Covid-19 Sentry

Contents

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

From Preprints

• Receptor binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2 -
  Neutralization assays are experimental surrogates for the effectiveness of infection- or vaccine-elicited polyclonal antibodies and therapeutic monoclonal antibodies targeting SARS-CoV-2. However, the measured neutralization can depend on details of the experimental assay. Here we systematically assess how ACE2 expression in target cells affects neutralization by antibodies to different spike epitopes in lentivirus pseudovirus neutralization assays. For high ACE2-expressing target cells, receptor binding domain (RBD) antibodies account for nearly all neutralizing activity in polyclonal human sera. But for lower ACE2-expressing target cells, antibodies targeting regions outside the RBD make a larger (although still modest) contribution to serum neutralization. These serum-level results are mirrored for monoclonal antibodies: N-terminal domain (NTD) antibodies and RBD antibodies that do not compete for ACE2 binding incompletely neutralize on high ACE2-expressing target cells, but completely neutralize on cells with lower ACE2 expression. Our results show that ACE2 expression level in the target cells is an important experimental variable, and that high ACE2 expression emphasizes the role of a subset of RBD-directed antibodies.
  🖺 Full Text HTML: Receptor binding domain (RBD) antibodies contribute more to SARS-CoV-2 neutralization when target cells express high levels of ACE2
• Entropic overcompensation of the N501Y mutation on SARS-CoV-2 S binding to ACE2 -
  Recent experimental work has shown that the N501Y mutation in the SARS-CoV-2 S glycoprotein’s receptor binding domain (RBD) increases binding affinity to the angiotensin-converting enzyme 2 (ACE2), primarily by overcompensating for a less favorable enthalpy of binding by a greatly reducing the entropic penalty for complex formation, but the basis for this entropic overcompensation is not clear [Pr’evost et al., J. Biol. Chem. (2021) 297;10115]. We use all-atom molecular dynamics simulations and free-energy calculations to qualitatively assess the impact of the N501Y mutation on enthalpy and entropy of binding of RBD to ACE2. Our calculations correctly predict that N501Y causes a less favorable enthalpy of binding to ACE2 relative to the original strain. Further, we show that this is overcompensated for by a more entropically favorable increase in large-scale quaternary flexibility and intra-protein root-mean squared fluctuations of residue positions upon binding in both RBD and ACE2. The enhanced quaternary flexibility stems from N501Y’s ability to remodel the interresidue interactions between the two proteins away from interactions central to the epitope and toward more peripheral interactions. These findings suggest that an important factor in determining protein-protein binding affinity is the degree to which fluctuations are distributed throughout the complex, and that residue mutations that may seem to result in weaker interactions than their wild-type counterparts may yet result increased binding affinity thanks to their ability to suppress unfavorable entropy changes upon binding.
  🖺 Full Text HTML: Entropic overcompensation of the N501Y mutation on SARS-CoV-2 S binding to ACE2
• Identifying Women with Post-Delivery Posttraumatic Stress Disorder using Natural Language Processing of Personal Childbirth Narratives -

  Background: Maternal mental disorders are considered a leading complication of childbirth and a common contributor to maternal death. In addition to undermining maternal welfare, untreated postpartum psychopathology can result in child emotional and physical neglect, and associated significant pediatric health costs. Some women may experience a traumatic childbirth and develop posttraumatic stress disorder (PTSD) symptoms following delivery (CB-PTSD). Although women are routinely screened for postpartum depression in the U.S., there is no recommended protocol to inform the identification of women who are likely to experience CB-PTSD. Advancements in computational methods of free text has shown promise in informing diagnosis of psychiatric conditions. Although the language in narratives of stressful events has been associated with post-trauma outcomes, whether the narratives of childbirth processed via machine learning can be useful for CB-PTSD screening is unknown. Objective: This study examined the utility of written narrative accounts of personal childbirth experience for the identification of women with provisional CB-PTSD. To this end, we developed a model based on natural language processing (NLP) and machine learning (ML) algorithms to identify CB-PTSD via classification of birth narratives. Study Design: A total of 1,127 eligible postpartum women who enrolled in a study survey during the COVID-19 era provided short written childbirth narrative accounts in which they were instructed to focus on the most distressing aspects of their childbirth experience. They also completed a PTSD symptom screen to determine provisional CB-PTSD. After exclusion criteria were applied, data from 995 participants was analyzed. An ML-based Sentence-Transformer NLP model was used to represent narratives as vectors that served as inputs for a neural network ML model developed in this study to identify participants with provisional CB-PTSD. Results: The ML model derived from NLP of childbirth narratives achieved good performance: AUC 0.75, F1-score 0.76, sensitivity 0.8, and specificity 0.70. Moreover, women with provisional CB-PTSD generated longer narratives (t-test results: t=2.30, p=0.02) and used more negative emotional expressions (Wilcoxon test: 9sadness9: p=8.90e-04, W=31,017; 9anger9: p=1.32e-02, W=35,005.50) and death-related words (Wilcoxon test: p=3.48e-05, W=34,538) in describing their childbirth experience than those with no CB-PTSD. Conclusions: This study provides proof of concept that personal childbirth narrative accounts generated in the early postpartum period and analyzed via advanced computational methods can detect with relatively high accuracy women who are likely to endorse CB-PTSD and those at low risk. This suggests that birth narratives could be promising for informing low-cost, non-invasive tools for maternal mental health screening, and more research that utilizes ML to predict early signs of maternal psychiatric morbidity is warranted.

