Covid-19 Sentry

Contents

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

From Preprints

• Gene amplification acts as a molecular foothold to facilitate cross-species adaptation and evasion of multiple antiviral pathways -
  Cross-species spillover events are responsible for many of the pandemics in human history including COVID-19; however, the evolutionary mechanisms that enable these events are poorly understood. We have previously modeled this process using a chimeric vaccinia virus expressing the rhesus cytomegalovirus-derived PKR antagonist RhTRS1 in place of its native PKR antagonists; E3L and K3L (VACV{delta}E{delta}K+RhTRS1). Using this virus, we demonstrated that gene amplification of rhtrs1 occurred early during experimental evolution and was sufficient to fully rescue virus replication in partially resistant African green monkey (AGM) fibroblasts. Notably, this rapid gene amplification also allowed limited virus replication in otherwise completely non-permissive human fibroblasts, suggesting that gene amplification may act as a ‘’molecular foothold’’ to facilitate viral adaptation to multiple species. In this study, we demonstrate that there are multiple barriers to VACV{delta}E{delta}K+RhTRS1 replication in human cells, mediated by both PKR and RNase L. We experimentally evolved three AGM-adapted virus populations in human fibroblasts. Each population adapted to human cells bimodally, via an initial 10-fold increase in replication after only two passages followed by a second 10-fold increase in replication by passage nine. Using our Illumina-based pipeline, we found that some SNPs which had evolved during the prior AGM adaptation were rapidly lost, while 13 single-base substitutions and short indels increased over time, including two SNPs unique to HFF adapted populations. Many of these changes were associated with components of the viral RNA polymerase, although no variant was shared between all three populations. Taken together, our results demonstrate that rhtrs1 amplification was sufficient to increase viral tropism after passage in an ‘’intermediate species’’ and subsequently enabled the virus to adopt different, species-specific adaptive mechanisms to overcome distinct barriers to viral replication in AGM and human cells.
  🖺 Full Text HTML: Gene amplification acts as a molecular foothold to facilitate cross-species adaptation and evasion of multiple antiviral pathways
• Design and Immunogenicity of SARS-CoV-2 DNA vaccine encoding RBD-PVXCP fusion protein -
  The potential of immune evasive mutations accumulation of the SARS-CoV-2 virus has led to its rapid spread causing over 600 million confirmed cases and more than 6.5 million confirmed deaths. Huge demand for the rapid development and deployment of low-cost and effective vaccines against emerging variants renews interest in DNA vaccine technology. Here we report a rapid generation and immunological evaluation of novel DNA vaccine candidates against Wuhan-Hu-1 and Omicron variants, based on the RBD protein fused with the Potato virus X coat protein (PVXCP). Delivery of DNA vaccines using electroporation in a two-doses regimen induced high antibody titers and profound cellular response in mice. Antibody titers induced against Omicron variant of the vaccine were sufficient for the effective protection against both the Omicron and Wuhan-Hu-1 virus infections. PVXCP protein in the vaccine construct shifted immune response to the favorable Th1-like type and provided oligomerization of RBD-PVXCP protein. A naked DNA delivery by the needle-free injection device allowed us to achieve antibody titers comparable with the mRNA-LNP delivery in rabbits. This data identifies the RBD-PVXCP DNA vaccine platform as a promising solution for robust and effective SARS-CoV-2 protection, supporting further translational study.
  🖺 Full Text HTML: Design and Immunogenicity of SARS-CoV-2 DNA vaccine encoding RBD-PVXCP fusion protein
• Long-term passaging of replication competent pseudo-typed SARS-CoV-2 reveals the antiviral breadth of monoclonal and bispecific antibody cocktails -
  The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses challenges to the effectiveness of neutralizing antibodies. Rational design of antibody cocktails is a realizable approach addressing viral immune evasion. However, evaluating the breadth of antibody cocktails is essential for understanding the development potential. Here, based on a replication competent vesicular stomatitis virus model that incorporates the spike of SARS-CoV-2 (VSV-SARS-CoV-2), we evaluated the breadth of a number of antibody cocktails consisting of monoclonal antibodies and bispecific antibodies by long-term passaging the virus in the presence of the cocktails. Results from over two-month passaging of the virus showed that 9E12+10D4+2G1 and 7B9-9D11+2G1 from these cocktails were highly resistant to random mutation, and there was no breakthrough after 30 rounds of passaging. As a control, antibody REGN10933 was broken through in the third passage. Next generation sequencing was performed and several critical mutations related to viral evasion were identified. These mutations caused a decrease in neutralization efficiency, but the reduced replication rate and ACE2 susceptibility of the mutant virus suggested that they might not have the potential to become epidemic strains. The 9E12+10D4+2G1 and 7B9-9D11+2G1 cocktails that picked from the VSV-SARS-CoV-2 system efficiently neutralized all current variants of concern and variants of interest including the most recent variants Delta and Omicron, as well as SARS-CoV-1. Our results highlight the feasibility of using the VSV-SARS-CoV-2 system to develop SARS-CoV-2 antibody cocktails and provide a reference for the clinical selection of therapeutic strategies to address the mutational escape of SARS-CoV-2.
  🖺 Full Text HTML: Long-term passaging of replication competent pseudo-typed SARS-CoV-2 reveals the antiviral breadth of monoclonal and bispecific antibody cocktails
• Is The Stalk of the SARS-CoV-2 Spike Protein Druggable? -
  The SARS-CoV-2 virus spike protein (SP) is the vector of the virus infectivity. The high propensity to mutate in key regions responsible for the recognition of the human angiotensin-converting enzyme 2 (hACE2) or the antibodies produced by the immune system following infection or vaccination makes subunit 1 of the SP a difficult to target and, to date, efforts have not delivered any ACE2 binding inhibitor yet. The inherent flexibility of the stalk region, within subunit S2, is key to SARS-CoV-2 high infectivity because it facilitates the receptor binding domain encounter with ACE2. Thus, it could be a valuable therapeutic target. By employing a fragment-based strategy, we computationally studied the druggability of the conserved part of the SP stalk by means of an integrated approach that combines molecular docking with high-throughput molecular dynamics simulations. Our results suggest that the druggability of the stalk is challenging and provide the structural basis for such difficulty.
  🖺 Full Text HTML: Is The Stalk of the SARS-CoV-2 Spike Protein Druggable?
• Digital Omicron Detection using Unscripted Voice Samples from Social Media -

