Although various COVID-19 vaccines have shown efficacy against placebo in randomized clinical trials, no head-to-head comparisons are yet available. This study aims to compare the efficacy of available COVID-19 vaccines. Vaccine trials searched in May 2021 were included. Data were extracted from Kaplan-Meier (KM) curves using the WebPlotDigitizer program for the individual participant (IP) data simulation. A mixed-effect acceleration failure model with log-logistic and Weibull distributions was used to estimate relative effects for individual vaccines as well as grouped by class: inactivated virus, mRNA, and viral vector. Primary studies were considered as the random effect in the model. Hazard ratios (HR) were estimated and compared across vaccine groups. All vaccines were efficacious in lowering symptomatic infection compared to placebo. CoronaVac, Ad26.COV2.S, ChAdOx1 nCoV-19, rAd26/rAd5, WIV04, HB02, and BNT162b2 showed 7.61 (4.50, 12.87), 6.77 (4.08, 11.24), 5.01 (2.93, 8.57), 4.50 (2.52, 8.01), 3.90 (2.04, 7.45), 3.18 (1.62, 6.21), and 2.15 (1.22, 3.78) times significantly higher risk of infection than mRNA-1273. mRNA vaccines were the most efficacious vaccine group compared to inactivated virus and viral vectors with HRs (95% CI) of 0.27 (0.20, 0.37) and 0.28 (0.21, 0.37), respectively. Although all vaccines showed significant protection compared to no vaccination. mRNA vaccines, including mRNA-1273 and BNT162b2, showed the highest efficacy in preventing symptomatic COVID-19 infection. Simulated IP data from the KM curve might allow treatment comparison when there is no primary study comparing active treatments.
We report SARS-CoV-2 neutralizing antibody titers in sera of triple-vaccinated individuals who received a booster dose of an original monovalent or a bivalent BA.1- or BA.4/BA.5-adapted vaccine, or had a breakthrough infection with Omicron variants BA.1, BA.2 or BA.4/BA.5. A bivalent BA.4/BA.5 booster or Omicron-breakthrough infection induced increased Omicron-neutralization titers compared with the monovalent booster. The XBB.1.5 variant effectively evaded neutralizing-antibody responses elicited by current vaccines and/or infection with previous variants.
This study investigated temporal variational structures of the COVID-19 pandemic in Japan using a time series analysis incorporating maximum entropy method (MEM) spectral analysis, which produces power spectral densities (PSDs). This method was applied to daily data of COVID-19 cases in Japan from January 2020 to February 2023. The analyses confirmed that the PSDs for data in both the pre- and post-Tokyo Olympics periods show exponential characteristics, which are universally observed in PSDs for time series generated from nonlinear dynamical systems, including the so-called susceptible/exposed/infectious/recovered (SEIR) model, well-established as a mathematical model of temporal variational structures of infectious disease outbreaks. The magnitude of the gradient of exponential PSD for the pre-Olympics period was smaller than that of the post-Olympics period, because of the relatively high complex variations of the data in the pre-Olympics period caused by a deterministic, nonlinear dynamical system and/or undeterministic noise. A 3-dimensional spectral array obtained by segment time series analysis indicates that temporal changes in the periodic structures of the COVID-19 data are already observable before the commencement of the Tokyo Olympics and immediately after the introduction of mass and workplace vaccination programs. Lessons from theoretical studies for measles control programs may be applicable to COVID-19.