  🖺 Full Text HTML: Identifying Women with Post-Delivery Posttraumatic Stress Disorder using Natural Language Processing of Personal Childbirth Narratives
• A case-crossover study of the effect of vaccination on SARS-CoV-2 transmission relevant behaviours during a period of national lockdown in England and Wales -

  Background: Studies of COVID-19 vaccine effectiveness show increases in COVID-19 cases within 14 days of a first dose, potentially reflecting post-vaccination behaviour changes associated with SARS-CoV-2 transmission before vaccine protection. However, direct evidence for a relationship between vaccination and behaviour is lacking. We aimed to examine the association between vaccination status and self-reported non-household contacts and non-essential activities during a national lockdown in England and Wales. Methods: Participants (n=1,154) who had received the first dose of a COVID-19 vaccine reported non-household contacts and non-essential activities from February to March 2021 in monthly surveys during a national lockdown in England and Wales. We used a case-crossover study design and conditional logistic regression to examine the association between vaccination status (pre-vaccination vs. 14 days post-vaccination) and self-reported contacts and activities within individuals. Stratified subgroup analyses examined potential effect heterogeneity by sociodemographic characteristics such as sex, household income or age group. Results: 457/1,154 (39.60%) participants reported non-household contacts post-vaccination compared with 371/1,154 (32.15%) participants pre-vaccination. 100/1,154 (8.67%) participants reported use of non-essential shops or services post-vaccination compared with 74/1,154 (6.41%) participants pre-vaccination. Post-vaccination status was associated with increased odds of reporting non-household contacts (OR 1.65, 95% CI 1.31-2.06, p<0.001) and use of non-essential shops or services (OR 1.50, 95% CI 1.03-2.17, p=0.032). This effect varied between men and women and different age groups. Conclusion: Participants had higher odds of reporting non-household contacts and use of non-essential shops or services within 14 days of their first COVID-19 vaccine compared to pre-vaccination. Public health emphasis on maintaining protective behaviours during this post-vaccination time period when individuals have yet to develop full protection from vaccination could reduce risk of SARS-CoV-2 infection.

  🖺 Full Text HTML: A case-crossover study of the effect of vaccination on SARS-CoV-2 transmission relevant behaviours during a period of national lockdown in England and Wales
• Polygenic Risk Scores for Asthma and Allergic Disease Predict COVID-19 Severity in 9/11 Responders -

  Background. Genetic factors contribute to individual differences in the severity of coronavirus disease 2019 (COVID-19). A portion of genetic predisposition can be captured using polygenic risk scores (PRS). Relatively little is known about the associations between PRS and COVID-19 severity or post-acute COVID-19 in community-dwelling individuals. Methods. Participants in this study were 983 World Trade Center responders infected for the first time with SARS-CoV-2 (mean age at infection=56.06, standard deviation [SD]=7.37, 918 (93.4%) male, 813 (82.7%) European ancestry). Seventy-five (7.6%) responders were in the severe COVID-19 category, that included hospitalization and other adverse outcomes; 306 (31.1%) reported at least one post-acute COVID-19 symptom at the 4-week follow-up. Analyses were adjusted for population stratification and demographic covariates. Findings. In responders with European ancestry, the asthma PRS was associated with severe COVID-19 category (odds ratio [OR]=1.61, 95% confidence interval: 1.17-2.21) and more severe COVID-19 symptomatology (β=.09, p=.01), independently of respiratory disease diagnosis. The allergic disease PRS similarly associated with severe COVID-19 category (OR=1.97, [1.26-3.07]). The PRS for COVID-19 hospitalization was associated with the risk of severe COVID-19 category (OR=1.35, [1.01-1.82]), but this association was smaller than for the asthma PRS. PRS for coronary artery disease and type II diabetes were not associated with COVID-19 severity. Interpretation. Taken together, the results indicate that recently developed polygenic biomarkers for asthma, allergic disease, and COVID-19 hospitalization capture some of the individual differences in severity and clinical course of COVID-19 illness in a community population. Funding. National Institute for Occupational Safety and Health, CDC.

