Covid-19 Sentry

Contents

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

From Preprints

• COVID-19 on mind: Daily worry about the coronavirus is linked to negative affect experienced during mind-wandering but not during dreaming -
  Despite a surge of studies on the effects of COVID-19 on our well-being, we know little about how the pandemic is reflected in people’s spontaneous thoughts and experiences, such as mind-wandering (or daydreaming) during wakefulness and dreaming during sleep. We investigated whether and how COVID-19 related general concern, anxiety, and daily worry are associated with the daily fluctuation of the affective quality of mind-wandering and dreaming, and to what extent these associations can be explained by poor sleep quality. We used ecological momentary assessment by asking participants to rate the affect they experienced during mind-wandering and dreaming in daily logs over a two-week period. Our preregistered analyses based on 1758 dream logs from 172 individuals and 1517 mind-wandering logs from 153 individuals showed that, on days when people experienced more worry, they reported higher levels of negative affect, and lower levels of positive affect, during mind-wandering. Only daily sleep quality was associated with affect experienced during dreaming: on nights with poorer sleep quality people reported experiencing more negative and less positive affect in dreams and were more likely to experience nightmares. Exploratory analyses demonstrated that: (a) COVID-19 related general concern, anxiety, and daily worry were not related to daily sleep quality; (b) individuals who experienced more negative affect during mind-wandering also experienced more negative affect during dreaming, and (c) negative affect during mind-wandering fully mediated the relationship between daily COVID-19 worry and dream affect at the between-person level. As such, daily COVID-19 worry is linked to the affective quality of mind-wandering but not to that of dreaming.
  🖺 Full Text HTML: COVID-19 on mind: Daily worry about the coronavirus is linked to negative affect experienced during mind-wandering but not during dreaming
• Highlighting COVID-19 Racial Disparities Can Reduce Support for Safety Precautions Among White U.S. Residents -
  U.S. media has extensively covered racial disparities in COVID-19 infections and deaths. In two preregistered studies, we examined whether perceptions of COVID-19 racial disparities predict White U.S. residents’ attitudes toward COVID-19 (and people of color). Utilizing a correlational design (N = 498), we found that those who perceived COVID-19 racial disparities to be greater reported reduced fear of COVID-19, which predicted reduced support for COVID-19 safety precautions. In Study 2, we manipulated exposure to information about COVID-19 racial disparities (N = 1,505). Reading about the persistent inequalities that produced COVID-19 racial disparities reduced fear of COVID-19, empathy for those vulnerable to COVID-19, and support for safety precautions. As the racial majority group in the U.S., White residents’ attitudes toward COVID-19 (and other future public health concerns) have the potential to considerably influence public health policies. These findings suggest that publicizing racial health disparities could create a vicious cycle wherein raising awareness reduces support for the very policies that could protect public health and reduce disparities.
  🖺 Full Text HTML: Highlighting COVID-19 Racial Disparities Can Reduce Support for Safety Precautions Among White U.S. Residents
• Model evolution in SARS-CoV-2 spike protein sequences using a generative neural network -
  Modelling evolutionary elements inherent in protein sequences, emerging from one clade into another of the SARS- CoV-2 virus, would provide insights to augment our understanding of its impact on public health and may help in formulating better strategies to contain its spread. Deep learning methods have been used to model protein sequences for SARS-CoV-2 viruses. A few significant drawbacks in these studies include being deficient in modelling end-to-end protein sequences, modelling only those genomic positions that show high activity and upsampling the number of sequences at each genomic position for balancing the frequency of mutations. To mitigate such drawbacks, the current approach uses a generative model, an encoder-decoder neural network, to learn the natural progression of spike protein sequences through adjacent clades of the phylogenetic tree of Nextstrain clades. Encoder transforms a set of spike protein sequences from the source clade (20A) into its latent representation. Decoder uses the latent representation, along with Gaussian distributed noise, to generate a different set of protein sequences that are closer to the target clade (20B). The source and target clades are adjacent nodes in the phylogenetic tree of different evolving clades of the SARS-CoV-2 virus. Sequences of amino acids are generated, for the entire length, at each genomic position using the latent representation of the amino acid generated at a previous step. Using trained models, protein sequences from the source clade are used to generate sequences that form a collection of evolved sequences belonging to all children clades of the source clade. A comparison of this predicted evolution (between source and generated sequences) of proteins with the true evolution (between source and target sequences) shows a high pearson correlation (> 0.7). Moreover, the distribution of the frequencies of substitutions per genomic position, including high- and low-frequency positions, in source-target sequences and source-generated sequences exhibit a high resemblance (pearson correlation > 0.7). In addition, the model partially predicts a few substitutions at specific genomic positions for the sequences of unseen clades (20J (Gamma)) where they show little activity during training. These outcomes show the potential of this approach in learning the latent mechanism of evolution of SARS-CoV-2 viral sequences.
  🖺 Full Text HTML: Model evolution in SARS-CoV-2 spike protein sequences using a generative neural network
• Genome wide screen of RNAi molecules against SARS-CoV-2 creates a broadly potent prophylaxis -
  Expanding the arsenal of prophylactic approaches against SARS-CoV-2 is of utmost importance, specifically those strategies that are resistant to antigenic drift in Spike. Here, we conducted a screen with over 16,000 RNAi triggers against the SARS-CoV-2 genome using a massively parallel assay to identify hyper-potent siRNAs. We selected 10 candidates for in vitro validation and found five siRNAs that exhibited hyper-potent activity with IC50<20pM and strong neutralisation in live virus experiments. We further enhanced the activity by combinatorial pairing of the siRNA candidates to develop siRNA cocktails and found that these cocktails are active against multiple types of variants of concern (VOC). We examined over 2,000 possible mutations to the siRNA target sites using saturation mutagenesis and identified broad protection against future variants. Finally, we demonstrated that intranasal administration of the siRNA cocktail effectively attenuates clinical signs and viral measures of disease in the Syrian hamster model. Our results pave the way to development of an additional layer of antiviral prophylaxis that is orthogonal to vaccines and monoclonal antibodies.
  🖺 Full Text HTML: Genome wide screen of RNAi molecules against SARS-CoV-2 creates a broadly potent prophylaxis
• Discrimination of SARS-CoV-2 Omicron sub-lineages BA.1 and BA.2 using a high-resolution melting-based assay: A pilot study -
  The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. As of March 2022, Omicron variant BA.2 is rapidly replacing variant BA.1. As variant BA.2 may cause more severe disease than variant BA.1, variant BA.2 requires continuous monitoring. The current study aimed to develop a novel high-resolution melting (HRM) assay for variants BA.1 and BA.2 and to determine the sensitivity and specificity of our method using clinical samples. Here, we focused on the mutational spectra at three regions in the spike receptor-binding domain (RBD; R408, G446/L452, and S477/T478) for the variant-selective HRM analysis. Each variant was identified based on the mutational spectra as follows: no mutations (Alpha variant); L452R and T478K (Delta variant); G446S and S477N/T478K (Omicron variant BA.1); and R408S and S477N/T478K (Omicron variant BA.2). Upon analysis of mutation-coding RNA fragments, the melting peaks of the wild-type fragments were distinct from those of the mutant fragments. The sensitivity and specificity of this method were determined as 100% and more than 97.5%, respectively, based on 128 clinical samples (40 Alpha, 40 Delta, 40 Omicron variants BA.1/BA.1.1, and 8 Omicron BA.2). These results suggest that this HRM-based assay is a promising screening method for monitoring the transmission of Omicron variants BA.1 and BA.2.
  🖺 Full Text HTML: Discrimination of SARS-CoV-2 Omicron sub-lineages BA.1 and BA.2 using a high-resolution melting-based assay: A pilot study
