Rationale: Opaganib, an oral sphingosine kinase-2 inhibitor with antiviral and anti-inflammatory properties, was shown to inhibit SARS-CoV-2 replication in vitro. We thus considered that opaganib could be beneficial for moderate to severe COVID-19 pneumonia. Objectives: To evaluate the effect of opaganib on supplemental oxygen requirements, time to hospital discharge and its safety in COVID-19 pneumonia hospitalized patients requiring supplemental oxygen. Methods: This Phase 2a, randomized, double-blind, placebo-controlled study, was conducted between July and December 2020 in eight sites in the USA. Forty-two enrolled patients received opaganib (n=23) or placebo (n=19) added to standard of care for up to 14 days and were followed up for 28 days after their last dose of investigational product. Main Results: By Day 14, 50.0% of patients in the opaganib and 22.2% in the placebo group no longer required supplemental oxygen for at least 24 hours, while 86.4% and 55.6%, respectively, were discharged from hospital. The relative decrease in total supplemental oxygen requirement from baseline to Day 14 was 61.6% in the opaganib versus 46.7% in the placebo arms. The incidence of ≥ Grade 3 treatment-emergent adverse events was 17.4% and 33.3% in the opaganib and placebo groups, respectively. Three deaths occurred in each group. Conclusions: In this proof-of-concept study, patients receiving oral opaganib required less supplemental oxygen, resulting in earlier hospital discharge, with no safety concerns arising. These findings support further evaluation of opaganib in this population.
The COVID-19 trajectories worldwide have shown several surprising features which are outside the purview of classical epidemiological models. These include (a) almost constant and low daily case rates over extended periods of time, (b) sudden waves emerging from the above solution despite no or minimal change in the level of non-pharmaceutical interventions (NPI), and (c) reduction or flattening of case counts even after relaxation of NPI. To explain these phenomena, we add contact tracing to our recently developed cluster seeding and transmission (CST) model, which is predicated on heterogeneous rather than homogeneous mixing of people in society. With this addition, we find no fewer than four effects which make prediction of epidemic trajectories uncertain. These are (a) cryptogenic instability, where a small increase in population-averaged contact rate causes a large increase in cases, (b) critical mass effect, where a wave can manifest after weeks of quiescence with no change in parameter values, (c) knife-edge effect, where a small change in parameter across a critical value can cause a huge change in the response of the system, and (d) hysteresis effect, where the timing and not just the strength of a particular NPI determines the subsequent evolution of the epidemic. Despite these effects however, it is a robust conclusion that a good contact tracing program can effectively substitute for much more invasive measures. We further find that the contact tracing capacity ratio - a metric of the stress to which the tracers are subject - can act as a reliable early warning indicator of an imminent epidemic wave. Extensive simulations demonstrate that whenever there is a drop in capacity ratio during a period of low daily infections, there is a very high probability of the case counts rising significantly in the immediate future.
Background There was a national roll out of “COVID Virtual Wards” (CVW) during England9s second COVID-19 wave (Autumn 2020 - Spring 2021). These services used remote pulse oximetry monitoring for COVID-19 patients following discharge from hospital. A key aim was to enable rapid detection of patient deterioration. It was anticipated that the services would support early discharge and avoid readmissions, reducing pressure on beds. This study is an evaluation of the impact of the CVW services on hospital activity. Methods Using retrospective patient-level hospital admissions data, we built multivariate models to analyse the relationship between the implementation of CVW services and hospital activity outcomes: length of COVID-19 related stays and subsequent COVID-19 readmissions within 28 days. We used data from more than 98% of recorded COVID-19 hospital stays in England, where the patient was discharged alive between mid- August 2020 and late February 2021. Findings We found a longer length of stay for COVID-19 patients discharged from hospitals where a CVW was available, when compared to patients discharged from hospitals where there was no CVW (adjusted IRR 1.05, 95% CI 1.01 to 1.09). We found no evidence of a relationship between the availability of CVW and subsequent rates of readmission for COVID-19 (adjusted OR 0.95, 95% CI 0.89 to 1.02). Interpretation We found no evidence of early discharges or reduced readmissions associated with the roll out of COVID Virtual Wards across England. Our analysis made pragmatic use of national-scale hospital data, but it is possible that a lack of specific data (for example, on which patients were enrolled) may have meant that true impacts, especially at a local level, were not ultimately discernible. Funding This is independent research funded by the National Institute for Health Research, Health Services & Delivery Research programme and NHSEI.
