Covid-19 Sentry

Contents

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

From Preprints

• Long-range regulatory effects of Neandertal DNA in modern humans -
  The admixture between modern humans and Neandertals has resulted in ~2% of the genomes of present-day non-Africans still being composed of Neandertal DNA. Association studies have shown that introgressed DNA still significantly influences skin and hair traits, immunity and behavioral phenotypes in people today. Several of the phenotype-associated archaic variants had links to regulatory effects as well. In general, analyses of allele-specific expression, regulatory sequence composition and cis-eQTL have demonstrated a significant contribution of this introgressed DNA to the transcriptomic landscape in people today. However, little is known about the impact of Neandertal DNA on trans-eQTLs
• long-range regulatory effects that have been shown to explain ~20% of expression variation. Here, we used blood eQTL results from >30,000 individuals from eQTLGen Consortium. The cohort size allowed for a robust identification of trans-eQTLs and in addition enabled quantifying the role of transcription factors (TF) in mediating long-range regulatory effects. In our study we used this information to (i) annotate trans-eQTLs that are linked to Neandertal variants and (ii) predict long-range regulatory effects that are induced by Neandertal DNA by screening for the predicted target genes of TFs that are cis-eQTLs linked to Neandertal variants. We show that both trans-eQTL-associated Neandertal variants and those predicted to have long-range regulatory effects affect genes in genomic regions devoid of Neandertal DNA. In addition, both types of variants included candidates for local adaptation and show associations with autoimmune disorders, a severe Covid-19 phenotype, blood cell type composition and anthropometric measures. Our results suggest that the regulatory reach of Neandertal DNA goes beyond the 40% of genomic sequence that it still covers in present-day non-Africans and that via this mechanism Neandertal DNA additionally influences the phenotypic variation in people today.
  🖺 Full Text HTML: Long-range regulatory effects of Neandertal DNA in modern humans
• Central Banking and Inequalities: Old Tropes and New Practices -
  This paper presents a critical analysis of the stance taken on inequality by two central banks since 2015: the Bank of Canada (BoC) and the Federal Reserve (Fed). The analysis is informed by a computer-assisted discourse analysis of how central bankers from the two institutions position themselves when it comes to issues of inequality. We observe that the position on inequality of the two central banks has changed in recent years and continues to do so. We argue that the stance on inequality taken by the BoC and the Fed suffers from a number of both inconsistencies and shortcomings. On the one hand, the BoC and the Fed claim that monetary policy instruments are too blunt to target specific sectors of the economy. On the other hand, with their response to COVID-19, they have demonstrated that such targeting is possible after all.
  🖺 Full Text HTML: Central Banking and Inequalities: Old Tropes and New Practices
• Inferring the COVID-19 infection fatality rate in the community-dwelling population: a simple Bayesian evidence synthesis of seroprevalence study data and imprecise mortality data -

  Estimating the COVID-19 infection fatality rate (IFR) has proven to be particularly challenging –and rather controversial– due to the fact that both the data on deaths and the data on the number of individuals infected are subject to many different biases. We consider a Bayesian evidence synthesis approach which, while simple enough for researchers to understand and use, accounts for many important sources of uncertainty inherent in both the seroprevalence and mortality data. With the understanding that the results of one9s evidence synthesis analysis may be largely driven by which studies are included and which are excluded, we conduct two separate parallel analyses based on two lists of eligible studies obtained from two different research teams. The results from both analyses are rather similar. With the first analysis, we estimate the COVID-19 IFR to be 0.37% (95% credible interval of (0.19%, 0.61%)) for a typical population where 9% of the population is aged over 65 years and where the GDP (at purchasing-power parity (PPP)) per capita is $17.8k (the approximate worldwide average). With the second analysis, we obtain 0.37% (95% credible interval of (0.22%, 0.55%)). Our results suggest that, as one might expect, lower IFRs are associated with younger populations (and may also be associated with wealthier populations). For a typical population with the age and wealth of the United States we estimate an IFR of 0.61% and 0.59%; and for a typical population with the age and wealth of the European Union, we obtain IFR estimates of 0.90% and 0.62%.

