Background The pandemic of coronavirus disease-19 (Covid-19) continues to afflict the lives and livelihoods of many as global demand for vaccine supply remains unmet. Methods Phase 1 of this trial (N=42) assessed the safety, tolerability and immunogenicity of ascending levels of one-dose ARCT-021, a self-amplifying mRNA vaccine against Covid-19. Phase 2 (N=64) tested two-doses of ARCT-021 given 28 days apart. Both young and older adults were enrolled. The primary safety outcomes were local and systemic solicited adverse events (AEs) reported immediately and up to 7 days post-inoculation and unsolicited events reported up to 56 days after inoculation. Secondary and exploratory outcomes were antibody and T cell responses to vaccination, respectively. Results ARCT-021 was well tolerated up to one 7.5 μg dose and two 5.0 μg doses. Local solicited AEs, namely injection-site pain and tenderness, as well as systemic solicited AEs, such as fatigue, headache and myalgia, were more common in ARCT-021 than placebo recipients, and in younger than older adults. Seroconversion rate for anti-S IgG was 100% in all cohorts except for the 1 μg one-dose in younger adults and the 7.5 μg one-dose in older adults, which were each 80%. Neutralizing antibody titers increased with increasing dose although the responses following 5.0 μg and 7.5 μg ARCT-021 were similar. Anti-S IgG titers overlapped with those in Covid-19 convalescent plasma. ARCT-021 also elicited T-cell responses against the S glycoprotein. Conclusion Taken collectively, the favorable safety and immunogenicity profiles support further clinical development of ARCT-021.
Background: Airborne particulate matter has been suggested as a co-factor for SARS-CoV-2 infection. Besides the deleterious effect this pollutant has on pulmonary immunity and the propagation of respiratory ACE-2 receptors (angiotensin converting enzyme II), the SARS-CoV-2 point of entry, particulate matter has also been proposed as a vector for this virus transmission. Particulate matter may also be a marker for anthropogenic activity acting as a surrogate for increased human to human contact, increasing both transmission and the mutagenic viral load. Genes coding for SARS-CoV-2 have been detected on airborne particulate matter and its proximity to the virus, may have caused this pollutant to act as a mutagen causing the inception of SARS-CoV-2 variants and simultaneously being genotoxic to the progenitor viruses, differentially favouring variant emergence. Since the initial phases of the pandemic, a multitude of SARS-CoV-2 variants have been detected, but the few that survive to promulgate human infection have increased transmissibility. It also appears that there is a limited set of persistent mutations SARS-CoV-2 can produce. This set of mutations has been found in widely disparate and distant regions. This may suggest that besides intra-host mutation in an inflammatory ambience, an ubiquitous factor such as an environmental mutagen, may have resulted in convergent evolution leading to the emergence of similar variants. This paper examines a possible association in a multi-modal manner between the airborne pollutant PM2.5 and the emergence of ten of the most clinically and epidemiologically relevant SARS-CoV-2 variants. Methods: The daily average levels of PM2.5 of a number of cities, where variants were detected, were obtained from the World Air Quality Index (WAQI), a real-time assessment of atmospheric pollution. PM2.5 levels were correlated with SARS-CoV-2 variants including Variants of Concern (VOC) or Variants of Interest (VOI). These variants included the G614 variant in Beijing, the 20A.EU1 variant in Valencia, the B.1.351 variant in South Africa, the B.1.1.7 variant in the UK, the USA variants B.1.429 in Los Angeles, B.1.2 in Louisiana and New Mexico, the B.1.526 variant found in New York, the variant B.1.1.248 in Brazil. During mid-March 2021, the B.1.617 variant first detected in October 2020, surged in Nagpur, India and the R.1 variant was detected in Kentucky U.S.A. The average daily PM2.5 levels were assessed, the evaluation initiating just before the occurrence of the first spike/s in this pollutant s atmospheric concentration, till after the emergence of the variants. Where available the daily number of new cases of COVID-19 diagnosed was matched to the PM2.5 levels. Results: There appears a common pattern of PM2.5 in most of the regions prior and during the emergence of the SARS-CoV-2 variants. An initial spike/s of PM2.5 were noted on average 50 days prior to the emergence of the variants and another smaller spike/s in PM2.5 were noted just before or contemporaneous with the emergence of the variant. Prior to the emergence of to the G614 variant in Beijing, the average PM2.5 level during its peaks was 153.4mug/m3 (SD+/-63.9) to settle to a baseline of 94.4mug/m3 (SD+/-47.8)(p<0.001). Before the appearance of the 20A.EU1 variant in