Three safe and effective vaccines against SARS-CoV-2 (the Pfizer-BioNTech, Moderna and Johnson & Johnson vaccines) have played a major role in combating the COVID-19 pandemic in the United States. However, the effectiveness of these vaccines and vaccination programs has been challenged by the emergence of new SARS- CoV-2 variants of concern. A new mathematical model is formulated to assess the population-level impact of the waning and boosting of vaccine-derived and natural immunity against the Omicron variant in the United States. To account for gradual waning of vaccine-derived immunity, we considered three vaccination classes (V1, V2 and V3; where subscripts 1, 2 and 3 represent high, moderate and low levels of immunity, respectively). The disease-free equilibrium of the model was shown to be globally-asymptotically stable, for two special cases, whenever a certain associated epidemiological quantity, known as the vaccination reproduction number of the model, is less than one. The model was fitted using observed daily case data for the Omicron BA.1 variant in the United States. Simula- tions of the resulting parameterized model showed that, for the case where the high-level of the vaccine-derived protective efficacy received by individuals in the first vaccinated class (V1) is set at its baseline value (85%; while the vaccine-protective efficacy for individuals in the V2 and V3 classes, as well as natural immunity, are maintained at baseline), population-level herd immunity can be achieved in the United States via vaccination-boosting strat- egy, if at least 59% of the susceptible populace is fully-vaccinated followed by the boosting of about 71.5% of the fully-vaccinated individuals whose vaccine-derived immunity has waned to moderate or low level. However, if the high level of vaccine-induced efficacy for individuals in the V1 class is reduced to 55%, for instance, achiev- ing herd immunity requires fully-vaccinating at least 91% of the susceptible population (followed by marginal boosting of those in whom the vaccine-derived immunity has waned to moderate or low level). In the absence of boosting of vaccine-derived and natural immunity, waning of immunity (both vaccine-derived and natural) only causes a marginal increase in the average number of new cases at the peak of the pandemic. Boosting of both immunity types at baseline could result in a dramatic reduction in the average number of daily new cases at the peak, in comparison to the corresponding waning scenario without boosting of immunity. Furthermore, boosting of vaccine-derived immunity (at baseline) is more beneficial (in reducing the burden of the pandemic) than boosting of natural immunity (at baseline). Specifically, for the fast waning of immunity scenario (where both vaccine-derived and natural immunity are assumed to wane within three months), boosting vaccine-derived immunity at baseline reduces the average number of daily cases at the peak by 90% (in comparison to the corresponding scenario without boosting of the vaccine-derived immunity), whereas boosting of natural immunity (at baseline) only reduced the corresponding peak daily cases (in comparison to the corresponding scenario without boosting of natural immunity) by 62%. It was further shown that boosting of vaccine-derived (implemented near the baseline level) increased the prospects of altering the trajectory of COVID-19 from persistence to possible elimination (even for the fast waning scenario of vaccine-derived immunity). Thus, a vaccination strategy that emphasizes boosting of immunity would significantly enhance the prospects of SARS-CoV-2 elimination in the United States.
Background: There is a lack of studies on large-sample, medium-, or long-term follow-up data of peripheral neuropathy (PNP) in the COVID-19 survivors. This study evaluated the characteristics and related risk factors of PNP in the medium- and long-term rehabilitation,which provided real-world study data for the complete recovery of COVID-19 patients. Methods: This study was a prospective cohort study of the COVID-19 survivors. We collected data on baseline characteristics, symptoms at onset and after discharge during the 6-month and 12-month follow-up. Peripheral nerves were measured by electromyography and inducible potentiometer. We used multivariable logistic regression to analyze the influencing factors of PNP. Additionally, we compared the difference between the two measurements among the population who completed both measurements. Results: 313 patients were included in the study and all of them underwent nerve conduction study. 67 patients completed two measurements at 6-month and 12-month follow-up. Commonly reported symptoms contained memory loss (86%), hair loss (28%), anxiety (24%), and sleep difficulties (24%). 232 patients (74%) were found with PNP, including 51 (16%) with mononeuropathy and 181 (58%) with generalized PNP. Patients with measurement at 12-month follow-up had a higher prevalence of generalized PNP (p=0.006). For pathological types, 64 (20%) patients had only axonal loss, 67 (21%) had only demyelination, and 101 (32%) had a mixed type. There was no significant difference in the prevalence of accompanying symptoms after discharge between the two groups with or without PNP. After adjustment, age was positively associated with PNP (OR=1.22 per 10-year increase of age, 95% CI, 1.05-1.41). Compared with less than the median amount of IgG at discharge, higher amount of IgG was associated with decreased risk of F-wave abnormality (OR=0.32, 95%CI, 0.11-0.82), but no significant difference in other types of PNP. Conclusions and Relevance: SARS-CoV-2 could cause PNP in hospital survivors with COVID-19, which persisted and was associated with age, education, and IgG antibody at discharge, but had no significant correlation with symptoms after discharge.