  🖺 Full Text HTML: Inferring the COVID-19 infection fatality rate in the community-dwelling population: a simple Bayesian evidence synthesis of seroprevalence study data and imprecise mortality data
• Discovery of Potent Triple Inhibitors of Both SARS-CoV-2 Proteases and Human Cathepsin L -
  There are currently no FDA approved inhibitors of SARS-CoV-2 viral proteases with specific treatment for post- exposure of SARS-CoV-2. Here, we discovered inhibitors containing thiuram disulfide or dithiobis-(thioformate) tested against three key proteases in SARS CoV-2 replication including SARS CoV-2 Main Protease (Mpro), SARS CoV-2 Papain Like Protease (PLpro), and human cathepsin L. The use of thiuram disulfide and dithiobis-(thioformate) covalent inhibitor warheads was inspired by disulfiram, a currently prescribed drug commonly used to treat chronic alcoholism that at the present time is in Phase 2 clinical trials against SARS-CoV-2. At the maximal allowed dose, disulfiram is associated with adverse effects. Our goal was to find more potent inhibitors that target both viral proteases and one essential human protease to reduce the dosage and minimize the adverse effects associated with these agents. We found that compounds coded as RI175, JX 06, and RI172 are the most potent inhibitors from an enzymatic assay against SARS-CoV-2 Mpro, SARS-CoV-2 PLpro, and human cathepsin L with IC50s of 330, 250 nM, and 190 nM about 4.5, 17, and 11.5-fold more potent than disulfiram, respectively. The identified protease inhibitors in this series were also tested against SARS CoV-2 in a cell-based and toxicity assay and were shown to have similar or greater antiviral effect than disulfiram. The identified triple protease inhibitors and their derivatives are promising candidates for treatment of the Covid-19 virus and related variants.
  🖺 Full Text HTML: Discovery of Potent Triple Inhibitors of Both SARS-CoV-2 Proteases and Human Cathepsin L
• Oral Lisinopril Raises Tissue Levels of ACE2, the SARS-CoV-2 Receptor, in Healthy Male and Female Mice -
  Angiotensin-converting enzyme 2 (ACE2) is the established cellular receptor for SARS-CoV-2. However, it is unclear whether ACE1 inhibitors (e.g., lisinopril) or angiotensin receptor blockers (e.g., losartan) alter tissue ACE2 expression. This study sought to determine whether lisinopril or losartan, as monotherapies or in combination, change tissue levels of ACE2 in healthy male and female mice. Mice were treated for 21 days with drinking water containing lisinopril (10 mg/kg/day), losartan (10 mg/kg/day), or both. A control group was given water without drug. ACE2 protein index, the ratio of ACE2 protein to total protein, was determined on tissues from the small intestine, lung, kidney, and brain. Oral lisinopril increased ACE2 protein index across all tissues (p < 0.0001 vs vehicle control). In contrast, the combination of lisinopril plus losartan did not increase ACE2 levels in any tissue (p = 0.89 vs vehicle control), and even decreased tissue expression of the Ace2 gene compared to controls (p = 0.0004). In a second cohort evaluated twenty-one days after cessation of drug treatment, the group previously treated with lisinopril had higher ACE2 than the group previously treated with vehicle control (p = 0.02). ACE2 protein index differed across tissues (p < 0.0001). Across both cohorts, plasma ACE2 did not correlate with ACE2 protein index in any tissue; however, a sex difference was observed: kidney ACE2 levels were higher in males than females (p < 0.0001). These results demonstrate that oral lisinopril increases ACE2, the cellular receptor for SARS-CoV-2, in tissues that are relevant to the transmission and pathogenesis of COVID-19. Remarkably, the addition of losartan prevented lisinopril- induced increases in ACE2 across tissues. These results suggest that ACE inhibitors and angiotensin receptor blockers interact to determine tissue levels of ACE2.
  🖺 Full Text HTML: Oral Lisinopril Raises Tissue Levels of ACE2, the SARS-CoV-2 Receptor, in Healthy Male and Female Mice
• Post-entry, spike-dependent replication advantage of B.1.1.7 and B.1.617.2 over B.1 SARS-CoV-2 in an ACE2-deficient human lung cell line -
  Epidemiological data demonstrate that B.1.1.7, and even more, B.1.617.2 SARS-CoV-2 are more transmissible and infections are associated with a higher mortality than B.1 virus infection. Intrinsic properties underlying their enhanced spread in the human population remain unknown. B.1.1.7 virus isolates displayed inferior or equivalent spread in most cell lines and primary cells compared to B.1 SARS-CoV-2, and were outcompeted by the latter. Lower infectivity and delayed entry kinetics of B.1.1.7 viruses were accompanied by inefficient proteolytic processing of spike. B.1.1.7 viruses failed to escape from neutralizing antibodies, but slightly dampened induction of innate immunity. The lung cell line NCI-H1299 supported 24- and 595-fold increased growth of B.1.1.7 and B.1.617.2 viruses, respectively, in the absence of detectable ACE2 expression and in a spike-determined fashion. Superior spread in ACE2-deficient NCI-H1299 cells suggests that variants of concern employ a distinct set of cellular cofactors that may be unavailable in standard cell culture lines.
  🖺 Full Text HTML: Post-entry, spike-dependent replication advantage of B.1.1.7 and B.1.617.2 over B.1 SARS-CoV-2 in an ACE2-deficient human lung cell line
• An intranasally administrated SARS-CoV-2 beta variant subunit booster vaccine prevents beta variant viral replication in rhesus macaques -
  Emerging of SARS-CoV-2 variants and waning of vaccine/infection-induced immunity poses threats to curbing the COVID-19 pandemic. An effective, safe, and convenient booster vaccine will be needed. We hypothesized that a variant- modified mucosal booster vaccine might induce local immunity to prevent SARS-CoV-2 infection at the port of entry. The beta-variant is hardest to cross-neutralize. Herein we assessed the protective efficacy of an intranasal booster composed of beta variant-spike protein S1 with IL-15 and TLR agonists in previously immunized macaques. The macaques were first vaccinated with Wuhan strain S1 with the same adjuvant. One year later, negligibly detectable SARS- CoV-2-specific antibody remained. Nevertheless, the booster induced vigorous humoral immunity including serum- and bronchoalveolar lavage (BAL)-IgG, secretory nasal- and BAL-IgA, and neutralizing antibody against the original strain and/or beta variant. Beta-variant S1-specific CD4+ and CD8+ T cell responses were also elicited in PBMC and BAL. Following SARS-CoV-2 beta variant challenge, the vaccinated group demonstrated significant protection against viral replication in the upper and lower respiratory tracts, with almost full protection in the nasal cavity. The fact that one intranasal beta-variant booster administrated one year after the first vaccination provoked protective immunity against beta variant infections may inform future SARS-CoV-2 booster design and administration timing.
  🖺 Full Text HTML: An intranasally administrated SARS- CoV-2 beta variant subunit booster vaccine prevents beta variant viral replication in rhesus macaques
• Transcriptome data from human nasal epithelial cells infected by H3N2 influenza virus indicate early unbalanced ROS/RNA levels, temporarily increased aerobic fermentation linked to enhanced α-tubulin and rapid energy-dependent IRF9-marked immunization -
  Background: Unbalanced ROS/RNS levels that connect to increased aerobic fermentation, which links to alpha-tubulin- based cell restructuration and cell cycle control, was identified as major complex trait for early de novo programming (CoV-MAC-TED) for SARS-CoV-2 infection using diverse cell systems. Recently, this trait was also detected in human nasal epithelial cells (NECs) infected by two SARS-CoV-2 variants, making CoV-MAC-TED tested in nasal cells promising for standardized identification of anti-SARS-CoV-2 targets. To explore the use of this marker/host cell system for targeting anti-viral strategies in general, testing of further virus types is required. Results: Transcriptome level profiles of H3N2 influenza-infected human NECs indicate ROS/RNS level changes and increased transcript accumulation of genes related to glycolysis, lactic fermentation and alpha-tubulin as early as 8 hours post infection. These changes linked to energy-dependent, IRF9-marked rapid immunization. Preliminary results point to the importance of host cell origins. Conclusion: The complex trait CoV-MAC-TED can identify early responses of SARS-CoV-2 and influenza H3N2 viruses. This indicates its appropriateness to search for common anti-viral targets in view of therapeutic design strategies. For standardization, human NECs can be used. The marker/cell system is also promising to identify differential early cell responses upon viral infections depending on individual cell origin.
  🖺 Full Text HTML: Transcriptome data from human nasal epithelial cells infected by H3N2 influenza virus indicate early unbalanced ROS/RNA levels, temporarily increased aerobic fermentation linked to enhanced α-tubulin and rapid energy-dependent IRF9-marked immunization
• Major complex trait for early de novo programming ‘CoV-MAC-TED’ detected in human nasal epithelial cells infected by two SARS-CoV-2 variants is promising for designing therapeutic strategies -
  Background: Early metabolic reorganization was only recently recognized as essentially integrated part of immunology. In this context, unbalanced ROS/RNS levels that connected to increased aerobic fermentation, which linked to alpha-tubulin-based cell restructuration and control of cell cycle progression, was identified as major complex trait for early de novo programming (CoV-MAC-TED) during SARS-CoV-2 infection. This trait was highlighted as critical target for developing early anti-viral/anti-SARS-CoV-2 strategies. To obtain this result, analyses had been performed on transcriptome data from diverse experimental cell systems. A call was released for wide data collection of the defined set of genes for transcriptome analyses, named ReprogVirus, which should be based on strictly standardized protocols and data entry into the ReprogVirus Platform. This platform is currently under development. However, so far an in vitro cell system from primary target cells for virus attacks that could ideally serve for standardizing data collection of early SARS-CoV-2 infection responses was not defined. Results: Here, we demonstrate transcriptome level profiles of the most critical ReprogVirus gene sets for identifying CoV-MAC-TED in cultured human nasal epithelial cells. Our results

