Covid-19 Sentry

Contents

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

From Preprints

• Keep kind and carry on. Everyday kindness enhances well-being and prosocial behavior in the time of COVID-19. -
  Acts of everyday kindness are voluntary, low-cost actions aimed at the well-being of others in everyday situations. In two pre-registered studies, conducted during the COVID-19 pandemic, we examined whether practicing everyday kindness can promote people’s well-being and prosocial orientation. In a correlational Study 1 (N = 497), self-reported everyday kindness was positively linked to well-being and a willingness to engage in personally costly prosocial behavior. In an experimental Study 2 (N = 482) practicing acts of everyday kindness increased well-being and actual prosocial behavior. The results suggest that simple online interventions can be used to elicit everyday kindness and have a positive effect even in the psychologically challenging times of a pandemic.
  🖺 Full Text HTML: Keep kind and carry on. Everyday kindness enhances well-being and prosocial behavior in the time of COVID-19.
• Factors Mediating the Psychological Well-Being of Healthcare Workers Responding to Global Pandemics: A Systematic Review -
  The worldwide outbreak of the novel coronavirus (COVID-19) and the likelihood of future pandemics has raised the attention to the effects of pandemics on the psychological well-being of individuals. Given their indispensable role in such situations, healthcare workers are at greater risk of mental health issues. This paper aimed to review the mediators of psychological well-being among healthcare workers responding to global pandemics. After registration on PROSPERO, a systematic review was performed in four databases. Following study selection (PRISMA guidelines), inclusion criteria and analysis methods were assessed. The quality of the included studies was assessed using the EPHPP criteria. Out of 1467 references, 39 studies were included in this review. In most studies, worse well-being outcomes, such as stress, depressive symptoms, anxiety, and burnout were related to demographic characteristics, direct contact with infected patients, and poor perceived support. In turn, self-efficacy, coping ability, altruism, and support from employers and organisations were found to be protective factors. Despite some limitations in the quality of the available evidence, this review highlights the prevalence of poor mental health outcomes in healthcare workers responding to global pandemics. Future interventions should target the identified mediators to promote psychological well-being among this population, particularly social and organisational support, which may improve workers’ mental health and reduce burnout and turnover.
  🖺 Full Text HTML: Factors Mediating the Psychological Well-Being of Healthcare Workers Responding to Global Pandemics: A Systematic Review
• Individual differences in the effect of the COVID-19 pandemic on optimism and meaning in life -
  We investigated the effect of the COVID-19 pandemic and lockdown on optimism and meaning in life in a sample of the Netherlands Twin Register. Participants completed questions before (N=9964) and during the pandemic (N= 17464). A subsample completed both (N=6461). We applied twin models to investigate changes in the genetic architecture due to the pandemic. Around 15-20% of the sample was negatively affected by the pandemic, but the majority was stable (64-68%) or increased (15%) in optimism and meaning in life. Especially women, higher educated people, and people with poorer health experienced negative effects. Twin modelling indicated stable genetic variance and increasing person-specific environmental variance. The lower than unity genetic correlations across time (.75 and .63) suggest gene-environment interactions. Some people decrease in well-being, while others get more optimistic and consider their lives as more meaningful during the pandemic. These differences are partly explained by individual differences in genetic sensitivity.
  🖺 Full Text HTML: Individual differences in the effect of the COVID-19 pandemic on optimism and meaning in life
• SARS-CoV-2 subgenomic RNA kinetics in longitudinal clinical samples -

  Given the persistence of viral RNA in clinically recovered COVID-19 patients, subgenomic RNAs (sgRNA) have been reported as potential molecular viability markers for SARS-CoV-2. However, few data are available on their longitudinal kinetics, compared with genomic RNA (gRNA), in clinical samples. We analyzed 536 samples from 205 patients with COVID-19 from placebo-controlled, outpatient trials of Peginterferon Lambda-1a (Lambda; n=177) and favipiravir (n=359). Nasal swabs were collected at three time points in the Lambda (Day 1, 4 and 6) and favipiravir (Day 1, 5, and 10) trials. N-gene gRNA and sgRNA were quantified by RT-qPCR. To investigate the decay kinetics in vitro, we measured gRNA and sgRNA in A549ACE2+ cells infected with SARS-CoV-2, following treatment with remdesivir or DMSO control. At six days in the Lambda trial and ten days in the favipiravir trial, sgRNA remained detectable in 51.6% (32/62) and 49.5% (51/106) of the samples, respectively. Cycle threshold (Ct) values for gRNA and sgRNA were highly linearly correlated (Pearsons r=0.87) and the rate of increase did not differ significantly in Lambda (1.36 cycles/day vs 1.36 cycles/day; p = 0.97) or favipiravir (1.03 cycles/day vs 0.94 cycles/day; p=0.26) trials. From samples collected 15-21 days after symptom onset, sgRNA was detectable in 48.1% (40/83) of participants. In SARS CoV-2 infected A549ACE2+ cells treated with remdesivir, the rate of Ct increase did not differ between gRNA and sgRNA. In clinical samples and in vitro, sgRNA was highly correlated with gRNA and did not demonstrate different decay patterns to support its application as a molecular viability marker.