Background Coronavirus disease 2019 (COVID-19) is also associated with other co-morbidities among with previous and current pulmonary tuberculosis (PTB). PTB is a risk factor for COVID-19, both in terms of severity and mortality, regardless of human immunodeficiency virus (HIV) status. However, there is less information available on COVID-19 associated with PTB in point of view incidence and mortality rates in sub-Saharan Africa (SSA) as a high burden TB region. This systematic review served to provide data synthesis of available evidence on COVID-19/PTB incidence and case fatality rates, and mortality rate found in clinical and post-mortem COVID-19/PTB diagnostics in SSA. Methods We conducted a systematic electronic search in the PubMed, Medline, Google Scholar, Medrxix and COVID-19 Global literature on coronavirus disease databases for studies including COVID-19 associated with PTB in sub-Saharan Africa. The main outcomes were the proportion of people with COVID-19 associated to current /or previous PTB and the case fatality associated to COVID-19/PTB. The combination method was based on methodological similarities in the included random effect model studies using Prometa 3 software. We further undertook sensitivity analysis and meta-regression. Results From the 548 references extracted by the literature search, 25 studies were selected and included in the meta-analysis with a total of 191, 250 COVID-19 infected patients and 11, 452 COVID-19 deaths. The pooled COVID-19/PTB incidence was 2% [1%-3%] and mortality of 10% [4%-20%]. The pooled estimates for case fatality rate among COVID-19/PTB were 6% [3%-11%] for clinical PTB diagnostic and 26% [14%-48%] for post-mortem PTB diagnostic. Meta-regression model including the effect sizes and cumulative COVID-19 cases (P= 0.032), HIV prevalence (P= 0.041) and TB incidence (P= 0.002) to explained high heterogeneity between studies. Conclusion As a summary, the incidence of TB associated with COVID-19 and case fatality rates are higher in SSA. However, COVID-19 associated to TB may be underreported in the studies conducted in SSA as the post-mortem TB diagnostic was higher. Large-scale cohort studies that adequately clear tool on previous and/or current TB diagnostic tools are required to confirmed COVID-19/TB incidence and case fatality in SSA.
Background COVID-19 has highlighted the need for new methods of pharmacovigilance. Here we use community volunteers to obtain systematic information on vaccine effectiveness and the nature and severity of breakthrough infections. Methods Between December 15, 2020 to September 16, 2021, 10,412 unpaid community-based participants reported the following information to an on-line registry: COVID-19 test results, vaccination (Pfizer, Moderna, or Johnson & Johnson), COVID-19 symptoms and perceived severity using a 4-point scale. COVID-19 infections were described for those who were 1) fully vaccinated, 2) partially vaccinated (received first of two dose vaccines or were <14 days post- final dose), or 3) unvaccinated. Results Of 8,554 who were vaccinated, COVID-19 infections were reported by 74 (1.0%) of those who were fully vaccinated and 198 (2.3%) of those who were partially vaccinated. Among the 74 participants who reported a breakthrough infection after full vaccination, the median time to reported positive test result was 104.5 days (Interquartile range: 77-135 days), with no difference among vaccine manufactures. One quarter (25.7%) of breakthrough infections in the fully vaccinated cases were asymptomatic. More than 97% of fully vaccinated participants reported no moderate/severe symptoms compared to 89.3% of the unvaccinated cases; and only 1.4% of fully vaccinated participants reported experiencing at least 3 moderate to severe symptoms compared to 7.8% in the unvaccinated. Conclusion Person-generated health data, also referred to as patient-reported outcomes, is a useful resource for quantifying breakthrough infections and their severity, showing here that fully vaccinated participants report no or very mild COVID-19 symptoms.
Objective To conduct a comprehensive systematic review and meta-analysis of all recommended SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) vaccines in people living with HIV (PLWH), as well as an overview of the safety, tolerability, and efficacy of the vaccines in PLWH. Methods We searched six databases, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Medline, Medrxiv, Global research on COVID-19 database, and Google Scholar for studies investigating the effects of SARS-CoV-2 vaccines on PLWH. Results of the association were summarised by SARS- CoV-2 IgG seroconversion and level, vaccines efficacy and tolerability. A meta-analysis was performed for studies, using random-effects model and a pooled RR with 95% CI was reported. Results Twenty-three of the 1052 studies screened met the inclusion criteria. The review included 28, 246 participants among whom 79.55% (22,469/28, 246) were PLWH with median CD4 >=200 cells/mm3. The pooled estimate of SARS-CoV-2 IgG seroconversion and positive neutralizing antibodies after the second vaccination dose between PLWH vs HIV negative were RR 0.95 (95%CI: 0.92 to 0.99, P = 0.006) and 0.88 (95%CI: 0.82 to 0.95, P = 0.0007), respectively. The mean difference of IgG antibodies level (BAU/ml) was found higher in mRNA vaccines MD -1444.97 (95%CI: -1871.39 to -1018.55). PLWH with CD4 less than 500 cells/mm3 had 15% risk reduction of neutralizing antibodies response compared to those with CD4>=500 cells/mm3 (P = 0.003). The SARS-CoV-2 vaccine effectiveness was 65% (95%CI: 56% to 72%, P <0.001) among vaccinated compared to unvaccinated PLWH. PLWH with CD4 count <350 cells/mm3 had lower vaccine effectiveness compared to CD4 count >=350 cells/mm3 with 59% vs 72%, respectively. Vaccine tolerability was the same between PLWH and HIV negatives. Conclusion According to our findings, PLWH with CD4>=200 cells/mm3 had lower immunogenicity and antigenicity in COVID-19 vaccines than HIV negatives. Additional doses of SARS-CoV-2 vaccination are needful in PLWH.