1. validate Cov-MAC-TED as crucial trait for early SARS-CoV-2 reprogramming and (b) demonstrate its relevance in cultured human nasal epithelial cells. Conclusion: In vitro-cultured human nasal epithelial cells proved to be appropriate for standardized transcriptome data collection in the ReprogVirus Platform. Thus, this cell system is highly promising to advance integrative data analyses by help of Artificial Intelligence methodologies for designing anti- SARS-CoV-2 strategies.
   🖺 Full Text HTML: Major complex trait for early de novo programming ‘CoV-MAC-TED’ detected in human nasal epithelial cells infected by two SARS-CoV-2 variants is promising for designing therapeutic strategies

• Emotional Trajectories During a Global Crisis: Average Patterns and Individual Differences -
  Major stressors often challenge emotional well-being—increasing negative emotions and decreasing positive emotions. But how long do these emotional hits last? Prior theory and research contain conflicting views. Some research suggests that most individuals’ emotional well-being will return to, or even surpass, baseline levels relatively quickly. Others have challenged this view, arguing that this type of resilient response is uncommon. The present research provides a strong test of resilience theory by examining emotional trajectories over the first six months of the COVID-19 pandemic. In two pre-registered longitudinal studies (total N =1,147), we examined average emotional trajectories and predictors of individual differences in emotional trajectories across 13 waves of data from February through September

2020. The pandemic had immediate detrimental effects on emotional well-being. Negative emotions decreased across six months, with the greatest improvements occurring almost immediately. Yet, positive emotions remained depleted relative to baseline levels, illustrating the limits of resilience. Individuals also differed substantially around these average emotional trajectories and these individual differences were predicted by socio-demographic characteristics and stress exposure. We discuss theoretical implications of these findings that we hope will contribute to more nuanced approaches to studying, understanding, and improving resilience in response to major stressors.
      🖺 Full Text HTML: Emotional Trajectories During a Global Crisis: Average Patterns and Individual Differences

• Monoclonal Antibody Treatment of Breakthrough COVID-19 in Fully Vaccinated Individuals with High-Risk Comorbidities -

  Abstract Breakthrough COVID-19 may occur in fully vaccinated persons. In this cohort of 1395 persons (mean age, 54.3 years; 60% female; median body mass index, 30.7) who developed breakthrough COVID-19, there were 107 (7.7%) who required hospitalization by day 28. Hospitalization was significantly associated with the number of medical comorbidities. Anti-spike monoclonal antibody treatment was significantly associated with a lower risk of hospitalization (Odds Ratio: 0.227; 95% confidence interval, 0.128 - 0.403; p<0.001). The number needed to treat to prevent one hospitalization was 225 among the lowest-risk patient group compared to 4 among the groups with highest numbers of medical comorbidity.