Valencia, the PM2.5 spikes averaged at 61.3mug/m3 (SD+/-21.8) to decrease to a mean of 41.2mug/m3 (SD+/-15.5) (p<0.04). In Kent, U.K. a solitary PM2.5 spike averaged 82mug/m3 (SD+/-29) before the detection of the B.1.1.7 and following the PM2.5 spike the baseline level of this pollutant was 27.8mug/m3 (SD+/-18.0) (p<0.03). In Nelson Mandela Bay South Africa, where B.1.351 was first detected, the PM2.5 mean baseline level was reported as 40.4mug/m3 (SD+/-14.0), while prior to this variant s emergence, the PM2.5 spike averaged 85.1mug/m3 (SD +/-17.3)(p<0.0001). In Brazil the average PM2.5 during its spike was 107.4mug/m3 (SD+/-34.2) before B.1.1.248 variant emerged and after the spike the baseline PM2.5 was 48.3mug/m3 (SD+/-18) (p<0.0001). In the USA the average PM2.5 peak levels prior to the emergence of the SARS-CoV-2 variants were 118mug/m3 (SD+/-28.8) in Los Angeles (baseline 66.1mug/m3 (SD+/-25.1), 75+/-27.8mug/m3 (baseline 43.3(SD+/-14.4)mug/m3 in Louisiana, 71.4+/-11.3mug/m3 (baseline 43.6(SD+/-12.4)mug/m3 New Mexico, 54.3+/-13.8mug/m3 (baseline 34.4(SD+/-11.6)mug/m3 in New York and 37.7+/-7mug/m3 (baseline 28.5 SD+/-6.8)mug/m3 in Eastern Kentucky. All the spike patterns of PM2.5 levels noted in the USA were significantly higher when compared to their respective baselines (p<0.0001). Prior to the surge of the variant in India, the PM2.5 spike in Nagpur averaged 166.8+/-10.8mug/m3 (baseline 123.2SD+/-16.9mug/m3) (p<0.0001). In the regions where the quantity of daily new cases was available, a number of significant correlations were obtained between PM2.5 levels and the number of new cases of SARS-CoV-2 in most of the regions reviewed. Conclusion: There appears to be an association between the levels of atmospheric PM2.5 and the emergence of SARS-CoV-2 variants. In most regions two groups of spike/s of PM2.5 were noted prior to the emergence of these variants. The first PM2.5 spike/s approximately 50 days before the variant emergence may suggest that anthropogenic activity was increased possibly reflecting augmented human to human contact, consequently increasing the viral burden of the progenitor virus. The first PM2.5 spike may also have made populations more susceptible to SARS-CoV-2 through the propagation of the respiratory ACE receptor. There is the potential that coronavirus-laden, PM2.5 induced mutagenesis in the SARS-CoV-2 genome resulted in establishing persistent variants and contemporaneously was genotoxic to the progenitor virus, expediting the latter s disappearance. PM2.5 may have further diminished the pulmonary immunity inviting further viral invasion. The second spike/s prior to the emergence of variants, may suggest another anthropogenic spike in human activity. With the second spike/s in PM2.5, this airborne pollutant may have acted as a viral vector encouraging variant emergence. This may have not only led to increasing viral transmission, catalysed by the preceding risk factors, but resulted in an overwhelming viral load, providing fertile ground for variant emergence. The above findings suggest that antecedent spikes in PM2.5 prior to variant emergence not only contributed to transmission, but also impacted the immediate viral environs which resulted in its natural selection, effecting SARS-CoV-2 evolution. Keywords: PM2.5;SARS-CoV-2; COVID-19;Mutations;Variant emergence; Evolution.
Background: In healthcare settings in low- and middle-income countries, which frequently rely upon natural ventilation, the risk of aerosol transmission of SARS-CoV-2 remains poorly understood. We aimed to evaluate the risk of exposure to SARS-CoV-2 in naturally-ventilated hospital settings by measuring parameters of ventilation and comparing these findings with results of bioaerosol sampling. Methods: We measured outdoor and room CO2 to estimate absolute ventilation (liters per second [L/s]) from 9 hospitals in Bangladesh during October 2020 - February 2021. We estimated infectious risk across different spaces using a modified Wells-Riley equation. We collected air samples from these same spaces at 12.5 L/min over 30 minutes and performed RT-qPCR to detect SARS-CoV-2 N-gene. We used multivariable linear regression and calculated elasticity to identify characteristics associated with ventilation. Results: Based on ventilation of 86 patient care areas and COVID-19 case numbers, we found that over a 40-hour exposure period, outpatient departments posed the highest median risk for infection (5.4%), followed by COVID intensive care units (1.8%). We detected SARS-CoV-2 RNA in 18.6% (16/86) of air samples. Ceiling height and total open area of doors and windows were found to have the greatest impact on ventilation. Conclusion: Our findings provide evidence that naturally-ventilated healthcare settings may pose a high risk for exposure to SARS-CoV-2, particularly among non-COVID designated spaces, but improving parameters of ventilation can mitigate this risk.