  🖺 Full Text HTML: SARS-CoV-2 subgenomic RNA kinetics in longitudinal clinical samples
• SARS-CoV-2 infections in nasal epithelial cells from smokers versus non-smokers -

  Whether smoking exacerbates Coronavirus disease 2019 is still debated. Ex-vivo Infection of reconstituted epithelial tissues from smoker versus non-smoker donors suggested comparable susceptibility to SARS-CoV-2 in epithelia from both groups.

  🖺 Full Text HTML: SARS-CoV-2 infections in nasal epithelial cells from smokers versus non-smokers
• Early and ongoing importations of SARS-CoV-2 in Canada -

  Tracking the emergence and spread of SARS–CoV–2 is critical to inform public health interventions. Phylodynamic analyses have quantified SARS–CoV–2 migration on global and local scales, yet they have not been applied to determine transmission dynamics in Canada. We quantified SARS-CoV-2 migration into, within, and out of Canada in the context of COVID-19 travel restrictions. To minimize sampling bias, global sequences were subsampled with probabilities corrected for their countries9 monthly contribution to global new diagnoses. A time–scaled maximum likelihood tree was used to estimate most likely ancestral geographic locations (country or Canadian province), enabling identification of sublineages, defined as introduction events into Canada resulting in domestic transmission. Of 402 Canadian sublineages identified, the majority likely originated from the USA (54%), followed by Russia (7%), India (6%), Italy (6%), and the UK (5%). International introductions were mostly into Ontario (39%) and Quebec (38%). Among Pango lineages, B.1 was imported at least 191 separate times from 11 different countries. Introduction rates peaked in late March then diminished but were not eliminated following national interventions including restrictions on non–essential travel. We further identified 1,380 singleton importations, international importations that did not result in further sampled transmission, whereby representation of lineages and location were comparable to sublineages. Although proportion of international transmission decreased over time, this coincided with exponential growth of within–province transmission – in fact, total number of sampled transmission events from international or interprovincial sources increased from winter 2020 into spring 2020 in many provinces. Ontario, Quebec, and British Columbia acted as sources of transmission more than recipients, within the caveat of higher sequence representation. We present strong evidence that international introductions and interprovincial transmission of SARS–CoV–2 contributed to the Canadian COVID–19 burden throughout 2020, despite initial reductions mediated by travel restrictions in 2020. More stringent border controls and quarantine measures may have curtailed introductions of SARS–CoV–2 into Canada and may still be warranted.

  🖺 Full Text HTML: Early and ongoing importations of SARS-CoV-2 in Canada
• Information about herd immunity through vaccination and empathy promote COVID-19 vaccination intentions -
  Objective: An effective vaccine against COVID-19 is a desired solution to curb the spread of the disease. However, vaccine hesitancy might hinder high uptake rates and thus undermine efforts to eliminate COVID-19 once an effective vaccine became available. The present contribution addresses this issue by examining two ways of increasing the intention to get vaccinated against COVID-19. Methods: Two pre-registered online studies were conducted (N = 2,315 participants from the UK) in which knowledge about and beliefs in herd immunity through vaccination, as well as empathy for those most vulnerable to the virus, were either measured (Study 1) or manipulated (Study 2). As a dependent variable, individuals’ self-reported vaccination intention once a vaccine against COVID-19 became available was assessed. Results: In Study 1 (N = 310), the intention to get vaccinated against COVID-19 was correlated with knowledge about and belief in herd immunity (r = .58, p < .001), as well as with empathy for those most vulnerable to the virus (r = .26, p < .001). In Study 2 (N = 2,005), information about herd immunity (Cohen’s d = 0.13, p = .003) and empathy (Cohen’s d = 0.22, p < .001) independently promoted vaccination intention. Conclusions: The motivation to get vaccinated against COVID-19 was related to and could be causally promoted by both mere information about herd immunity and by empathy. As such, the present research provides a better understanding of the intention to get vaccinated against COVID-19.
  🖺 Full Text HTML: Information about herd immunity through vaccination and empathy promote COVID-19 vaccination intentions
• Mutation-specific SARS-CoV-2 PCR Screen: Rapid and Accurate Detection of Variants of Concern and the Identification of a Newly Emerging Variant with Spike L452R Mutation -