Objectives: This study aims to evaluate the effect of coronavirus disease 2019 (COVID-19) on the long-term risk of digestive diseases in the general population. Design: Large-scale population-based cohort study based on a prospective cohort. Setting: UK Biobank cohort linked to multiple nationwide electronic health records databases. Participants: The cohort consisted of 112,311 individuals who survived the initial 30 days following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as two control groups: a contemporary group (n = 359,671) without any history of COVID-19, and a historical control group (n = 370,979) that predated the COVID-19 outbreak. Main outcome measures: Main outcomes were predefined digestive diseases. Hazard ratios and corresponding 95% confidence intervals (CI) were computed utilizing the Cox regression models after inverse probability weighting. Results: Compared with the contemporary control group, patients with previous COVID-19 infection had higher risks of digestive diseases, including functional gastrointestinal disorders (hazard ratios [HR] 1.95 (95% CI 1.62 to 2.35)); peptic ulcer disease (HR 1.27 (1.04 to 1.56)); gastroesophageal reflux disease (GERD) (HR 1.46 (1.34 to 1.58)); inflammatory bowel diseases (HR 1.40 (1.02 to 1.90)); gallbladder disease (HR 1.28 (1.13 to 1.46)); severe liver disease (HR 1.46 (1.12 to 1.90)); non-alcoholic liver disease (HR 1.33 (1.15 to 1.55)); and pancreatic disease (HR 1.43 (1.17 to 1.74)). The risks of GERD were stepwise increased with severity of the acute phase of COVID-19 infection. The results were consistent when using the historical cohort as the control group. Conclusions: Our study provides important insights into the association between COVID-19 and the long-term risk of digestive system disorders. COVID-19 patients are at a higher risk of developing gastrointestinal disorders, with stepwise increased risk with the severity and persisting even after one year follow-up.
Background: Vaccines have substantially mitigated the disproportional impact of SARS-CoV-2 on the high morbidity and mortality experienced by nursing home residents. However, variation in vaccine efficacy, immune senescence and waning immunity all undermine vaccine effectiveness over time. The introduction of the bivalent vaccine in September 2022 aimed to counter this increasing susceptibility and consequences of breakthrough infection, however data on the durability and protection of the vaccine are limited. We evaluated the durability of immunity and protection after the first bivalent vaccination to SARS-CoV-2 in nursing home residents. Methods: For the immunologic evaluation, community nursing home volunteers agreed to serial blood sampling before, at two weeks, three and six months after each vaccination for antibodies to spike protein and pseudovirus neutralization activity over time. Concurrent clinical outcomes were evaluated by reviewing electronic health record data from residents living in Veterans Administration managed nursing home units. Residents without recent infection but prior vaccination to SARS-CoV-2 were followed over time beginning with administration of the newly available bivalent vaccine using a target trial emulation (TTE) approach; TTE compared time to breakthrough infection, hospitalization and death between those who did and did not receive the bivalent vaccine. Results: We evaluated antibodies in 650 nursing home residents; 452 had data available following a first monovalent booster, 257 following a second monovalent booster and 321 following a bivalent vaccine. We found a rise in BA.5 neutralization activity from the first and second monovalent boosters through the bivalent vaccination regardless of prior SARS-CoV-2 history. Titers declined at three and six months after the bivalent vaccination but generally exceeded those at three months compared to either prior boost. BA.5 neutralization titers six months after the bivalent vaccination were diminished but had detectable levels in 80% of infection-naive and 100% of prior infected individuals. TTE evaluated 5903 unique subjects, of whom 2235 received the bivalent boost. TTE demonstrated 39% or greater reduction in risk of infection, hospitalization or death at four months following the bivalent boost. Conclusion: Immunologic results mirrored those of the TTE and suggest bivalent vaccination added substantial protection for up to six months after bivalent vaccination with notable exceptions. However, the level of protection declined over this period, and by six months may open a window of added vulnerability to infection before the next updated vaccine becomes available. We strongly agree with the CDC recommendation that those who have not received a bivalent vaccination receive that now and these results support a second bivalent booster for those at greatest risk which includes many nursing home residents.