The interplay between the virus, infected cells and the immune responses to SARS-CoV-2 is still under debate. Extending the basic model of viral dynamics we propose here a formal approach to describe the neutralizing versus weakly (or non-)neutralizing scenarios and compare with the possible effects of antibody-dependent enhancement (ADE). The theoretical model is consistent with data available from the literature; we show that weakly neutralizing antibodies or ADE can both give rise to either final virus clearance or disease progression, but the immuno-dynamic is different in each case. Given that a significant part of the world population is already naturally immunized or vaccinated, we also discuss the implications on secondary infections, infections following vaccination or in presence of immune system dysfunctions.
Background: An accurate system to predict mortality in patients requiring intubation for COVID-19 could help to inform consent, frame family expectations and assist end-of-life decisions. Research objective: To develop and validate a mortality prediction system called C-TIME (COVID-19 Time of Intubation Mortality Evaluation) using variables available before intubation, determine its discriminant accuracy, and compare it to APACHE IVa and SOFA. Methods: A retrospective cohort was set in 18 medical-surgical ICUs, enrolling consecutive adults, positive by SARS-CoV 2 RNA by reverse transcriptase polymerase chain reaction or positive rapid antigen test, and undergoing endotracheal intubation. All were followed until hospital discharge or death. The combined outcome was hospital mortality or terminal extubation with hospice discharge. Twenty-five clinical and laboratory variables available 48 hours prior to intubation were entered into multiple logistic regression (MLR) and the resulting model was used to predict mortality of validation cohort patients. AUROC was calculated for C-TIME, APACHE IVa and SOFA. Results: The median age of the 2,440 study patients was 66 years; 61.6 percent were men, and 50.5 percent were Hispanic, Native American or African American. Age, gender, COPD, minimum mean arterial pressure, Glasgow Coma scale score, and PaO2/FiO2 ratio, maximum creatinine and bilirubin, receiving factor Xa inhibitors, days receiving non-invasive respiratory support and days receiving corticosteroids prior to intubation were significantly associated with the outcome variable. The validation cohort comprised 1,179 patients. C-TIME had the highest AUROC of 0.75 (95%CI 0.72-0.79), vs 0.67 (0.64-0.71) and 0.59 (0.55-0.62) for APACHE and SOFA, respectively (Chi2 P<0.0001). Conclusions: C-TIME is the only mortality prediction score specifically developed and validated for COVID-19 patients who require mechanical ventilation. It has acceptable discriminant accuracy and goodness-of-fit to assist decision-making just prior to intubation. The C-TIME mortality prediction calculator can be freely accessed on-line at https://phoenixmed.arizona.edu/ctime.
Background: Neutralizing monoclonal antibodies (mAbs) are authorized for early symptomatic COVID-19 patients. Whether mAbs are effective against the SARS-CoV-2 Delta variant, among vaccinated patients, or for prevention of mortality remains unknown. Objective: To evaluate the effectiveness of mAb treatment in preventing progression to severe disease during the Delta phase of the pandemic and based on key baseline risk factors. Design, Setting, and Patients: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from November 2020-October 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data. Using propensity matching, we selected approximately 2.5 patients not receiving mAbs for each patient who received mAbs. Exposure: Neutralizing mAb treatment under emergency use authorization Main Outcomes: The primary outcome was 28-day hospitalization; secondary outcomes included mortality and severity of hospitalization. Results: Of 36,077 patients with SARS-CoV-2 infection, 2,675 receiving mAbs were matched to 6,677 not receiving mAbs. Compared to mAb-untreated patients, mAb-treated patients had lower all-cause hospitalization (4.0% vs 7.7%; adjusted OR 0.48, 95%CI 0.38-0.60) and all-cause mortality (0.1% vs. 0.9%; adjusted OR 0.11, 95%CI 0.03-0.29) to day 28; differences persisted to day 90. Among hospitalized patients, mAb-treated patients had shorter hospital length of stay (5.8 vs. 8.5 days) and lower risk of mechanical ventilation (4.6% vs. 16.6%). Relative effectiveness was similar in preventing hospitalizations during the Delta variant phase (adjusted OR 0.35, 95%CI 0.25-0.50) and across subgroups. Lower number-needed-to-treat (NNT) to prevent hospitalization were observed for subgroups with higher baseline risk of hospitalization (e.g., multiple comorbidities (NNT=17) and not fully vaccinated (NNT=24) vs. no comorbidities (NNT=88) and fully vaccinated (NNT=81). Conclusion: Real-world evidence demonstrated mAb effectiveness in reducing hospitalization among COVID-19 outpatients, including during the Delta variant phase, and conferred an overall 89% reduction in 28-day mortality. Early outpatient treatment with mAbs should be prioritized, especially for individuals with highest risk for hospitalization.