• Broadly neutralizing antibodies target the coronavirus fusion peptide -
  The potential for future coronavirus outbreaks highlights the need to develop strategies and tools to broadly target this group of pathogens. Here, using an epitope-agnostic approach, we identified six monoclonal antibodies that bound to spike proteins from all seven human-infecting coronaviruses. Epitope mapping revealed that all six antibodies target the conserved fusion peptide region adjacent to the S2’ cleavage site. Two antibodies, COV44-62 and COV44-79, broadly neutralize a range of alpha and beta coronaviruses, including SARS-CoV-2 Omicron subvariants BA.1 and BA.2, albeit with lower potency than RBD-specific antibodies. In crystal structures of Fabs COV44-62 and COV44-79 with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine at the S2’ cleavage site. Importantly, COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings identify the fusion peptide as the target of the broadest neutralizing antibodies in an epitope-agnostic screen, highlighting this site as a candidate for next-generation coronavirus vaccine development.
  🖺 Full Text HTML: Broadly neutralizing antibodies target the coronavirus fusion peptide
• The SARS-CoV-2 receptor-binding domain facilitates neutrophil transepithelial migration and nanoparticle uptake in the mice airways -
  SARS-CoV-2-induced infection is still dangerous. Mouse models are convenient to the investigation of virus- activated immune response mechanisms. However, mice are not proper model organisms to study COVID-19 due to decreased interaction affinity between the SARS-CoV-2 receptor-binding domain (RBD) and mouse angiotensin-converting enzyme 2 (ACE2) compared with human ACE2. In the present study, we propose a mouse model that allows estimating the influence of SARS-CoV-2 on the immune system. To mimic the effects of RBD-ACE2 high-affinity interaction, mice received the ACE2 inhibitor MLN-4760. To simulate virus loading, we applied 100 nm particles suspended in the solution of RBD via the oropharyngeal route to mice. In this model, MLN-4760 application enhanced neutrophil egress from the bone marrow to the bloodstream and RBD attracted neutrophils to the luminal side of the conducting airway epithelium. By contrast, inert 100 nm particles were not potent to stimulate neutrophil recruitment to the conducting airway mucosa. Using this model, and by altering the dosage of the ACE2 inhibitor, nanoparticles, and RBD, one can adapt it to investigate different COVID-19 states characterized with mild or severe airway inflammation.
  🖺 Full Text HTML: The SARS- CoV-2 receptor-binding domain facilitates neutrophil transepithelial migration and nanoparticle uptake in the mice airways
• A high potent synthetic nanobody with broad-spectrum activity neutralizes SARS-Cov-2 virus and Omicron variant through a unique binding mode -
  COVID-19 continues to be a severe public health thread worldwide. The major challenge to control this pandemic is the rapid mutation rate of the SARS-Cov-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is pivotal to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-Cov-2 variants. In this study, we first got a synthetic nanobody (named C5) which could interfere with ACE2 binding to SARS-Cov-2 spike protein and its RBD domain. The affinity matured format of C5 clone, named C5G2, has a single digit nanomolar affinity to RBD domain and inhibit its binding to ACE2 with an IC50 of 3.7 nM. Pseudovirus assay indicated that the monovalent C5G2 could protect the cells from the infection of SARS-Cov-2 wild type virus as well as most of the virus of concern, i.e. Alpha, Beta, Gamma and Omicron variants. Strikingly, C5G2 has the highest potency against omicron among all the variants with the IC50 of 4.9ng/ml (0.3 nM). We further solved the Cryo-EM structure of C5G2 in complex with the Spike trimer. The structure data showed that C5G2 bind to RBD mainly through its CDR3 at a vast region that not overlapping with the ACE2 binding surface. Surprisingly, C5G2 also bind to a distinct epitope residing in the NTD domain of spike protein through the same CDR3 loop, which may further increase its potency against the virus infection. Thus, this bi-paratopic nanobody may be served as an effective drug for the prophylaxis and therapy of the Omicron infection.
  🖺 Full Text HTML: A high potent synthetic nanobody with broad-spectrum activity neutralizes SARS-Cov-2 virus and Omicron variant through a unique binding mode
• How the replication and transcription complex functions in jumping transcription of SARS-CoV-2 -
  Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). Although unprecedented efforts are underway to develop therapeutic strategies against this disease, scientists have acquired only a little knowledge regarding the structures and functions of the CoV replication and transcription complex (RTC) and 16 non-structural proteins, named NSP1-16. Results: In the present study, we determined the theoretical arrangement of NSP12-16 in the global RTC structure. This arrangement answered how the CoV RTC functions in the “leader-to-body fusion” process. More importantly, our results revealed the associations between multiple functions of the RTC, including RNA synthesis, NSP15 cleavage, RNA methylation, and CoV replication and transcription at the molecular level. As the most important finding, transcription regulatory sequence (TRS) hairpins were reported for the first time to help understand the multiple functions of CoV RTCs and the strong recombination abilities of CoVs. Conclusions: TRS hairpins can be used to identify recombination regions in CoV genomes. We provide a systematic understanding of the structures and functions of the RTC, leading to the eventual determination of the global CoV RTC structure. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, providing a basis for future studies. Future drug design targeting SARS-CoV-2 needs to consider protein-protein and protein-RNA interactions in the RTC, particularly the complex structure of NSP15 and NSP16 with the TRS hairpin.
  🖺 Full Text HTML: How the replication and transcription complex functions in jumping transcription of SARS-CoV-2
• Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants -
  SARS-CoV-2 infection in the upper airway and the subsequent immune response are early, critical factors in COVID-19 pathogenesis. By studying infection of human biopsies in vitro and in a hamster model in vivo, we demonstrated a transition in tropism from olfactory to respiratory epithelium as the virus evolved. Analyzing each variants revealed that SARS-CoV-2 WA1 or Delta infects a proportion of olfactory neurons in addition to the primary target sustentacular cells. The Delta variant possesses broader cellular invasion capacity into the submucosa, while Omicron displays longer retention in the sinonasal epithelium. The olfactory neuronal infection by WA1 and the subsequent olfactory bulb transport via axon is more pronounced in younger hosts. In addition, the observed viral clearance delay and phagocytic dysfunction in aged olfactory mucosa is accompanied by a decline of phagocytosis related genes. Furthermore, robust basal stem cell activation contributes to neuroepithelial regeneration and restores ACE2 expression post-infection. Together, our study characterized the nasal tropism of SARS-CoV-2 strains, immune clearance, and regeneration post infection. The shifting characteristics of viral infection at the airway portal provides insight into the variability of COVID-19 clinical features and may suggest differing strategies for early local intervention.
  🖺 Full Text HTML: Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants
• An ACAT inhibitor regulates SARS-CoV-2 replication and antiviral T cell activity -
  The severity of disease following infection with SARS-CoV-2 is determined by viral replication kinetics and host immunity, with early T cell responses and/or suppression of viraemia driving a favourable outcome. Recent studies have uncovered a role for cholesterol metabolism in the SARS-CoV-2 life cycle and in T cell function. Here we show that blockade of the enzyme Acyl-CoA:cholesterol acyltransferase (ACAT) with Avasimibe inhibits SARS-CoV-2 entry and fusion independent of transmembrane protease serine 2 expression in multiple cell types. We also demonstrate a role for ACAT in regulating SARS-CoV-2 RNA replication in primary bronchial epithelial cells. Furthermore, Avasimibe boosts the expansion of functional SARS-CoV-2-specific T cells from the blood of patients sampled in the acute phase of infection. Thus, re-purposing of available ACAT inhibitors provides a compelling therapeutic strategy for the treatment of COVID-19 to achieve both antiviral and immunomodulatory effects.
  🖺 Full Text HTML: An ACAT inhibitor regulates SARS-CoV-2 replication and antiviral T cell activity
• Remdesivir for the treatment of hospitalised patients with COVID-19: final results from the DisCoVeRy randomised, controlled, open-label trial -