  🖺 Full Text HTML: Polygenic Risk Scores for Asthma and Allergic Disease Predict COVID-19 Severity in 9/11 Responders
• Can SARS-CoV-2 transmit from a dead body? -
  Although it has been 2.5 years since the COVID-19 pandemic began, the transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a dead infected body remains unclear, and often, in Japan bereaved family members are not allowed to view in-person a loved one who has died from COVID-19. In this study, we analyzed the possibility of SARS-CoV-2 transmission from a dead body by using the hamster model. We also analyzed the effect of Angel-care–in which the pharynx, nostril, and rectum are plugged–and embalming on reducing transmissibility from dead bodies. We found that SARS-CoV-2 could be transmitted from the body of animals that died within a few days of infection; however, Angel-care and embalming were effective in preventing transmission from the dead body. These results suggest that protection from infection is essential when in contact with a SARS-CoV-2-infected dead body, and that sealing the cavities of a dead body is an important infection control step if embalming is not done.
  🖺 Full Text HTML: Can SARS-CoV-2 transmit from a dead body?
• Molecular fate-mapping of serum antibodies reveals the effects of antigenic imprinting on repeated immunization -
  The ability of serum antibody to protect against pathogens arises from the interplay of antigen-specific B cell clones of different affinities and fine specificities. These cellular dynamics are ultimately responsible for serum-level phenomena such as antibody imprinting or “Original Antigenic Sin” (OAS), a proposed propensity of the immune system to rely repeatedly on the first cohort of B cells that responded to a stimulus upon exposure to related antigens. Imprinting/OAS is thought to pose a barrier to vaccination against rapidly evolving viruses such as influenza and SARS-CoV-2. Precise measurement of the extent to which imprinting/OAS inhibits the recruitment of new B cell clones by boosting is challenging because cellular and temporal origins cannot readily be assigned to antibodies in circulation. Thus, the extent to which imprinting/OAS impacts the induction of new responses in various settings remains unclear. To address this, we developed a “molecular fate-mapping” approach in which serum antibodies derived from specific cohorts of B cells can be differentially detected. We show that, upon sequential homologous boosting, the serum antibody response strongly favors reuse of the first cohort of B cell clones over the recruitment of new, naive-derived B cells. This “primary addiction” decreases as a function of antigenic distance, allowing secondary immunization with divergent influenza virus or SARS-CoV-2 glycoproteins to overcome imprinting/OAS by targeting novel epitopes absent from the priming variant. Our findings have implications for the understanding of imprinting/OAS, and for the design and testing of vaccines aimed at eliciting antibodies to evolving antigens.
  🖺 Full Text HTML: Molecular fate-mapping of serum antibodies reveals the effects of antigenic imprinting on repeated immunization
• Differences in anti-viral immune responses in individuals of Indian and European origin: relevance for the COVID-19 pandemic -
  During the COVID-19 pandemic, large differences in susceptibility and mortality due to SARS-CoV-2 infection have been reported between populations in Europe and South Asia. While both host and environmental factors (including BCG vaccination) have been proposed to explain this, the potential biological substrate of these differences is unknown. We purified peripheral blood mononuclear cells from individuals living in India and the Netherlands at baseline and 10-12 weeks after BCG vaccination. We compared chromatin accessibility between the two populations at baseline, as well as gene transcription profiles and cytokine production capacities upon viral stimulation with influenza and SARS-CoV-2. The chromatin accessibility of genes important for adaptive immunity was higher in Indians compared to Europeans, while the latter had more accessible chromatin regions in genes of the innate immune system. At the transcriptional level, we observed that Indian volunteers displayed a more tolerant immune response to viral stimulation, in contrast to a more exaggerated response in Europeans. BCG vaccination strengthened the tolerance program in Indians, but not in Europeans. These differences may partly explain the different impact of COVID-19 on the two populations.
  🖺 Full Text HTML: Differences in anti-viral immune responses in individuals of Indian and European origin: relevance for the COVID-19 pandemic
• Insights into COVID-19 epidemiology and control from temporal changes in serial interval distributions in Hong Kong -