  The emergence of more transmissible and/or more virulent SARS-CoV-2 variants of concern (VOCs) has triggered intensive genomic surveillance, which is costly and difficult to sustain operationally over the long-term. To address this problem, we developed a set of four multiplex mutation-specific PCR-based assays with same-day reporting that can detect five VOCs and three variants of interest (VOIs), as defined in the March 2021 guidelines from the United States (US) Centers for Disease Control and Prevention. The screening results were compared to the whole genome sequencing (WGS) and showed 100% concordance for strain typing for B.1.1.7 (25) and P.1 (5) variants using Spike (S) mutations N501Y, E484K and H69_V70del assays. The S L450R assay, designed to detect the B.1.427/429 VOCs, also identified multiple isolates of a newly emerging multiply-mutated B.1.526.1 variant that is now rapidly increasing in the Eastern US. PCR approaches can be easily adopted in clinical laboratories, provide rapid screening methods to allow early detection of newly emergent variants and to efficiently triage cases for full genomic sequencing.

  🖺 Full Text HTML: Mutation-specific SARS-CoV-2 PCR Screen: Rapid and Accurate Detection of Variants of Concern and the Identification of a Newly Emerging Variant with Spike L452R Mutation
• Children develop strong and sustained cross-reactive immune responses against Spike protein following SARS-CoV-2 infection, with enhanced recognition of variants of concern -

  SARS-CoV-2 infection is generally mild or asymptomatic in children but the biological basis for this is unclear. We studied the profile of antibody and cellular immunity in children aged 3-11 years in comparison with adults. Antibody profiles in children were strong, with high titres against Spike protein and receptor binding domain (RBD). SARS-CoV-2 seroconversion in children strongly boosted antibody responses against seasonal beta-coronaviruses, partly through cross-recognition of the S2 domain, indicating a broad humoral response that was not seen in adults. T cell responses against Spike were also >2-fold higher in children compared to adults and displayed a strong Th1 cytokine profile. SARS-CoV-2 Spike-reactive cellular responses were present in more than half the seronegative children, indicating pre-existing cross-reactive responses or prior sensitization against SARS-CoV-2. Importantly, all children retained high antibody titres and cellular responses for more than 6 months after infection whilst relative antibody waning was seen in adults. Significantly Children at this timepoint also had high antibody titres to B1.1.7, B1.351 and P1 variants. Children thus distinctly generate robust, cross-reactive and sustained immune responses after SARS-CoV-2 infection, with focussed specificity against Spike protein. These observations demonstrate several novel features of SARS-CoV-2-specific immune responses in children and may provide insights into relative clinical protection in this group. Such information on the profile of natural infection will help to guide the introduction of vaccination regimens into the paediatric population.