Prior research has established that American Indian, Alaska Native, Black, Hispanic, and Pacific Islander populations in the United States have experienced substantially higher mortality rates from Covid-19 compared to non-Hispanic white residents during the first year of the pandemic. What remains less clear is how mortality rates have changed for each of these racial/ethnic groups during 2021, given the increasing prevalence of vaccination. In particular, it is unknown how these changes in mortality have varied geographically. In this study, we used provisional data from the National Center for Health Statistics (NCHS) to produce age-standardized estimates of Covid-19 mortality by race/ethnicity in the United States from March 2020 to February 2022 in each metro-nonmetro category, Census region, and Census division. We calculated changes in mortality rates between the first and second years of the pandemic and examined mortality changes by month. We found that when Covid-19 first affected a geographic area, non-Hispanic Black and Hispanic populations experienced extremely high levels of Covid-19 mortality and racial/ethnic inequity that were not repeated at any other time during the pandemic. Between the first and second year of the pandemic, racial/ethnic inequities in Covid-19 mortality decreased but were not eliminated for Hispanic, non-Hispanic Black, and non-Hispanic AIAN residents. These inequities decreased due to reductions in mortality for these populations alongside increases in non-Hispanic white mortality. Though racial/ethnic inequities in Covid-19 mortality decreased, substantial inequities still existed in most geographic areas during the pandemic9s second year: Non-Hispanic Black, non-Hispanic AIAN, and Hispanic residents reported higher Covid-19 death rates in rural areas than in urban areas, indicating that these communities are facing serious public health challenges. At the same time, the non-Hispanic white mortality rate worsened in rural areas during the second year of the pandemic, suggesting there may be unique factors driving mortality in this population. Finally, vaccination rates were associated with reductions in Covid-19 mortality for Hispanic, non-Hispanic Black, and non-Hispanic white residents, and increased vaccination may have contributed to the decreases in racial/ethnic inequities in Covid-19 mortality observed during the second year of the pandemic. Despite reductions in mortality, Covid-19 mortality remained elevated in nonmetro areas and increased for some racial/ethnic groups, highlighting the need for increased vaccination delivery and equitable public health measures especially in rural communities. Taken together, these findings highlight the continued need to prioritize health equity in the pandemic response and to modify the structures and policies through which systemic racism operates and has generated racial health inequities.
Tuberculosis (TB) afflicts over 10 million people every year and its global burden is projected to increase dramatically due to multidrug-resistant TB (MDR-TB). The Covid-19 pandemic has resulted in reduced access to TB diagnosis and treatment, reversing decades of progress in disease management globally. It is thus crucial to analyze real-world multi-domain information from patient health records to determine personalized predictors of TB treatment outcome and drug resistance. We conduct a retrospective analysis on electronic health records of 5060 TB patients spanning 10 countries with high burden of MDR-TB including Ukraine, Moldova, Belarus and India available on the NIAID-TB portals database. We analyze over 200 features across multiple host and pathogen modalities representing patient social demographics, disease presentations as seen in cChest X rays and CT scans, and genomic records with drug susceptibility features of the pathogen strain from each patient. Our machine learning model, built with diverse data modalities outperforms models built using each modality alone in predicting treatment outcomes, with an accuracy of 81% and AUC of 0.768. We determine robust predictors across countries that are associated with unsuccessful treatment outcomes, and validate our predictions on new patient data from TB Portals. Our analysis of drug regimens and drug interactions suggests that synergistic drug combinations and those containing the drugs Bedaquiline, Levofloxacin, Clofazimine and Amoxicillin see more success in treating MDR and XDR TB. Features identified via chest imaging such as percentage of abnormal volume, size of lung cavitation and bronchial obstruction are associated significantly with pathogen genomic attributes of drug resistance. Increased disease severity was also observed in patients with lower BMI and with co-morbidities. Our integrated multi-modal analysis thus revealed significant associations between radiological, microbiological, therapeutic, and demographic data modalities, providing a deeper understanding of personalized responses to aid in the clinical management of TB.