  The success of artificial intelligence in clinical environments relies upon the diversity and availability of training data. In some cases, social media data may be used to counterbalance the limited amount of accessible, well-curated clinical data, but this possibility remains largely unexplored. In this study, we mined YouTube to collect voice data from individuals with self- declared positive COVID-19 tests during time periods in which Omicron was the predominant variant, while also sampling non-Omicron COVID-19 variants, other upper respiratory infections (URI), and healthy subjects. The resulting dataset was used to train a DenseNet model to detect the Omicron variant from voice changes. Our model achieved 0.85/0.80 sensitivity/specificity in separating Omicron samples from healthy samples and 0.76/0.70 sensitivity/specificity in separating Omicron samples from symptomatic non-COVID samples. In comparison with past studies, which used scripted voice samples, we showed that leveraging the intra-sample variance inherent to unscripted speech enhanced generalization. Our work introduced novel design paradigms for audio-based diagnostic tools and established the potential of social media data to train digital diagnostic models suitable for real-world deployment.

  🖺 Full Text HTML: Digital Omicron Detection using Unscripted Voice Samples from Social Media
• Evaluation of the Abbott PanbioTM COVID-19 antigen detection rapid diagnostic test among healthcare workers in elderly care -

  Background Coronavirus disease 2019 (COVID-19) has been especially dangerous for elderly people. To reduce the risk of transmission from healthcare workers to elderly people, it is of utmost importance to detect possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive healthcare workers as early as possible. We aimed to determine whether the Abbott PanbioTM COVID-19 antigen detection rapid diagnostic test (Ag-RDT) could be used as an alternative to reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The second aim was to compare the cycle threshold (Ct) in RT-qPCR with the results of the Ag-RDT. Methods A prospective diagnostic evaluation of the Abbott PanbioTM COVID-19 Ag-RDT among healthcare workers across three elderly care facilities as well as home-based elderly care workers who met clinical criteria for COVID-19 during the second wave of the COVID-19 pandemic. Per healthcare worker, the first nasopharyngeal swab was obtained to perform the Ag-RDT and the second swab for RT-qPCR. A Ct-value of < 40 was interpreted as positive, ≥ 40 as negative. Results A total of 683 healthcare workers with COVID-19 symptoms were sampled for detection of SARS-CoV-2 by both Ag-RDT and RT-qPCR. Sixty-three healthcare workers (9.2%) tested positive for SARS-CoV-2 by RT-qPCR. The overall sensitivity of Ag-RDT was 81.0% sensitivity (95%CI: 69.6-88.8%) and 100% specificity (95%CI: 99.4-100%). Using a cut-off Ct-value of 32, the sensitivity increased to 92.7% (95% CI: 82.7-97.1%). Negative Ag-RDT results were moderately associated with higher Ct-values (r = 0.62) compared to positive Ag-RDT results. Conclusion The PanbioTM COVID-19 Ag-RDT can be used to quickly detect positive SARS-CoV-2 healthcare workers. Negative Ag-RDT should be confirmed by RT-qPCR. In case of severe understaffing and with careful consideration, fully vaccinated healthcare workers with Ag-RDT negative results could work with a mask pending PCR results.