  Background: The antiviral efficacy of remdesivir is still controversial. We aimed at evaluating its clinical effectiveness in hospitalised patients with COVID-19, with indication of oxygen and/or ventilator support. Following prior publication of preliminary results, here we present the final results after completion of data monitoring. Methods: In this European multicentre, open-label, parallel-group, randomised, controlled trial (DisCoVeRy, NCT04315948, EudraCT2020-000936-23), participants were randomly allocated to receive usual standard of care (SoC) alone or in combination with remdesivir, lopinavir/ritonavir, lopinavir/ritonavir and IFN-beta-1a, or hydroxychloroquine. Adult patients hospitalised with COVID-19 were eligible if they had clinical evidence of hypoxemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzyme, severe chronic kidney disease, any contra- indication to one of the studied treatments or their use in the 29 days before randomization, or use of ribavirin, as well as pregnancy or breast-feeding. Here, we report results for remdesivir + SoC versus SoC alone. Remdesivir was administered as 200 mg infusion on day 1, followed by once daily infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. Treatment assignation was performed via web-based block randomisation stratified on illness severity and administrative European region. The primary outcome was the clinical status at day 15 measured by the WHO 7-point ordinal scale, assessed in the intention-to-treat population. Findings: Between March 22nd, 2020 and January 21st, 2021, 857 participants were randomised to one of the two arms in 5 European countries and 843 participants were included for the evaluation of remdesivir (control, n=423; remdesivir, n=420). At day 15, the distribution of the WHO ordinal scale was as follow in the remdesivir and control groups, respectively: Not hospitalized, no limitations on activities: 62/420 (14.8%) and 72/423 (17.0%); Not hospitalized, limitation on activities: 126/420 (30%) and 135/423 (31.9%); Hospitalized, not requiring supplemental oxygen: 56/420 (13.3%) and 31/423 (7.3%); Hospitalized, requiring supplemental oxygen: 75/420 (17.9%) and 65/423 (15.4%); Hospitalized, on non-invasive ventilation or high flow oxygen devices: 16/420 (3.8%) and 16/423 (3.8%); Hospitalized, on invasive mechanical ventilation or ECMO: 64/420 (15.2%) and 80/423 (18.9%); Death: 21/420 (5%) and 24/423 (5.7%). The difference between treatment groups was not statistically significant (OR for remdesivir, 1.02, 95% CI, 0.62 to 1.70, P=0.93). There was no significant difference in the occurrence of Serious Adverse Events between treatment groups (remdesivir, n=147/410, 35.9%, versus control, n=138/423, 32.6%, p=0.29). Interpretation: Remdesivir use for the treatment of hospitalised patients with COVID-19 was not associated with clinical improvement at day 15. Funding: European Union Commission, French Ministry of Health, DIM One Health Ile-de-France, REACTing, Fonds Erasme-COVID-ULB; Belgian Health Care Knowledge Centre (KCE), AGMT gGmbH, FEDER “European Regional Development Fund”, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Remdesivir was provided free of charge by Gilead.