Background Data on risk factors for COVID-19-associated hospitalisation and mortality in high HIV prevalence settings are limited. Methods Using existing syndromic surveillance programs for influenza-like-illness and severe respiratory illness at sentinel sites in South Africa, we identified factors associated with COVID-19 hospitalisation and mortality. Results From April 2020 through March 2022, SARS-CoV-2 was detected in 24.0% (660/2746) of outpatient and 32.5% (2282/7025) of inpatient cases. Factors associated with COVID-19-associated hospitalisation included: older age (25-44 [adjusted odds ratio (aOR) 1.8, 95% confidence interval (CI) 1.1-2.9], 45-64 [aOR 6.8, 95%CI 4.2-11.0] and ≥65 years [aOR 26.6, 95%CI 14.4-49.1] vs 15-24 years); black race (aOR 3.3, 95%CI 2.2-5.0); obesity (aOR 2.3, 95%CI 1.4-3.9); asthma (aOR 3.5, 95%CI 1.4-8.9); diabetes mellitus (aOR 5.3, 95%CI 3.1-9.3); HIV with CD4 ≥200/mm3 (aOR 1.5, 95%CI 1.1-2.2) and CD4<200/mm3 (aOR 10.5, 95%CI 5.1-21.6) or tuberculosis (aOR 12.8, 95%CI 2.8-58.5). Infection with Beta (aOR 0.5, 95%CI 0.3-0.7) vs Delta variant and being fully vaccinated (aOR 0.1, 95%CI 0.1-0.3) were less associated with COVID-19 hospitalisation. In-hospital mortality was increased in older age (45-64 years [aOR 2.2, 95%CI 1.6-3.2] and ≥65 years [aOR 4.0, 95%CI 2.8-5.8] vs 25-44 years) and male sex (aOR1.3, 95%CI 1.0-1.6) and was lower in Omicron -infected (aOR 0.3, 95%CI 0.2-0.6) vs Delta-infected individuals. Conclusion Active syndromic surveillance encompassing clinical, laboratory and genomic data identified setting-specific risk factors associated with COVID-19 severity that will inform prioritization of COVID-19 vaccine distribution. Elderly, people with tuberculosis or people living with HIV, especially severely immunosuppressed should be prioritised for vaccination.
Accurate stratification of patients with post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) would allow precision clinical management strategies. However, the natural history of long COVID is incompletely understood and characterized by an extremely wide range of manifestations that are difficult to analyze computationally. In addition, the generalizability of machine learning classification of COVID-19 clinical outcomes has rarely been tested. We present a method for computationally modeling PASC phenotype data based on electronic healthcare records (EHRs) and for assessing pairwise phenotypic similarity between patients using semantic similarity. Our approach defines a nonlinear similarity function that maps from a feature space of phenotypic abnormalities to a matrix of pairwise patient similarity that can be clustered using unsupervised machine learning procedures. Using k-means clustering of this similarity matrix, we found six distinct clusters of PASC patients, each with distinct profiles of phenotypic abnormalities. There was a significant association of cluster membership with a range of pre-existing conditions and with measures of severity during acute COVID-19. Two of the clusters were associated with severe manifestations and displayed increased mortality. We assigned new patients from other healthcare centers to one of the six clusters on the basis of maximum semantic similarity to the original patients. We show that the identified clusters were generalizable across different hospital systems and that the increased mortality rate was consistently observed in two of the clusters. Semantic phenotypic clustering can provide a foundation for assigning patients to stratified subgroups for natural history or therapy studies on PASC.
Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p=5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.
Prolonged infections of immunocompromised individuals have been proposed as a crucial source of new variants of SARS-CoV-2 during the COVID-19 pandemic. In principle, sustained within-host antigenic evolution in immunocompromised hosts could allow novel immune escape variants to emerge more rapidly, but little is known about how and when immunocompromised hosts play a critical role in pathogen evolution. Here, we use a simple mathematical model to understand the effects of immunocompromised hosts on the emergence of immune escape variants in the presence and absence of epistasis. We show that when the pathogen does not have to cross a fitness valley for immune escape to occur (no epistasis), immunocompromised individuals have no qualitative effect on antigenic evolution (although they may accelerate immune escape if within-host evolutionary dynamics are faster in immunocompromised individuals). But if a fitness valley exists between immune escape variants at the between-host level (epistasis), then persistent infections of immunocompromised individuals allow mutations to accumulate, therefore facilitating rather than simply speeding up antigenic evolution. Our results suggest that better genomic surveillance of infected immunocompromised individuals and better global health equality, including improving access to vaccines and treatments for individuals who are immunocompromised (especially in lower- and middle-income countries), may be crucial to preventing the emergence of future immune escape variants of SARS-CoV-2.