  The serial interval distribution is used to approximate the generation time distribution, an essential parameter to predict the effective reproductive number “R_t”, a measure of transmissibility. However, serial interval distributions may change as an epidemic progresses rather than remaining constant. Here we show that serial intervals in Hong Kong varied over time, closely associated with the temporal variation in COVID-19 case profiles and public health and social measures that were implemented in response to surges in community transmission. Quantification of the variation over time in serial intervals led to improved estimation of R_t, and provided additional insights into the impact of public health measures on transmission of infections.

  🖺 Full Text HTML: Insights into COVID-19 epidemiology and control from temporal changes in serial interval distributions in Hong Kong
• UB-612 Multitope Vaccine Targeting SARS-CoV-2 Spike and Non-Spike Proteins Provides Broad and Durable Immune Responses -

  IRBThe SARS-CoV-2 non-Spike (S) structural protein targets of nucleocapsid (N), membrane (M) and envelope (E), critical in the host cell interferon response and memory T-cell immunity, have been grossly overlooked since the inception of COVID vaccine development. To pursue a universal (pan-sarbecovirus) vaccine against ever-emergent future mutants, we explored booster immunogenicity of UB-612, a multitope-vaccine that contains S1-RBD-sFc protein and sequence-conserved rationally designed promiscuous Th and CTL epitope peptides on the Sarbecovirus N, M and S2 proteins. To a subpopulation of infection-free participants (aged 18-85 years) involved in a two-dose Phase-2 trial, a UB-612 booster (third dose) was administered 6-8 months after the second dose. The immunogenicity was evaluated at 14 days post-booster with overall safety monitored until the end of study. The booster induced high viral-neutralizing antibodies against live Wuhan WT (VNT50, 1,711) and Delta (VNT50, 1,282); and against pseudovirus WT (pVNT50, 11,167) vs. Omicron BA.1/BA.2/BA.5 variants (pVNT50, 2,314/1,890/854), respectively. The lower primary neutralizing antibodies in the elderly were uplifted upon boosting to approximately the same high level in young adults. UB-612 also induced potent, durable Th1-oriented (IFN-γ+-) responses (peak/pre-boost/post-boost SFU/106 PBMCs, 374/261/444) along with robust presence of cytotoxic CD8+ T cells (peak/pre-boost/post-boost CD107a+-Granzyme B+, 3.6%/1.8%/1.8%). Booster vaccination is safe and well tolerated without SAEs. By recognition against epitopes on Spike (S1-RBD and S2) and non-Spike (N and M) structure proteins, UB-612 provides potent, broad and long-lasting B-cell and T-cell memory immunity and offers a potential as a universal vaccine to fend off Omicrons and new VoCs.

  🖺 Full Text HTML: UB-612 Multitope Vaccine Targeting SARS-CoV-2 Spike and Non-Spike Proteins Provides Broad and Durable Immune Responses
• The effect of variation of individual infectiousness on SARS-CoV-2 transmission in households -

  Quantifying variation of individual infectiousness is critical to inform disease control. Previous studies reported substantial heterogeneity in transmission of many infectious diseases (including SARS-CoV-2). However, those results are difficult to interpret since the number of contacts is rarely considered in such approaches. Here, we analyze data from 17 SARS-CoV-2 household transmission studies conducted in periods dominated by ancestral strains, in which the number of contacts was known. By fitting individual-based household transmission models to these data, accounting for number of contacts and baseline transmission probabilities, the pooled estimate suggests that the 20% most infectious cases have 3.1-fold (95% confidence interval: 2.2-4.2 fold) higher infectiousness than average cases, which is consistent with the observed heterogeneity in viral shedding. Household data can inform the estimation of transmission heterogeneity, which is important for epidemic management.