  🖺 Full Text HTML: Evaluation of the Abbott PanbioTM COVID-19 antigen detection rapid diagnostic test among healthcare workers in elderly care
• SARS-CoV-2 infection alkalinizes the ERGIC and lysosomes through the viroporin activity of the viral envelope protein -
  The coronavirus SARS-CoV-2, the agent of the deadly COVID-19 pandemic, is an enveloped virus propagating within the endocytic and secretory organelles of host mammalian cells. Enveloped viruses modify the ionic homeostasis of organelles to render their intra-luminal milieu permissive for viral entry, replication, and egress. Here, we show that infection of Vero E6 cells with the delta variant of the SARS-CoV-2 alkalinizes the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) as well as lysosomes, mimicking the effect of inhibitors of vacuolar proton ATPases. We further show the envelope protein of SARS-CoV-2 accumulates in the ERGIC when expressed in mammalian cells and selectively dissipates the ERGIC pH. This viroporin effect is not associated with acute cellular toxicity but is prevented by mutations within the channel pore of E. We conclude that the envelope protein acts as a proton channel in the ERGIC to mitigate the acidity of this intermediate compartment. The altered pH homeostasis of the ERGIC likely contributes to the virus fitness and pathogenicity, making the E channel an attractive drug target for the treatment of COVID-19.
  🖺 Full Text HTML: SARS-CoV-2 infection alkalinizes the ERGIC and lysosomes through the viroporin activity of the viral envelope protein
• Three-dose vaccination-induced immune responses protect against SARS-CoV-2 Omicron-BA.2 -
  Background: The ongoing outbreak of SARS-CoV-2 Omicron BA.2 infections in Hong Kong, the model city of universal masking of the world, has resulted in a major public health crisis. Although the third vaccination resulted in strong boosting of neutralization antibody, vaccine efficacy and corelates of immune protection against the major circulating Omicron BA.2 remains to be investigated. Methods: We investigated the vaccine efficacy against the Omicron BA.2 breakthrough infection among 470 public servants who had received different SARS-CoV-2 vaccine regimens including two-dose BNT162b2 (2xBNT, n=169), three-dose BNT162b2 (3xBNT, n=170), two-dose CoronaVac (2xCorV, n=34), three-dose CoronaVac (3xCorV, n=67) and third-dose BNT162b2 following 2xCorV (2xCorV+1BNT, n=32). Humoral and cellular immune responses after three-dose vaccination were further characterized and correlated with clinical characteristics of BA.2 infection. Findings: During the BA.2 outbreak, 27.7% vaccinees were infected. The timely third-dose vaccination provided significant protection with lower incidence rates of breakthrough infections (2xBNT 49.2% vs 3xBNT 13.1%, p<0.0001; 2xCorV 44.1% vs 3xCoV 19.4%, p=0.003). Investigation of immune response on blood samples derived from 92 subjects in three-dose vaccination cohorts collected before the BA.2 outbreak revealed that the third-dose vaccination activated spike (S)-specific memory B cells and Omicron cross-reactive T cell responses, which correlated with reduced frequencies of breakthrough infections and disease severity rather than with types of vaccines. Moreover, the frequency of S-specific activated memory B cells was significantly lower in infected vaccinees than uninfected vaccinees before vaccine-breakthrough infection whereas IFN-{gamma}+ CD4 T cells were negatively associated with age and viral clearance time. Critically, BA.2 breakthrough infection boosted cross-reactive memory B cells with enhanced cross-neutralizing antibodies to Omicron sublineages, including BA.2.12.1 and BA.4/5, in all vaccinees tested. Interpretation: Our results imply that the timely third vaccination and immune responses are likely required for vaccine-mediated protection against Omicron BA.2 pandemic. Although BA.2 conferred the highest neutralization resistance compared with variants of concern tested before the emergence of BA.2.12.1 and BA.4/5, the third dose vaccination-activated S-specific memory B cells and Omicron cross-reactive T cell responses contributed to reduced frequencies of breakthrough infection and disease severity. Neutralizing antibody potency enhanced by BA.2 breakthrough infection with previous 3 doses of vaccines (CoronaVac or BNT162b2) may reduce the risk for infection of ongoing BA.2.12.1 and BA.4/5.
  🖺 Full Text HTML: Three-dose vaccination-induced immune responses protect against SARS-CoV-2 Omicron-BA.2
• Vaccines alone cannot slow the evolution of SARS-CoV-2 -