  🖺 Full Text HTML: Children develop strong and sustained cross-reactive immune responses against Spike protein following SARS-CoV-2 infection, with enhanced recognition of variants of concern
• Prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine. -
  The influenza A non-structural protein 1 (NS1) is known for its ability to hinder the synthesis of type I interferon (IFN) during viral infection. Influenza viruses lacking NS1 ({Delta}NS1) are under clinical development as live attenuated human influenza virus vaccines and induce potent influenza virus-specific humoral and cellular adaptive immune responses. Attenuation of {Delta}NS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a {Delta}NS1 virus results in an immediate antiviral state which prevents subsequent replication of homologous and heterologous viruses, preventing disease from virus respiratory pathogens, including SARS-CoV-2. Our studies suggest that {Delta}NS1 influenza viruses could be used for the prophylaxis of influenza, SARS-CoV-2 and other human respiratory viral infections, and that an influenza virus vaccine based on {Delta}NS1 live attenuated viruses would confer broad protection against influenza virus infection from the moment of administration, first by non-specific innate immune induction, followed by specific adaptive immunity.
  🖺 Full Text HTML: Prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine.
• Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drive rapid and potent immunogenicity capable of single-dose protection -
  Antibodies from SARS-CoV-2 vaccines may target epitopes which reduce durability or increase the potential for escape from vaccine-induced immunity. Using a novel synthetic vaccinology pipeline, we developed rationally immune focused SARS-CoV-2 Spike-based vaccines. N-linked glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and comprehensive in vitro screening, we incorporated glycans into the Spike Receptor-Binding Domain (RBD) and assessed antigenic profiles. We developed glycan coated RBD immunogens and engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicited potent neutralizing antibodies in guinea pigs, hamsters and multiple mouse models, including human ACE2 and human B cell repertoire transgenics. RBD nanoparticles encoding wild-type and the P.1 SARS-CoV-2 variant induced high levels of cross-neutralizing antibodies. Single, low dose immunization protected against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of novel, potent coronavirus vaccines.
  🖺 Full Text HTML: Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drive rapid and potent immunogenicity capable of single-dose protection
• Recombination patterns in coronaviruses -
  As shown during the SARS-CoV-2 pandemic, phylogenetic and phylodynamic methods are essential tools to study the spread and evolution of pathogens. One of the central assumptions of these methods is that the shared history of pathogens isolated from different hosts can be described by a branching phylogenetic tree. Recombination breaks this assumption. This makes it problematic to apply phylogenetic methods to study recombining pathogens, including, for example, coronaviruses. Here, we introduce a Markov chain Monte Carlo approach that allows inference of recombination networks from genetic sequence data under a template switching model of recombination. Using this method, we first show that recombination is extremely common in the evolutionary history of SARS-like coronaviruses. We then show how recombination rates across the genome of the human seasonal coronaviruses 229E, OC43 and NL63 vary with rates of adaptation. This suggests that recombination could be beneficial to fitness of human seasonal coronaviruses. Additionally, this work sets the stage for Bayesian phylogenetic tracking of the spread and evolution of SARS-CoV-2 in the future, even as recombinant viruses become prevalent.
  🖺 Full Text HTML: Recombination patterns in coronaviruses
• Regulation of Lysosome-Associated Membrane Protein 3 (LAMP3) in Lung Epithelial Cells by Coronaviruses (SARS-CoV-1/2) and Type I Interferon Signaling -
  Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major risk factor for mortality and morbidity in critical care hospitals around the world. Lung epithelial type II cells play a major role in several physiological processes, including recognition and clearance of respiratory viruses as well as repair of lung injury in response to environmental toxicants. Gene expression profiling of lung epithelial type II-specific genes led to the identification of lysosomal-associated membrane protein 3 (LAMP3). Intracellular locations of LAMP3 include plasma membrane, endosomes, and lysosomes. These intracellular organelles are involved in vesicular transport and facilitate viral entry and release of the viral RNA into the host cell cytoplasm. In this study, regulation of LAMP3 expression in human lung epithelial cells by several respiratory viruses and type I interferon signaling was investigated. Coronaviruses including SARS-CoV-1 and SARS-CoV-2 significantly induced LAMP3 expression in lung epithelial cells within 24 hours after infection that required the presence of ACE2 viral entry receptor. Time-course experiments revealed that the induced expression of LAMP3 by SARS-CoV-2 was correlated with the induced expression of interferon-beta1 (IFNB1) and signal transducers and activator of transcription 1 (STAT1) mRNA levels. LAMP3 was also induced by direct IFN-beta treatment or by infection with influenza virus lacking the non-structural protein1(NS1) in NHBE bronchial epithelial cells. LAMP3 expression was induced in human lung epithelial cells by several respiratory viruses, including respiratory syncytial virus (RSV) and the human parainfluenza virus 3 (HPIV3). Location in lysosomes and endosomes as well as induction by respiratory viruses and type I Interferon suggests that LAMP3 may have an important role in inter-organellar regulation of innate immunity and a potential target for therapeutic modulation in health and disease. Furthermore, bioinformatics revealed that a subset of lung type II cell genes were differentially regulated in the lungs of COVID-19 patients.