  🖺 Full Text HTML: The effect of variation of individual infectiousness on SARS-CoV-2 transmission in households
• GHSI COVID-19 puzzle: did highly developed countries indeed fare worse? -

  Global Health Security Index (GHSI) categories are formulated to assess the capacity of world countries to deal with infectious disease risks. Thus, higher values of these indices were expected to translate to lower COVID-19 severity. However, it turned out to be the opposite, surprisingly suggesting that higher estimated country preparedness to epidemics may lead to higher disease mortality. To address this puzzle, we: i) use a model-derived measure of COVID-19 severity; ii) employ a range of statistical learning approaches, including non-parametric machine learning methods; iii) consider the overall excess mortality, in addition to official COVID-19 fatality counts. Our results suggest that the puzzle is, to a large extent, an artifact of oversimplified data analysis and a consequence of misclassified COVID-19 deaths, combined with the higher median age of the population and earlier epidemics onset in countries with high GHSI scores.

  🖺 Full Text HTML: GHSI COVID-19 puzzle: did highly developed countries indeed fare worse?
• Organizational impact of an ID NOW COVID-19 point-of-care testing for SARS-CoV2 detection in a maternity ward -

  Background SARS-CoV-2 has been responsible for more than 550 million cases of COVID-19 worldwide. RT-PCR is considered the gold standard for the diagnosis of patients suspected of having COVID-19. During the heightened waves of the pandemic, more rapid tests have been required. Point-of-care tests (POCT) for COVID-19 include antigen tests, serological tests, and other molecular-based platforms. The ID NOW COVID-19 assay (Abbott) performs an isothermal gene amplification of a target encoding the RNA-dependent RNA polymerase of SARSCoV-2. The main objective of this study was to evaluate the organizational impact following the implementation of a POC testing platform ID NOW in a maternity ward. Materials and Methods This retrospective study included pregnant women admitted for Groupe Hospitalier Paris Saint- Joseph Paris. The study was conducted over 2 periods lasting 6 months each. The first period (P1) corresponded to the 2nd wave in France (July to December 2020) whereas the second (P2) period focused on the 3rd wave (February to July 2021). During P1, viral detection was performed by RT-PCR at the laboratory. During P2, it was performed with the ID NOW COVID-19 test directly in the delivery room by nursing staff after training and certification. Our primary endpoint was the length of time in the birth room from admission to discharge in the postpartum period. Results 2447 pregnant women were included, 1053 during P1 and 1394 during P2. The median age, percentage of singleton pregnancies, mean gestational age, percentage of nulliparous individuals, percentage of vaginal deliveries, and COVID19 positivity rate were comparable between the two periods. During P2, the length of stay in the delivery room was significantly shorter than during P1 (17.9 vs 14.7 hours, p<0.001). Conclusion Analysis of the data from this study following the implementation of the ID NOW POCT in the maternity ward indicates a significant decrease in the length of stay in the birth room. This outcome needs to be confirmed in a multicenter cohort, in particular to precise the specific impact of COVID-19 care on delays.

  🖺 Full Text HTML: Organizational impact of an ID NOW COVID-19 point-of-care testing for SARS-CoV2 detection in a maternity ward
• A Computational Pipeline to Identify and Characterize Binding Sites and Interacting Chemotypes in SARS-CoV-2 -
  Minimizing the human and economic costs of the COVID-19 pandemic and of future pandemics requires the ability to develop and deploy effective treatments for novel pathogens as soon as possible after they emerge. To this end, we introduce a unique, computational pipeline for the rapid identification and characterization of binding sites in the proteins of novel viruses as well as the core chemical components with which these sites interact. We combine molecular-level structural modeling of proteins with clustering and cheminformatic techniques in a computationally efficient manner. Similarities between our results, experimental data, and other computational studies provide support for the effectiveness of our predictive framework. While we present here a demonstration of our tool on SARS-CoV-2, our process is generalizable and can be applied to any new virus, as long as either experimentally solved structures for its proteins are available or sufficiently accurate homology models can be constructed.
  🖺 Full Text HTML: A Computational Pipeline to Identify and Characterize Binding Sites and Interacting Chemotypes in SARS-CoV-2
• Towards a new stable state: Equitably assessing trainee writing productivity post-COVID-19 -
  The current academic ‘ecosystem’ prioritizes publications and has remained in this stable state despite increasing calls for change. Although writing is a strong determinant of academic success, certain groups may experience publishing barriers that may be amplified by disruptive events like the COVID-19 pandemic. Here we surveyed 342 graduate students and postdoctoral scholars to assess (1) how identity predicted publishing outputs and (2) how the pandemic influenced feelings of writing productivity based on identity. We show that there were differential publication totals across identities. Respondents reported feeling less productive and motivated during the pandemic, despite having more time to write. BIPOC graduate students reported being the most negatively impacted. Since the pandemic disproportionately affected historically excluded groups, we urge the academic ‘ecosystem’ to transition away from an overemphasis on publication outputs and reach a new, more equitable stable state that evaluates accomplishments more holistically.
  🖺 Full Text HTML: Towards a new stable state: Equitably assessing trainee writing productivity post-COVID-19

