Background Recent evidence indicates a potential therapeutic role of fluvoxamine for COVID-19. In the TOGETHER randomized platform clinical trial for acutely symptomatic patients with COVID-19, we assessed the efficacy of fluvoxamine vs. placebo in preventing either extended emergency room observation or hospitalization due to COVID-19. Herein, we report the preliminary findings. Methods This placebo-controlled, randomized, adaptive, platform trial conducted among symptomatic Brazilian adults confirmed positive for SARS-CoV-2 included eligible patients with a known risk factor for progression to severe disease. Patients were randomly assigned to either fluvoxamine (100 mg twice daily for 10 days) or placebo. The primary endpoint was a composite outcome of emergency room observation for >6 hours or hospitalization from COVID-19 up to 28 days post randomization. Secondary outcomes included viral clearance at day 7, time to hospitalization, mortality, and adverse drug reactions. We used a Bayesian analytic framework to determine effects along with probability of success of intervention compared to placebo. The trial is registered at clinicaltrials.gov (NCT04727424) and is ongoing. Results The study team screened 9020 potential participants for this trial. The trial was initiated on June 2, 2020, with the current protocol reporting randomization from January 15, 2021 to August 6th 2021, when the trial arms were stopped for superiority. A total of 3238 patients were allocated to fluvoxamine (n=739), placebo (n=733) and other treatments (n=1766). Herein, we report the effectiveness of fluvoxamine vs. a concurrent placebo control. The average age of participants was 50 years (range 18-102 years); 57% were female. The proportion of patients observed in an emergency room for >6 hours or admitted to hospital due to COVID-19 was lower for the fluvoxamine group compared to placebo (77/739 vs 108/733; Relative Risk [RR]: 0.71; 95% Bayesian Credible Interval [95% BCI]: 0.54 - 0.93), with a probability of superiority of 99.4% surpassing the prespecified superiority threshold of 97.6% (risk difference 4.3%). Of the composite primary outcome events, 88% were hospitalizations. We found no significant relative effects between the fluvoxamine and placebo groups on viral clearance at day 7 (Odds ratio [OR]: 0.75; 95% Confidence Intervals [95% CI]: 0.53 - 1.07), mortality (OR: 0.70; 95% CI: 0.36 - 1.30), time to death (Hazard ratio [HR]: 0.79; 95% CI: 0.58 - 1.08), days hospitalized (Mean Difference (MD) 1.22 days; 95% CI: 0.98 - 1.53), number of days ventilated (MD 1.10; 95% CI: 0.70 - 1.73) or other secondary outcomes. Data capturing all 28 days of follow-up will be reported after August 26th, 2021. Conclusions Treatment with fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19, reduced the need for extended emergency room observation or hospitalization. Funding The trial was supported by FastGrants and The Rainwater Foundation.
The increasing prevalence of variant lineages during the COVID-19 pandemic has the potential to disrupt molecular diagnostics due to mismatches between primers and variant templates. Point-of-care molecular diagnostics, which often lack the complete functionality of their high throughput laboratory counterparts, are particularly susceptible to this type of disruption, which can result in false negative results. To address this challenge, we have developed a robust Loop Mediated Isothermal Amplification assay with single tube multiplexed multi-target redundancy and an internal amplification control. A convenient and cost-effective target specific fluorescence detection system allows amplifications to be grouped by signal using adaptable probes for pooled reporting of SARS-COV-2 target amplifications or differentiation of the Internal Amplification Control. Over the course of the pandemic, primer coverage of viral lineages by the three redundant sub-assays has varied from assay to assay as they have diverged from the Wuhan-Hu-1 isolate sequence, but aggregate coverage has remained high for all variant sequences analyzed, with a minimum of 97.4% (Variant of Interest: Eta). In three instances (Delta, Gamma, Eta), a high frequency mismatch with one of the three sub- assays was observed, but overall coverage remained high due to multi-target redundancy. When challenged with extracted human samples the multiplexed assay showed 100% sensitivity for samples containing greater than 30 copies of viral RNA per reaction, and 100% specificity. These results are further evidence that conventional laboratory methodologies can be leveraged at the point-of-care for robust performance and diagnostic stability over time.