  The rapid emergence of immune-evading viral variants of SARS-CoV-2 calls into question the practicality of a vaccine-only public health strategy for managing the ongoing COVID-19 pandemic. It has been suggested that widespread vaccination is necessary to prevent the emergence of future immune-evading mutants. Here we examine that proposition using stochastic computational models of viral transmission and mutation. Specifically, we look at the likelihood of emergence of immune escape variants requiring multiple mutations, and the impact of vaccination on this process. Our results suggest that the transmission rate of intermediate SARS-CoV-2 mutants will impact the rate at which novel immune-evading variants will appear. While vaccination can lower the rate at which new variants appear, other interventions that reduce transmission can also have the same effect. Crucially, relying solely on widespread and repeated vaccination (vaccinating the entire population multiple times a year) is not sufficient to prevent the emergence of novel immune-evading strains if transmission rates remain high within the population. Thus, vaccines alone are incapable of slowing the pace of evolution of immune evasion, and vaccinal protection against severe and fatal outcomes for COVID-19 patients is therefore not assured.

  🖺 Full Text HTML: Vaccines alone cannot slow the evolution of SARS-CoV-2
• Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose -

  The emergence of the SARS-CoV-2 Omicron sublineages resulted in drastically increased transmission rates and reduced protection from vaccine-induced immunity. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remains sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed worldwide, particularly in China, and South America. However, whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses and whether these responses vary across age groups remain unknown. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals in central and south America that received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccines. We found that both IgG levels against SARS-CoV-2 spike or RBD, as well as neutralization titers against Omicron sublineages, were substantially reduced in participants that received homologous CoronaVac when compared to heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients older than 50 years of age. In this group, CoronaVac booster induced low virus-specific IgG levels and failed to elevate their neutralization titers against any omicron sublineage. Our results point to significant inefficiency in mounting protective anti-viral humoral immunity in those who were primed with CoronaVac followed by CoronaVac booster, particularly among older adults, urging a heterologous regimen in high-risk populations fully vaccinated with CoronaVac.

  🖺 Full Text HTML: Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose
• Effectiveness and duration of a second COVID-19 vaccine booster -

  Using a prospective national cohort of 3.75 million individuals aged 20 or older, we evaluated the effectiveness against COVID-19 related ICU admissions and death of mRNA-based second vaccine boosters for four different three-dose background regimes: BNT162b2 primary series plus a homologous booster, and CoronaVac primary series plus an mRNA booster, a homologous booster, and a ChAdOx-1 booster. We estimated the vaccine effectiveness weekly from February 14 to August 15, 2022, by estimating hazard ratios of immunization over non-vaccination, accounting for relevant confounders. The overall adjusted effectiveness of a second mRNA booster shot was 88.2% (95%CI, 86.2-89.9) and 90.5% (95%CI 89.4-91.4) against ICU admissions and death, respectively. Vaccine effectiveness showed a mild decrease for all regimens and outcomes, probably associated with the introduction of BA.4 and BA.5 Omicron sub-lineages and immunity waning. The duration of effectiveness suggests that no additional boosters are needed six months following a second booster shot.