From Clinical Trials

• A Clinical Study to Evaluate the Efficacy and Safety of SIM0417 Orally Co-Administered With Ritonavir in Symptomatic Adult Participants With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: SIM0417;   Drug: Placebo
  Sponsor:   Jiangsu Simcere Pharmaceutical Co., Ltd.
  Not yet recruiting

• Self-management of Post COVID-19 Syndrome Using Wearable Biometric Technology - Condition:   COVID-19
  Intervention:   Other: Self-management of post COVID-19 respiratory outcomes
  Sponsor:   University of Manitoba
  Not yet recruiting

• The Role of BCG Vaccine in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 Vaccines - Condition:   COVID-19
  Interventions:   Biological: BCG (Bacillus Calmette-Guérin) vaccine;   Other: Placebo
  Sponsors:   Oswaldo Cruz Foundation;   University of Sao Paulo;   Federal University of Juiz de Fora
  Recruiting

• Performance Evaluation of LumiraDx COVID-19 (SARS-CoV-2) Ag ULTRA Test (ASPIRE-2) - Condition:   COVID-19
  Interventions:   Diagnostic Test: Nasal Swab;   Diagnostic Test: Nasopharyngeal swab
  Sponsor:   LumiraDx UK Limited
  Recruiting

• A Novel Parameter LIT/N That Predicts Survival in COVID-19 ICU Patients - Condition:   COVID-19 Pneumonia
  Intervention:   Diagnostic Test: the LIT test
  Sponsors:   Gazi University;   Oxford MediStress
  Completed

• Phase 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults. - Condition:   COVID-19
  Intervention:   Drug: Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine, SARS-CoV-2 rS (CovovaxTM), BNT162b2 (Pfizer)
  Sponsors:   The Aurum Institute NPC;   Coalition for Epidemic Preparedness Innovations
  Recruiting

• UNAIR Inactivated COVID-19 Vaccine Phase III (Immunobridging Study) - Conditions:   COVID-19 Pandemic;   COVID-19 Vaccines
  Interventions:   Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg;   Biological: CoronaVac Biofarma COVID-19 Vaccine
  Sponsors:   Dr. Soetomo General Hospital;   Indonesia-MoH;   Universitas Airlangga;   Biotis Pharmaceuticals, Indonesia
  Recruiting

• Hydrogen-Oxygen Generator With Nebulizer for Rehabilitation Treatment of COVID-19 - Conditions:   COVID-19;   AMS-H-03;   Hydrogen-oxygen Gas
  Interventions:   Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03;   Other: basic treatment
  Sponsor:   Shanghai Zhongshan Hospital
  Recruiting

• COVID Protection After Transplant - Sanofi GSK (CPAT-SG) Study - Conditions:   COVID-19;   Kidney Transplant
  Intervention:   Biological: Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine
  Sponsors:   National Institute of Allergy and Infectious Diseases (NIAID);   PPD;   Johns Hopkins University;   Sanofi Pasteur, a Sanofi Company
  Not yet recruiting

• Safety and Immunogenicity of COVID-19 Vaccine, AdCLD-CoV19-1 - Conditions:   COVID-19;   Vaccines
  Intervention:   Biological: AdCLD-CoV19-1
  Sponsors:   International Vaccine Institute;   Cellid Co., Ltd.
  Not yet recruiting

• Canadian Adaptive Platform Trial for Long COVID - Condition:   Long COVID, Post COVID Condition, Post Acute Sequelae of COVID-19
  Interventions:   Drug: Ibudilast;   Dietary Supplement: Whey Protein Isolate;   Drug: Pentoxifylline;   Other: Placebo
  Sponsor:   University Health Network, Toronto
  Not yet recruiting

• Clinical Trial of Jinzhen Oral Liquid in Treating Children With COVID-19 Infection - Conditions:   COVID-19;   Child, Only
  Intervention:   Drug: Jinzhen oral liquid or Jinhuaqinggan granules
  Sponsor:   The Affiliated Hospital of Qingdao University
  Recruiting