Introduction: Ethiopia registered its first case of COVID-19 on March 13, 2020. We aimed to assess maternal, newborn, and child health care (MNCH) utilization during the first six months of the COVID-19 pandemic, as well as potential barriers and enablers of service utilization from health care providers and clients. Methods: Mixed study design was conducted as part of the Birhan Health and Demographic Surveillance System in Ethiopia. The trend of service utilization during the first six months of COVID-19 was compared to corresponding time and data points of the preceding year. Result: Service utilization of new family planning visits (43.2 to 28.5/month, p = 0.014) and sick under five child visits (225.0 to 139.8/month, P = 007) declined during the initial six months of the pandemic compared to the same period in the preceding year. Antenatal and postnatal care visits, facility delivery rates, and child routine immunization visits also decreased although this did not reach statistical significance. Interviews with health care providers and clients highlighted several barriers to service utilization during COVID-19, including fear of disease transmission, economic hardship, and transport service disruptions and restrictions. Enablers of service utilization included communities9 decreased fear of COVID-19, and awareness-raising activities. Conclusion: Provision of essential MNCH services is crucial to ascertain favorable maternal and child health outcomes. In low- and middle-income country settings like Ethiopia, health systems might be fragile to withstand the caseloads and priority setting due to the pandemic. Our study presents early findings on the utilization of MNCH services that were maintained except sick child and new family planning visits. Government leaders, policy makers, and clinicians who wish to improve the resilience of their health system will need to continuously monitor service utilization and clients9 evolving concerns during the pandemic to prevent increases in maternal and child morbidity and mortality.
Phase III Study of Novaferon in Non-hospitalized Adult Patients With Mild COVID-19 - Condition: Covid19
Interventions: Biological: Novaferon; Biological: Placebo
Sponsors: Genova Inc.; Tokyo Shinagawa Hospital
Recruiting
Evaluation of Safety & Efficacy of MIR 19 ® Inhalation Solution in Patients With Moderate COVID-19 - Condition: COVID-19
Interventions: Drug: MIR 19 ®; Combination Product: Standard COVID-19 therapy
Sponsors: National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia; St. Petersburg Research Institute of Vaccines and Sera
Completed
Human COVID-19 Immunoglobulin (COVID-HIG) Therapy for COVID-19 Patients - Condition: COVID-19
Interventions: Biological: Human COVID-19 immunoglobulin (pH4) for intravenous injection; Drug: Placebo
Sponsors: Sinopharm Wuhan Plasma-derived Biotherapies Co., Ltd.; China National Biotec Group Company Limited; Beijing Tiantan Biological Products Co., Ltd.
Not yet recruiting
A Telemedicine Brief Mindfulness Intervention in Post-COVID-19 - Condition: Post COVID-19
Intervention: Other: Mindfulness
Sponsors:
Fondazione Don Carlo Gnocchi Onlus; Catholic University of the Sacred Heart
Recruiting
Immunogenicity and Safety of a Booster Dose of the SpikoGen COVID-19 Vaccine - Condition: COVID-19
Interventions: Biological: SARS-CoV-2 recombinant spike protein + Advax-SM adjuvant; Biological: Saline placebo
Sponsors: Cinnagen; Vaxine Pty Ltd
Active, not recruiting
Plasma Exchange in Covid-19 Patients With Anti-interferon Autoantibodies - Condition: COVID-19
Intervention: Drug: Therapeutic plasma exchange
Sponsor:
Centre Hospitalier St Anne
Recruiting
Randomized Multicenter Study on the Efficacy and Safety of Favipiravir for Parenteral Administration Compared to Standard of Care in Hospitalized Patients With COVID-19 - Condition: COVID-19
Interventions: Drug: Favipiravir; Drug: Remdesivir
Sponsors: Promomed, LLC; Solyur Pharmaceuticals Group
Completed
Quality of Life and Lung Function on Post Covid-19 Patient - Condition: COVID-19
Intervention: Other: breathing exercise, Aerobic exercises
Sponsor: Qassim University
Recruiting
A Safety, Tolerability, and Efficacy Study of IBI314 in Mild to Moderate Patients With COVID-19 - Condition: COVID-19
Interventions: Biological: IBI314(low dose); Biological: IBI314(high dose); Biological: IBI314(medium dose); Other: Placebo
Sponsor:
Innovent Biologics (Suzhou) Co. Ltd.