  🖺 Full Text HTML: Effectiveness and duration of a second COVID-19 vaccine booster
• Key performance indicators of COVID-19 contact tracing in Belgium from September 2020 to December 2021 -

  Background Contact tracing aims to prevent onward transmission of infectious diseases and data obtained during tracing provide unique information on transmission characteristics. A key performance indicator that has been proposed to evaluate contact tracing is the proportion of cases arising from known contacts. However, few empirical studies have investigated the effectiveness of contact tracing. Methods Using data collected between September 2020 and December 2021 in Belgium, we investigated the impact of contact tracing on SARS-CoV-2 transmission. We compared confirmed cases that were previously identified as a close contact to those that were not yet known, in terms of their traced contacts and secondary cases as well as the serial interval. In addition, we established contact and transmission patterns by age. Findings Previously traced, hence 9known9, cases comprised 20% of all cases and they were linked to relatively fewer close contacts as well as fewer secondary cases and a lower secondary attack rate compared to cases that were not already known. In addition we observed a shorter serial interval for 9known9 cases. There was a relative increase in transmission from children to adults during circulation of the Delta and Omicron variants, without an increase in the extent of contact between these age groups. Interpretation These results suggest that contact tracing in Belgium has been effective in reducing onward transmission and that individuals aware of their exposure to SARSCoV- 2 seemed more reserved in their social contact behaviour. Data from a reference period or region are needed to measure the impact of contact tracing in terms of the number of cases and deaths averted.

  🖺 Full Text HTML: Key performance indicators of COVID-19 contact tracing in Belgium from September 2020 to December 2021
• Potential use of Immunodaat (Botanical extract of Elderberry -Sambucus Nigra L.) in the management of Post Covid-19 symptoms- a comparative, multi-centric, randomized, clinical study -

  Background: Immunodaat, a proprietary botanical extract, contains a standardized extract of Elderberry (Sambucus Nigra L.). Elderberry is used as an immunity enhancer for the prevention and management of various respiratory diseases and as an antioxidant. Objectives: The present study evaluated the effect of Immunodaat, in Post Covid-19 recovery. Methods: An open-labeled, comparative, randomized, multi-centric, prospective clinical study was conducted on 74 subjects who had post-COVID-19 symptoms recovery from mild-moderate COVID-19 within the last 15 days. Subjects were divided equally, with 37 subjects in trial and control groups each, where subjects in the trial group were given Immunodaat capsules in a dose of 250 mg Capsules twice daily along with the standard care for COVID-19 for consecutive 30 days while subjects in the control group were given only the standard care for Post Covid. Subjects were evaluated for post-clinical recovery signs and symptoms (like cough, fatigue, Myalgia, Joint pain, confusion, altered mood, anxiety, insomnia, etc.) and lab parameters. Subjects were evaluated for quality of life using WHO QOL BREF. Results: Continuous 30 days of administration of Immunodaat showed a significant difference in reducing physical and mental symptoms compared to the control group. Also, a significant improvement in quality of life was observed on the WHO QOL BREF scale with Immunodaat compared to the control group. The overall quality of life, energy levels, and stamina levels improved with the use of Immunodaat. Subjects showed excellent tolerability and did not have any adverse effects with the use of Immunodaat. Conclusion: The study concludes that the use of Immunodaat over 30 days aided to normalize the physical and mental symptoms that occurred due to Post COVID and long COVID. Immunodaat can be considered a safe and effective natural ingredient in managing Post COVID-19 or long COVID conditions.

  🖺 Full Text HTML: Potential use of Immunodaat (Botanical extract of Elderberry -Sambucus Nigra L.) in the management of Post Covid-19 symptoms- a comparative, multi-centric, randomized, clinical study
• Low-dose IL-2 reduces IL-21+ T cells and induces a long-lived anti-inflammatory gene expression signature inversely modulated in COVID-19 patients -

  Despite early clinical successes, the mechanisms of action of low-dose interleukin-2 (LD-IL-2) immunotherapy remain only partly understood. Here, we examined the effects of interval administration of low-dose recombinant IL-2 (iLD-IL-2) using high-resolution, single-cell multiomics and flow cytometry. We confirmed that iLD-IL-2 selectively expands thymic-derived FOXP3+HELIOS+ Tregs and CD56br NK cells, and showed that treatment reduced the frequency of IL-21-producing CD4+ T cells and of two subsets of innate-like CD8+ T cells, mucosal-associated invariant T cells and Vγ9Vδ2 T cells. The cellular changes induced by LD-IL-2 were associated with an anti-inflammatory gene expression signature, which remains detectable in all T and NK cell subsets analysed one month after treatment. The anti-inflammatory nature of this gene expression signature was supported by the observation that the same genes were also modulated in COVID-19 patients, but in the opposite direction. These findings warrant continued investigations of the potential clinical benefits of iLD-IL-2 in immunotherapy and further understanding of the development of long-term sequelae in convalescent COVID-19 patients.