• Smartphone Intervention for Overdose and COVID-19 - Conditions:   Substance Use Disorders;   Overdose;   COVID-19
  Intervention:   Device: iThrive WI Intervention
  Sponsors:   University of Wisconsin, Madison;   National Institute on Drug Abuse (NIDA)
  Not yet recruiting

• Phase 2 Study of the Safety and Immunogenicity of COVID-19 and Influenza Combination Vaccine - Conditions:   COVID-19;   Influenza
  Interventions:   Drug: CIC Vaccine;   Drug: qNIV Vaccine;   Drug: SARS-CoV-2 rS Vaccine;   Drug: Influenza Vaccine
  Sponsor:   Novavax
  Not yet recruiting

• Study to Assess Efficacy and Safety of Treamid for Patients With Reduced Exercise Tolerance After COVID-19 - Conditions:   SARS-CoV-2 Infection;   Lung Fibrosis
  Interventions:   Drug: Treamid;   Drug: Treamid twice a day;   Drug: Treamid once a day;   Drug: Placebo
  Sponsor:   PHARMENTERPRISES LLC
  Not yet recruiting

From PubMed

• Homologous and Heterologous Boosting of the Chadox1-S1-S COVID-19 Vaccine With the SCB-2019 Vaccine Candidate: A Randomized, Controlled, Phase 2 Study - CONCLUSIONS: Boosting ChAdOx1-S-primed adults with SCB-2019 induced higher levels of antibodies against a wild-type strain and SARS-CoV-2 variants than a homologous ChAdOx1-S booster, with the highest responses being with the 30-μg SCB-2019 + CpG + aluminium hydroxide formulation.

• 5-HT/CGRP pathway and Sumatriptan role in Covid-19 - Coronavirus disease 2019 (Covid-19) is a pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In Covid-19, there is uncontrolled activation of immune cells with a massive release of pro-inflammatory cytokines and the development of cytokine storm. These inflammatory changes induce impairment of different organ functions, including the central nervous system (CNS), leading to acute brain injury and substantial changes in the neurotransmitters, including serotonin…

• A potent neutralizing antibody provides protection against SARS-CoV-2 Omicron and Delta variants via nasal delivery - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still rapidly spreading worldwide. Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 infections. However, the emergence of SARS-CoV-2 variants of concern (VOCs), such as Delta (B.1.617.2) and the recently emerged Omicron (B.1.1.529), has seriously challenged the application of current therapeutics. Therefore, there is still a pressing need for identification of…

• Brequinar and dipyridamole in combination exhibits synergistic antiviral activity against SARS-CoV-2 in vitro: Rationale for a host-acting antiviral treatment strategy for COVID-19 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the associated global pandemic resulting in >400 million infections worldwide and several million deaths. The continued evolution of SARS-CoV-2 to potentially evade vaccines and monoclonal antibody (mAb)-based therapies and the limited number of authorized small-molecule antivirals necessitates the need for development of new drug treatments. There remains an unmet…

• Nafamostat Mesylate for Treatment of COVID-19 in Hospitalised Patients: A Structured, Narrative Review - The search for clinically effective antivirals against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is ongoing. Repurposing of drugs licensed for non-coronavirus disease 2019 (COVID-19) indications has been extensively investigated in laboratory models and in clinical studies with mixed results. Nafamostat mesylate (nafamostat) is a drug licensed in Japan and Korea for indications including acute pancreatitis and disseminated intravascular coagulation. It is available only…

• Crystal structure of SARS-CoV-2 nsp10-nsp16 in complex with small molecule inhibitors, SS148 and WZ16 - SARS-CoV-2 nsp10-nsp16 complex is a 2’-O-methyltransferase (MTase) involved in viral RNA capping, enabling the virus to evade the immune system in humans. It has been considered a valuable target in the discovery of antiviral therapeutics, as the RNA cap formation is crucial for viral propagation. Through cross-screening of the inhibitors that we previously reported for SARS-CoV-2 nsp14 MTase activity against nsp10-nsp16 complex, we identified two compounds (SS148 and WZ16) that also inhibited…

• Human Claudin-Derived Peptides Block the Membrane Fusion Process of Zika Virus and Are Broad Flavivirus Inhibitors - Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged in the Pacific islands in 2007 and spread to the Americas in 2015. The infection remains asymptomatic in most cases but can be associated with severe neurological disorders. Despite massive efforts, no specific drug or vaccine against ZIKV infection is available to date. Claudins are tight-junction proteins that favor the entry of several flaviviruses, including ZIKV. In this study, we identified two peptides derived from the…