Not yet recruiting
Inhaled Heparin for Hospitalised Patients With Coronavirus Disease 2019 (COVID-19) - Condition: COVID-19
Intervention: Drug: unfractionated Heparin
Sponsors:
Australian National University; The George Institute; St George Hospital, Australia; St Vincent’s Hospital Melbourne; John Hunter Hospital; Royal North Shore Hospital
Not yet recruiting
PTX-COVID19-B, an mRNA Humoral Vaccine, Intended for Prevention of COVID-19 in a General Population. This Study is Designed to Demonstrate the Safety, Tolerability, and Immunogenicity of PTX-COVID19-B in Comparison to the Pfizer- BioNTech COVID-19 Vaccine. - Condition: Covid19 Vaccine
Interventions: Biological: PTX-COVID19-B; Biological: Pfizer- BioNTech COVID-19 vaccine; Biological: Placebo
Sponsor: Providence Therapeutics Holdings Inc.
Recruiting
COVID-19 Messaging for Vaccination - Conditions: Vaccination Refusal; COVID-19 Pandemic
Interventions: Behavioral: Doctor Videos; Behavioral: Sharing Videos; Behavioral: Sharing Videos (Influencers); Behavioral: Vaccine Ambassador; Behavioral: Video framing; Behavioral: Video order
Sponsors: Massachusetts Institute of Technology; Facebook, Inc.; Code3; Stanford University; Harvard University; Yale University; Johns Hopkins University; Massachusetts General Hospital; Ludwig-Maximilians - University of Munich; National Institutes of Health (NIH)
Recruiting
Multicenter Double Blind, Parallel-group Phase 2/3 Trial, to Study Raloxifene in Adult COVID-19 Patients. - Condition: SARS CoV 2 Infection
Interventions: Drug: Raloxifene; Other: Placebo
Sponsor: Dompé Farmaceutici S.p.A
Completed
Safety & Immunogenicity of Booster SARS-CoV-2 Vaccine (Vero Cell) - Condition: COVID-19
Intervention: Biological: SARS-COV-2 Vaccine (Vero Cell-Sinopharm) Inactivated
Sponsor: PT. Kimia Farma (Persero) Tbk
Not yet recruiting
Spa Rehabilitation, Antioxidant and Bioenergetic Supportive Treatment of Patients With Post-Covid-19 Syndrome - Condition: COVID-19 Respiratory Infection
Interventions: Dietary Supplement: ubiquinol (reduced coenzyme Q10); Other: mountain spa rehabilitation; Diagnostic Test: 2x14 ml of peripheral blood collected in a tube with anticoagulant
Sponsors: Comenius University; Sanatórium of Dr. Guhr, n.o.
Completed
Considerable escape of SARS-CoV-2 Omicron to antibody neutralization - The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa^(1-3). It has since then spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of about 32 mutations in the spike, located mostly in the N-terminal domain (NTD) and the receptor binding domain (RBD), which may enhance viral fitness and allow antibody evasion. Here, we isolated an infectious Omicron virus in Belgium, from a…
Evaluation of Xa inhibitors as potential inhibitors of the SARS-CoV-2 Mpro protease - Based on previous large-scale in silico screening several factor Xa inhibitors were proposed to potentially inhibit SARS-CoV-2 Mpro. In addition to their known anticoagulants activity this potential inhibition could have an additional therapeutic effect on patients with COVID-19 disease. In this study we examined the binding of the Apixaban, Betrixaban and Rivaroxaban to the SARS-CoV-2 Mpro with the use of the MicroScale Thermophoresis technique. Our results indicate that the experimentally…
Screening for Inhibitors of Main Protease in SARS-CoV-2: In Silico and In Vitro Approach Avoiding Peptidyl Secondary Amides - In addition to vaccines, antiviral drugs are essential for suppressing COVID-19. Although several inhibitor candidates were reported for SARS-CoV-2 main protease, most are highly polar peptidomimetics with poor oral bioavailability and cell membrane permeability. Here, we conducted structure-based virtual screening and in vitro assays to obtain hit compounds belonging to a new chemical space, excluding peptidyl secondary amides. In total, 180 compounds were subjected to the primary assay at 20…
Lead optimization, pharmacophore development and scaffold design of protein kinase CK2 inhibitors as potential COVID-19 therapeutics - Therapeutic agents being designed against COVID-19 have targeted either the virus directly or the host cellular machinery. A particularly attractive host target is the ubiquitous and constitutively active serine-threonine kinase, Protein kinase CK2 (CK2). CK2 enhances viral protein synthesis by inhibiting the sequestration of host translational machinery as stress granules and assists in viral egression via association with the N-protein at filopodial protrusions of the infected cell. CK2…