Objectives: We aimed to harness IDentif.AI 2.0, a clinically actionable AI platform to rapidly pinpoint and prioritize optimal combination therapy regimens against COVID-19. Methods: A pool of starting candidate therapies was developed in collaboration with a community of infectious disease clinicians and included EIDD-1931 (metabolite of EIDD-2801), baricitinib, ebselen, selinexor, masitinib, nafamostat mesylate, telaprevir (VX-950), SN-38 (metabolite of irinotecan), imatinib mesylate, remdesivir, lopinavir, and ritonavir. Following the initial drug pool assessment, a focused, 6-drug pool was interrogated at 3 dosing levels per drug representing nearly 10,000 possible combination regimens. IDentif.AI 2.0 paired prospective, experimental validation of multi-drug efficacy on a SARS-CoV-2 live virus (propagated, original strain and B.1.351 variant) and Vero E6 assay with a quadratic optimization workflow. Results: Within 3 weeks, IDentif.AI 2.0 realized a list of combination regimens, ranked by efficacy, for clinical go/no-go regimen recommendations. IDentif.AI 2.0 revealed EIDD-1931 to be a strong candidate upon which multiple drug combinations can be derived. Conclusions: IDentif.AI 2.0 rapidly revealed promising drug combinations for a clinical translation. It pinpointed dose-dependent drug synergy behavior to play a role in trial design and realizing positive treatment outcomes. IDentif.AI 2.0 represents an actionable path towards rapidly optimizing combination therapy following pandemic emergence.
Emerging SARS-CoV-2 variants have shaped the second year of the COVID-19 pandemic and the public health discourse around effective control measures. Evaluating the public health threat posed by a new variant is essential for appropriately adapting response efforts when community transmission is detected. However, this assessment requires that a true comparison can be made between the new variant and its predecessors because factors other than the virus genotype may influence spread and transmission. In this study, we develop a framework that integrates genomic surveillance data to estimate the relative effective reproduction number (Rt) of co-circulating lineages. We use Connecticut, a state in the northeastern United States in which the SARS-CoV-2 variants B.1.1.7 and B.1.526 co-circulated in early 2021, as a case study for implementing this framework. We find that the Rt of B.1.1.7 was 6-10% larger than that of B.1.526 in Connecticut in the midst of a COVID-19 vaccination campaign. To assess the generalizability of this framework, we apply it to genomic surveillance data from New York City and observe the same trend. Finally, we use discrete phylogeography to demonstrate that while both variants were introduced into Connecticut at comparable frequencies, clades that resulted from introductions of B.1.1.7 were larger than those resulting from B.1.526 introductions. Our framework, which uses open-source methods requiring minimal computational resources, may be used to monitor near real-time variant dynamics in a myriad of settings.
Background: Potential therapy and confounding factors including typical co‐administered medications, patient9s disease states, disease prevalence, patient demographics, medical histories, and reasons for prescribing a drug often are incomplete, conflicting, missing, or uncharacterized in spontaneous adverse drug event (ADE) reporting systems. These missing or incomplete features can affect and limit the application of quantitative methods in pharmacovigilance for meta-analyses of data during randomized clinical trials. Methods: In this study, we implemented adaptive signal detection approaches to correct spurious association, hidden factors, and confounder misclassification when the covariates are unknown or unmeasured on medications affecting the renin-angiotensin system (RAS), potentially creating an increased risk of life-threatening outcomes in high-risk patients. Results: Following multiple filtering stages to exclude insignificant and noise-driven reports, we found that drugs from antihypertensives agents, urologicals, and antithrombotic agents (macitentan, bosentan, epoprostenol, selexipag, sildenafil, tadalafil, and beraprost) form a similar class with a significantly higher incidence of pADEs. Macitentan and bosentan were associates with 64% and 56% of pADEs, respectively. Because these two medications are prescribed in diseases affecting pulmonary function and may be likely to emerge among the highest reported pADEs, in fact, they serve to validate the methods utilized here. Conversely, doxazosin and rilmenidine were found to have the least pADEs in selected drugs from hypertension patients. Nifedipine and candesartan were also found by our signal detection methods to form a drug cluster, shown by several studies an effective combination of these drugs on lowering blood pressure and appeared an improved side effect profile in comparison with single-agent monotherapy. Conclusions: We consider pulmonary ADE (pADE) profiles in a long-standing group of therapeutics, RAS-acting agents, in patients with hypertension associated with high-risk for COVID-19. Using these techniques, we confirmed our hypothesis that drugs from the same drug class could have very different pADE profiles affecting outcomes in acute respiratory illness. We found that several indidvual drugs have significant differences between their drug classes and compared to other drug classes. Funding: GJW and MJD accepted funding from BioNexus KC for funding on this project but BioNexus KC had no direct role in this article.