  🖺 Full Text HTML: Low-dose IL-2 reduces IL-21+ T cells and induces a long-lived anti-inflammatory gene expression signature inversely modulated in COVID-19 patients
• SARS-CoV-2 variants in the making: Sequential intrahost evolution and forward transmissions in the context of persistent infections -

  Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. Although intrahost evolution has been documented, to our knowledge, no direct evidence of subsequent transmission and stepwise adaptation is available. Here we describe sequential persistent SARS-CoV-2 infections in three individuals that led to the emergence, forward transmission, and continued evolution of a new Omicron sublineage, BA.1.23, over an eight-month period. The initially transmitted BA.1.23 variant encoded seven additional amino acid substitutions within the spike protein (E96D, R346T, L455W, K458M, A484V, H681R, A688V), and displayed substantial resistance to neutralization by sera from boosted and/or Omicron BA.1-infected study participants. Subsequent continued BA.1.23 replication resulted in additional substitutions in the spike protein (S254F, N448S, F456L, M458K, F981L, S982L) as well as in five other virus proteins. Our findings demonstrate that the Omicron BA.1 lineage can diverge further from its already exceptionally mutated genome during persistent infection in more than one host, and also document ongoing transmission of these novel variants. There is an urgent need to implement strategies to prevent prolonged SARS-CoV-2 replication and to limit the spread of newly emerging, neutralization-resistant variants in vulnerable patients.

  🖺 Full Text HTML: SARS-CoV-2 variants in the making: Sequential intrahost evolution and forward transmissions in the context of persistent infections

From Clinical Trials

• The Efficacy and Safety of TADIOS as an Adjuvant Therapy in Patients Diagnosed With Mild to Moderate COVID-19 - Condition:   COVID-19
  Interventions:   Drug: TADIOS;   Drug: Placebo
  Sponsor:   Helixmith Co., Ltd.
  Completed

• A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir - Condition:   COVID-19
  Interventions:   Drug: nirmatrelvir;   Drug: ritonavir;   Drug: placebo for nirmatrelvir
  Sponsor:   Pfizer
  Not yet recruiting

• COVID-19 iCura SARS-CoV-2 Ag OTC: Clinical Evaluation - Conditions:   SARS-CoV-2 Infection;   COVID-19
  Interventions:   Device: iCura COVID-19 Antigen Rapid Home Test;   Diagnostic Test: RT-PCR Test
  Sponsors:   EDP Biotech;   Paragon Rx Clinical, Inc.;   iCura Diagnostics, LLC
  Recruiting

• Study Evaluating Diltiazem in Combination With Standard Treatment in the Management of Patients Hospitalized With COVID-19 Pneumonia - Condition:   COVID-19
  Intervention:   Drug: DILTIAZEM TEVA 60 mg or placebo
  Sponsors:   Hospices Civils de Lyon;   Signia Therapeutics
  Not yet recruiting

• FMT for Post-acute COVID-19 Syndrome - Conditions:   Post-Acute COVID19 Syndrome;   COVID-19
  Intervention:   Procedure: Faecal Microbiota Transplantation
  Sponsor:   Chinese University of Hong Kong
  Recruiting

• COVID-19 Booster Dose Reminder/Recall for Adolescents - Condition:   COVID-19 Vaccines
  Intervention:   Behavioral: Reminder/Recall Sent Via Preferred Method of Communication
  Sponsor:   Marshfield Clinic Research Foundation
  Active, not recruiting

• VAX-MOM COVID-19: Increasing Maternal COVID-19 Vaccination - Conditions:   Immunization; Infection;   Pregnancy Related;   COVID-19
  Interventions:   Behavioral: VAX-MOM COVID-19 Intervention;   Other: Standard of Care
  Sponsors:   University of Rochester;   Centers for Disease Control and Prevention;   University of California, Los Angeles
  Not yet recruiting

• Research on Community Based ATK Test Study to Control Spread of COVID-19 in Migrant Community - Condition:   COVID-19 Pandemic
  Intervention:   Device: STANDARD Q COVID-19 Ag Test
  Sponsor:   University of Oxford
  Active, not recruiting