ABSTRACT Importance: Thromboses after the COVID-19 vaccine ChAdOx1-S have been reported. Better understanding of population-level thrombotic risks after COVID-19 vaccination is needed. Objective: Quantify associations of vaccination with ChAdOx1-S and BNT162b2 with major arterial, venous and thrombocytopenic events. Design: Cohort study based on linked electronic health records, with follow up from December 8th, 2020, to March 18th, 2021. Setting and participants: Adults registered with an NHS general practice in England and alive on December 8th, 2020. Exposures: First dose of vaccination with ChAdOx1-S and BNT162b2. Main Outcomes and Measures: Incidence rates and hazard ratios (HRs) for major arterial, venous and thrombocytopenic outcomes 1-28 and >28 days after first vaccination with ChAdOx1-S or BNT162b2 vaccine. Analyses were performed separately for ages <70 and ≥70 years, and adjusted for age, sex, comorbidities, and social and demographic factors. Results: Of 46,162,942 adults, 21,193,814 (46%) had their first vaccination during follow-up. Adjusted HRs 1-28 days after ChAdOx1-S, compared with pre-vaccination rates, at ages <70 and ≥70 respectively, were 0.97 (95% CI: 0.9-1.05) and 0.58 (0.53-0.63) for venous thromboses, and 0.90 (0.86-0.95) and 0.76 (0.73-0.79) for arterial thromboses. Corresponding HRs for BNT162b2 were 0.81 (0.74-0.88) and 0.57 (0.53-0.62) for venous thromboses, and 0.94 (0.90-0.99) and 0.72 (0.70-0.75) for arterial thromboses. HRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines. Rates of intracranial venous thrombosis (ICVT) and thrombocytopenia in adults aged <70 years were higher 1-28 days after ChAdOx1-S (adjusted HRs 2.27, 95% CI:1.33-3.88 and 1.71, 1.35-2.16 respectively), but not after BNT162b2 (0.59, 0.24-1.45 and 1.00, 0.75-1.34) compared with pre-vaccination. The corresponding absolute excess risks of ICVT 1-28 days after ChAdOx1-S were 0.9-3 per million, varying by age and sex. Conclusions and Relevance: Increases in ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years are small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic, events were generally lower after either vaccine.
Background: Results of a randomised trial showed the safety and efficacy of Gam-COVID-Vac against COVID-19. However, compared to other vaccines used across the globe, the real-world data on the effectiveness of Gam-COVID-Vac, especially against the disease caused by Delta variant of concern, was not available. We aimed to assess the effectiveness of vaccination mainly conducted with Gam-COVID-Vac in St. Petersburg, Russia. Methods: We designed a case- control study to assess the vaccine effectiveness (VE) against lung injury and referral to hospital. Self-reported vaccination status was collected for individuals with confirmed SARS-CoV-2 infection who were referred for initial low- dose computed tomography triage in two outpatient centres in July 3 – August 9, 2021 in St. Petersburg, Russia. We used logistic regression models to estimate the adjusted (for age, and triage centre) VE for complete (>14 days after the second dose) and partial vaccination (>14 days after the first dose). We estimated the VE against referral for hospital admission, COVID-19-related lung injury assessed with LDCT, and decline in oxygen saturation. Results: In the final analysis, 13,894 patients were included, 1,291 (9.3%) of patients met our criteria for complete vaccination status, and 495 (3.6%) were referred to hospital. In the primary analysis, the adjusted VE against referral to hospital was 81% (95% CI: 68-88) for complete vaccination. The effect of the partial vaccination was not statistically significant. The VE against referral to hospital was more pronounced in women (84%, 95% CI: 66-92) compared to men (76%, 95% CI: 51-88). Vaccine protective effect increased with increasing lung injury categories, from 54% (95% CI: 48-60) against any sign of lung injury to 76% (95% CI: 59-86) against more than 50% lung involvement. A sharp increase was observed in the probability of hospital admission with age for non-vaccinated patients in relation to an almost flat relationship for the completely vaccinated group. Conclusions: COVID-19 vaccination was effective against referral to hospital in patients with symptomatic SARS-CoV-2 infection in St. Petersburg, Russia. This protection is probably mediated through VE against lung injury associated with COVID-19.