Indias COVID-19 lockdown is widely believed to have disrupted critical health services, but its effect on non-COVID health outcomes is largely unknown. Comparing mortality trends among dialysis patients in the eight months around the lockdown with the previous year, we document a 64% increase in mortality between March and May 2020 and an estimated 22-25% total excess mortality through July 2020. The mortality increase is greater among females and disadvantaged groups. Barriers to transportation and disruptions in hospital services appear to be the main drivers of increased morbidity and mortality. The results highlight the unintended consequences of the lockdown on critical and life-saving non-COVID health services that must be taken into account in the implementation of future policy efforts to control the spread of pandemics.
SARS-CoV-2 vaccines are powerful tools to combat the COVID-19 pandemic, but vaccine hesitancy threatens these vaccines9 effectiveness. To address COVID-19 vaccine hesitancy and ensure equitable distribution, understanding the extent of and factors associated with vaccine acceptance and uptake is critical. We report the results of a large nationwide study conducted December 2020-May 2021 of 34,470 users from COVID-19-focused smartphone-based app How We Feel on their willingness to receive a COVID-19 vaccine. Nineteen percent of respondents expressed vaccine hesitancy, the majority being undecided. Of those who were undecided or unlikely to get a COVID-19 vaccine, 86% reported they ultimately did receive a COVID-19 vaccine. We identified sociodemographic and behavioral factors that were associated with COVID-19 vaccine hesitancy and uptake, and we found several vulnerable groups at increased risk of COVID-19 burden, morbidity, and mortality were more likely to be vaccine hesitant and had lower rates of vaccination. Our findings highlight specific populations in which targeted efforts to develop education and outreach programs are needed to overcome vaccine hesitancy and improve equitable access, diversity, and inclusion in the national response to COVID-19.
Background: We report the clinical efficacy against COVID 19 infection of BBV152, a whole virion inactivated SARS CoV 2 vaccine formulated with a Toll like receptor 7/8 agonist molecule adsorbed to alum (Algel IMDG). Methods: We did a double-blind, randomised, multicentre, phase 3 clinical trial in 25 Indian hospitals to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Healthy adults (age 18 to 98 years) randomised 1:1 using a sponsor-supplied randomisation scheme received two intramuscular doses of vaccine or placebo administered four weeks apart. The primary outcome was laboratory confirmed symptomatic COVID 19, occurring at least 14 days after the second dose. Secondary outcomes were efficacy in subgroups for age (18 to < 60 years and >=60 years) and in participants with pre-existing stable medical conditions. We also evaluated safety, reactogenicity, and consistency of immune responses for three consecutive manufacturing lots. Findings: Between November 16, 2020 and January 7, 2021 we recruited 25,798 participants who were randomised to BBV152 or placebo groups; 24,419 received two doses of BBV152 (n = 12,221) or placebo (n = 12,198). In a case-driven analysis, 130 cases of symptomatic COVID-19 were reported in 16,973 (0.77%) participants with follow-up at least two weeks after the second vaccination; 24 occurred in the vaccine group and 106 in placebo recipients giving an overall vaccine efficacy of 77.8% (95% CI: 65.2,86.4). Sixteen cases, one vaccinee and 15 placebo recipients, met the severe symptomatic COVID-19 case definition giving a vaccine efficacy of 93.4% (57.1,99.8). Efficacy against asymptomatic COVID 19 was 63.6% (29.0, 82.4). BBV152 conferred 65.2% (95% CI: 33.1, 83.0) protection against the SARS CoV 2 Variant of Concern, B.1.617.2 (Delta). BBV152 was well tolerated with no clinically or statistically significant differences in the distributions of solicited, unsolicited, or serious adverse events between vaccine and placebo groups. No cases of anaphylaxis or vaccine-related deaths were reported. Interpretation: BBV152 was immunogenic and highly efficacious against symptomatic and asymptomatic COVID 19 variant associated disease, particularly against severe disease in adults. Vaccination was well tolerated with an overall incidence of adverse events observed over a median of 146 days that was lower than that observed with other COVID-19 vaccines.
The absence of reliable registration of Covid-19 deaths in India has prevented the proper assessment and monitoring of what appears to be one of the worst episodes of coronavirus pandemic. India9s relatively young age structure tends to conceal the severity of Covid-19 mortality, which is concentrated in older age groups. In this paper, we present four different demographic samples of Indian populations for which we have information on both their demographic structures and death outcomes. We show that we can model the age gradient of Covid-19 mortality in India and use this modeling for estimating the most accurate level of Covid-19 mortality in the country. Our findings point to a death toll of about 2.2 million persons by late May 2021. Once India9s age structure taken into account, these figures correspond to one of the most severe examples of Covid-19 mortality in the world.
