviral responses, mechanistic studies into wildtype SARS-CoV-2-mediated induction and inhibition of human type I IFN responses are scarce….

• Single-Cell RNA Sequencing Analysis of the Immunometabolic Rewiring and Immunopathogenesis of Coronavirus Disease 2019 - Although immune dysfunction is a key feature of coronavirus disease 2019 (COVID-19), the metabolism-related mechanisms remain elusive. Here, by reanalyzing single-cell RNA sequencing data, we delineated metabolic remodeling in peripheral blood mononuclear cells (PBMCs) to elucidate the metabolic mechanisms that may lead to the progression of severe COVID-19. After scoring the metabolism-related biological processes and signaling pathways, we found that mono-CD14^(+) cells expressed higher levels…

• SARS-CoV-2 Infection Induces Psoriatic Arthritis Flares and Enthesis Resident Plasmacytoid Dendritic Cell Type-1 Interferon Inhibition by JAK Antagonism Offer Novel Spondyloarthritis Pathogenesis Insights - CONCLUSION: Entheseal pDCs link microbes to TNF/IFNα production. SARS-CoV-2 infection is associated with PsA Flares and JAK inhibition suppressed activated entheseal plasmacytoid dendritic Type-1 interferon responses as pointers towards a novel mechanism of PsA and SpA-related arthropathy.

From Patent Search

• A COMPREHENSIVE DISINFECTION SYSTEM DURING PANDEMIC FOR PERSONAL ITEMS AND PROTECTIVE EQUIPMENT (PPE) TO SAFEGUARD PEOPLE - The current Covid-19 pandemic has led to an enormous demand for gadgets / objects for personal protection. To prevent the spread of virus, it is important to disinfect commonly touched objects. One of the ways suggested is to use a personal UV-C disinfecting box that is “efficient and effective in deactivating the COVID-19 virus. The present model has implemented the use of a UV transparent material (fused silica quartz glass tubes) as the medium of support for the objects to be disinfected to increase the effectiveness of disinfection without compromising the load bearing capacity. Aluminum foil, a UV reflecting material, was used as the inner lining of the box for effective utilization of the UVC light emitted by the UVC lamps. Care has been taken to prevent leakage of UVC radiation out of the system. COVID-19 virus can be inactivated in 5 minutes by UVC irradiation in this disinfection box - link

• USE OF IMINOSUGAR COMPOUND IN PREPARATION OF ANTI-SARS-COV-2 VIRUS DRUG - - link

• Compositions and methods for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection - - link

• 用于检测新型冠状病毒的试纸和试剂盒 - 本发明涉及生物技术和免疫检测技术领域，具体涉及一种用于检测新型冠状病毒的试纸和试剂盒。所述试纸或试剂盒含有抗体1和/或抗体2，所述抗体1的重、轻链可变区的氨基酸序列分别如SEQ ID NO:1‑2所示，所述抗体2的重、轻链可变区的氨基酸序列分别如SEQ ID NO:3‑4所示。本发明对于大批量的新型冠状病毒样本，包括新型冠状病毒突变（英国、南非）与非突变株的人血清、鼻咽拭子等样本的检测有普遍检测意义，避免突变株的漏检。 - link

• METHOD FOR QUANTIFICATION OF PIRFENIDONE, A COVID-19 ANTI-FIBROTIC AGENT, BY SENSITIVE ANALYTICAL TECHNIQUES - This invention relates to the development of specific methods for quantification of pirfenidone, an anti-fibrotic drug which is used to treat Covid-19 for curing lung infections. Ultra-Violet spectroscopy detection and quantification conducted using HPLC grade water as solvent. Linearity constructed for the concentration range of 3-15µL for UV spectroscopy, 2-10 µg/ml for HPLC using methanol as diluent and 5-25µg/ml using methanol as diluent for HPTLC. The chromatographic system comprised of HPLC system equipped with quaternary gradient pump and Shim-Pack GIST C18 (250X 4.6 mm, 5µm) column with PDA detector monitored at 310nm. HPTLC performed on silica gel 60 F254 plates using mobile phase in the ratio of toluene and methanol 8:2 v/v. Analytical method validation done according to ICH Q2 (R1) guidelines. System suitability, intraday precision and inter day precision calculations performed and reported which found to be within limits (%RSD<2%). Recovery studies performed and amount recovered is found between 98.20-102.20%. - link