Background: The COVID-19 pandemic, extreme weather events, and the Russian invasion of Ukraine have highlighted global food system vulnerabilities and a lack of preparedness and prospective planning for increasingly complex disruptions. This has spurred an interest in food system resilience. Despite the elevated interest in food system resilience, there is a lack of comparative analyses of national-level food system resilience efforts. An improved understanding of the food system resilience landscape can support and inform future policies, programs, and planning. Methods: We conducted a cross-country comparison of national-level food system resilience activities from Australia, Aotearoa (New Zealand), Sweden, and the United States. We developed upon and adapted the resilience framework proposed by Harris and Spiegel to compare actions derived from thirteen national food system resilience documents. We coded the documents based on how the governments determined actions by food system resilience attribute utilized, part of the food supply chain, specific shocks or stressors, implementation level, the temporal focus of action, and the expected impact on food security. We analyzed and compared countries coded categories, subcategories, and category combinations. Results: The results showed that countries are using multi-pronged policy actions to address food system resilience issues and are focused on both retrospective reviews and prospective models of disruptive events to inform their decisions. Some work has been done towards preparing for climate change and other natural disasters, but not as much for other shocks or stressors. Conclusions: The analysis identified potential gaps, concentrations, and themes in national food systems resilience. The framework can be applied to augment existing policy, create new policy, as well as to supplement and complement other existing frameworks.
Background: Parkinson’s disease has been identified as a risk factor for severe Coronavirus disease 2019 (COVID-19) outcomes. However, whether the significant high risk of death from COVID-19 in people with Parkinson’s disease is specific to the disease itself or driven by other concomitant and known risk factors such as comorbidities, age, and frailty remains unclear. Objective: To investigate clinical profiles and outcomes of people with Parkinson’s disease and atypical parkinsonian syndromes who tested positive for COVID-19 in the hospital setting in a multicentre UK-based study. Methods: A retrospective cohort study of Parkinson’s disease patients with a positive COVID-19 test admitted to hospital between February 2020 and July 2021. An online survey was used to collect data from clinical care records, recording patient, Parkinson’s disease and COVID-19 characteristics. Associations with time-to-mortality and severe outcomes were analysed using either the Cox proportional hazards model or logistic regression models, as appropriate. Results: Data from 552 admissions were collected: 365 (66%) male; median (inter-quartile range) age 80 (74-85) years. The 34-day mortality rate was 38.4%; male sex, increased age and frailty, Parkinson’s dementia syndrome, requirement for respiratory support and no vaccination were associated with increased mortality risk. Community-acquired COVID-19 and co-morbid chronic neurological disorder were associated with increased odds of requiring respiratory support. Hospital-acquired COVID-19 and delirium were associated with requiring an increase in care level post-discharge. Conclusions: This first, multicentre, UK-based study on people with Parkinson’s disease or atypical parkinsonian syndromes, hospitalised with COVID-19, adds and expands previous findings on clinical profiles and outcomes in this population.
Background Data suggest that vaccine effectiveness against Covid-19-associated hospital admission and mortality is augmented with booster doses, but the benefit wanes within several months. However, the CDC recently concluded that second doses of bivalent vaccines this Spring were not warranted because existing data were insufficient to analyze the benefits of such a strategy. Therefore, our objective was to assess whether routinely boosting high-risk populations at least every 6 months may be warranted, depending on age and immune status. Methods Utilizing a database of 3,574,243 members of Clalit Health Services (CHS), we analyzed the medical records of individuals who received none, or at least one dose of the BNT162b2 mRNA COVID-19 vaccine between January 1, 2021, and April 5, 2022. We examined the risk of moderate-to-severe Covid-19 hospitalization or death stratified by age group, immune status and time since receipt of the last vaccine dose during the early Omicron wave in Israel (December 20, 2021 to April 5, 2022). The number needed to vaccinate (NNV) was calculated as the inverse of the absolute risk reduction for various subgroups and Covid-19 waves. Results Eligibility criteria were met by 3,381,480 CHS members. The absolute risk of Covid-19 moderate-to-severe hospitalization or death during the Omicron wave increased with age, immunocompromised status, and time since receipt of the last vaccine dose. The NNVs varied greatly by age and immune status and were contingent on various disease prevalence scenarios. Among the severely immunocompromised, boosting at the start of the Omicron wave had an NNV ranging from 87 (95% CI 70-109) in persons ages ≥80 to 1,037 (95% CI 999 -1,513) in persons ages 12-59. In the lower-prevalence periods, the NNV for 6-month booster cadencing remained favorable for immunocompromised people in all age groups and immunocompetent people ages ≥60. Conclusions Our study provides evidence for the potential benefit of a routine 6-month cadence for Covid-19 boosters for the highest-risk groups, and possibly more frequently, even during relatively lower Covid-19 prevalence.