  🖺 Full Text HTML: Remdesivir for the treatment of hospitalised patients with COVID-19: final results from the DisCoVeRy randomised, controlled, open-label trial
• Detection of COVID-19 and age-dependent dysosmia with paired crushable odorant ampules -

  Abstract Background Signs of anosmia can help detect COVID-19 infection when testing for viral positivity is not available. Inexpensive mass-produced disposable olfactory sensitivity tests suitable for worldwide use might serve not only as a screening tool for potential infection but also to identify cases at elevated risk of severe disease as anosmic COVID-19 patients have a better prognosis. Methods and Findings We adopted paired crushable ampules with two concentrations of a standard test odorant (n-butanol) as standard of care in several clinics as community prevalence of COVID-19 infection waxed and waned. This was not a clinical trial; a chart review was undertaken to evaluate the operating characteristics and potential utility of the test device as RT-PCR testing became routine. The risk of anosmia was greater in COVID-19 patients. Olfactory sensitivity was concentration-dependent, decreased with aging, and was sex- dependent at the highest concentration. Hyposmia was detected across a wider age range than expected from the literature, and tests can be optimized to characterize different age groups. Conclusions n-Butanol at 0.32 and 3.2% in crushable ampules can be used to characterize olfactory function quickly and inexpensively and thus has potential benefits in pandemic screening, epidemiology, and clinical decision-making.

  🖺 Full Text HTML: Detection of COVID-19 and age-dependent dysosmia with paired crushable odorant ampules
• The Adaptive Olfactory Measure of Threshold (ArOMa-T): A rapid test of olfactory function -

  Purpose: Many widely-used psychophysical tests of olfaction have limitations that can create barriers to adoption outside research settings. For example, tests that measure the ability to identify odors may confound sensory performance with memory recall, verbal ability, and past experience with the odor. Conversely, threshold-based tests typically avoid these issues, but are labor intensive. Additionally, many commercially available olfactory tests are slow and may require a trained administrator, making them impractical for use in a short wellness visit or other broad clinical assessment. Methods: We tested the performance of the Adaptive Olfactory Measure of Threshold (ArOMa-T) – a novel odor detection threshold test that employs an adaptive Bayesian algorithm paired with a disposable odor-delivery card – in a non-clinical sample of individuals (n=534) at the 2021 Twins Day Festival in Twinsburg, OH. Results: Participants successfully completed the test in under 3 min with a false alarm rate of 9.6% and a test-retest reliability of 0.61. Odor detection thresholds differed by sex (~3.2-fold) and between the youngest and oldest age groups (~8.7-fold), consistent with prior work. In an exploratory analysis, we failed to observe evidence of detection threshold differences between participants who reported a history of COVID-19 and matched controls who did not. We also found evidence for broad-sense heritability of odor detection thresholds. Conclusion: Together, these data indicate the ArOMa-T can determine odor detection thresholds. The ArOMa-T may be particularly valuable in clinical or field settings where rapid and portable assessment of olfactory function is needed.