• 5-(4-TERT-BUTOXY PHENYL)-3-(4N-OCTYLOXYPHENYL)-4,5-DIHYDROISOXAZOLE MOLECULE (C-I): A PROMISING DRUG FOR SARS-COV-2 (TARGET I) AND BLOOD CANCER (TARGET II) - The present invention relates to a method ofmolecular docking of crystalline compound (C-I) with SARS-COV 2 proteins and its repurposing with proteins of blood cancer, comprising the steps of ; employing an algorithmto carry molecular docking calculations of the crystalized compound (C-I); studying the compound computationally to understand the effect of binding groups with the atoms of the amino acids on at least four target proteins of SARS-COV 2; downloading the structure of the proteins; removing water molecules, co enzymes and inhibitors attached to the enzymes; drawing the structure using Chem Sketch software; converting the mol file into a PDB file; using crystalized compound (C-I) for comparative and drug repurposing with two other mutated proteins; docking compound into the groove of the proteins; saving format of docked molecules retrieved; and filtering and docking the best docked results. - link

• 新闻传播速度测评方法和系统 - 本发明实施例提供一种新闻传播速度测评方法和系统，核心是基于新闻媒体权重计算新闻事件主题的传播速度，再通过聚类分析确定传播速度测评体系，最后评定新闻事件主题的传播等级。其中方法包括：确定待测评的新闻事件主题，获取新闻事件主题的新闻数据；基于新闻数据中每一新闻文本的传播媒体信息，计算新闻事件主题的初始传播速度；基于初始传播速度，以及预先设定的传播速度测评体系，确定新闻事件主题的传播速度等级；其中，传播速度测评体系包括多个传播速度等级与初始传播速度之间的对应关系。本发明实施例提供的方法和系统，实现了基于大数据的新闻事件舆情监测，能够有效提高新闻事件舆情响应效率，有利于决策管理者及时做出舆情应对。 - link

• AQUEOUS ZINC OXIDE NANOSPRAY COMPOSITIONS - Disclosed herein is aqueous zinc oxide nano spray compositions comprising zinc oxide nanoparticles and a synthetic surfactant for controlling the spread of Covid-19 virus. - link

• Bettverlängerungssystem -

  Bettverlängerungssystem (1) für in Bauchlage beatmungspflichtige Patienten in Gestalt mit zumindest einer Platte (16), dadurch gekennzeichnet, dass die Platte (16) im Kopflagerungsbereich einen Luftwegezugangsdurchbruch (8) mit einem den Luftwegezugangsdurchbruch (8) umgebenden Auflagerbereich für ein durchbrochenes Kopfauflagepolster (14) aufweist, durch den von der Bettunterseite her und durch das Kopfauflagepolster (14) hindurch die Ver- und Entsorgungsschläuche für eine orotracheale Intubation oder eine nasotracheale Intubation ventral an das Gesicht des Patienten herangeführt werden können, und dass die Platte (16) im Bereich ihrer dem Kopfende eines Bettrosts (15) zugeordneten Stirnseite (6) ein Fixierelement (2) zur Befestigung der Platte (16) am Bettrost (15) nach Art eines einseitig frei über das Kopfende des Bettrosts hinausragenden Kragträgers aufweist.

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• 一种肝素类药物组合物、喷鼻剂及其制备方法及应用 - 本发明公开了一种肝素类药物组合物、喷鼻剂及其制备方法及应用。该肝素类药物组合物包括肝素钠和阿比朵尔。本发明中的肝素类药物组合物首次采用肝素钠和阿比朵尔联合使用，普通肝素钠联合1μM/L以上的阿比朵尔病毒抑制效率显著高于单独普通肝素钠或单独阿比多尔组（p<0.05）。 - link