  🖺 Full Text HTML: Regulation of Lysosome-Associated Membrane Protein 3 (LAMP3) in Lung Epithelial Cells by Coronaviruses (SARS-CoV-1/2) and Type I Interferon Signaling
• SARS-COV-2 induced Diarrhea is inflammatory, Ca2+ Dependent and involves activation of calcium activated Cl channels -
  Diarrhea occurs in 2-50% of cases of COVID-19 (~8% is average across series). The diarrhea does not appear to account for the disease mortality and its contribution to the morbidity has not been defined, even though it is a component of Long Covid or post-infectious aspects of the disease. Even less is known about the pathophysiologic mechanism of the diarrhea. To begin to understand the pathophysiology of COVID-19 diarrhea, we exposed human enteroid monolayers obtained from five healthy subjects and made from duodenum, jejunum, and proximal colon to live SARS-CoV-2 and virus like particles (VLPs) made from exosomes expressing SARS-CoV-2 structural proteins (Spike, Nucleocapsid, Membrane and Envelope). Results: 1) Live virus was exposed apically for 90 min, then washed out and studied 2 and 5 days later. SARS-Cov-2 was taken up by enteroids and live virus was present in lysates and in the apical>>basolateral media of polarized enteroids 48 h after exposure. This is the first demonstration of basolateral appearance of live virus after apical exposure. High vRNA concentration was detected in cell lysates and in the apical and basolateral media up to 5 days after exposure. 2 ) Two days after viral exposure, cytokine measurements of media showed significantly increased levels of IL-6, IL-8 and MCP-1. 3) Two days after viral exposure, mRNA levels of ACE2, NHE3 and DRA were reduced but there was no change in mRNA of CFTR. NHE3 protein was also decreased. 4) Live viral studies were mimicked by some studies with VLP exposure for 48 h. VLPs with Spike- D614G bound to the enteroid apical surface and was taken up; this resulted in decreased mRNA levels of ACE2, NHE3, DRA and CFTR. 4) VLP effects were determined on active anion secretion measured with the Ussing chamber/voltage clamp technique. S-D614G acutely exposed to apical surface of human ileal enteroids did not alter the short-circuit current (Isc). However, VLPS- D614G exposure to enteroids that were pretreated for ~24 h with IL-6 plus IL-8 induced a concentration dependent increase in Isc indicating stimulated anion secretion, that was delayed in onset by ~8 min . The anion secretion was inhibited by apical exposure to a specific calcium activated Cl channel (CaCC) inhibitor (AO1) but not by a specific CFTR inhibitor (BP027); was inhibited by basolateral exposure to the K channel inhibit clortimazole; and was prevented by pretreatment with the calcium buffer BAPTA-AM. 5) The calcium dependence of the VLP-induced increase in Isc was studied in Caco- 2/BBe cells stably expressing the genetically encoded Ca2+ sensor GCaMP6s. 24 h pretreatment with IL-6/IL-8 did not alter intracellular Ca2+. However, in IL-6/IL-8 pretreated cells, VLP S-D614G caused appearance of Ca2+waves and an overall increase in intracellular Ca2+ with a delay of ~10 min after VLP addition. We conclude that the diarrhea of COVID-19 appears to an example of a calcium dependent inflammatory diarrhea that involves both acutely stimulated Ca2+ dependent anion secretion (stimulated Isc) that involves CaCC and likely inhibition of neutral NaCl absorption (decreased NHE3 protein and mRNA and decreased DRA mRNA).
  🖺 Full Text HTML: SARS-COV-2 induced Diarrhea is inflammatory, Ca2+ Dependent and involves activation of calcium activated Cl channels
• A spike-ferritin nanoparticle vaccine induces robust innate immune activity and drives polyfunctional SARS-CoV-2-specific T cells -
  Potent cellular responses to viral infections are pivotal for long-lived protection. Evidence is growing that these responses are critical in SARS-CoV-2 immunity. Assessment of a SARS-CoV-2 spike ferritin nanoparticle (SpFN) immunogen paired with two distinct adjuvants, Alhydrogel (AH) or Army Liposome Formulation containing QS-21 (ALFQ) demonstrated unique vaccine evoked immune signatures. SpFN+ALFQ enhanced recruitment of highly activated classical and non-classical antigen presenting cells (APCs) to the vaccine-draining lymph nodes of mice. The multifaceted APC response of SpFN+ALFQ vaccinated mice was associated with an increased frequency of polyfunctional spike-specific T cells with a bias towards TH1 responses and more robust SARS-CoV-2 spike-specific recall response. In addition, SpFN+ALFQ induced Kb spike (539-546)-specific memory CD8+ T cells with effective cytolytic function and distribution to the lungs. This epitope is also present in SARS-CoV, thus suggesting that generation of cross-reactive T cells may provide protection against other coronavirus strains. Our study reveals that a nanoparticle vaccine, combined with a potent adjuvant, generates effective SARS-CoV-2 specific innate and adaptive immune T cell responses that are key components to inducing long-lived immunity.
  🖺 Full Text HTML: A spike-ferritin nanoparticle vaccine induces robust innate immune activity and drives polyfunctional SARS-CoV-2-specific T cells