  🖺 Full Text HTML: The Adaptive Olfactory Measure of Threshold (ArOMa-T): A rapid test of olfactory function
• Inequities in COVID-19 vaccine and booster coverage across Massachusetts ZIP codes: large gaps persist after the 2021/22 Omicron wave -

  Background. Inequities in COVID-19 vaccine coverage may contribute to future disparities in morbidity and mortality between Massachusetts (MA) communities. Methods. We obtained public-use data on residents vaccinated and boosted by ZIP code (and by age group: 5-19, 20-39, 40-64, 65+) from MA Department of Public Health. We constructed population denominators for postal ZIP codes by aggregating Census-tract population estimates from the 2015-2019 American Community Survey. We excluded non-residential ZIP codes and the smallest ZIP codes containing 1% of the state9s population. We mapped variation in ZIP-code level primary series vaccine and booster coverage and used regression models to evaluate the association of these measures with ZIP-code-level socioeconomic and demographic characteristics. Because age is strongly associated with COVID-19 severity and vaccine access/uptake, we assessed whether observed socioeconomic and racial inequities persisted after adjusting for age composition and plotted age-specific vaccine and booster coverage by deciles of ZIP-code characteristics. Results. We analyzed data on 418 ZIP codes. We observed wide geographic variation in primary series vaccination and booster rates, with marked inequities by ZIP-code-level education, median household income, essential worker share, and racial-ethnic composition. In age-stratified analyses, primary series vaccine coverage was very high among the elderly. However, we found large inequities in vaccination rates among younger adults and children, and very large inequities in booster rates for all age groups. In multivariable regression models, each 10 percentage point increase in “percent college educated” was associated with a 5.0 percentage point increase in primary series vaccine coverage and a 4.9 percentage point increase in booster coverage. Although ZIP codes with higher “percent Black/Latino/Indigenous” and higher “percent essential workers” had lower vaccine coverage, these associations became strongly positive after adjusting for age and education, consistent with high demand for vaccines among Black/Latino/Indigenous and essential worker populations. Conclusion. One year into MA9s vaccine rollout, large disparities in COVID-19 primary series vaccine and booster coverage persist across MA ZIP codes.

  🖺 Full Text HTML: Inequities in COVID-19 vaccine and booster coverage across Massachusetts ZIP codes: large gaps persist after the 2021/22 Omicron wave

From Clinical Trials

• Randomized Controlled Clinical Trial to Evaluate The Efficacy and Safety of Healthtone as Prophylaxis for COVID-19 - Condition:   COVID-19
  Intervention:   Dietary Supplement: Rhea® Health Tone
  Sponsor:   Indonesia University
  Completed

• Functional Capacity in Patients Post Mild COVID-19 - Condition:   COVID-19
  Intervention:   Device: Cardiopulmonary exercise test (CPET)
  Sponsor:   Rambam Health Care Campus
  Recruiting

• Aerobic Exercise in People With Post-COVID-19 - Condition:   COVID-19
  Interventions:   Other: Conventional rehabilitation;   Other: Aerobic exercise
  Sponsor:   Istituti Clinici Scientifici Maugeri SpA
  Recruiting

• Circuit Training Program in Post COVID-19 Patients - Condition:   COVID-19
  Interventions:   Other: Circuit Training Exercise Program;   Other: Aerobic Training Exercise Program
  Sponsor:   Riphah International University
  Not yet recruiting

• The Effect of Home-based Rehabilitation Program After COVID-19 Infection - Condition:   COVID-19
  Interventions:   Behavioral: Add-on telerehabilitation and home-based rehabilitation;   Behavioral: Home-based rehabilitation alone
  Sponsor:  
  National Taiwan University Hospital
  Recruiting

• Efficacy, Safety and Immunogenicity Study of COVID-19 Protein Subunit Recombinant Vaccine - Condition:   COVID-19
  Interventions:   Biological: SARS-CoV-2 protein subunit recombinant vaccine;   Biological: placebo
  Sponsors:   PT Bio Farma;   Faculty of Medicine, Universitas Indonesia, Jakarta;   Faculty of Medicine, Diponegoro University, Semarang;   Faculty of Medicine, Universitas Andalas, Padang;   Faculty of Medicine, Universitas Hassanudin, Makassar
  Not yet recruiting

• A Study to Evaluate the Effectiveness and Safety of SCTV01E (a Recombinant Protein COVID-19 Vaccine) in Population Aged ≥12 Years - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01E;   Biological: CoronaVac;   Biological: Sinopharm inactivated COVID-19 vaccine;   Biological: other approved COVID-19 vaccines
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• Tele-Rehabilitation in Individuals With Covid-19 - Condition:   COVID-19
  Intervention:   Other: Exercise
  Sponsor:  
  Hacettepe University
  Completed