  🖺 Full Text HTML: Monoclonal Antibody Treatment of Breakthrough COVID-19 in Fully Vaccinated Individuals with High-Risk Comorbidities
• Transmission and Unvaccinated-Only Testing in Populations of Mixed Vaccination Status -

  In populations with mixed vaccination status, testing programs focused on the unvaccinated have been proposed and enacted to mitigate the spread of SARS-CoV-2. While the benefits of universal SARS-CoV-2 screening are well established, it is unclear how the benefits of unvaccinated-only testing depend on population vaccination rate. Here, we introduce and analyze a model of SARS-CoV-2 transmission in which a variable fraction of the population is fully vaccinated and those who remain unvaccinated are proactively tested for infection, while varying transmission rates, vaccine performance parameters, and the degree of social mixing between vaccinated and unvaccinated populations. We find that unvaccinated testing programs are effective only when compliance is high and testing is frequent, and when vaccine coverage is low or moderate. However, in highly vaccinated populations, the impact of testing unvaccinated individuals decreases, and, by analyzing the possible modes of transmission within and between the unvaccinated and vaccinated populations, we show that the unvaccinated community ceases to be the dominant driver of transmission. By evaluating a wide range of scenarios, this work focuses on elucidating general principles, finding broadly that resources devoted to routine testing of the unvaccinated population could be reallocated to other needs when vaccine coverage is sufficiently high.

  🖺 Full Text HTML: Transmission and Unvaccinated-Only Testing in Populations of Mixed Vaccination Status
• Immunogenicity of BNT162b2 Vaccine in Patients with Inflammatory Bowel Disease on Infliximab Combination Therapy: A Multicenter Prospective Study -

  Background Vaccination is a promising strategy to protect vulnerable groups like inflammatory bowel disease (IBD) patients against COVID-19 and associated severe outcomes. COVID-19 Vaccines clinical trials excluded IBD patients taking infliximab with azathioprine or 6-mercaptopurine (infliximab combination). Therefore, we sought to evaluate serologic responses to COVID-19 vaccination with the mRNA vaccine, BNT162b2 in IBD patients receiving infliximab combination therapy compared to healthy participants. Methods This is a multicenter prospective study. IBD patients were recruited at the time of attendance at infusion center between August 1st, 2021, and September 15th, 2021. Our primary outcome was the concentrations of SARS-CoV-2 antibodies 4-10 weeks after vaccination with two doses of BNT162b2 vaccine in IBD patients taking infliximab combination therapy (study group) compared to healthy participants group (control group). Both study and healthy participants groups were matched for age, sex and time-since-last-vaccine-dose using optimal pair matching method. Results In total 116 participants were recruited in the study, 58 patients in the study group and 58 in the control group. Median (IQR) IgG concentrations were lower in the study group [99 BAU/mL (40, 177)] than the control group [139 BAU/mL (120, 188)], following vaccination (p = 0.0032). Neutralizing antibodies was also lower in the study group compared to the control group [64% (23, 94) vs 91% (85, 94), p <0.001]. The median IgA levels in the study group was also significantly lower when compared to the control group [6 U/ml (3, 34) vs 13 U/ml (7, 30), p =0.0097]. In the study group, the percentage of patients who achieved positive IgG, neutralizing antibody and IgA levels were 81%, 75% and 40% respectively. In the control group, all participants (100%) had positive IgG and neutralizing antibody levels while 62% had positive IgA levels. Conclusion In patients with IBD receiving infliximab combination therapy, IgG, IgA and neutralizing antibody levels after BNT162b2 vaccine were lower compared to healthy participants. However, most patients treated with infliximab combination therapy seroconverted after two doses of the vaccine.

  🖺 Full Text HTML: Immunogenicity of BNT162b2 Vaccine in Patients with Inflammatory Bowel Disease on Infliximab Combination Therapy: A Multicenter Prospective Study
• Impacts of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 variants Alpha and Delta on Coronavirus Disease 2019 transmission dynamics in the 15 most populous metropolitan statistical areas in the United States -

  To characterize Coronavirus Disease 2019 (COVID-19) transmission dynamics in each of the 15 most populous metropolitan statistical areas (MSAs) in the United States (US) from January 2020 to September 2021, we extended a previously reported compartmental model accounting for effects of multiple distinct periods of social distancing by adding consideration of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants Alpha (lineage B.1.1.7) and Delta (lineage B.1.617.2). For each MSA, we found region-specific parameterizations of the model using daily reports of new COVID-19 cases available from January 21, 2020 to August 24, 2021. In the process, we obtained estimates of the relative infectiousness of Alpha and Delta as well as their takeover times in each MSA. We find that 14-d ahead forecasts are reasonably accurate; these forecasts are being updated daily. Projections made on August 24, 2021 suggest that 5 of the 15 MSAs have already achieved herd immunity.