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

• 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

• Virgin Coconut Oil as Adjunctive Therapy for Hospitalized COVID-19 Patients - Condition:   Covid19
  Intervention:   Drug: Virgin Coconut Oil
  Sponsors:   University of the Philippines;   Philippine Coconut Authority;   Philippine Council for Health Research & Development
  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

• 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

• Safety and Immunogenicity of Demi-dose of Two Covid-19 mRNA Vaccines in Healthy Population - Condition:   Covid19
  Intervention:   Diagnostic Test: immunogenicity after first and second dose
  Sponsors:   Sciensano;   Mensura EDPB;   Institute of Tropical Medicine, Belgium;   Erasme University Hospital
  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.
  Not yet 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

• 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

• Pilot Study to Evaluate the Safety, Tolerability, and Efficacy of 5-ALA-Phosphate + SFC as an Immune System Enhancer Along With Vaccination Against COVID-19 - Conditions:   SARS-COV 2;   Covid19
  Intervention:   Dietary Supplement: 5-ALA-Phosphate + SFC (5-ALA+SFC)
  Sponsors:   Royal College of Surgeons in Ireland - Medical University of Bahrain;   Bahrain Defence Force Hospital
  Not yet recruiting

• COVID-19 Close Contact Self-Testing Study - Condition:   Covid19
  Interventions:   Behavioral: COVID-19 self-test;   Behavioral: COVID-19 test referral
  Sponsors:   University of Pennsylvania;   Public Health Management Corporation
  Not yet recruiting

• Lactoferrin in Covid-19 Hospitalized Patients - Condition:   Covid19
  Interventions:   Dietary Supplement: Bovine lactoferrin;   Dietary Supplement: Placebo administration
  Sponsor:   Paolo Manzoni
  Recruiting

• Remdesivir Efficacy In Management Of COVID-19 Patients - Condition:   Covid19
  Interventions:   Drug: Remdesivir;   Drug: Standard of care_1;   Drug: Standard of care_2
  Sponsor:   Ain Shams University
  Completed

• Assessment of Efficacy of KAN-JANG® in Mild COVID-19 - Condition:   Covid19
  Interventions:   Drug: Kan Jang capsules;   Other: Placebo capsules
  Sponsors:   Swedish Herbal Institute AB;   Tbilisi State Medical University;   Phytomed AB
  Not yet recruiting

From PubMed

• Rapid endotheliitis and vascular damage characterize SARS-CoV-2 infection in a human lung-chip model - Severe cases of SARS-CoV-2 infection are characterized by hypercoagulopathies and systemic endotheliitis of the lung microvasculature. The dynamics of vascular damage, and whether it is a direct consequence of endothelial infection or an indirect consequence of an immune-cell mediated cytokine storm remain unknown. Using a vascularised lung-on-chip model, we find that infection of alveolar epithelial cells leads to limited apical release of virions, consistent with reports of monoculture…

• A potently neutralizing anti-SARS-CoV-2 antibody inhibits variants of concern by binding a highly conserved epitope - With the emergence of SARS-CoV-2 variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here we developed a panel of neutralizing anti-SARS-CoV-2 mAbs that bind the receptor binding domain of the spike protein at distinct epitopes and block virus attachment to cells and its receptor, human angiotensin converting enzyme-2 (hACE2). While several potently neutralizing mAbs protected K18-hACE2 transgenic mice against…

• Multidose evaluation of 6,710 drug repurposing library identifies potent SARS-CoV-2 infection inhibitors In Vitro and In Vivo - The SARS-CoV-2 pandemic has caused widespread illness, loss of life, and socioeconomic disruption that is unlikely to resolve until vaccines are widely adopted, and effective therapeutic treatments become established. Here, a well curated and annotated library of 6710 clinical and preclinical molecules, covering diverse chemical scaffolds and known host targets was evaluated for inhibition of SARS-CoV-2 infection in multiple infection models. Multi-concentration, high-content…