• A Study to Evaluate the Immunogenicity and Safety of SCTV01C and SCTV01E (Two Recombinant Protein COVID-19 Vaccines) in Population Aged ≥12 Years - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01C;   Biological: SCTV01E;   Biological: mRNA vaccine manufactured by Pfizer or Moderna;   Biological: Sinopharm inactivated COVID-19 vaccine
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• A Study to Evaluate the Immunogenicity and Safety of Two Recombinant Protein COVID-19 Vaccines in Population Aged ≥18 Years as Booster Vaccines - Conditions:   COVID-19;   SARS-CoV-2 Infection
  Interventions:   Biological: SCTV01C;   Biological: SCTV01E;   Biological: Sinopharm inactivated COVID-19 vaccine;   Biological: mRNA-1273
  Sponsor:   Sinocelltech Ltd.
  Not yet recruiting

• COVID-19 Treatment Cascade Optimization Study - Condition:   COVID-19
  Interventions:   Behavioral: Navigation Services;   Behavioral: Brief Counseling;   Behavioral: Critical Dialogue;   Behavioral: Referral and Digital Brochure
  Sponsors:   University of Illinois at Urbana-Champaign;   National Institute of Allergy and Infectious Diseases (NIAID);   Comprehensive Behavioral Health Center;   North Jersey Community Research Initiative;   University of Michigan
  Not yet recruiting

• Safety and Efficacy of Enoxaparin and Hydroxychloroquine in COVID-19 - Condition:   COVID-19 Pandemic
  Intervention:   Drug: Enoxaparin, Hydroxychloroquine
  Sponsor:   Beni-Suef University
  Completed

• Phase 1&2 Study to Evaluate the Safety & Efficacy of Inhaled IBIO123 in Severe COVID-19 Illness - Condition:   COVID-19
  Interventions:   Biological: IBIO123;   Other: Placebo
  Sponsor:   Immune Biosolutions Inc
  Recruiting

• Clinical Evaluation of Rapid RNA Test for Covid-19 - Condition:   COVID-19
  Intervention:   Diagnostic Test: rapid RT-LAMP test to detect SARS-COV-2 RNA
  Sponsors:   University of Southampton;   West Hertfordshire Hospitals NHS Trust;   University of Oxford
  Completed

• Non-inferiority Trial on Treatments in Early COVID-19 - Condition:   COVID-19
  Interventions:   Drug: Sotrovimab;   Drug: Tixagevimab Cilgavimab;   Drug: Nirmatrelvir Ritonavir
  Sponsors:   Azienda Ospedaliera Universitaria Integrata Verona;   Agenzia Italiana del Farmaco;   Azienda Sanitaria-Universitaria Integrata di Udine
  Recruiting

From PubMed

• COVID-19 receptor and malignant cancers: Association of CTSL expression with susceptibility to SARS-CoV-2 - CTSL is expressed by cancerous tissues and encodes a lysosomal cysteine proteinase that regulates cancer progression and SARS-CoV-2 entry. Therefore, it is critical to predict the susceptibility of cancer patients for SARS-CoV-2 and evaluate the correlation between disease outcomes and the expression of CTSL in malignant cancer tissues. In the current study, we analyzed CTSL expression, mutation rate, survival and COVID-19 disease outcomes in cancer and normal tissues, using online databases. We…

• A multicenter, open-label, randomized, proof-of-concept phase II clinical trial to assess the efficacy and safety of icatibant in patients infected with SARS-CoV-2 (COVID-19) and admitted to hospital units without invasive mechanical ventilation: study protocol (ICAT-COVID) - BACKGROUND: COVID-19 has quickly become a global pandemic with a substantial number of deaths and is a considerable burden for healthcare systems worldwide. Although most cases are paucisymptomatic and limited to the viral infection- related symptoms, some patients evolve to a second phase, with an impaired inflammatory response (cytokine storm) that may lead to acute respiratory distress syndrome and death. This is thought to be caused by increased bradykinin synthesis.

• Gegen Qinlian pills alleviate carrageenan-induced thrombosis in mice model by regulating the HMGB1/NF-κB/NLRP3 signaling - CONCLUSION: Overall, we demonstrated that GQP could reduce inflammation-induced thrombosis by inhibiting HMGB1/NFκB/NLRP3 signaling and provided an accurate explanation for the multi-target, multi-function mechanism of GQP in the treatment of thromboinflammation, and provides a reference for the clinical usage of GQP.

• Exposure and Outcome in practice: a retrospective cohort study between fibrinolytic suppression and hypercoagulability, the severity of hypoxemia, and mortality in COVID-19 patients - CONCLUSION: Increased inflammatory and pro-coagulant markers such as PAI-1, MP- Tissue Factor, vWF levels are associated with severe hypoxemia and major thrombotic events, implicating fibrinolytic suppression in the microcirculatory system and subsequent micro- and macrovascular thrombosis in severe COVID-19.