  🖺 Full Text HTML: Impacts of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 variants Alpha and Delta on Coronavirus Disease 2019 transmission dynamics in the 15 most populous metropolitan statistical areas in the United States
• Factors affecting the mental health of pregnant women using UK maternity services during the COVID-19 pandemic: A qualitative interview study. -

  Background: People using maternity services in the United Kingdom (UK) have faced significant changes brought on by the COVID-19 pandemic and social distancing regulations. We focused on the experiences of pregnant women using UK maternity services during the pandemic and the impact of social distancing rules on their mental health and wellbeing. Methods: We conducted 23 qualitative semi-structured interviews from June 2020 to August 2021, with women from across the UK who experienced a pregnancy during the pandemic. Nineteen women in the study carried their pregnancy to term and four women experienced a miscarriage during the pandemic. Interviews took place remotely over video or telephone call, discussing topics such as mental health during pregnancy and use of UK maternity services. We used reflexive thematic analysis to analyse interview transcripts. Results: We generated six higher order themes: (1) Some pregnancy discomforts alleviated by social distancing measures, (2) The importance of relationships that support coping and adjustment, (3) Missed pregnancy and parenthood experiences, (4) The mental health consequences of birth partner and visitor restrictions, (5) Maternity services under pressure, and (6) Lack of connection with staff. Many participants felt a sense of loss over a pregnancy experience that differed so remarkably to what they had expected because of the pandemic. Supportive relationships were important to help cope with pregnancy and pandemic-related changes; but feelings of isolation were compounded for some participants because opportunities to build social connections through face-to-face parent groups were unavailable. Participants also described feeling alone due to restrictions on partners being present when accessing UK maternity services. Conclusions: Our findings highlight some of the changes that may have affected pregnant womens mental health during the COVID-19 pandemic. Reduced social support and being unable to have a partner or support person present during maternity service use were the greatest concerns reported by women in this study, as this absence removed a protective buffer in times of uncertainty and distress. This suggests that the availability of a birth partner or support person must be prioritised wherever possible to protect the mental health of women experiencing pregnancy and miscarriage in times of pandemics.

  🖺 Full Text HTML: Factors affecting the mental health of pregnant women using UK maternity services during the COVID-19 pandemic: A qualitative interview study.

From Clinical Trials

• Randomized Study to Evaluate Intranasal Dose of STI-2099 (COVI-DROPS™) in Outpatient Adults With Mild COVID-19 Infection - Condition:   COVID-19
  Interventions:   Biological: COVI-DROPS;   Drug: Placebo
  Sponsor:   Sorrento Therapeutics, Inc.
  Not yet recruiting

• Efficacy of Home Inspiratory Muscle Training in Post-covid-19 Patients: a Randomized Clinical Trial - Condition:   Covid19
  Intervention:   Device: Inspiratory muscle training
  Sponsor:  
  Universidade Federal do Rio Grande do Norte
  Recruiting

• Immunogenicity and Safety of Heterologous and Homologous Boosting With ChAdOx1-S and CoronaVac or a Formulation of SCB-2019 (COVID-19) - Condition:   Covid19
  Interventions:   Biological: ChAdOx1-S COVID-19 Vaccine(Fiocruz/Oxford- AstraZeneca);   Biological: CoronaVac (Sinovac Biotech);   Biological: Adjuvanted Recombinant SARS-CoV-2 TrimericS- protein Subunit Vaccine (SCB-2019 - Clover)
  Sponsors:   D’Or Institute for Research and Education;   Bill and Melinda Gates Foundation;   Instituto Fernandes Figueira
  Not yet recruiting

• Tocilizumab Versus Baricitinib in Patients With Severe COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Tocilizumab;   Drug: Baricitinib
  Sponsor:   University Hospital of Patras
  Recruiting

• The Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients (Phase3) - Condition:   COVID-19
  Interventions:   Drug: Pyramax;   Drug: Placebo
  Sponsor:  
  Shin Poong Pharmaceutical Co. Ltd.
  Recruiting

• Pulmonary Function in Patients Recovering From COVID19 Infection : a Pilot Study - Condition:   COVID-19
  Intervention:   Diagnostic Test: diaphragm ultrasonography
  Sponsor:   University Hospital, Limoges
  Not yet recruiting

• Effectiveness of Using Interactive Consulting System to Enhance Decision Aids of COVID-19 Vaccination - Condition:   COVID-19
  Intervention:   Device: Chatbot
  Sponsor:   Sun Yat- sen University
  Recruiting

• Evaluation of the Efficacy of Probiotics to Reduce the Occurrence of Long COVID - Condition:   COVID-19
  Interventions:   Dietary Supplement: Probiotics;   Dietary Supplement: Placebo
  Sponsors:   Centre de recherche du Centre hospitalier universitaire de Sherbrooke;   Lallemand Health Solutions
  Not yet recruiting

• Impact of Nudges on Downloads of COVID-19 Exposure Notification Smartphone Apps: A Randomized Trial - Condition:   COVID-19
  Interventions:   Behavioral: Self-Benefit/Social Norm;   Behavioral: Self- Benefit/No Social Norm;   Behavioral: Other Benefit/Social Norm;   Behavioral: Other Benefit/No Social Norm
  Sponsors:   University of Pennsylvania;   Pennsylvania Department of Health
  Completed