Cognitive and Psychological Disorders After Severe COVID-19 Infection - Condition: COVID 19
Interventions: Diagnostic Test: Cognitive assessment; Diagnostic Test: Imaging; Diagnostic Test: Routine care; Other: Psychiatric evaluation
Sponsors: Central Hospital, Nancy, France; Centre Hospitalier Universitaire de Besancon; University Hospital, Strasbourg, France; Centre Hospitalier Régional Metz-Thionville; Centre hospitalier Epinal; Hopitaux Civils de Colmar
Not yet recruiting
Phase 1 Study to Assess Safety, Tolerability, PD, PK, Immunogenicity of IV NTR-441 Solution in Healthy Volunteers and COVID-19 Patients - Condition: Covid19
Interventions: Drug: NTR-441; Drug: Placebo
Sponsor: Neutrolis
Recruiting
MP1032 Treatment in Patients With Moderate to Severe COVID-19 - Condition: COVID-19
Interventions: Drug: MP1032; Drug: Placebo
Sponsors: MetrioPharm AG; Syneos Health, LLC
Not yet recruiting
Study to Evaluate the Safety and Concentrations of Monoclonal Antibody Against Virus That Causes COVID-19 Disease. - Condition: COVID-19 Virus Disease
Interventions: Biological: MAD0004J08; Other: Placebo
Sponsors: Toscana Life Sciences Sviluppo s.r.l.; Cross Research S.A.
Active, not recruiting
Safety and Immunogenicity of LNP-nCOV saRNA-02 Vaccine Against SARS-CoV-2, the Causative Agent of COVID-19 - Condition: COVID-19
Intervention: Drug: LNP-nCOV saRNA-02 Vaccine
Sponsor: MRC/UVRI and LSHTM Uganda Research Unit
Not yet recruiting
Efficacy of Inhaled Therapies in the Treatment of Acute Symptoms Associated With COVID-19 - Condition: Covid19
Interventions: Drug: inhaled beclametasone; Drug: Inahaled beclomethasone / formoterol / glycopyrronium
Sponsors: UPECLIN HC FM Botucatu Unesp; Chiesi Farmaceutici S.p.A.
Not yet recruiting
Dapsone Coronavirus SARS-CoV-2 Trial (DAP-CORONA) COVID-19 - Condition: COVID-19
Interventions: Drug: Dapsone 85 mg PO BID; Drug: Placebo 85 mg PO BID
Sponsors: McGill University Health Centre/Research Institute of the McGill University Health Centre; Pulmonem Inc.
Not yet recruiting
Covid-19 Patients Management During Home Isolation - Condition: Covid19
Interventions: Procedure: Oxygen therapy and physical therapy; Device: Oxygen therapy
Sponsor: Cairo University
Not yet recruiting
Ivermectin Versus Standard Treatment in Mild COVID-19 - Condition: Covid19
Intervention: Drug: Ivermectin Tablets
Sponsor: Assiut University
Not yet recruiting
SCALE-UP Utah: Community-Academic Partnership to Address COVID-19 Testing Among Utah Community Health Centers - Condition: Covid19
Interventions: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)
Sponsors: University of Utah; Association for Utah Community Health; Utah Department of Health; National Institutes of Health (NIH)
Recruiting
SCALE-UP Utah: Community-Academic Partnership to Address COVID-19 Vaccination Rates Among Utah Community Health Centers - Condition: Covid19
Interventions: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)
Sponsors: University of Utah; Association for Utah Community Health; Utah Department of Health; National Institutes of Health (NIH)
Recruiting
Chinese Herbal Formula for COVID-19 - Condition: Covid19
Interventions: Drug: mQFPD; Drug: organic brown rice
Sponsor: University of California, San Diego
Not yet recruiting
Remdesivir- Ivermectin Combination Therapy in Severe Covid-19 - Condition: Covid19
Intervention: Drug: Ivermectin
Sponsor: Assiut University
Not yet recruiting
IRAK 4 Inhibitor (PF-06650833) in Hospitalized Patients With COVID-19 Pneumonia and Exuberant Inflammation. - Condition: COVID-19 Pneumonia
Interventions: Drug: PF-06650833; Drug: Matching Placebo
Sponsors: Giovanni Franchin, M.D, Ph.D; Pfizer
Recruiting
The Role of Chlorhexidine in Minimizing the Viral Load Among COVID-19 Patients - Condition: COVID-19
Intervention: Drug: Chlorhexidine digluconate, povidone iodine
Sponsor: King Abdulaziz University
Not yet recruiting
Phyllanthin and hypophyllanthin, the isolated compounds of Phyllanthus niruri inhibit protein receptor of corona virus (COVID-19) through in silico approach - CONCLUSIONS: In conclusion, phyllanthin and hypophyllanthin are predicted to have strong activity against COVID-19 through inhibiting spike glycoprotein and main protease under in silico study. Further research is needed to support the development of P. niruri as inhibitor agents of COVID-19 through bioassay studies.