• Semi-Mechanistic Pharmacokinetic-Pharmacodynamic Model of Camostat Mesylate-Predicted Efficacy against SARS-CoV-2 in COVID-19 - The SARS-CoV-2 coronavirus, which causes COVID-19, uses a viral surface spike protein for host cell entry and the human cell-surface transmembrane serine protease, TMPRSS2, to process the spike protein. Camostat mesylate, an orally available and clinically used serine protease inhibitor, inhibits TMPRSS2, supporting clinical trials to investigate its use in COVID-19. A one-compartment pharmacokinetic (PK)/pharmacodynamic (PD) model for camostat and the active metabolite FOY-251 was developed,…

• Peptide-Based Dual HIV and Coronavirus Entry Inhibitors - The continued HIV/AIDS epidemic worldwide and the battle against emerging infectious diseases caused by coronaviruses underscore the need for the development of an ever-expanding repertoire of antiviral drugs. Entry inhibitors are of particular interest because of their potential to be used as therapeutic or prophylactic treatments for blocking viral invasion. HIV and coronaviruses utilize class I fusion proteins to facilitate their entry and membrane fusion. Discovery of a common hexameric…

• Direct Thrombin Inhibition in Extracorporeal Membrane Oxygenation - Extracorporeal membrane oxygenation (ECMO) is a widely used technique to provide circulatory and/or respiratory support in critically ill patients. ECMO treatment usually necessitates systemic anticoagulation. Unfractionated Heparin (UFH) is a commonly used anticoagulant in patients on ECMO support. In situations where UFH is contraindicated, alternative anticoagulation strategies can be applied, such as the use of direct thrombin inhibitors (DTI). Bivalirudin and argatroban are the most widely…

• Targeted protein S-nitrosylation of ACE2 as potential treatment to prevent spread of SARS-CoV-2 infection - Prevention of infection and propagation of SARS-CoV-2 is of high priority in the COVID-19 pandemic. Here, we describe S-nitrosylation of multiple proteins involved in SARS-CoV-2 infection, including angiotensin converting enzyme 2 (ACE2), the receptor for viral entry. This reaction prevents binding of ACE2 to the SARS-CoV-2 Spike protein, thereby inhibiting viral entry, infectivity, and cytotoxicity. Aminoadamantane compounds also inhibit coronavirus ion channels formed by envelope (E) protein….

• Molecular docking, molecular dynamics simulation, and ADMET analysis of levamisole derivatives against the SARS- CoV-2 main protease (M^Pro) - Introduction: The new species of coronaviruses (CoVs), SARS-CoV-2, was reported as responsible for an outbreak of respiratory disease. Scientists and researchers are endeavoring to develop new approaches for the effective treatment against of the COVID-19 disease. There are no finally targeted antiviral agents able to inhibit the SARS-CoV-2 at present. Therefore, it is of interest to investigate the potential uses of levamisole derivatives, which are reported to be antiviral agents targeting the…

• Aptamer blocking S-TLR4 interaction selectively inhibits SARS-CoV-2 induced inflammation - No abstract

• Drug-Free Nasal Spray as a Barrier against SARS-CoV-2 and Its Delta Variant: In Vitro Study of Safety and Efficacy in Human Nasal Airway Epithelia - The nasal epithelium is a key portal for infection by respiratory viruses such as SARS-CoV-2 and represents an important target for prophylactic and therapeutic interventions. In the present study, we test the safety and efficacy of a newly developed nasal spray (AM-301, marketed as Bentrio) against infection by SARS-CoV-2 and its Delta variant on an in vitro 3D-model of the primary human nasal airway epithelium. Safety was assessed in assays for tight junction integrity, cytotoxicity and cilia…

• Identification of Entry Inhibitors against Delta and Omicron Variants of SARS-CoV-2 - Entry inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to control the outbreak of coronavirus disease 2019 (COVID-19). This study developed a robust and straightforward assay that detected the molecular interaction between the receptor-binding domain (RBD) of viral spike protein and the angiotensin- converting enzyme 2 (ACE2) receptor in just 10 min. A drug library of 1068 approved compounds was used to screen for SARS-CoV2 entry inhibition, and…

• The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality - The quantity of high-density lipoproteins (HDL) is represented as the serum HDL-C concentration (mg/dL), while the HDL quality manifests as the diverse features of protein and lipid content, extent of oxidation, and extent of glycation. The HDL functionality represents several performance metrics of HDL, such as antioxidant, anti-inflammatory, and cholesterol efflux activities. The quantity and quality of HDL can change during one’s lifetime, depending on infection, disease, and lifestyle, such…

• What Is Currently Known about the Role of CXCL10 in SARS-CoV-2 Infection? - Dysregulation of the immune response plays an important role in the progression of SARS-CoV-2 infection. A “cytokine storm”, which is a phenomenon associated with uncontrolled production of large amounts of cytokines, very often affects patients with COVID-19. Elevated activity of chemotactic cytokines, called chemokines, can lead to serious consequences. CXCL10 has an ability to activate its receptor CXCR3, predominantly expressed on macrophages, T lymphocytes, dendritic cells, natural killer…

• Antiviral Effects of Animal Toxins: Is There a Way to Drugs? - Viruses infect all types of organisms, causing viral diseases, which are very common in humans. Since viruses use the metabolic pathways of their host cells to replicate, they are difficult to eradicate without affecting the cells. The most effective measures against viral infections are vaccinations and antiviral drugs, which selectively inhibit the viral replication cycle. Both methods have disadvantages, which requires the development of new approaches to the treatment of viral diseases. In…

From Patent Search

• SYSTEM FOR MONITORING COVID-19 PATIENTS USING A VIRTUAL TELEPRESENCE ROBOT - Attached Separately - link

• MACHINE LEARNING TECHNIQUE TO ANALYZE THE WORK PRESSURE OF PARAMEDICAL STAFF DURING COVID 19 - Machine learning technique to analyse the work pressure of paramedical staff during covid 19 is the proposed invention that focuses on identifying the stress levels of paramedical staff. The invention focuses on analysing the level of stress that is induced on the paramedical staff especially during pandemic. - link