• Rapid decay of host basal mRNAs during SARS-CoV-2 infection perturbs host antiviral mRNA biogenesis and export - A key feature of the mammalian innate immune response to viral infection is the transcriptional induction of interferon (IFN) genes, which encode for secreted proteins that prime the antiviral response and limit viral replication and dissemination. A hallmark of severe COVID-19 disease caused by SARS-CoV-2 is the low presence of IFN proteins in patient serum despite elevated levels of IFN -encoding mRNAs, indicative of post-transcriptional inhibition of IFN protein production. Herein, we show…

• FACT subunit SUPT16H associates with BRD4 and contributes to silencing of antiviral interferon signaling - FACT ( FA cilitates C hromatin T ranscription) is a heterodimeric protein complex composed of SUPT16H and SSRP1, and a histone chaperone participating in chromatin remodeling during gene transcription. FACT complex is profoundly regulated, and contributes to both gene activation and suppression. Here we reported that SUPT16H, a subunit of FACT, is acetylated at lysine 674 (K674) of middle domain (MD), which involves TIP60 histone acetyltransferase. Such acetylation of SUPT16H is recognized by…

• A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19 - Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. Despite several emerging vaccines, there remains no verifiable therapeutic targeted specifically to the virus. Here we present a highly effective siRNA therapeutic against SARS-CoV-2 infection using a novel lipid nanoparticle delivery system. Multiple small-interfering RNAs (siRNAs) targeting highly conserved regions of the SARS-CoV-2 virus were screened and three…

• Nanotraps for the containment and clearance of SARS-CoV-2 - SARS-CoV-2 enters host cells through its viral spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells. Here, we show that functionalized nanoparticles, termed “Nanotraps,” completely inhibited SARS-CoV-2 infection by blocking the interaction between the spike protein of SARS-CoV-2 and the ACE2 of host cells. The liposomal-based Nanotrap surfaces were functionalized with either recombinant ACE2 proteins or anti-SARS-CoV-2 neutralizing antibodies and…

• Gene expression analysis of MCF7 cell lines of breast cancer treated with herbal extract of Cissampelos pareira revealed association with viral diseases - BACKGROUND: It is necessary to assess the cellular, molecular, and pathogenetic characteristics of COVID-19 and attention is required to understand highly effective gene targets and mechanisms. In this study, we suggest understandings into the fundamental pathogenesis of COVID-19 through gene expression analyses using the microarray data set GSE156445 publicly reachable at NIH/NCBI Gene Expression Omnibus database. The data set consists of MCF7 which is a human breast cancer cell line with…

• Developing effective siRNAs to reduce the expression of key viral genes of COVID-19 - The COVID-19 pandemic has been raging worldwide for more than a year. Many efforts have been made to create vaccines and develop new antiviral drugs to cope with the disease. Here, we propose the application of short interfering RNAs (siRNAs) to degrade the viral genome, thus reducing viral infection. By introducing the concept of the probability of binding efficiency (PBE) and combining the secondary structures of RNA molecules, we designed 11 siRNAs that target the consensus regions of three…

• A multi-targeting drug design strategy for identifying potent anti-SARS-CoV-2 inhibitors - The COVID-19, caused by SARS-CoV-2, is threatening public health, and there is no effective treatment. In this study, we have implemented a multi-targeted anti-viral drug design strategy to discover highly potent SARS-CoV-2 inhibitors, which simultaneously act on the host ribosome, viral RNA as well as RNA-dependent RNA polymerases, and nucleocapsid protein of the virus, to impair viral translation, frameshifting, replication, and assembly. Driven by this strategy, three alkaloids, including…

• Immunobiology and nanotherapeutics of severe acute respiratory syndrome 2 (SARS-CoV-2): a current update - The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes the most significant global public health challenge in a century. It has reignited research interest in coronavirus. While little information is available, research is currently in progress to comprehensively understand the general biology and immune response mechanism against SARS-CoV-2. The spike proteins (S protein) of SARS-CoV-2 perform a crucial function in viral infection establishment. ACE2 and…

