- Impact of COVID-19 on quality of care indicators in patients of carcinoma cervix treated with definitive radiotherapy: A cross-sectional study -
Introduction The COVID-19 pandemic has affected cancer care worldwide. We audited adherence to 19 predefined quality indicators (QI) of treatment in patients with carcinoma cervix in our institute. Methods Patients with carcinoma cervix treated with curative intent radical radiotherapy were eligible for this study. Patients who started treatment between 24 March 2019 and 24 March 2021 were evaluated. We divided participants into two groups, the pre pandemic period between 24 March 2019 and 23 March 2020, and the period of pandemic from 24 March 2020 - 24 March 2021. Adherence to 19 predefined QI was evaluated for each patient’s treatment course. Multivariable analysis of adherence to QI was performed using proportional odds regression. Results 154 patients underwent treatment, of whom 83 (53.9%) received treatment during the pandemic. 17 patients had COVID-19 infection before or during treatment. Adherence to QI decreased during the pandemic, primarily driven by delays in the start and delivery of treatment. The median number of QI adhered to in the pre pandemic period was 17 (IQR: 16 - 17.5) versus 17 during the pandemic (IQR: 16 - 17). Multivariable analysis showed that treatment during the pandemic period was associated with a lower adherence to QI (Odds ratio 3.30, 95% confidence intervals 1.70 - 6.50). Conclusions The COVID-19 pandemic was associated with reduced adherence to QI. Treatment delivery was affected not only by COVID-19 infection, but also logistic challenges due to restrictions related to the pandemic.
- Inhibition of the SARS-CoV-2 helicase at single-nucleotide resolution. -
The genome of SARS-CoV-2 encodes for a helicase called nsp13 that is essential for viral replication and highly conserved across related viruses, making it an attractive antiviral target. Here we use nanopore tweezers, a high-resolution single-molecule technique, to gain detailed insight into how nsp13 turns ATP-hydrolysis into directed motion along nucleic acid strands. We measured nsp13 both as it translocates along single-stranded DNA or unwinds short DNA duplexes. Our data confirm that nsp13 uses the inchworm mechanism to move along the DNA in single-nucleotide steps, translocating at ~1000 nt/s or unwinding at ~100 bp/s. Nanopore tweezers’ high spatio-temporal resolution enables observation of the fundamental physical steps taken by nsp13 even as it translocates at speeds in excess of 1000 nucleotides per second enabling detailed kinetic analysis of nsp13 motion. As a proof-of-principle for inhibition studies, we observed nsp13’s motion in the presence of the ATPase inhibitor ATP{gamma}S. Our data reveals that ATP{gamma}S interferes with nsp13’s action by affecting several different kinetic processes. The dominant mechanism of inhibition differs depending on the application of assisting force. These advances demonstrate that nanopore tweezers are a powerful method for studying viral helicase mechanism and inhibition.
- SiRNA Molecules as Potential RNAi Therapeutics to Silence RdRP Region and N-Gene of SARS-CoV-2: An In Silico Approach -
COVID-19 pandemic keeps pressing onward and effective treatment option against it is still far-off. Since the onslaught in 2020, 13 different variants of SARS-CoV-2 have been surfaced including 05 different variants of concern. Success in faster pandemic handling in the future largely depends on reinforcing therapeutics along with vaccines. As a part of RNAi therapeutics, here we developed a computational approach for predicting siRNAs, which are presumed to be intrinsically active against two crucial mRNAs of SARS-CoV-2, the RNA-dependent RNA polymerase (RdRp), and the nucleocapsid phosphoprotein gene (N gene). Sequence conservancy among the alpha, beta, gamma, and delta variants of SARS-CoV-2 was integrated in the analyses that warrants the potential of these siRNAs against multiple variants. We preliminary found 13 RdRP-targeting and 7 N gene-targeting siRNAs using the siDirect V.2.0. These siRNAs were subsequently filtered through different parameters at optimum condition including macromolecular docking studies. As a result, we selected 4 siRNAs against the RdRP and 3 siRNAs against the N-gene as RNAi candidates. Development of these potential siRNA therapeutics can significantly synergize COVID-19 mitigation by lessening the efforts, furthermore, can lay a rudimentary base for the in silico design of RNAi therapeutics for future emergencies.