Intricate relationship between SARS-CoV-2-induced shedding and cytokine storm generation: A signaling inflammatory pathway augmenting COVID-19 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its ability to induce cytokine release syndrome, can set up a generalized inflammatory response together with activating multiple inflammatory pathways, which contributes to a dramatic increase in the number of mortalities and morbidities worldwide. Reportedly, the manipulative nature of coronavirus disease 2019 (COVID-19), which targets the immune system, often focuses on specific inflammation- related pathways, usually…
Fractional order SIR epidemic model with Beddington-De Angelis incidence and Holling type II treatment rate for COVID-19 - In this paper, an attempt has been made to study and investigate a non-linear, non-integer SIR epidemic model for COVID-19 by incorporating Beddington-De Angelis incidence rate and Holling type II saturated cure rate. Beddington-De Angelis incidence rate has been chosen to observe the effects of measure of inhibition taken by both: susceptible and infective. This includes measure of inhibition taken by susceptibles as wearing proper mask, personal hygiene and maintaining social distance and the…
Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19 - Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and…
Coronaviruses Nsp5 Antagonizes Porcine Gasdermin D-Mediated Pyroptosis by Cleaving Pore-Forming p30 Fragment - Coronaviruses (CoVs) are a family of RNA viruses that typically cause respiratory, enteric, and hepatic diseases in animals and humans. Here, we use porcine epidemic diarrhea virus (PEDV) as a model of CoVs to illustrate the reciprocal regulation between CoV infection and pyroptosis. For the first time, we elucidate the molecular mechanism of porcine gasdermin D (pGSDMD)-mediated pyroptosis and demonstrate that amino acids R238, T239, and F240 within pGSDMD-p30 are critical for pyroptosis….
Alpha-Soluble NSF Attachment Protein Prevents the Cleavage of the SARS-CoV-2 Spike Protein by Functioning as an Interferon-Upregulated Furin Inhibitor - Loss of the furin cleavage motif in the SARS-CoV-2 spike protein reduces the virulence and transmission of SARS-CoV-2, suggesting that furin is an attractive antiviral drug target. However, lack of understanding of the regulation of furin activity has largely limited the development of furin-based therapeutic strategies. Here, we find that alpha-soluble NSF attachment protein (α-SNAP), an indispensable component of vesicle trafficking machinery, inhibits the cleavage of SARS-CoV-2 spike protein…
The Cognitive Consequences of the COVID-19 Pandemic on Members of the General Population in Italy: A Preliminary Study on Executive Inhibition - The pandemic period which has characterized the last two years has been associated with increasingly worsening psychological conditions, and previous studies have reported severe levels of anxiety, mood disorder, and psychopathological alteration in the general population. In particular, worldwide populations have appeared to present post-traumatic stress symptoms (PTSS). Surprisingly, no studies have evaluated the effect of COVID-related PTSS on cognitive functioning. This study focused on the…
Synthesis and In Vitro Study of Antiviral Activity of Glycyrrhizin Nicotinate Derivatives against HIV-1 Pseudoviruses and SARS-CoV-2 Viruses - When developing drugs against SARS-CoV-2, it is important to consider the characteristics of patients with different co- morbidities. People infected with HIV-1 are a particularly vulnerable group, as they may be at a higher risk than the general population of contracting COVID-19 with clinical complications. For such patients, drugs with a broad spectrum of antiviral activity are of paramount importance. Glycyrrhizinic acid (Glyc) and its derivatives are promising biologically active compounds…
Fruit Bromelain-Derived Peptide Potentially Restrains the Attachment of SARS-CoV-2 Variants to hACE2: A Pharmacoinformatics Approach - Before entering the cell, the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. Hence, this RBD is a critical target for the development of antiviral agents. Recent studies have discovered that SARS-CoV-2 variants with mutations in the RBD have spread globally. The purpose of this in silico study was to determine the potential of a fruit bromelain-derived peptide. DYGAVNEVK. to inhibit the entry of various SARS-CoV-2…