• Efficacy, Safety, and Immunogenicity Study of the Recombinant Two-component COVID-19 Vaccine (CHO Cell) - Condition:   COVID-19
  Interventions:   Biological: Recombinant two-component COVID-19 vaccine (CHO cell);   Biological: Placebo
  Sponsor:   Jiangsu Rec-Biotechnology Co., Ltd.
  Not yet recruiting

• Cardiovascular Assessment in Patient Recovered From COVID-19 and Recovery of Autonomic Nervous System in Association With the Severity of the Disease - Condition:   COVID-19
  Intervention:   Other: Non invasive cardiovascular monitoring with CNAP device of arterial pressure, ECG and respiratory activity
  Sponsor:   IRCCS Policlinico S. Donato
  Recruiting

• Safety and Efficacy of KOVIR (TD0068) in the Combination Regimen With Background Treatment in COVID-19 Patients (KOVIR) - Condition:   COVID-19
  Interventions:   Dietary Supplement: KOVIR (TD0068) oral capsule;   Dietary Supplement: Placebo oral capsule
  Sponsors:   Sunstar Joint Stock Company;   Vietstar Biomedical Research
  Recruiting

• A Safety and Tolerability Study of BDB-001 in Mild, Moderate COVID-19 Patients - Condition:   COVID-19
  Intervention:   Drug: BDB-001 injection
  Sponsors:  
  Staidson (Beijing) Biopharmaceuticals Co., Ltd;   Beijing Defengrui Biotechnology Co. Ltd
  Completed

• Acetylsalicylic Acid in COVID-19 (ASA-SARS) - Conditions:   SARS-CoV2 Infection;   Covid19
  Interventions:   Drug: Low-dose acetylsalicylic acid;   Drug: Placebo
  Sponsors:   Barcelona Institute for Global Health;   Hospital Universitario de Torrejón,Madrid;   Hospital Universitario Infanta Leonor;   Fundació Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau;   Hospital del Mar;   Hopsital Central de Maputo, Mozambique
  Not yet recruiting

• Safety and Immunogenicity Study of Booster Vaccination With Medium-dosage or High-dosage SARS-CoV-2 Inactivated Vaccine for Prevention of COVID-19 - Condition:   COVID-19
  Interventions:   Biological: High-dosage SARS-CoV-2 vaccine;   Biological: Medium-dosage SARS-CoV-2 vaccine
  Sponsor:   Sinovac Biotech Co., Ltd
  Not yet recruiting

From PubMed

• Identification of novel TMPRSS2 inhibitors for COVID-19 using e-pharmacophore modelling, molecular docking, molecular dynamics and quantum mechanics studies - SARS coronavirus 2 (SARS-CoV-2) has spread rapidly around the world and continues to have a massive global health effect, contributing to an infectious respiratory illness called coronavirus infection-19 (COVID-19). TMPRSS2 is an emerging molecular target that plays a role in the early stages of SARS-CoV-2 infection; hence, inhibiting its activity might be a target for COVID-19. This study aims to use many computational approaches to provide compounds that could be optimized into clinical…

• Transparent Air Filters with Active Thermal Sterilization - The worldwide proliferation of COVID-19 poses the urgent need for sterilizable and transparent air filters to inhibit virus transmission while retaining ease of communication. Here, we introduce copper nanowires to fabricate transparent and self-sterilizable air filters. Copper nanowire air filter (CNAF) allowed visible light penetration, thereby can exhibit facial expressions, helpful for better communication. CNAF effectively captured particulate matter (PM) by mechanical and electrostatic…

• Engineering Extracellular Vesicles Enriched with Palmitoylated ACE2 as COVID-19 Therapy - Angiotensin converting enzyme 2 (ACE2) is a key receptor present on cell surfaces that directly interacts with the viral spike (S) protein of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is proposed that inhibiting this interaction can be promising in treating COVID-19. Here, the presence of ACE2 in extracellular vesicles (EVs) is reported and the EV-ACE2 levels are determined by protein palmitoylation. The Cys141 and Cys498 residues on ACE2 are S-palmitoylated by zinc…

• Current treatment strategies for COVID-19 (Review) - The spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) emerged suddenly at the end of 2019 and the disease came to be known as coronavirus disease 2019 (COVID‑19). To date, there is no specific therapy established to treat COVID‑19. Identifying effective treatments is urgently required to treat patients and stop the transmission of SARS‑CoV‑2 in humans. For the present review, >100 publications on therapeutic agents for COVID‑19, including in vitro and in vivo…

• Niclosamide for Covid-19: bridging the gap - CONCLUSIONS: NCL has anti-inflammatory and immune regulatory effects by modulating the release of pro-inflammatory cytokines, inhibition of NF-κB /NLRP3 inflammasome and mTOR signaling pathway. NCL has an anti-SARS-CoV-2 effect via interruption of viral life-cycle and/or induction of cytopathic effect. Prospective clinical studies and clinical trials are mandatory to confirm the potential role of NCL in patients with Covid-19 concerning the severity and clinical outcomes.