Structure-Guided Design of Conformationally Constrained Cyclohexane Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 3CL Protease - A series of nondeuterated and deuterated dipeptidyl aldehyde and masked aldehyde inhibitors that incorporate in their structure a conformationally constrained cyclohexane moiety was synthesized and found to potently inhibit severe acute respiratory syndrome coronavirus-2 3CL protease in biochemical and cell-based assays. Several of the inhibitors were also found to be nanomolar inhibitors of Middle East respiratory syndrome coronavirus 3CL protease. The corresponding latent aldehyde bisulfite…
Macrolactin A as a Novel Inhibitory Agent for SARS-CoV-2 M(pro): Bioinformatics Approach - COVID-19 is a disease that puts most of the world on lockdown and the search for therapeutic drugs is still ongoing. Therefore, this study used in silico screening to identify natural bioactive compounds from fruits, herbaceous plants, and marine invertebrates that are able to inhibit protease activity in SARS-CoV-2 (PDB: 6LU7). We have used extensive screening strategies such as drug likeliness, antiviral activity value prediction, molecular docking, ADME, molecular dynamics (MD) simulation,…
Prognostic Role of Neutrophil to Lymphocyte Ratio in COVID-19 Patients: Still Valid in Patients That Had Started Therapy? - COVID-19 may appear with a widely heterogeneous clinical expression. Thus, predictive markers of the outcome/progression are of paramount relevance. The neutrophil/lymphocyte ratio (NLR) has been suggested as a good predictive marker of disease severity and mortality. Accordingly, we found that NLR significantly increased in parallel with the WHO severity stage in COVID-19 patients during the I^(st) wave (March-May 2020; n = 49), due to the significant reduction of lymphocyte and the significant…
Investigation of a Model-Based Working Memory Training With and Without Distractor Inhibition and Its Comparative Efficacy: A Randomized Controlled Trial on Healthy Old Adults - Background: Various working memory (WM) trainings have been tested, but differences in experimental designs, the lack of theoretical background, and the need of identifying task-related processes such as filtering efficiency limit conclusions about their comparative efficacy. Objectives: In this study, we compared the efficacy of a model-based WM training with (MB^(+)) and without (MB) distractor inhibition on improving WM capacity to a dual n-back and active control condition. Methods: This…
The RNA sensor MDA5 detects SARS-CoV-2 infection - Human cells respond to infection by SARS-CoV-2, the virus that causes COVID-19, by producing cytokines including type I and III interferons (IFNs) and proinflammatory factors such as IL6 and TNF. IFNs can limit SARS-CoV-2 replication but cytokine imbalance contributes to severe COVID-19. We studied how cells detect SARS-CoV-2 infection. We report that the cytosolic RNA sensor MDA5 was required for type I and III IFN induction in the lung cancer cell line Calu-3 upon SARS-CoV-2 infection. Type I…
Postinfection treatment with a protease inhibitor increases survival of mice with a fatal SARS-CoV-2 infection - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to be a serious global public health threat. The 3C-like protease (3CLpro) is a virus protease encoded by SARS-CoV-2, which is essential for virus replication. We have previously reported a series of small-molecule 3CLpro inhibitors effective for inhibiting replication of human coronaviruses including SARS-CoV-2 in cell culture and in animal models. Here we generated a series of deuterated variants of a 3CLpro…