Background: Artificial intelligence (AI) technologies can help solve the significant problem of missed findings in radiology studies. An important issue is assessing the economic benefits of implementing AI. Aim: to evaluate the frequency of missed pathologies detection and the economic potential of AI technology for chest CT, validated by expert radiologists, compared with radiologists without access to AI in a private medical center. Methods: An observational, single-center retrospective study was conducted. The study included chest CTs without IV contrast performed from 01.06.2022 to 31.07.2022 in “Yauza Hospital” LLC, Moscow. The CTs were processed using a complex AI algorithm for ten pathologies: pulmonary infiltrates, typical for viral pneumonia (COVID-19 in pandemic conditions); lung nodules; pleural effusion; pulmonary emphysema; thoracic aortic dilatation; pulmonary trunk dilatation; coronary artery calcification; adrenal hyperplasia; osteoporosis (vertebral body height and density changes). Two experts analyzed CTs and compared results with AI. Further routing was determined according to clinical guidelines for all findings initially detected and missed by radiologists. The lost potential revenue (LPR) was calculated for each patient according to the hospital price list. Results: From the final 160 CTs, the AI identified 90 studies (56%) with pathologies, of which 81 studies (51%) were missing at least one pathology in the report. The “second-stage” LPR for all pathologies from 81 patients was RUB 2,847,760 (＄37,251 or CNY 256,218). LPR only for those pathologies missed by radiologists but detected by AI was RUB 2,065,360 (＄27,017 or CNY 185,824). Conclusion: Using AI for chest CTs as an “assistant” to the radiologist can significantly reduce the number of missed abnormalities. AI usage can bring 3.6 times more benefits compared to the standard model without AI. The use of complex AI for chest CT can be cost-effective.
The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the cellular disease dynamics remains limited. In our unique COVID-19 human challenge study we used single cell genomics of nasopharyngeal swabs and blood to temporally resolve abortive, transient and sustained infections in 16 seronegative individuals challenged with preAlpha-SARS-CoV-2. Our analyses revealed rapid changes in cell type proportions and dozens of highly dynamic cellular response states in epithelial and immune cells associated with specific timepoints or infection status. We observed that the interferon response in blood precedes the nasopharynx, and that nasopharyngeal immune infiltration occurred early in transient but later in sustained infection, and thus correlated with preventing sustained infection. Ciliated cells showed an acute response phase, upregulated MHC class II while infected, and were most permissive for viral replication, whilst nasal T cells and macrophages were infected non-productively. We resolve 54 T cell states, including acutely activated T cells that clonally expanded while carrying convergent SARS-CoV-2 motifs. Our novel computational pipeline (Cell2TCR) identifies activated antigen-responding clonotype groups and motifs in any dataset. Together, we show that our detailed time series data (covid19cellatlas.org) can serve as a 9Rosetta stone9 for the epithelial and immune cell responses, and reveals early dynamic responses associated with protection from infection.
The COVID-19 pandemy has created a radically new situation where most countries provide raw measurements of their daily incidence and disclose them in real time. This enables new machine learning forecast strategies where the prediction might no longer be based just on the past values of the current incidence curve, but could take advantage of observations in many countries. We present such a simple global machine learning procedure using all past daily incidence trend curves. Each of the 27,418 COVID-19 incidence trend curves in our database contains the values of 56 consecutive days extracted from observed incidence curves across 61 world regions and countries. Given a current incidence trend curve observed over the past four weeks, its forecast in the next four weeks is computed by matching it with the first four weeks of all samples, and ranking them by their similarity to the query curve. Then the 28 days forecast is obtained by a statistical estimation combining the values of the 28 last observed days in those similar samples. Using comparison performed by the European Covid-19 Forecast Hub with the current state of the art forecast methods, we verify that the proposed global learning method, EpiLearn, compares favorably to methods forecasting from a single past curve.