- An alternative mechanism for skeletal muscle dysfunction in long-term post-viral lung disease -
Chronic lung disease is often accompanied by disabling extrapulmonary symptoms, notably skeletal muscle dysfunction and atrophy. Moreover, the severity of respiratory symptoms correlates with decreased muscle mass and in turn lowered physical activity and survival rates. Previous models of muscle atrophy in chronic lung disease often modeled COPD and relied on cigarette smoke exposure and LPS-stimulation, but these conditions independently affect skeletal muscle even without accompanying lung disease. Moreover, there is an emerging and pressing need to understand the extrapulmonary manifestations of long-term post-viral lung disease (PVLD) as found in Covid-19. Here, we examine the development of skeletal muscle dysfunction in the setting of chronic pulmonary disease using a mouse model of PVLD caused by infection due to the natural pathogen Sendai virus. We identify a significant decrease in myofiber size when PVLD is maximal at 49 d after infection. We find no change in the relative types of myofibers, but the greatest decrease in fiber size is localized to fast-twitch type IIB myofibers based on myosin heavy chain immunostaining. Remarkably, all biomarkers of myocyte protein synthesis and degradation (total RNA, ribosomal abundance, and ubiquitin-proteasome expression) were stable throughout the acute infectious illness and chronic post-viral disease process. Together, the results demonstrate a distinct pattern of skeletal muscle dysfunction in a mouse model of long-term PVLD. The findings thereby provide new insight into prolonged limitations in exercise capacity in patients with chronic lung disease after viral infections and perhaps other types of lung injury.
- When Lockdowns Force “Everyone” to Work From Home: Inequalities in Telework During COVID-19 in Uruguay -
Working from home arrangements have been on the rise globally throughout the 21st century. Despite this trajectory, developing economies have trailed developed countries in adopting such arrangements. However, because of COVID-19 lockdowns and social distancing measures, countries such as Uruguay, where teleworking was scarce and unregulated, were forced to adopt this practice to ensure business continuity. Under such conditions, preexisting organizational and individual disparities stratified the likelihood of working from home during the pandemic. Conventional wisdom holds that the main determinants potential-to-telework stems almost exclusively from the nature of jobs themselves. This article expands the traditional understanding of telework determinants by showing that during the first stages of the pandemic individual features of the worker, and organizational and managerial features of the employer, were both determinative of the likelihood that a given worker would work from home. We conducted a secondary data analysis of the March 2020 wave of the Work Monitor, a web-based survey of 847 employed Uruguayan adults. We fitted several multivariate regression models predicting a) the odds of working for a company which adopted COVID-19-related teleworking policies at least for some workers and b) the odds of working from home as a consequence of COVID-19. As the adoption of telework was largely unplanned and abrupt, result show that disparities on organizational adoption of teleworking policies were related to pre-pandemic differences across organizations in terms of preparedness, technological investment, and management practices. Results also show that employers’ willingness to enable working from home policies was the strongest predictor, at any level, of the likelihood of individuals to telework during the national emergency. Individual disparities in terms of human capital also have a great impact on the likelihood of teleworking during lockdowns, but their effect depends on the existence of organizational teleworking policies. Findings’ implications for the present and future of telework in developing countries are discussed.
- Using analogy-based messages to influence attitudes toward workplace COVID-19 vaccination mandates -
Workplace mandates are a highly effective strategy for increasing COVID-19 vaccination rates, and their adoption by United States employers grew throughout 2021. Still, public opinion on these mandates has remained starkly polarized. Drawing from the widespread use of analogies in health communication during the pandemic, we investigated whether analogies to widely-accepted workplace safety rules could affect attitudes toward vaccination mandates. In a survey experiment conducted in September-October 2021, 1194 respondents were randomized to one of three messages about workplace COVID-19 vaccination mandates that included (1) no analogy; (2) an analogy to workplace hard hat policies; or (3) an analogy to workplace smoking bans. Only the smoking analogy increased support for (b = 0.41; p < .001) and perceived effectiveness of (b = 0.20; p = .037) workplace vaccination mandates. Moreover, the smoking analogy’s effect on perceived effectiveness was greater for unvaccinated respondents (b = 0.54; p = .015 for interaction) and was mediated via the perceived strength of mandate enforcement (indirect effect = 0.05; 95% confidence interval = [0.01, 0.10]; P = .006). Our results demonstrate that policymakers and administrators may use a simple analogy to boost public opinion on workplace mandates for COVID-19 vaccination.