• Peptidomimetic Small-Molecule Inhibitors of 3CLPro Activity and Spike-ACE2 Interaction: Toward Dual-Action Molecules against Coronavirus Infections - The development of molecules able to target protein-protein interactions (PPIs) is of interest for the development of novel therapeutic agents. Since a high percentage of PPIs are mediated by α-helical structure at the interacting surface, peptidomimetics that reproduce the essential conformational components of helices are useful templates for the development of PPIs inhibitors. In this work, the synthesis of a constrained dipeptide isostere and insertion in the short peptide epitope EDLFYQ of…

• Nonstructural Protein 1 of Variant PEDV Plays a Key Role in Escaping Replication Restriction by Complement C3 - Zoonotic coronaviruses represent an ongoing threat to public health. The classical porcine epidemic diarrhea virus (PEDV) first appeared in the early 1970s. Since 2010, outbreaks of highly virulent PEDV variants have caused great economic losses to the swine industry worldwide. However, the strategies by which PEDV variants escape host immune responses are not fully understood. Complement component 3 (C3) is considered a central component of the three complement activation pathways and plays a…

• Anti-viral organic coatings for high touch surfaces based on smart-release, Cu²⁺ containing pigments - Viruses such as SARS-CoV-2 can remain viable on solid surfaces for up to one week, hence fomites are a potential route of exposure to infectious virus. Copper has well documented antiviral properties that could limit this problem, however practical deployment of copper surfaces has been limited due to the associated costs and the incompatibility of copper metal in specific environments and conditions. We therefore developed an organic coating containing an intelligent-release Cu^(2+) pigment…

• The motivations and their conditions which drive students to seek higher education in a foreign country - This article summarizes a vast literature tracing the plethora of motivations of international students to study abroad. We detail the push factors (i.e., personal goals) and pull factors (i.e., attracting elements) for this decision to pursue higher education overseas. To elaborate, the push factors are around the attainment and/or increase of three main capitals: human, financial and psychological. Pull factors are around the attracting capacity of three main entities: the destination country,…

• Exploring the mechanism of action of Xuanfei Baidu granule (XFBD) in the treatment of COVID-19 based on molecular docking and molecular dynamics - CONCLUSION: For the first time, it was found that the important active chemical components in XFBD, such as I-SPD, Pachypodol and Vestitol, reduce inflammatory response and apoptosis by inhibiting the activation of NLRP3, and reduce the production of inflammatory factors and chemotaxis of inflammatory cells by inhibiting the activation of CSF2. Therefore, XFBD can effectively alleviate the clinical symptoms of COVID-19 through NLRP3 and CSF2.

• Complanatuside alleviates inflammatory cell damage induced by pro-inflammatory cytokines in skin keratinocytes - Cytokine-mediated inflammatory response is considered a cause of skin lesion in COVID-19 patients. Complanatuside is a flavonol glycoside isolated from Astragalus complanatus. Flavonoids from Astragalus complanatus were reported to have anti-inflammatory and anticancer activities but the potential protective effect of complanatuside on cytokine-induced inflammatory damage in skin keratinocytes is not known. The aim of this study is to explore the inhibitory effect of complanatuside on…

• Probiotic-Based Bacteriocin: Immunity Supplementation Against Viruses. An Updated Review - Viral infections are a major cause of severe, fatal diseases worldwide. Recently, these infections have increased due to demanding contextual circumstances, such as environmental changes, increased migration of people and product distribution, rapid demographic changes, and outbreaks of novel viruses, including the COVID-19 outbreak. Internal variables that influence viral immunity have received attention along with these external causes to avert such novel viral outbreaks. The gastrointestinal…

• Synthesis, characterization, DFT, antioxidant, antibacterial, pharmacokinetics and inhibition of SARS-CoV-2 main protease of some heterocyclic hydrazones - Three hydrazone derivatives have been synthesized using condensation reaction of 4-hydrazinylbenzoic acid with three aromatic aldehydes namely: thiophene-2-carbaldehyde, thiophene-3-carbaldehyde and 2-furaldehyde in ethanol at 78 °C reflux. The synthesized molecules have been characterized using spectroscopic and physicochemical methods including UV-Vis, IR, ¹H NMR, ^(13)C NMR, ^(15)N NMR and melting point determination. Optimized molecular structures, UV-Vis and IR spectra modeling, the…

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