Efficacy and Safety of Nirmatrelvir/Ritonavir for Treating Omicron Variant of COVID-19 - Condition: Omicron Variant of COVID-19
Intervention: Drug: Nirmatrelvir/Ritonavir
Sponsor: Xiangao Jiang
Completed
A Study of mRNA-1283.222 Injection Compared With mRNA-1273.222 Injection in Participants ≥12 Years of Age to Prevent COVID-19 - Condition: COVID-19
Interventions: Biological: mRNA-1283.222; Biological: mRNA-1273.222
Sponsor: ModernaTX, Inc.
Recruiting
Postoperative Sugammadex After COVID-19 - Conditions: General Anesthesia; COVID-19
Interventions: Drug: Sugammadex Sodium; Drug: neostigmine 50µg/kg + glycopyrollate 0.01mg/kg
Sponsor: Korea University Ansan Hospital
Not yet recruiting
Evaluation of the RD-X19 Treatment Device in Individuals With Mild COVID-19 - Condition: COVID-19
Interventions: Device: RD-X19; Device: Sham
Sponsor: EmitBio Inc.
Recruiting
Assessment of Immunogenicity, Safety and Reactogenicity of a Booster Dose of Various COVID-19 Vaccine Platforms in Individuals Primed With Several Regimes. - Condition: COVID-19
Interventions: Biological: SCB-2019/Clover; Biological: AstraZeneca/Fiocruz; Biological: Pfizer/Wyeth
Sponsors: D’Or Institute for Research and Education; Bill and Melinda Gates Foundation
Active, not recruiting
A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study to Determine the Safety and Effectiveness of Azeliragon in the Treatment of Patients Hospitalized for Coronavirus Disease 2019 (COVID-19) - Condition: COVID-19
Interventions: Drug: Azeliragon; Drug: Placebo
Sponsor: Salim S. Hayek
Recruiting
To Evaluate the Safety and Efficacy of Meplazumab in Treatment of Post-COVID-19 - Condition: Post-COVID-19
Interventions: Biological: Meplazumab for injection; Other: Normal saline
Sponsor: Jiangsu Pacific Meinuoke Bio Pharmaceutical Co Ltd
Recruiting
Cognitive-behavioral Therapy for Mental Disorder in COVID-19 Survivors - Condition: Post Acute COVID-19 Syndrome
Intervention: Behavioral: mindfulness-based stress reduction (MBSR) and cognitive behavioral therapy (CBT)
Sponsor: Azienda Socio Sanitaria Territoriale di Lecco
Recruiting
Efficacy of Lactobacillus Paracasei PS23 for Patients With Post-COVID-19 Syndrome - Condition: Post-COVID-19 Syndrome
Intervention: Dietary Supplement: PS23 heat-treated
Sponsors: Mackay Memorial Hospital; Bened Biomedical Co., Ltd.