• 基于SARS-CoV-2的S蛋白的疫苗及其用途 - 本公开提供了基于SARS‑CoV‑2的S蛋白的疫苗及其用途，并具体涉及重组SARS‑CoV‑2刺突蛋白(S蛋白)及编码其的mRNA和DNA。本公开还涉及包含编码重组S蛋白的DNA序列的重组质粒。本公开的重组质粒经转录得到mRNA，其包含SEQ ID NO.12所示的序列。本公开进一步涉及包含前述mRNA的mRNA‑载体颗粒例如脂质纳米颗粒(LNP)和组合物例如疫苗组合物。 - link

• CBD Covid 19 Protection - - link

• 一种双价可电离脂质化合物、组合物及其应用 - 本发明涉及核酸药物递送技术领域，特别是关于一种双价可电离脂质化合物、组合物及其应用。本发明提供多种可以递送核酸药物的可电离阳离子脂质，具备较强的可设计性、可生物降解性及高效的体内外转染效率，由其组成的脂质纳米递送系统用于递送mRNA，在细胞水平上，优于目前上市的产品，并且在动物水平也具有良好的递送效率，可以作为核酸药物的递送新的方法，促进核酸药物的发展。 - link

• 一种双价可电离脂质化合物、组合物及其应用 - 本发明涉及核酸药物递送技术领域，特别是关于一种双价可电离脂质化合物、组合物及其应用。本发明提供多种可以递送核酸药物的可电离阳离子脂质，具备较强的可设计性、可生物降解性及高效的体内外转染效率，由其组成的脂质纳米递送系统用于递送mRNA，在细胞水平上，优于目前上市的产品，并且在动物水平也具有良好的递送效率，可以作为核酸药物的递送新的方法，促进核酸药物的发展。 - link

• 新冠肺炎CT图像分割方法及终端设备 - 本发明公开了一种新冠肺炎CT图像分割方法及终端设备，方法包括获取待分割新冠肺炎CT图像；将该图像输入至训练好的分割模型中，得到新冠肺炎病灶区域的图像；其中分割模型包括依次连接的多个下采样模块和下采样模块对应的上采样模块；每个采样模块均包括依次连接的第一提取单元和第二提取单元；上述两个提取单元的卷积模块均为结构重参数化卷积模块。本发明的结构重参数化卷积模块为训练时使用多分支结构，加强模型表达能力，推理时使用单路结构，加快推理速度，快速得出诊断结果。同时，为从不同尺度特征图中学习分层表示，加强模型对图像边缘信息提取，并使梯度更快回流，上采样每一侧输出都连接混合损失函数，实现图像的像素级分割。 - link

• 一种一步法核酸检测方法及其所用的密封性核酸检测装置 - 本发明涉及一种一步法核酸检测方法及其所用的密封性核酸检测装置，该密封性核酸检测装置，主体为PCR管，包括管盖、管体，管体内分为三层，最下层为PCR冻干试剂层，是将PCR冻干试剂密封在第一石蜡层中构成；中间层为盐酸溶液；最上层为核酸提取试剂层，核酸提取试剂层与盐酸溶液之间通过第二石蜡层隔离；核酸提取试剂层中放置核酸检测所需的一步法核酸提取试剂。本发明实现同一PCR管内的空间隔离，做到只需一次加样，即可完成PCR检测，无需中间繁琐的核酸提取过程和核酸加样操作，反应完成后，也无需开盖分析，核酸提取和检测过程做到真正的零污染，且整个过程操作简单，大大降低了检测成本。 - link

• Vorrichtung zur Aufnahme von Proben -

  Vorrichtung (1) zur Aufnahme von Proben, insbesondere Speichelproben zum Nachweis von SARS-CoV-2 Virus im Speichel, mit

• einem Aufnahmebehälter (2) mit einer ersten Öffnung (4),
• einer Verschlusseinrichtung (6), die an die Öffnung (4) des Aufnahmebehälters (2) angepasst ist, so dass die Öffnung (4) des Aufnahmebehälters (2) mit der Verschlusseinrichtung (6) verschließbar ist,

• einer Probenentnahmeeinrichtung (8), die an einem ersten freien Ende (10) zumindest ein erstes Entnahmeelement (12) aufweist, mit dem die Probe entnehmbar ist, und wobei die Probenentnahmeeinrichtung (8) in den Aufnahmebehälter (2) einführbar ist, dadurch gekennzeichnet, dass die Probenentnahmeeinrichtung (8) an einem dem ersten freien Ende (10) gegenüberliegenden zweiten Ende (14) mit der Verschlusseinrichtung (6) verbunden ist, so dass die Probenentnahmeeinrichtung (8) mittels der Verschlusseinrichtung (6) in den Aufnahmebehälter (2) einführbar ist.

• link

• 一种氮化硅消毒喷剂 - 一种氮化硅消毒喷剂，所述氮化硅消毒喷剂包括：氮化硅粉5重量份；溶剂50‑500重量份；增稠剂0.05‑0.6重量份；所述氮化硅消毒喷剂粘度为30 cP‑300 cP。本发明提供的氮化硅消毒喷剂能够杀灭包括新冠病毒在内的多种细菌、病毒，并且具有长效杀毒效果。 - link