• Safety and Immunogenicity of COVID-19 Vaccine in Population Aged 18 Years and Above - Condition:   COVID-19
  Interventions:   Biological: low-dose LYB001;   Biological: Recombinant COVID-19 Vaccine (CHO Cell);   Biological: high-dose LYB001
  Sponsors:   Guangzhou Patronus Biotech Co., Ltd.;   Yantai Patronus Biotech Co., Ltd.
  Recruiting

• The Efficacy and Safety of BioBlock® Intranasally Administered Virus-Neutralizing Bovine Colostrum Nasal Spray in Preventing of COVID-19 (Coronavirus Disease-19) Infection in Healthy Volunteer Individuals - Condition:   SARS CoV 2 Infection
  Intervention:   Biological: BioBlock® antiviral nasal spray
  Sponsor:   Chemi-Pharm AS
  Recruiting

• Personalized Computerized Training Program for Cognitive Dysfunction After COVID-19 - Conditions:   Post-Acute COVID-19;   Long COVID
  Intervention:   Device: CogniFit’s CCT Post COVID-19
  Sponsor:   Universidad Antonio de Nebrija
  Completed

• 3EO Health SARS-CoV-2 OTC At Home Test - Condition:   COVID-19 Pandemic
  Intervention:   Diagnostic Test: In Vitro
  Sponsor:   3EO Health
  Recruiting

• Understanding the Impact of Death Conditions Linked to the COVID-19 Crisis on the Grieving Process in Bereaved Families - Condition:   Psychological Disorder
  Intervention:   Other: Qualitative research interview
  Sponsor:   Assistance Publique - Hôpitaux de Paris
  Not yet recruiting

• Sequential Enhanced Safety Study of a Novel Coronavirus Messenger RNA (mRNA) Vaccine in Adults Aged 18 Years and Older. - Condition:   Corona Virus Disease 2019(COVID-19)
  Intervention:   Biological: 0.3ml of mRNA vaccine
  Sponsor:   Yu Qin
  Enrolling by invitation

• Bringing Optimised COVID-19 Vaccine Schedules To ImmunoCompromised Populations (BOOST-IC): an Adaptive Randomised Controlled Clinical Trial - Conditions:   HIV;   Organ Transplantation;   Lymphoma, Non-Hodgkin;   Chronic Lymphocytic Leukemia;   Multiple Myeloma;   COVID-19 Vaccines
  Interventions:   Biological: BNT162b2;   Biological: mRNA-1273;   Biological: NVX-COV2373
  Sponsors:   Bayside Health;   Monash University
  Not yet recruiting

From PubMed

• Comparison of Intracellular Transcriptional Response of NHBE Cells to Infection with SARS-CoV-2 Washington and New York Strains - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019 and caused a global pandemic resulting in millions of deaths and tens of millions of patients positive tests. While studies have shown a D614G mutation in the viral spike protein are more transmissible, the effects of this and other mutations on the host response, especially at the cellular level, are yet to be fully elucidated. In this experiment we infected normal human bronchial…

• Inhibition of nonstructural protein 15 of SARS-CoV-2 by golden spice: A computational insight - The quick widespread of the coronavirus and speedy upsurge in the tally of cases demand the fast development of effective drugs. The uridine-directed endoribonuclease activity of nonstructural protein 15 (Nsp15) of the coronavirus is responsible for the invasion of the host immune system. Therefore, developing potential inhibitors against Nsp15 is a promising strategy. In this concern, the in silico approach can play a significant role, as it is fast and cost-effective in comparison to the trial…

• Apelin as a new therapeutic target for COVID-19 treatment - CONCLUSION: Apelin is a potential therapeutic candidate against SARS-CoV-2 infection.

• Two Cases of Acute Myocarditis in Young Male Adults After mRNA Vaccines Against COVID-19: Similarities and Differences - CONCLUSION: The benefits of vaccination against Covid-19 outweigh possible untoward effects and especially myocarditis. Health workers must close monitor the vaccinated patients for possible future cardiovascular complications.