• Monoclonal antibody therapy in COVID-19 induced by SARS-CoV-2 - Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) infection causes coronavirus disease-2019 (COVID-19) which is associated with inflammation, thrombosis edema, hemorrhage, intra-alveolar fibrin deposition, and vascular and pulmonary damage. In COVID-19, the coronavirus activates macrophages by inducing the generation of pro-inflammatory cytokines [interleukin (IL)-1, IL-6, IL-18 and TNF] that can damage endothelial cells, activate platelets and neutrophils to produce thromboxane A2…

• Targeting SARS-CoV-2 Spike Protein/ACE2 Protein-Protein Interactions: a Computational Study - The spike glycoprotein (S) of the SARS-CoV-2 virus surface plays a key role in receptor binding and virus entry. The S protein uses the angiotensin converting enzyme (ACE2) for entry into the host cell and binding to ACE2 occurs at the receptor binding domain (RBD) of the S protein. Therefore, the protein-protein interactions (PPIs) between the SARS-CoV-2 RBD and human ACE2, could be attractive therapeutic targets for drug discovery approaches designed to inhibit the entry of SARS-CoV-2 into the…

• NeutrobodyPlex-monitoring SARS-CoV-2 neutralizing immune responses using nanobodies - In light of the COVID-19 pandemic, there is an ongoing need for diagnostic tools to monitor the immune status of large patient cohorts and the effectiveness of vaccination campaigns. Here, we present 11 unique nanobodies (Nbs) specific for the SARS-CoV-2 spike receptor-binding domain (RBD), of which 8 Nbs potently inhibit the interaction of RBD with angiotensin-converting enzyme 2 (ACE2) as the major viral docking site. Following detailed epitope mapping and structural analysis, we select two…

• New alpha-Hydrazinophosphonic acid: Synthesis, characterization, DFT study and in silico prediction of its potential inhibition of SARS-CoV-2 main protease - A new α-Hydrazinophosphonic acid (HDZPA) has been synthesized and its molecular structure was determined using spectroscopic methods. The Density Functional Theory (DFT) at the B3LYP/6-31G (d,p) level was utilized to determine the electronic properties, vibrational modes and active sites of the examined molecule. In this context, some quantum chemical parameters have been calculated in order to discuss the reactivity of the studied molecule. Also, the inhibition activity of the investigated…

From Patent Search

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

• 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.

• link

• 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

• USING CLINICAL ONTOLOGIES TO BUILD KNOWLEDGE BASED CLINICAL DECISION SUPPORT SYSTEM FOR NOVEL CORONAVIRUS (COVID-19) WITH THE ADOPTION OF TELECONFERENCING FOR THE PRIMARY HEALTH CENTRES/SATELLITE CLINICS OF ROYAL OMAN POLICE IN SULTANATE OF OMAN - - link

• 抗SARS-COV-2中和抗体 - 本公开提供了针对SARS‑COV‑2的新颖中和抗体和其抗原结合片段。还提供了包括其的药物组合物和试剂盒以及其用途。 - link

• Peptides and their use in diagnosis of SARS-CoV-2 infection - - link

• Method and compositions for treating coronavirus infection - A method of treating viral infection, such as viral infection caused by a virus of the Coronaviridae family, is provided. A composition having at least oleandrin is used to treat viral infection. - link

• Luftdesinfektionssäule -

  Luftreinigungssäule (1) mit einer Luftaufnahme (2) und einer Luftausgabe (3), wobei zwischen der Luftaufnahme (2) und der Luftausgabe (3) ein luftleitender Bereich (4) mit einem Gebläse (7) und einer UV-Lichtdesinfektionseinrichtung (5) angeordnet ist, dadurch gekennzeichnet, dass der luftleitende Bereich (4) photokathalysatorisch beschichtete Oberflächen (9) aufweist und/oder ein photokathalysatorisch beschichtetes Gitter (11) angeordnet ist, wobei photokathalysatorisch beschichtetes Gitter (11) und die photokathalysatorisch beschichtete Oberflächen (9) mit Titandioxid (TiO₂) beschichtet sind, wobei die UV-Lichtdesinfektionseinrichtung (5) UV-A-LEDs (12), die UV-A-Strahlung im Wellenlängenbereich 380-315 nm ausstrahlt und UV-C-LEDs (8) die UV-Strahlung im Wellenlängenbereich UV-C 280-200 nm (8) ausstrahlen aufweist und wobei ein Akku (13) zur netzunabhängigen Stromversorgung angeordnet ist.

• link