- Upregulation of CD55 complement regulator in distinct PBMC subpopulations of COVID-19 patients is associated with suppression of interferon responses. -
Complement activation has been verified in COVID-19 patients by both increased serum levels of complement factors C3a and C5b-9 and increased complement deposition at the tissue levels. Complement regulatory proteins (CRPs) CD55, CD46, CD59 and CR1 act to control complement overactivation and eliminate complement deposition and cell lysis. The aim of the study was to investigate the expression of CRPs in COVID-19 in order to identify potential dysregulated expression patterns of CRPs and address whether these may contribute to disease pathogenesis. Single cell RNA-sequencing (scRNA-seq) analysis performed on isolated PBMCs revealed an increase of CD55 expression in severe and critical COVID-19 patients compared to healthy controls. This increase was also detected upon integrated subclustering analysis of the monocyte, T cell and B cell populations. Flow cytometric analysis verified the distinct pattern of upregulated CD55 expression in monocyte and T cell sub populations of severe COVID-19 patients. This upregulation was associated with decreased expression of interferon stimulated genes (ISGs) in patients with severe COVID-19 suggesting a potential suppressor effect of CD55 on interferon responses. The present study identifies a COVID-19 specific CD55 expression pattern in PBMC subpopulations that coincides with reduced interferon responses thus indicating that the complement regulator CD55 may contribute to COVID-19 pathogenesis.
- Identification of motif-based interactions between SARS-CoV-2 protein domains and human peptide ligands pinpoint antiviral targets. -
The infection and replication cycle of all viruses depend on interactions between viral and host proteins. Each of these protein-protein interactions is therefore a potential drug target. These host-virus interactions often involve a disordered protein region on one side of the interface and a folded protein domain on the other. Here, we used proteomic peptide phage display (ProP-PD) to identify peptides from the intrinsically disordered regions of the human proteome that bind to folded protein domains encoded by the SARS-CoV-2 genome. Eleven folded domains of SARS-CoV-2 proteins were found to bind peptides from human proteins. Of 281 high/medium confidence peptides, 23 interactions involving eight SARS-CoV-2 protein domains were tested by fluorescence polarization, and binding was observed with affinities spanning the whole micromolar range. The key specificity determinants were established for six of these domains, two based on ProP-PD and four by alanine scanning SPOT arrays. Finally, two cell-penetrating peptides, targeting Nsp9 and Nsp16, respectively, were shown to function as inhibitors of viral replication. Our findings demonstrate how high-throughput peptide binding screens simultaneously provide information on potential host-virus interactions and identify ligands with antiviral properties.
- Development of SARS-CoV-2 mRNA vaccines encoding spike N-terminal and receptor binding domains -
With the success of mRNA vaccines against coronavirus disease 2019 (COVID-19), strategies can now focus on improving vaccine potency, breadth, and stability. We present the design and preclinical evaluation of domain-based mRNA vaccines encoding the wild-type spike-protein receptor-binding (RBD) and/or N-terminal domains (NTD). An NTD-RBD linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2-8{degrees}C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses and protection from viral challenge were observed against wild-type, beta, delta, or omicron (BA.1) compared with mRNA-1273 immunized mice, especially at lower vaccine dosages. These results support clinical assessment of mRNA-1283 (NCT05137236).
- Fate and plasticity of SARS-CoV-2-specific B cells during memory and recall response in humans -
B cell responses to different pathogens recruit tailored effector mechanisms, resulting in functionally specialized subsets. For human memory B cells (MBCs), these include CD21+ resting, CD21-CD27+ activated, and CD21-CD27- atypical cells. Whether these subsets follow deterministic or interconnected fates is unknown. We demonstrate in COVID-19 patients that single clones of SARS-CoV-2-specific MBCs followed multiple fates with distinctive phenotypic and functional characteristics. 6-12 months after infection, most circulating MBCs were CD21+ resting cells, which also accumulated in peripheral lymphoid organs where they acquired markers of tissue residency. Conversely, at acute infection and following SARS-CoV-2-specific immunization, CD21- MBCs became the predominant subsets, with atypical MBCs expressing high T-bet, inhibitory molecules, and distinct chemokine receptors. B cell receptor sequencing allowed tracking of individual MBC clones differentiating into CD21+, CD21-CD27+, and CD21-CD27- cell fates. Collectively, single MBC clones can adopt functionally different trajectories, thus contributing to immunity to infection.