Computational Study of SARS-CoV-2 RNA Dependent RNA Polymerase Allosteric Site Inhibition - The COVID-19 pandemic has caused millions of fatalities since 2019. Despite the availability of vaccines for this disease, new strains are causing rapid ailment and are a continuous threat to vaccine efficacy. Here, molecular docking and simulations identify strong inhibitors of the allosteric site of the SARS-CoV-2 virus RNA dependent RNA polymerase (RdRp). More than one hundred different flavonoids were docked with the SARS-CoV-2 RdRp allosteric site through computational screening. The three…
Evaluating In Silico the Potential Health and Environmental Benefits of Houseplant Volatile Organic Compounds for an Emerging ‘Indoor Forest Bathing’ Approach - The practice of spending time in green areas to gain the health benefits provided by trees is well known, especially in Asia, as ‘forest bathing’, and the consequent protective and experimentally detectable effects on the human body have been linked to the biogenic volatile organic compounds released by plants. Houseplants are common in houses over the globe and are particularly appreciated for aesthetic reasons as well for their ability to purify air from some environmental volatile pollutants…
Exploring the Catalytic Mechanism of the RNA Cap Modification by nsp16-nsp10 Complex of SARS-CoV-2 through a QM/MM Approach - The inhibition of key enzymes that may contain the viral replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have assumed central importance in drug discovery projects. Nonstructural proteins (nsps) are essential for RNA capping and coronavirus replication since it protects the virus from host innate immune restriction. In particular, nonstructural protein 16 (nsp16) in complex with nsp10 is a Cap-0 binding enzyme. The heterodimer formed by nsp16-nsp10 methylates the…
IDENTIFICATION AND ALARM SYSTEM FOR FACIAL CORONA MASK USING CNN BASED IMAGE PROCESSING - tThe covid-19 epidemic is the world’s largest wake-up call for people to pay attention to their own and society’s health. One thing to keep in mind is that there is a segment of the population that has been exposed to the covid-19 virus and has generated antibodies without developing any significant illnesses and is continuing to be healthy. This indicates that a significant section of the population, even excluding the elderly, lacks the necessary bodily immunity to combat a Viral infection. As terrible as covid-19 is on a global scale, developing personal health standards and preventative measures for any pathogenic virus as a community would have spared many lives. In’this work, a camera is combined with an image processing system to recognise facial masks, which may be improved in a variety of ways. First and foremost, this method is meant to identify masks on a single person’s face. While this method is efficient in identifying someone has a mask, it does not ensure that they will wear it all of the time. The most effective update for this task is to install a camera with a wide field of view so that many individuals can be seen in the frame, and the faces of those who aren’t wearing markings can be identified, as well as the number of people and the timing. - link
RNA 검출 방법 - 본 발명은 RNA의 분석 및 검출 방법에 관한 것이다. 특히, 본 발명은 특히, 본 발명은 짧은 염기서열의 RNA까지 분석이 가능하면서도 높은 민감도 및 정확도로 정량적 검출까지 가능하여 감염증, 암 등 여러 질환의 진단 용도로도 널리 활용될 수 있다. - link
REUNION OF PHOTOTHERMAL THERAPY WITH MXENE ADSORBED UREMIC TOXINS AND CYTOKINES: A SHILED FOR COVID-19 PATENTS - The COVID-19 pandemic has created havoc throughout the world. The disease has proved to be more fatalfor patients having comorbidities like diabetics, lungs and kidney infections, etc. In the case of COVID-19 patientsI having kidney injury, the. removal of uremic toxins from the blood is hindered and there is a rapid surge in the levelj of cytokine hormone resulting in the death of the patient in a short interval of time. To resolve this issue,iI; researchers have examined that the immediate removal of these toxins can improve the condition of the patient to a |greater extent. Studies have also found the presence of SARS CoV-2 viral RNAs in the blood of COVID-19patients, which risks their life as well as impacts the blood transfusion process, especially in the case ofasymptomatic patients. Hence it is required to control the surge of cytokines and uremic toxins as well as disinfectthe blood of the patient from the virus. MXenes, having a foam-like porous structure and hydrophilic negativesurface