• Therapeutic Approaches in COVID-19 Patients: The Role of the Renin-Angiotensin System - Two and a half years after COVID-19 was first reported in China, thousands of people are still dying from the disease every day around the world. The condition is forcing physicians to adopt new treatment strategies while emphasizing continuation of vaccination programs. The renin-angiotensin system plays an important role in the development and progression of COVID-19 patients. Nonetheless, administration of recombinant angiotensin-converting enzyme 2 has been proposed for the treatment of the…

• The Integral Membrane Protein ZMPSTE24 Protects Cells from SARS-CoV-2 Spike-Mediated Pseudovirus Infection and Syncytia Formation - COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating impact on global public health, emphasizing the importance of understanding innate immune mechanisms and cellular restriction factors that cells can harness to fight viral infections. The multimembrane-spanning zinc metalloprotease ZMPSTE24 is one such restriction factor. ZMPSTE24 has a well-characterized proteolytic role in the maturation of prelamin A, precursor of the nuclear…

• Booster vaccination against SARS-CoV-2 induces potent immune responses in people with HIV - CONCLUSIONS: In PWH receiving a third vaccine dose, there were significant increases in B and T cell immunity, including to known VOCs.

• Body Weight is Inversely Associated with Anti-SARS-CoV-2 Antibody Levels after BNT162b2 mRNA Vaccination in Young and Middle Aged Adults - CONCLUSION: Anti-SARS-CoV-2 antibody was inversely correlated with weight and BMI, which may be used as a marker to predict immune response of BNT162b2 mRNA vaccination in young and middle aged adults.

• A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo - “Pan-coronavirus” antivirals targeting conserved viral components can be designed. Here, we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high mannose found on viral proteins but seldom on healthy human cells, potently inhibits Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (including Omicron), and other human-pathogenic coronaviruses at nanomolar concentrations….

• Assessment of Practices Affecting Racial and Ethnic COVID-19 Vaccination Equity in 10 Large US Cities - CONCLUSIONS: Lack of consistent public reporting and transparency of COVID-19 vaccination data has likely hindered public health responses by impeding the ability to track the effectiveness of strategies that target vaccine equity.

• SARS-CoV-2 3CL^pro mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376 - Protease inhibitors are among the most powerful antiviral drugs. Nirmatrelvir is the first protease inhibitor against the SARS-CoV-2 protease 3CL^(pro) that has been licensed for clinical use. To identify mutations that confer resistance to this protease inhibitor, we engineered a chimeric vesicular stomatitis virus (VSV) that expressed a polyprotein composed of the VSV glycoprotein G, the SARS-CoV-2 3CL^(pro), and the VSV polymerase L. Viral replication was thus dependent on the autocatalytic…

• Reducing delayed transfer of care in older people: A qualitative study of barriers and facilitators to shorter hospital stays - CONCLUSION: Poor quality and availability of information, and poor communication, inhibit effective transfer of care. Communication is fundamental to patient-centred care and even more important in discharge models characterized by limited assessments and quicker discharge. Interventions at the service level and targeted patient information about what to expect in discharge assessments and after discharge could help to address poor communication and support for improving discharge of older…

• RNA-dependent RNA polymerase (RdRp) natural antiviral inhibitors: a review - Viral diseases are the cause of many global epidemics, leading to deaths, affecting the quality of life of populations, and impairing public health. The limitations in the treatment of viral diseases and the constant resistance to conventional antiviral treatments encourage researchers to discover new compounds. In this perspective, this literature review presents isolated molecules and extracts of natural products capable of inhibiting the activity of the nonstructural protein that acts as the…

• Novel α-aminophosphonate derivates synthesis, theoretical calculation, Molecular docking, and in silico prediction of potential inhibition of SARS-CoV-2 - Using the Density Functional Theory approach and in silico docking, the current study analyzes the inhibitory role of a novel α-aminophosphonate derivative against SARS-CoV-2 major protease (Mpro) and RNA dependent RNA polymerase (RdRp) of SARS-CoV-2. FT-IR, UV-Vis, and NMR (1H, 13C, 31P) approaches were used to produce and confirm the novel α-aminophosphonate derivative. The quantum chemical parameters were detremined, and the reactivity of the synthesized molecule was discussed using DFT at…

• Immunogenicity decay and case incidence six months post Sinovac-CoronaVac vaccine in autoimmune rheumatic diseases patients - The determination of durability and vaccine-associated protection is essential for booster doses strategies, however data on the stability of SARS-CoV-2 immunity are scarce. Here we assess anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2^(nd) dose of Sinovac-CoronaVac inactivated vaccine (D210) in 828 autoimmune rheumatic diseases patients compared with 207 age/sex-balanced control individuals. The primary outcome is the presence of anti-S1/S2 SARS-CoV-2 IgG at 6…

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