Puerto Rico COVID-19 Vaccine Uptake Study - Condition: COVID-19
Intervention: Other: Educational intervention
Sponsors: University of Puerto Rico; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)
Recruiting
Bank of Human Leukocytes From COVID-19 Convalescent Donors With an Anti-SARS-CoV-2 Cellular Immunity - Condition: COVID-19
Intervention: Other: Generation of a biobank allowing the cryopreservation of leucocytes from COVID19 convalescent donors
Sponsor: Central Hospital, Nancy, France
Not yet recruiting
Beta-glucans for Hospitalised Patients With COVID-19 - Condition: COVID-19
Interventions: Drug: MC 3x3; Drug: Placebo
Sponsors: Concentra Educacion e Investigación Biomédica; Wohlstand Pharmaceutical
Not yet recruiting
A Randomised, Multi-centre, Double-blind, Phase 3 Study to Observe the Effectiveness, Safety and Tolerability of Molnupiravir Compared to Placebo Administered Orally to High-risk Adult Outpatients With Mild COVID-19 Receiving Local Standard of Care in South Africa - Condition: COVID-19
Intervention: Drug: Molnupiravir 200 mg
Sponsors: University of Witwatersrand, South Africa; Bill and Melinda Gates Foundation
Not yet recruiting
Engaging Staff to Improve COVID-19 Vaccination Response at Long-Term Care Facilities - Condition: COVID-19
Interventions: Behavioral: Full Intervention; Other: Enhanced Usual Care
Sponsors: Kaiser Permanente; Patient-Centered Outcomes Research Institute; Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)
Recruiting
Topical Antibacterial Agents for Prevention of COVID-19 - Conditions: COVID-19; SARS-CoV2 Infection
Interventions: Drug: Neosporin; Other: Vaseline
Sponsors: Yale University; Bill and Melinda Gates Foundation
Not yet recruiting
**NanoMn®_COVID-19 A Prospective, Multicenter, Randomized, Placebo-controlled, Parallel-group, Double-blind Trial to Evaluate the Clinical Efficacy of NanoManganese® on Top of Standard of Care, in Adult Patients With Moderate to Severe Coronavirus Disease 2019 (COVID-19)** - Condition: COVID-19 Pandemic
Interventions: Drug: Placebo; Drug: Experimental drug
Sponsor: Medesis Pharma SA
Recruiting
Safety and Immunogenicity of Recombinant COVID-19 Vaccine (Sf9 Cell) as a Booster - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: Recombinant COVID-19 Vaccine (Sf9 Cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated
Sponsor: WestVac Biopharma Co., Ltd.
Recruiting
Safety and Immunogenicity of Recombinant COVID-19 Variant Vaccine (Sf9 Cell) as a Booster - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: Recombinant COVID-19 variant Vaccine (Sf9 Cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated; Biological: mRNA COVID-19 vaccine (Moderna); Biological: Viral Vector COVID-19 vaccine (AstraZeneca)
Sponsor: WestVac Biopharma Co., Ltd.