• A review on protective roles and potential mechanisms of metformin in diabetic patients diagnosed with COVID-19 - The novel coronavirus disease 2019 (COVID-19), is currently the leading threat to public health and a huge challenge to the healthcare systems across the globe and caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Obesity, a state of chronic inflammation, and diabetes mellitus are risk factors for severe SARS-CoV-2. Metformin is one of the most commonly used antidiabetic medications that displayed immunomodulatory activity through AMP-activated protein kinase. Metformin has…

• SARS-CoV-2 promotes RIPK1 activation to facilitate viral propagation - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the ongoing global pandemic that poses substantial challenges to public health worldwide. A subset of COVID-19 patients experience systemic inflammatory response, known as cytokine storm, which may lead to death. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important mediator of inflammation and cell death. Here, we examined the interaction of RIPK1-mediated…

• Visible blue light inhibits infection and replication of SARS-CoV-2 at doses that are well-tolerated by human respiratory tissue - The delivery of safe, visible wavelengths of light can be an effective, pathogen-agnostic, countermeasure that would expand the current portfolio of SARS-CoV-2 intervention strategies beyond the conventional approaches of vaccine, antibody, and antiviral therapeutics. Employing custom biological light units, that incorporate optically engineered light-emitting diode (LED) arrays, we harnessed monochromatic wavelengths of light for uniform delivery across biological surfaces. We demonstrated that…

• Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19 - COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to…

• Proton-pump inhibitor use is not associated with severe COVID-19-related outcomes: a propensity score-weighted analysis of a national veteran cohort - No abstract

• The therapeutic promises of Lianhuaqingke in the mice model of coronavirus pneumonia (HCoV-229E and SARS-CoV-2) - CONCLUSIONS: Our results demonstrate that LHQK exerts therapeutic effects on pneumonia caused by HCoVs (HCoV-229E and SARS-CoV-2) in mice, and that the anti-HCoV effects might depend on its immunomodulatory capacities. All these results suggest that LHQK serves as a potential adjuvant for anti-HCoV therapies.

• Resistance of SARS-CoV-2 Beta and Gamma variants to plasma collected from Canadian blood donors during the Spring of 2020 - CONCLUSIONS: This preliminary data can be used as a justification for limiting the use of first wave plasma products in upcoming clinical trials but cannot be used to speculate on general trends in the immunity of Canadian blood donors to SARS-CoV-2. This article is protected by copyright. All rights reserved.

• Electrophysiological and Proarrhythmic Effects of Hydroxychloroquine Challenge in Guinea-Pig Hearts - Hydroxychloroquine (HCQ), clinically established in antimalarial and autoimmune therapy, recently raised cardiac arrhythmogenic concerns when used alone or with azithromycin (HCQ+AZM) in Covid-19. We report complementary, experimental, studies of its electrophysiological effects. In patch clamped HEK293 cells expressing human cardiac ion channels, HCQ inhibited I(Kr) and I(K1) at a therapeutic concentrations (IC(50)s: 10 ± 0.6 and 34 ± 5.0 μM). I(Na) and I(CaL) showed higher IC(50)s; I(to) and…

• Complement inhibition for the treatment of COVID-19 triggered thrombotic microangiopathy with cardiac failure: a case report - CONCLUSION: The aetiology of cardiogenic shock observed in this patient cannot simply be explained by his focal and chronic coronary findings. Although viral myocarditis was not formally excluded, both the clinical features of TMA and the rapid resolution of all clinical signs and symptoms after pharmacological complement inhibition suggest a SARS- CoV-2-driven microangiopathic origin of heart failure.

• Search for RNA aptamers against non-structural protein of SARS-CoV-2: Design using molecular dynamics approach - CONCLUSIONS: The study identifies the potential aptamer candidate against less investigated but significant antiviral target i.e., NSP10/NSP16 interface complex.

From Patent Search

• 휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수물 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 약 90% 이며, 건강한 성인이면, 육각수 물은 약 62% 이며, COVID-19 환자, 사고의 부상, 17만개의 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수 물을 평소보다 많이 흡수 하면서 동반 산소부족 상태가 되며, 육각수물 보충 없이 산소 호흡기를 사용하면 심각한 후유증이 발병 할 수 있다.

육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수 물을 62% ~ 80% 이상, 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link

• 휴대용 자화 육각수물 발생기 - 본인의 발명은, 사람의 신체에서 육각수 생성에는 한계가 있으며, 동맥혈관, 정맥혈관 내부 혈액은 수분이 90% 이며, 육각수물은 약 62% 이며, COVID-19, 사고 부상, 질병, 질환으로 조직세포가 손상되면 자기 신체수복을 위해서 육각수물을 평소보다 많이 흡수하면서 산소부족 상태가 되며, 육각수 보충 없이 산소호흡기를 사용하면 심각한 후유증이 발병 할 수 있다 육각수물 부족 상태를 해결하기 위해서, 객관적인 과학적으로 네오디뮴(원자번호 = 60) 3.000 가우스의 자기장을 이용하여서 육각수물을 62% ~ 80% 상시 유지 시켜주는 제조 방법이며, 휴대용으로 항시 착용 가능하다. 결론은 COVID-19, 질병, 질환의 근본적인 원인은, 육각수물 부족 상태가 되면 동반 산소 부족 상태가 되면서, 염증 -> 통증 -> 극심한 통증 -> 석회화, 섬유화, 암 까지 발병 한다. - link

• 用于检测新冠病毒的配对抗体及其应用 - 本发明涉及一种用于检测新冠病毒的配对抗体及其应用，其包括第一检测抗体和第二检测抗体；第一检测抗体具有如SEQ ID NO:1~3所示的轻链互补决定区，以及如SEQ ID NO:4~6所示的重链互补决定区，第二检测抗体具有如SEQ ID NO:7~9所示的轻链互补决定区，以及如SEQ ID NO:10~12所示的重链互补决定区。本发明筛选得到具有上述互补决定区序列的配对抗体，其识别N蛋白的不同表位，且由于两种抗体识别的是N蛋白非核酸结合区域，不会受核酸负电荷干扰，对核酸抗原表现出了兼容性，具有较好的稳定性，同时上述配对抗体具有较高的亲和力，病毒N蛋白检测灵敏度高。 - link