- Incipient parallel evolution of SARS-CoV-2 Deltacron variant in South Brazil -
With the coexistence of multiple lineages and increased international travel, recombination and gene flow are likely to become increasingly important in the adaptive evolution of SARS-CoV-2. This could result in the incipient parallel evolution of multiple recombinant lineages. However, identifying recombinant lineages is challenging, and the true extent of recombinant evolution in SARS-CoV-2 may be underestimated. This study describes the first SARS-CoV-2 Deltacron recombinant case identified in Brazil. We demonstrate that the recombination breakpoint is at the beginning of Spike gene (S). The 5’ genome portion (circa 22 kb) resembles the AY.101 lineage (VOC Delta), and the 3’ genome portion (circa 8 kb nucleotides) is most similar to the BA.1.1 lineage (VOC Omicron). Furthermore, evolutionary genomic analyses indicate that the new strain emerged after a single recombination event between lineages of diverse geographical locations in December 2021 in South Brazil. This Deltacron, named AYBA-RS, is one out of almost 30 recombinants described this year. The submission of only four sequences in the GISAID database suggests that this Brazilian lineage had a minor epidemiological impact. On the other hand, the recent emergence of this and various other Deltacron recombinant lineages (i.e., XD, XF, and XS) suggests that gene flow and recombination may play an increasingly important role in the COVID-19 pandemic. We explain the evolutionary and population genetic theory that support this assertion, and we conclude that this stresses the need for continued genomic and epidemiological surveillance. This is particularly important for countries where multiple variants are present, as well as for countries that receive significant inbound international travel.
- Baculoviral COVID-19 Delta DNA vaccine cross-protects against SARS-CoV2 variants in K18-ACE2 transgenic mice -
After severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) made the world tremble with a global pandemic, SARS-CoV2 vaccines were developed. However, due to the coronavirus’s intrinsic nature, new variants emerged, such as Delta and Omicron, refractory to the vaccines derived using the original Wuhan strain. We developed an HERV-enveloped recombinant baculoviral DNA vaccine against SARS-CoV2 (AcHERV-COVID19S). A non-replicating recombinant baculovirus that delivers the SARS-CoV2 spike gene showed a protective effect against the homologous challenge in a K18-hACE2 Tg mice model; however, it offered only a 50% survival rate against the SARS-CoV2 Delta variant. Therefore, we further developed the AcHERV-COVID19 Delta vaccine (AcHERV-COVID19D). Cross-protection experiments revealed that mice vaccinated with the AcHERV-COVID19D showed 100% survival upon challenge with Delta and Omicron variants and 71.4% survival against prototype SARS-CoV2. These results support the potential of the viral vector vaccine, AcHERV-COVID19D, in preventing the spread of coronavirus variants such as Omicron and SARS-CoV2 variants.
- Neutralization of SARS-CoV-2 Omicron BA.4/BA.5 subvariant by a booster dose of bivalent adjuvanted subunit vaccine containing Omicron BA.4/BA.5 and BA.1 subvariants -
The dominance of SARS-CoV-2 variants of concern (VoC), such as the Omicron subvariants, is a threat to the current vaccination scheme due to increased resistance to immune neutralization and greater transmissibility. To develop the next generation of prefusion SARS-CoV-2 spike protein (S-2P) subunit vaccine adjuvanted with CpG1018 and aluminum hydroxide, mice immunized with two doses of the adjuvanted ancestral Wuhan strain (W) followed by the third dose of the W or Omicron variants (BA.1 or BA.4/BA.5) S-2P, or a combination of the above bivalent S-2Ps. Antisera from mice were tested against pseudovirus neutralization assay of ancestral SARS-CoV-2 (WT) and Omicron BA.4/BA.5 subvariant. Boosting with bivalent mixture of Omicron BA.4/BA.5 and W S-2P achieved the highest neutralizing antibody titers against BA.4/BA.5 subvariant pseudovirus compared to other types of S-2P as boosters.