Not yet recruiting
Evaluation of Effectiveness of Proprietary Rehabilitation Program in Patients After COVID-19 Infection - Conditions: COVID-19; Rehabilitation
Interventions: Other: Respiratory training with the use of resistance set on respiratory muscle trainer; Other: Respiratory training without resistance set on respiratory muscle trainer
Sponsor: Medical University of Bialystok
Recruiting
Developing an Integrative, Recovery-Based, Post-Acute COVID-19 Syndrome (PACS) Psychotherapeutic Intervention - Condition: Post-acute COVID-19 Syndrome
Intervention: Behavioral: PACS Coping and Recovery (PACS-CR) Intervention
Sponsor: VA Office of Research and Development
Not yet recruiting
Mineralocorticoid Use in COVID-19 Patients - Conditions: COVID-19; ARDS
Intervention: Drug: Fludrocortisone Acetate 0.1 MG
Sponsor: Ain Shams University
Completed
An Observer-blind, Cohort Randomized, Exploratory Phase 3 Study to Evaluate the Safety and Immunogenicity of Recombinant Covid-19 Vaccine, mRNA Covid-19 Vaccine and Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine as 4th Dose in Individuals Primed/ Boosted With Various Regimens - Condition: COVID-19
Interventions: Biological: AstraZeneca/Fiocruz; Biological: Pfizer/Wyeth; Biological: Clover SCB-2019
Sponsors: D’Or Institute for Research and Education; Bill and Melinda Gates Foundation; University of Oxford
Not yet recruiting
Xanthohumol as an Adjuvant Therapy in Critically Ill COVID-19 Patients - Condition: COVID-19 Respiratory Infection
Intervention: Biological: Xanthohumol - prenylated chalcone extracted from female inflorescences of hop cones (Humulus lupus). Hop-RXn™, BioActive-Tech Ltd, Lublin, Poland; http://xanthohumol.com.pl/
Sponsor: Medical University of Lublin
Suspended
A Clinical Trial of Immuno-bridging Between Different Manufacture Scales of Recombinant COVID-19 Vaccine (Sf9 Cell) - Conditions: COVID-19; SARS-CoV-2 Pneumonia
Intervention: Biological: Recombinant COVID-19 vaccine (Sf9 cell)
Sponsor: WestVac Biopharma Co., Ltd.
Not yet recruiting
Secondary metabolites of Livistona decipiens as potential inhibitors of SARS-CoV-2 - In late December 2019, a pandemic coronavirus disease 2019 (COVID-19) emerged in Wuhan, China and spread all over the globe. One of the promising therapeutic techniques of viral infection is to search for enzyme inhibitors among natural phytochemicals using molecular docking to obtain leads with the least side effects. The COVID-19 virus main protease (M^(pro)) is considered as an attractive target due to its pivotal role in controlling viral transcription and replication. Metabolic profiling of…
Endothelial Cells as a Key Cell Type for Innate Immunity: A Focused Review on RIG-I Signaling Pathway - The vascular endothelium consists of a highly heterogeneous monolayer of endothelial cells (ECs) which are the primary target for bacterial and viral infections due to EC’s constant and close contact with the bloodstream. Emerging evidence has shown that ECs are a key cell type for innate immunity. Like macrophages, ECs serve as sentinels when sensing invading pathogens or microbial infection caused by viruses and bacteria. It remains elusive how ECs senses danger signals, transduce the signal…
Application of green synthesised copper iodide particles on cotton fabric-protective face mask material against COVID-19 pandemic - Microorganisms cause variety of diseases that constitutes a severe threat to mankind. Due to the upsurge of many infectious diseases, there is a high requirement and demand for the development of safety products finished with antimicrobial properties. The study involves the antimicrobial activity of natural cotton coated with copper iodide capped with Hibiscus rosa-sinensis L. flower extract (CuI-FE) which is rich in anthocyanin, cyanidin-3-sophoroside by ultrasonication method. The coated and…
The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants - The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative…
Detection of neutralizing antibodies against multiple SARS-CoV-2 strains in dried blood spots using cell-free PCR - An easily implementable serological assay to accurately detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies is urgently needed to better track herd immunity, vaccine efficacy and vaccination rates. Herein, we report the Split-Oligonucleotide Neighboring Inhibition Assay (SONIA) which uses real-time qPCR to measure the ability of neutralizing antibodies to block binding between DNA-barcoded viral spike protein subunit 1 and the human angiotensin-converting…
SARS-CoV-2 spike protein inhibits megalin-mediated albumin endocytosis in proximal tubule epithelial cells - Patients with COVID-19 have high prevalence of albuminuria which is used as a marker of progression of renal disease and is associated with severe COVID-19. We hypothesized that SARS-CoV-2 spike protein (S protein) could modulate albumin handling in proximal tubule epithelial cells (PTECs) and, consequently contribute to the albuminuria observed in patients with COVID-19. In this context, the possible effect of S protein on albumin endocytosis in PTECs was investigated. Two PTEC lines were used:…
A new circular RNA-encoded protein BIRC6-236aa inhibits transmissible gastroenteritis virus (TGEV)-induced mitochondrial dysfunction - Transmissible gastroenteritis virus (TGEV), a member of the coronavirus family, is the pathogen responsible for transmissible gastroenteritis, which results in mitochondrial dysfunction in host cells. Previously, we identified 123 differentially-expressed (DE) circular RNAs (circRNAs) from the TGEV-infected porcine intestinal epithelial cell line jejunum 2 (IPEC-J2). Previous bioinformatics analysis suggested that, of these, circBIRC6 had the potential to regulate mitochondrial function….