Potential In Vitro Inhibition of Selected Plant Extracts against SARS-CoV-2 Chymotripsin-Like Protease (3CL(Pro)) Activity - Antiviral treatments inhibiting Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication may represent a strategy complementary to vaccination to fight the ongoing Coronavirus disease 19 (COVID-19) pandemic. Molecules or extracts inhibiting the SARS-CoV-2 chymotripsin-like protease (3CL^(Pro)) could contribute to reducing or suppressing SARS-CoV-2 replication. Using a targeted approach, we identified 17 plant products that are included in current and traditional cuisines as…
Antiviral Activity of Vitis vinifera Leaf Extract against SARS-CoV-2 and HSV-1 - Vitis vinifera represents an important and renowned source of compounds with significant biological activity. Wines and winery bioproducts, such as grape pomace, skins, and seeds, are rich in bioactive compounds against a wide range of human pathogens, including bacteria, fungi, and viruses. However, little is known about the biological properties of vine leaves. The aim of this study was the evaluation of phenolic composition and antiviral activity of Vitis vinifera leaf extract against two…
Antiviral Effects of Green Tea EGCG and Its Potential Application against COVID-19 - (-)-Epigallocatechin-3-O-gallate (EGCG), the most abundant component of catechins in tea (Camellia sinensis (L.) O. Kuntze), plays a role against viruses through inhibiting virus invasiveness, restraining gene expression and replication. In this paper, the antiviral effects of EGCG on various viruses, including DNA virus, RNA virus, coronavirus, enterovirus and arbovirus, were reviewed. Meanwhile, the antiviral effects of the EGCG epi-isomer counterpart (+)-gallocatechin-3-O-gallate (GCG) were…
Identification of 13 Guanidinobenzoyl- or Aminidinobenzoyl-Containing Drugs to Potentially Inhibit TMPRSS2 for COVID-19 Treatment - Positively charged groups that mimic arginine or lysine in a natural substrate of trypsin are necessary for drugs to inhibit the trypsin-like serine protease TMPRSS2 that is involved in the viral entry and spread of coronaviruses, including SARS-CoV-2. Based on this assumption, we identified a set of 13 approved or clinically investigational drugs with positively charged guanidinobenzoyl and/or aminidinobenzoyl groups, including the experimentally verified TMPRSS2 inhibitors Camostat and…
Antimicrobial Peptides and Physical Activity: A Great Hope against COVID 19 - Antimicrobial peptides (AMPs), α- and β-defensins, possess antiviral properties. These AMPs achieve viral inhibition through different mechanisms of action. For example, they can: (i) bind directly to virions; (ii) bind to and modulate host cell-surface receptors, disrupting intracellular signaling; (iii) function as chemokines to augment and alter adaptive immune responses. Given their antiviral properties and the fact that the development of an effective coronavirus disease 2019 (COVID-19)…
Influence of Different Glycoproteins and of the Virion Core on SERINC5 Antiviral Activity - Host plasma membrane protein SERINC5 is incorporated into budding retrovirus particles where it blocks subsequent entry into susceptible target cells. Three structurally unrelated proteins encoded by diverse retroviruses, human immunodeficiency virus type 1 (HIV-1) Nef, equine infectious anemia virus (EIAV) S2, and ecotropic murine leukemia virus (MLV) GlycoGag, disrupt SERINC5 antiviral activity by redirecting SERINC5 from the site of virion assembly on the plasma membrane to an internal RAB7+…