Recruiting
A Coping and Resilience Intervention for Adolescents - Condition: COVID-19 Pandemic
Interventions: Behavioral: Coping and Resilience Intervention for Adolescents; Other: Printing materials of Coping and Resilience Intervention for Adolescents
Sponsor: Taipei Medical University
Enrolling by invitation
Effect of Telerehabilitation Practice in Long COVID-19 Patients - Conditions: Long COVID-19; Long COVID; Post COVID-19 Condition; Post-COVID-19 Syndrome; Post-COVID Syndrome
Interventions: Behavioral: Telerehabilitation; Behavioral: Standard rehabilitation care
Sponsor: Indonesia University
Recruiting
The Safety, Tolerability and Pharmacokinetics Study of RAY1216 in Healthy Adult Participants - Condition: COVID-19 (Coronavirus Disease 2019)
Interventions: Drug: RAY1216 dose 1; Drug: RAY1216 dose 2; Drug: RAY1216 dose 3; Drug: RAY1216 dose 4 &ritonavir Drug: RAY1216 dose 5; Drug: RAY1216 dose 6; Drug: RAY1216 dose 7; Drug: RAY1216 dose 8; Drug: RAY1216 dose 9; Drug: RAY1216 dose 10
Sponsor: Guangdong Raynovent Biotech Co., Ltd
Completed
Computerized Training of Attention and Working Memory in Post COVID-19 Patients With Cognitive Complaints - Conditions: COVID-19; Cognitive Impairment; Cognition Disorder; Memory Disorders; Attention Deficit; Memory Impairment; Memory Loss; Attention Impaired
Intervention: Device: RehaCom
Sponsor: Erasmus Medical Center
Not yet recruiting
Strategies and Treatments for Respiratory Infections &Amp; Viral Emergencies (STRIVE): Immune Modulation Strategy Trial - Condition: COVID-19
Interventions: Drug: abatacept infusion; Drug: Placebo group
Sponsor: University of Minnesota
Not yet recruiting
A Study of Silmitasertib (CX-4945) in Healthy Subject - Condition: COVID-19
Intervention: Drug: CX-4945
Sponsor: Senhwa Biosciences, Inc.
Active, not recruiting
RAAS inhibition and beyond-cardiovascular medications in patients at risk of or affected by COVID-19 - The COVID-19 pandemic led to an enormous burden on healthcare systems worldwide. Causal therapy is still in its infancy. Contrary to initial views that the use of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin II receptor blockers (ARBs) may increase the risk for a deleterious disease course, it has been shown that these agents may actually be beneficial for patients affected by COVID-19. In this article, we provide an overview of the three most commonly used classes of drugs in…
Identification and Comparison of the Sialic Acid-Binding Domain Characteristics of Avian Coronavirus Infectious Bronchitis Virus Spike Protein - Infectious bronchitis virus (IBV) infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host factors and fuses the viral and cell membranes. The N-terminal domain of the S1 subunit of IBV S protein binds to sialic acids, but the precise location of the sialic acid binding domain (SABD) and the role of the SABD in IBV-infected chickens remain unclear. Here, we identify the S1 N-terminal amino acid (aa) residues 19 to 227 (209 aa total) of IBV strains SD (GI-19) and…
Antiviral Nanobiologic Therapy Remodulates Innate Immune Responses to Highly Pathogenic Coronavirus - Highly pathogenic coronavirus (CoV) infection induces a defective innate antiviral immune response coupled with the dysregulated release of proinflammatory cytokines and finally results in acute respiratory distress syndrome (ARDS). A timely and appropriate triggering of innate antiviral response is crucial to inhibit viral replication and prevent ARDS. However, current medical countermeasures can rarely meet this urgent demand. Here, an antiviral nanobiologic named CoVR-MV is developed, which…
The human E3 ligase RNF185 is a regulator of the SARS-CoV-2 envelope protein - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks multiple human proteins during infection and viral replication. To examine whether any viral proteins employ human E3 ubiquitin ligases, we evaluated the stability of SARS-CoV-2 proteins with inhibition of the ubiquitin proteasome pathway. Using genetic screens to dissect the molecular machinery involved in the degradation of candidate viral proteins, we identified human E3 ligase RNF185 as a regulator of protein stability for…
Production and optimization of novel Sphorolipids from Candida parapsilosis grown on potato peel and frying oil wastes and their adverse effect on Mucorales fungal strains - CONCLUSION: The findings demonstrated the potential application of the SLs produced economically from agricultural waste as an effective and safer alternative for the treatment of infection caused by black fungus.
Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2 - Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2 (IC(50) = 8.26 μM), while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 μM (EC(50))….