functionalization have greater adsorption efficiency as well as superior photothermal activity. Utilizingthese properties of MXenes, the MXene membranes can be used in the dialyzer that can help in the efficient andBiuick removal of the uremic toxins, cytokines, and other impurities from the blood. Along with this the greaterTJAdsorption efficiency of MXenes to amino acids result in the trapping of the SARS CoV-2 viruses on the surface J)3>f the MXene. Many researchers as well as the WHO have proved the efficient reduction of the viral copy numbersjjvith the increase of temperature. Hence, followed by the trapping of the viruses, the implementation of"Zphotothermal Therapy can result in the inactivation and denaturation of the viruses and their respective viral RNAsBJlby the produced heat. The same process can be repeated several times to get better results. This whole process canr>oQ-esult in impurity-free and infection-free blood, that can be returned back to the body of the patient or can be!— I Sitilized for the blood transfusion process without any risk of infection.IM - link
Hung Thanh Phan COVID-19 NEW SOLUTION - - link
A METHOD TO REVEAL MOTIF PATTERNS OF COVID-19 USING MULTIPLE SEQUENCE ALIGNMENT - This present invention consists of different levels of computation and work in a pipeline manner i.e., input of one will be output of another and it is sequential process. Input data given in form of nucleotide sequence (DNA) of different COVID-19 patients (1). Using these nucleotide sequence perform mutation if possible and arrange them in a sequential order (2). Arrange number of nucleotide sequences of different patients in row wise and also compute number of characters in each row. (3). Compute frequency of occurrence of character in column wise and create a matrix having 4 rows and maximum sequence length will be the column size (4). Find the character like A, T, C, and G which one has maximum score and similarly find for each column to produce a final sequence (5). - link
REUSABILITY OF ANTIMICROBIAL MULTILAYER NANOFIBER MASK WITH HIGH PROTECTIVE - According to the present Invention, an antimicrobial multi-layer protective mask has a body section including at least first and second fabric layers having random fiber configuration; a middle layer including nanofiber membrane; and third and fourth fabric layers. There are two layers of fabric sandwiched between the nanofiber membrane and the third fabric layer. Fabric layers 1 through 4 each include a synergistic mixture of at least two metal oxide powders that exhibit synergistic antibacterial capabilities, such as the first metal’s mixed-oxidation state oxide and a second metal’s single-oxidation-state oxide. - link
METHODS OF TREATING SARS-COV-2 INFECTION - - link
一种具有广谱中和活性的新型冠状病毒重组蛋白及其制备方法 - 本发明涉及一种具有广谱中和活性的新型冠状病毒重组蛋白及其制备方法，所述新型冠状病毒重组蛋白为CRM‑RBD重组蛋白，所述CRM‑RBD重组蛋白的氨基酸序列如SEQ ID NO：1所示，编码所述CRM‑RBD重组蛋白的核苷酸序列如SEQ ID
NO：2所示，利用所述核苷酸序列通过以下步骤制备得到重组纳米蛋白颗粒：构建得到大肠杆菌重组表达菌；培养大肠杆菌重组表达菌得到发酵液；获得包涵体粗提物；变性溶解得到包涵体变性蛋白；纯化得到纯化重组蛋白；复性得到复性后蛋白；对复性后蛋白进行分离纯化，得到重组纳米蛋白颗粒。本发明的新型冠状病毒重组蛋白对新冠病毒原型株、贝塔变异株、德尔塔变异株均具有中和保护效果。 - link
METHOD AND SYSTEM TO DETECT THE VITAL HEALTH PARAMETERS OF A PERSON - The present invention relates to detect the vital health parameters of a person through SPO2, a blood oxygen saturation sensor. The blood oxygen saturation sensor is arranged within a first shape body of a wearable glove; determining, a temperature through the temperature sensor, arranged within a second shape body of the wearable glove; determining, a pulse rate through a cardiac sensor, arranged within a third shape body of the wearable glove. Further, at a control unit, the detected blood oxygen level signal, temperature signal and pulse rate are received. The control unit is arranged on a palm shape body of the wearable glove to convert, segregate and transmit, the digital blood oxygen level signal, the digital temperature signal and the digital cardiac signal, on a cloud-based storage or a computing terminal. - link
머신러닝 기반 수요예측을 이용한 피킹 로케이션 보충 서비스 제공 방법 - 머신러닝 기반 수요예측을 이용한 피킹 로케이션 보충 서비스 제공 방법이 제공되며, 물류창고에 적재된 아이템의 카테고리, 부피 및 계절성을 포함하는 속성 데이터를 수집하는 단계, 적어도 하나의 인공지능 알고리즘을 이용하여 아이템의 1일 예상 출고량을 출력하는 단계, 물류창고 내 피킹 로케이션(Picking Location)의 부피를 아이템의 부피로 나누어 최대 재고수량을 산출하는 단계, 1일 예상 출고량의 제 1 배를 최소 출고수량으로 설정하고, 최대 재고수량의 제 2 배를 최소 재고수량으로 결정하는 단계, 피킹 로케이션 내 현재 재고수량을 추출하는 단계, 피킹 로케이션 내 현재 재고수량이 최소 출고수량 또는 최소 재고수량보다 작은지의 여부를 확인하는 단계 및 현재 재고수량이 최소 출고수량 또는 최소 재고수량보다 작은 경우, 보충수량을 계산하고 재고보충지시를 할당하는 단계를 포함한다. - link