Seleno-Functionalization of Quercetin Improves the Non-Covalent Inhibition of M(pro) and Its Antiviral Activity in Cells against SARS-CoV-2 - The development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from the COVID-19 pandemic complementary to the vaccination. Considering this, the viral main protease (M^(pro)) is among the most promising molecular targets in light of its importance during the viral replication cycle. The natural flavonoid quercetin 1 has been recently reported to be a potent M^(pro) inhibitor in vitro, and we explored the effect produced by the…
Statins in COVID-19 Therapy - Inhibitors of 3-hydroxy-3methylgultaryl-coenzyme A reductase (statins) are one of the main groups of drugs used in preventing and treating cardiovascular diseases worldwide. They are widely available, cheap, and well-tolerated. Based on statins’ pleiotropic properties, including improvement of endothelial dysfunction, antioxidant properties, atherosclerotic plaque stabilization, and inhibition of inflammatory responses, it can be hypothesized that the use of statins, at least as an adjuvant in…
Differential detection kit for common SARS-CoV-2 variants in COVID-19 patients - - link
SARS-CoV-2 anti-viral therapeutic - - link
A POLYHERBAL ALCOHOL FREE FORMULATION FOR ORAL CAVITY - The present invention generally relates to a herbal composition. Specifically, the present invention relates to a polyherbal alcohol free composition comprising of Glycyrrhiza glabra root extract, Ocimum sanctum leaf extract, Elettaria cardamomum fruit extract, Mentha spicata (Spearmint) oil and Tween 80 and method of preparation thereof. The polyherbal alcohol free composition of the present invention possesses excellent antimicrobial properties and useful for oral cavity. - link
一种新冠病毒肺炎重症化预测系统及方法 - 本发明涉及疾病预测技术领域，公开了一种新冠病毒肺炎重症化预测系统及方法，包括以下步骤：步骤一，采集患者血常规信息和用户信息；步骤二，将患者血常规信息按照用户信息进行等级分类；步骤三，将已经等级分类的患者血常规信息与对应等级的标准信息进行比较；步骤四，当患者血常规信息在标准信息范围内则判定患者为轻症患者，当患者血常规信息在标准信息范围外则判定患者为重症患者。本发明能够准确快速地区分轻症和重症。 - link
一种诊断标志物及其在COVID-19诊断及冠状病毒既往感染检测中的应用 - 本发明公开一种诊断标志物及在COVID‑19诊断及冠状病毒既往感染检测中的应用。所述诊断标志物包括肽段COVID19‑V001，所述肽段COVID19‑V001的氨基酸序列为：包含FKEELDKYFKNH中5个及5个以上连续氨基酸的序列；或所述肽段COVID19‑V001的氨基酸序列为：包含FKEELDKYFKNH中1个到几个氨基酸的取代或/和缺失或/和添加所形成的序列。基于本发明的诊断标志物应用间接法定性检测人血清中抗肽段的IgG抗体的水平。通过基于本发明所建立的检测试剂盒，可作为新型冠状病毒肺炎(COVID‑19)及诊断的一种辅助手段，还可作为区分感染和疫苗接种的手段。 - link
MEDIDOR DE SATURACION - - link
폐마스크 밀봉 회수기 - 본 발명은 마스크 착용 후 버려지는 일회용 폐마스크를 비닐봉지에 넣은 후 밀봉하여 배출함으로써, 2차 감염을 예방하고 일반 생활폐기물과 선별 분리 배출하여 환경오염을 방지하는 데 그 목적이 있다. - link
백신 냉각 및 해동 기능을 갖는 백신 보관장치 - 본 발명은 백신 냉각 및 해동 기능을 갖는 백신 보관장치에 관한 것으로, 상, 하부하우징의 제1상, 하부누출방지공간에 냉각물질이 충입된 냉각파이프를 설치하되, 제2상, 하부누출방지공간에 가열물질이 충입된 가열파이프를 설치하여, 구획판부에 의해 구획된 백신냉각공간 및 백신해동공간 각각을 냉각 및 가열하고, 보조도어를 통해 백신냉각공간 내에 수용된 백신을 구획판부의 백신출구도어를 통해 백신해동공간으로 이동시켜, 백신해동공간 내에서 백신을 해동함으로써, 즉시 사용이 가능한 백신을 인출도어를 통해 인출할 수 있다. 본 발명에 따르면, 냉각파이프에 저장된 냉매에 의해 백신냉각공간 내의 온도가 극저온 상태로 변화되고, 극저온 상태를 유지하는 백신냉각공간 내에 백신을 저장하여, 안전하게 보관 할 수 있으며, 백신냉각공간 내의 백신을 백신해동공간 내로 이동시켜, 백신해동공간 내에서 백신을 해동할 수 있고, 이 해동된 백신을 인출도어를 통해 인출한 후 즉시 사용할 수 있어 백신을 해동하는 시간이 단축되며, 보조도어를 통해 백신냉각공간 내의 백신을 백신해동공간으로 이동시켜, 백신이 외기에 노출될 우려가 없으며, 백신냉각공간 내의 백신을 백신해동공간으로 이동시키거나 또는 인출도어를 통해 백신 인출시 정렬장치가 백신을 보조도어 및 인출도어 직하방에 자동 위치시킨다. - link
一种基于新型冠状病毒S蛋白的纳米抗体及其应用 - 本发明属于生物医药技术领域，尤其涉及一种基于新型冠状病毒S蛋白的纳米抗体及其应用。本发明利用纳米抗体文库，以2019新型冠状病毒的Spike S1+S2ECD为靶点，筛选获得一种针对2019新型冠状病毒的纳米抗体，经ELISA检测，不仅能够特异性识别2019新型冠状病毒的Spike S1+S2ECD靶点，还同时能够识别Spike RBD靶点，且结合信号较强。将相应抗体序列构建至原核表达载体中进行表达纯化，成功表达出目标抗体，纯化后纯度大于90％；且经VHH抗体ELISA检测发现，纯化后的纳米抗体对两种靶点均具有较高的亲和力。 - link
一种基于新型冠状病毒S蛋白S1亚基的纳米抗体及其应用 - 本发明属于生物医药技术领域，尤其涉及一种基于新型冠状病毒S蛋白S1亚基的纳米抗体及其应用。本发明利用纳米抗体文库，以2019新型冠状病毒的Spike RBD为靶点，筛选获得一种针对2019新型冠状病毒的纳米抗体，经ELISA检测，不仅能够特异性识别2019新型冠状病毒的Spike RBD靶点，还同时能够识别SPIKE S1+S2ECD靶点，且结合信号较强。将相应抗体序列构建至原核表达载体中进行表达纯化，成功表达出目标抗体，纯化后纯度大于90％；且经VHH抗体ELISA检测发现，纯化后的纳米抗体对两种靶点均具有较高的亲和力。 - link