• 抗KL-6双特异性抗体及基因、重组载体、药物、试剂盒 - 本发明公开了抗KL‑6双特异性抗体或其变体、或其功能性片段，所述抗KL‑6双特异性抗体或其变体、或其功能性片段包括抗PTS域和抗SEA域，所述抗PTS域的重链可变区的CDR1、CDR2和CDR3分别具有SEQ ID NO.1~3所示的氨基酸序列。本发明还提供了基因、重组载体、药物、试剂盒。本发明的抗KL‑6双特异性抗体或其变体、或其功能性片段用于与KL‑6蛋白特异性结合，基因、重组载体用于抗KL‑6双特异性抗体的制备，药物用于治疗KL‑6蛋白引起的相关疾病，试剂盒用于KL‑6蛋白的定量检测。 - link

• 基于决策树模型与逻辑回归模型组合的感染筛查方法 - 本发明公开了一种基于决策树模型与逻辑回归模型组合的感染筛查方法，其检测操作方便，可提高感染筛查准确性，该方法基于生命体征监护仪实现，生命体征监护仪与远程数据服务平台通信连接，远程数据服务平台依据临床数据进行感染筛查，该方法包括：通过生命体征监护仪检测获取用户临床数据，将临床数据随机划分为训练集、测试集，将训练集均分为两份：训练集A、训练集B，基于训练集A构建决策树模型，同时，对训练集A进行特征选择，将关键特征向量作为已构建的决策树模型的输入，获取新构造特征向量，基于组合特征向量，构造逻辑回归模型，基于决策树模型和逻辑回归模型组合，对测试集进行预测分类，获取分类结果。 - link

• 病毒中和抗体与非中和抗体联合检测方法、检测卡及应用 - 一种病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用，通过病毒受体结合蛋白夹心法原理检测中和抗体，其为通过提前设置病毒受体结合蛋白和能阻断中和抗体与其结合的作为配体的蛋白所形成的复合物，将靶向受体蛋白的非中和抗体提前捕获，保证后续通过夹心法检测中和抗体的特异性。解决了现有技术中中和抗体检测灵敏度低、特异性差以及不能区分中和抗体与非中和抗体的问题，提供了一种简便、快速、灵敏度高、特异性高的病毒中和抗体与非中和抗体联合检测方法、检测卡及其应用。 - link

• 广谱抗冠状病毒和流感病毒及口腔致病菌复合IgY及其制剂 - 本发明提供一种广谱抗冠状病毒IgY和广谱抗流感病毒IgY以及抗口腔致病菌IgY及其组合抗体和制剂。本发明提供制备广谱抗冠状病毒IgY和广谱抗流感病毒IgY以及抗口腔致病菌IgY及其组合抗体和制剂的方法。广谱抗冠状病毒IgY和广谱抗流感病毒IgY可结合保守的抗原表位，达到广谱中和效果，解决新冠病毒和流感病毒变异的问题。本发明将广谱抗新冠病毒IgY和广谱抗流感病毒IgY以及抗口腔致病菌IgY及其组合抗体制成系列制剂，包括牙膏和口含片以及潄口水和其它日用品、口鼻喷雾剂、消毒剂、洗手液、粉剂、片剂、糖果、滴鼻剂、滴眼剂、口服剂、胶囊剂，应用于防治新冠和流感以及口腔疾病的药物、消毒产品、保健品和医疗器械中。 - link

• 스몰 RNA 검출 방법 - 본 발명은 스몰(small) RNA의 분석 및 검출 방법에 관한 것이다. 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

• SARS-CoV2潜在突变位点的筛选方法及其应用 - 本发明涉及生物信息学和生物医药技术领域，尤其是SARS‑CoV2潜在突变位点的筛选方法，包括：1）下载得到SARS‑CoV2的基因序列，对下载的序列进行快速注释文件和序列比对，从全基因组序列中提取出所有编码基因的序列；2）计算出每个位点的突变频率，筛选出高频率的突变热点，再结合毒株的采样时间和地理分布信息，筛选出在种群中具有显著选择优势的突变位点；3）下载已有的编码基因对应蛋白质的三级结构信息；4）根据预测的B细胞和T细胞表位，筛选位于免疫表位上或其附近的突变位点，评估其对宿主免疫反应的可能影响，鉴定出SARS‑CoV‑2在流行传播中基因组上潜在的可能和病毒感染及宿主适应相关的关键变异位点。 - link

• 健康智能检测方法、装置、电子设备及可读存储介质 - 本申请公开了一种健康智能检测方法、装置、电子设备及可读存储介质，其方法包括获取音频信号，并对所述音频信号进行预处理，得到检测信号；将所述检测信号转化为矩阵数字矩阵；将得到的矩阵数字矩阵作为检测样本，输入健康智能检测模型中，以获取检测结果；其中，所述健康智能检测模型是采用迁移学习和卷积神经网络对训练样本进行训练得到的。本申请由于卷积神经网络各组件或部分组件基于迁移学习进行了重新训练，显著提升了对人们健康检测的准确度；且本申请中的健康智能检测模型为分类模型，计算量小，可将其部署于人们的移动终端中，使用方便，极大程度上提升了用户的使用感受。 - link