Hemoptysis after COVID-19 and the importance of differential diagnosis: Birt-Hogg-Dubé syndrome - Birt-Hogg-Dubé syndrome is a genodermatosis of autosomal dominant inheritance characterized by mutations in the folliculin (FLCN) gene. There is an inappropriate inhibition/activation of a protein, the foliculin, which may cause tumor lesions in skin, renal and lung lesions; they could have more risk of developing pneumothorax compared to the normal population. A 38-year-old male patient with bronchial asthma who consulted for hemoptysis three weeks after recovery from COVID-19 infection. A…
Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19 - The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory…
Role of Cytochrome P450 2C9 in COVID-19 Treatment: Current Status and Future Directions - The major human liver drug metabolising cytochrome P450 (CYP) enzymes are downregulated during inflammation and infectious disease state, especially during coronavirus disease 2019 (COVID-19) infection. The influx of proinflammatory cytokines, known as a ‘cytokine storm’, during severe COVID-19 leads to the downregulation of CYPs and triggers new cytokine release, which further dampens CYP expression. Impaired drug metabolism, along with the inevitable co-administration of drugs or ’combination…
Design and statistical optimisation of emulsomal nanoparticles for improved anti-SARS-CoV-2 activity of N-(5-nitrothiazol-2-yl)-carboxamido candidates: in vitro and in silico studies - In this article, emulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a-3g) in an attempt to improve their biological availability and antiviral activity. Next, both cytotoxicity and anti-SARS-CoV-2 activities of the examined compounds loaded EMLs (F3a-g) were assessed in Vero E6 cells via MTT assay to calculate the CC(50) and inhibitory concentration 50 (IC(50)) values. The most potent 3e-loaded EMLs (F3e) elicited a selectivity index of 18 with…
Barriers to recruiting primary care practices for implementation research during COVID-19: A qualitative study of practice coaches from the Stop Unhealthy (STUN) Alcohol Use Now trial - Background: The COVID-19 pandemic has brought widespread change to health care practice and research. With heightened stress in the general population, increased unhealthy alcohol use, and added pressures on primary care practices, comes the need to better understand how we can continue practice-based research and address public health priorities amid the ongoing pandemic. The current study considers barriers and facilitators to conducting such research, especially during the COVID-19 pandemic,…
Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury - INTRODCUTION: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is therefore necessary.
An Azapeptide Platform in Conjunction with Covalent Warheads to Uncover High-Potency Inhibitors for SARS-CoV-2 Main Protease - Main protease (M (Pro) ) of SARS-CoV-2, the viral pathogen of COVID-19, is a crucial nonstructural protein that plays a vital role in the replication and pathogenesis of the virus. Its protease function relies on three active site pockets to recognize P1, P2, and P4 amino acid residues in a substrate and a catalytic cysteine residue for catalysis. By converting the P1 Cα atom in an M (Pro) substrate to nitrogen, we showed that a large variety of azapeptide inhibitors with covalent warheads…
Repurposing niclosamide as a novel anti-SARS-Cov-2 drug by restricting entry protein CD147 - Background The burst of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the global COVID-19 pandemic. But until today only limited numbers of drugs are discovered to treat COVID-19 patients. Even worse, the rapid mutations of SARS-CoV-2 compromise the effectiveness of existing vaccines and neutralizing antibodies due to the increased viral transmissibility and immune escape. CD147-spike protein, one of the entries of SRAR-CoV-2 into host cells, has been reported as a…
The 3’UTR region of the DNA repair gene PARP-1 May increase the severity of COVID-19 by altering the binding of antiviral miRNAs - COVID-19 may cause the release of systemic inflammatory cytokines resulting in severe inflammation. PARP-1 has been identified as a nuclear enzyme that is activated by DNA strand breaks. It has been suggested that PARP-1 has a role in the cytokine storm shown as a cause of mortality in COVID-19, and its inhibition may adversely affect the replication of SARS -CoV-2. We aimed to investigate the relationship between PARP-1 gene polymorphisms and the clinical severity of COVID-19. rs8679 TT…