- Projecting the seasonality of endemic COVID-19 -
Importance: Successive waves of infection by SARS-CoV-2 have left little doubt that COVID-19 will transition to an endemic disease, yet the future seasonality of COVID-19 remains one of its most consequential unknowns. Foreknowledge of spatiotemporal surges would have immediate and long-term consequences for medical and public health decision-making. Objective: To estimate the impending endemic seasonality of COVID-19 in temperate population centers via a phylogenetic ancestral and descendent states approach that leverages long-term data on the incidence of circulating coronaviruses. Design: We performed a comparative evolutionary analysis on literature-based monthly verified cases of HCoV-NL63, HCoV-229E, HCoV-HKU1, and HCoV-OC43 infection within populations across the Northern Hemisphere. Ancestral and descendent states analyses on human-infecting coronaviruses provided projections of the impending seasonality of endemic COVID-19. Setting: Quantitative projections of the endemic seasonality of COVID-19 were based on human endemic coronavirus infection incidence data from New York City (USA); Denver (USA); Tampere (Finland); Trondelag (Norway); Gothenburg (Sweden); Stockholm (Sweden); Amsterdam (Netherlands); Beijing (China); South Korea (Nationwide); Yamagata (Japan); Hong Kong; Nakon Si Thammarat (Thailand); Guangzhou (China); and Sarlahi (Nepal). Main Outcome(s) and Measure(s): The primary projection was the monthly relative frequency of SARS-CoV-2 infections in each geographic locale. Four secondary outcomes consisted of empirical monthly relative frequencies of the endemic human-infecting coronaviruses HCoV-NL63, -229E, -HKU1, and -OC43. Results: We project asynchronous surges of SARS-CoV-2 across locales in the Northern Hemisphere. In New York City, SARS-CoV-2 incidence is projected in late fall and winter months (Nov.-Jan.), In Tampere, Finland; Yamagata, Japan; and Sarlahi, Nepal incidence peaks in February. Gothenburg and Stockholm in Sweden reach peak incidence between November and February. Guangzhou, China; and South Korea. In Denver, incidence peaks in early Spring (Mar.). In Amsterdam, incidence rises in late fall (Dec.), and declines in late spring (Apr.). In Hong Kong, the projected apex of infection is in late fall (Nov.-Dec.), yet variation in incidence is muted across other seasons. Seasonal projections for Nakhon Si Thammarat, Thailand and for Beijing, China are muted compared to other locations. Conclusions and Relevance: This knowledge of likely spatiotemporal surges of COVID-19 is fundamental to medical preparedness and expansions of public health interventions that anticipate the impending endemicity of this disease and mitigate COVID-19 transmission. These results provide crucial guidance for adaptive public health responses to this disease, and are vital to the long-term mitigation of COVID-19 transmission.
- COVID-19: impact of original, Gamma, Delta, and Omicron variants of SARS-CoV-2 in vaccinated and unvaccinated pregnant and postpartum women -
Introduction This study compares the clinical characteristics and disease progression of vaccinated and unvaccinated pregnant and postpartum women positive for the original, Gamma, Delta, and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using Brazilian epidemiological data. Methods Data of pregnant or postpartum patients with coronavirus disease 2019 (COVID-19) SARS-CoV-2 confirmed using polymerase chain reaction from February 2020 to July 2022 were extracted from a Brazilian national database. The patients were divided based on vaccination status and viral variant (original, Gamma, Delta, and Omicron). The patients demographic data, clinical characteristics, comorbidities, signs, symptoms, and outcomes were retrospectively compared. Results Data from 10,003 pregnant and 2,361 postpartum women were extracted from the database. Among unvaccinated patients, postpartum women were more likely to be admitted to the intensive care unit (ICU). These patients were more likely to require invasive ventilation when infected with the original, Gamma, and Omicron variants and were more likely to die when infected with the original and Gamma variants. Patients who were vaccinated had reduced adverse outcomes including ICU admission, requirement for invasive ventilation, and death. Conclusion Postpartum women were more likely to develop severe COVID-19 that required ICU admission or invasive ventilatory support or led to death, among all variants, especially when the patients were unvaccinated. Therefore, the risk of severe COVID-19 should not be underestimated after delivery. Vaccinated patients had a lower risk of severe outcomes. Vaccination should be a top priority in pregnant and postpartum patients.