Discovery of potent benzoxaborole inhibitors against SARS-CoV-2 main and dengue virus proteases - The RNA viruses SARS-CoV-2 and dengue pose a major threat to human health worldwide and their proteases (M^(pro); NS2B/NS3) are considered as promising targets for drug development. We present the synthesis and biological evaluation of novel benzoxaborole inhibitors of these two proteases. The most active compound achieves single-digit micromolar activity against SARS-CoV-2 M^(pro) in a biochemical assay. The most active substance against dengue NS2B/NS3 protease has submicromolar activity in…
Angiotensin-Converting Enzyme 2 Potentiates SARS-CoV-2 Infection by Antagonizing Type I Interferon Induction and Its Down-Stream Signaling Pathway - The innate interferon (IFN) response constitutes the first line of host defense against viral infections. It has been shown that IFN-I/III treatment could effectively contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. However, how SARS-CoV-2 survives through the innate antiviral mechanism remains to be explored. Our study uncovered that human angiotensin-converting enzyme 2 (ACE2), identified as a primary receptor for SARS-CoV-2 entry, can disturb the…
A Retinol Derivative Inhibits SARS-CoV-2 Infection by Interrupting Spike-Mediated Cellular Entry - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the global pandemic and life-threatening coronavirus disease 2019 (COVID-19). Although vaccines and therapeutic antibodies are available, their efficacy is continuously undermined by rapidly emerging SARS-CoV-2 variants. Here, we found that all-trans retinoic acid (ATRA), a vitamin A (retinol) derivative, showed potent antiviral activity against all SARS-CoV-2 variants in both human cell lines and human…
New Perspectives on Antimicrobial Agents: Molnupiravir and Nirmatrelvir/Ritonavir for Treatment of COVID-19 - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged to cause pandemic respiratory disease in the past 2 years, leading to significant worldwide morbidity and mortality. At the beginning of the pandemic, only nonspecific treatments were available, but recently two oral antivirals have received emergency use authorization from the U.S. Food and Drug Administration for the treatment of mild to moderate coronavirus disease (COVID-19). Molnupiravir targets the viral polymerase…
Species-Specific Molecular Barriers to SARS-CoV-2 Replication in Bat Cells - Bats are natural reservoirs of numerous coronaviruses, including the potential ancestor of SARS-CoV-2. Knowledge concerning the interaction between coronaviruses and bat cells is sparse. We investigated the ability of primary cells from Rhinolophus and Myotis species, as well as of established and novel cell lines from Myotis myotis, Eptesicus serotinus, Tadarida brasiliensis, and Nyctalus noctula, to support SARS-CoV-2 replication. None of these cells were permissive to infection, not even the…
Resilience Enhancement Online Training for Nurses (REsOluTioN): Protocol for a Pilot Randomised Controlled Trial - CONCLUSIONS: The REsOluTioN trial will enable preliminary data to be gathered to indicate the online training’s effectiveness in enhancing nurses’ resilience in the workplace, with the potential for larger scale follow-on studies to identify its value to nurses working across a range of healthcare settings.
Selection of Bis-Indolyl Pyridines and Triphenylamines as New Inhibitors of SARS-CoV-2 Cellular Entry by Modulating the Spike Protein/ACE2 Interfaces - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent that has caused the current coronavirus disease (COVID) pandemic. Viral infection relies on the viral S (spike) protein/cellular receptor ACE2 interaction. Disrupting this interaction would lead to early blockage of viral replication. To identify chemical tools to further study these functional interfaces, 139,146 compounds from different chemical libraries were screened through an S/ACE2 in silico virtual…
Self-Masked Aldehyde Inhibitors of Human Cathepsin L Are Potent Anti-CoV-2 Agents - Cysteine proteases comprise an important class of drug targets, especially for infectious diseases such as Chagas disease (cruzain) and COVID-19 (3CL protease, cathepsin L). Peptide aldehydes have proven to be potent inhibitors for all of these proteases. However, the intrinsic, high electrophilicity of the aldehyde group is associated with safety concerns and metabolic instability, limiting the use of aldehyde inhibitors as drugs. We have developed a novel class of compounds, self-masked…