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
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
PAPR: PAP + MBSR for Front-line Healthcare Provider COVID-19 Related Burnout - Conditions: Depression; Burnout, Professional
Interventions: Drug: Psilocybin; Behavioral: Mindfulness-Based Stress Reduction (MBSR)
Sponsors: University of Utah; Heffter Research Institute; Usona Institute
Not yet recruiting
Physiology of Long COVID and the Impact of Cardiopulmonary Rehabilitation on Quality-of-Life and Functional Capacity - Condition: Post-acute Sequelae of SARS-CoV-2 Infection
Intervention: Behavioral: Exercise
Sponsor: University of Colorado, Denver
Not yet recruiting
Phase 3 Study to Evaluate Immunogenicity and Safety of BBV154 Booster Dose - Condition: COVID-19 Respiratory Infection
Interventions: Biological: BBV154 Intranasal Vaccine; Biological: Intramuscular vaccine COVAXIN; Biological: Covishield
Sponsor: Bharat Biotech International Limited
Completed
Evaluation of quality and antimicrobial efficacy of locally manufactured alcohol-based hand sanitizers marketed in Addis Ababa, Ethiopia in the era of COVID-19 - CONCLUSION: One-third of the tested ABHS did not comply with the WHO ethanol content limit and the majority of the products failed to meet the label claim for hydrogen peroxide content. Besides, nearly all products proved that they have activity against all the tested pathogenic microorganisms at a minimum concentration from 10 to 80%; though, they did not show 99.9% bacteriostatic or bactericidal activities as claimed. The study findings suggested regular monitoring of the quality of marketed…
An overview on nanoparticle-based strategies to fight viral infections with a focus on COVID-19 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to COVID-19 and has become a pandemic worldwide with mortality of millions. Nanotechnology can be used to deliver antiviral medicines or other types of viral reproduction-inhibiting medications. At various steps of viral infection, nanotechnology could suggest practical solutions for usage in the fight against viral infection. Nanotechnology-based approaches can help in the fight against SARS-CoV-2 infection. Nanoparticles can play…
The inhibitory activity of methoxyl flavonoids derived from Inula britannica flowers on SARS-CoV-2 3CLpro - In our ongoing efforts to identify effective natural antiviral agents, four methoxy flavonoids (1-4) were isolated from the Inula britannica flower extract. Their structures were elucidated using nuclear magnetic resonance. Flavonoids 1-4 exhibited inhibitory activity against SARS- CoV-2 3CLpro with IC(50) values of 41.6 ± 2.5, 35.9 ± 0.9, 32.8 ± 1.2, and 96.6 ± 3.4 μM, respectively. Flavonoids 1-3 inhibited 3CLpro in a competitive manner. Based on molecular simulations, key amino acids that…
Recruitment of chalcone’s potential in drug discovery of anti-SARS-CoV-2 agents - Chalcone is an interesting scaffold found in the structure of many naturally occurring molecules. Medicinal chemists are commonly interested in designing new chalcone-based structures because of having the α, β-unsaturated ketone functional group, which allows these compounds to participate in Michael’s reaction and create strong covalent bonds at the active sites of the targets. Some studies have identified several natural chalcone-based compounds with the ability to inhibit the severe acute…
Calcium dobesilate reduces SARS-CoV-2 entry into endothelial cells by inhibiting virus binding to heparan sulfate - Recent reports demonstrate that SARS-CoV-2 utilizes cell surface heparan sulfate as an attachment factor to facilitate the initial interaction with host cells. Heparan sulfate interacts with the receptor binding domain of SARS-CoV-2 spike glycoprotein, and blocking this interaction can decrease cell infection. We and others reported recently that the family of compounds of 2,5-dihydroxyphenylic acid interferes with the binding of the positively charged groove in growth factor molecules to…
Combating the SARS-CoV-2 Omicron (BA.1) and BA.2 with potent bispecific antibodies engineered from non-Omicron neutralizing antibodies - The highly mutated and transmissible Omicron (BA.1) and its more contagious lineage BA.2 have provoked serious concerns over their decreased sensitivity to the current COVID-19 vaccines and evasion from most anti-SARS-CoV-2 neutralizing antibodies (NAbs). In this study, we explored the possibility of combating the Omicron and BA.2 by constructing bispecific antibodies based on non-Omicron NAbs. We engineered 10 IgG-like bispecific antibodies with non-Omicron NAbs named GW01, 16L9, 4L12, and…
The use of adenoviral vectors in gene therapy and vaccine approaches - Adenovirus was first identified in the 1950s and since then this pathogenic group of viruses has been explored and transformed into a genetic transfer vehicle. Modification or deletion of few genes are necessary to transform it into a conditionally or non-replicative vector, creating a versatile tool capable of transducing different tissues and inducing high levels of transgene expression. In the early years of vector development, the application in monogenic diseases faced several hurdles,…
Therapeutic potential of metal ions for COVID-19: insights from the papain-like protease of SARS-CoV-2 - Coronaviruses have been responsible for multiple challenging global pandemics, including coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Papain-like protease (PLpro), one of two cysteine proteases responsible for the maturation and infectivity of SARS-CoV-2, processes and liberates functional proteins from the viral polyproteins and cleaves ubiquitin and ISG15 modifications to inhibit innate immune sensing. Consequently, PLpro…
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.