The COVID-19 pandemic has challenged healthcare systems and research worldwide. Data is collected all over the world and needs to be integrated and made available to other researchers quickly. However, the various heterogeneous information systems that are used in hospitals can result in fragmentation of health data over multiple data 9silos9 that are not interoperable for analysis. Consequently, clinical observations in hospitalised patients are not prepared to be reused efficiently and timely. There is a need to adapt the research data management in hospitals to make COVID-19 observational patient data machine actionable, i.e. more Findable, Accessible, Interoperable and Reusable (FAIR) for humans and machines. We therefore applied the FAIR principles in the hospital to make patient data more FAIR. In this paper, we present our FAIR approach to transform COVID-19 observational patient data collected in the hospital into machine actionable digital objects to answer medical doctors9 research questions. With this objective, we conducted a coordinated FAIRification among stakeholders based on ontological models for data and metadata, and a FAIR based architecture that complements the existing data management. We applied FAIR Data Points for metadata exposure, turning investigational parameters into a FAIR dataset. We demonstrated that this dataset is machine actionable by means of three different computational activities: federated query of patient data along open existing knowledge sources across the world through the Semantic Web, implementing Web APIs for data query interoperability, and building applications on top of these FAIR patient data for FAIR data analytics in the hospital. Our work demonstrates that a FAIR research data management plan based on ontological models for data and metadata, open Science, Semantic Web technologies, and FAIR Data Points is providing data infrastructure in the hospital for machine actionable FAIR digital objects. This FAIR data is prepared to be reused for federated analysis, linkable to other FAIR data such as Linked Open Data, and reusable to develop software applications on top of them for hypothesis generation and knowledge discovery.
The COVID-19 pandemic has underscored the need for rapid novel diagnostic strategies to detect and characterize pathogens from clinical specimens. The MinION sequencing device allows for rapid, cost-effective, high-throughput sequencing; useful features for translation to clinical laboratory settings. Metagenomic Next-Generation Sequencing (mNGS) approaches provide the opportunity to examine the entire genomic material of a sample; allowing for detection of emerging and clinically relevant pathogens that may be missed in targeted assays. Here we present a pilot study on the performance of Sequence-Independent Single Primer Amplification (SISPA) to amplify RNA randomly for the detection and characterization of SARS-CoV-2. We designed a classifier that corrects for barcode crosstalk between specimens. Our assay yielded 100% specificity overall and 95.2% sensitivity for specimens with a RT-qPCR cycle threshold value less than 30. We assembled 10 complete (>95% coverage at 20x depth), and one near-complete (>80% coverage at 20x depth) genomes from 20 specimens that were classified as positive by mNGS. We characterized these genomes through phylogenetic analysis and found that 10/11 specimens from British Columbia had a closest relative to another British Columbian specimen. Of five samples that we had both assembled genomes, as well as Variant of Concern (VOC) PCR results, we found 100% concordance between these results. Additionally, our assay was able to distinguish between the Alpha and Gamma variants, which was not possible with our VOC PCR technique. This study supports future work examining the broader feasibility of SISPA as a diagnostic strategy for the detection and characterization of viral pathogens.
Although pregnancy poses a greater risk for severe COVID-19, the underlying immunological changes associated with SARS-CoV-2 infection during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in pregnant and non-pregnant women during acute and convalescent COVID-19 up to 258 days post symptom onset, quantifying 217 immunological parameters. Additionally, matched maternal and cord blood were collected from COVID-19 convalescent pregnancies. Although serological responses to SARS-CoV-2 were similar in pregnant and non-pregnant women, cellular immune analyses revealed marked differences in key NK cell and unconventional T cell responses during COVID-19 in pregnant women. While NK cells, γδ T cells and MAIT cells displayed pre-activated phenotypes in healthy pregnant women when compared to non-pregnant age-matched women, activation profiles of these pre-activated NK and unconventional T cells remained unchanged at acute and convalescent COVID-19 in pregnancy. Conversely, activation dynamics of NK and unconventional T cells were prototypical in non-pregnant women in COVID-19. In contrast, activation of αβ CD4+ and CD8+ T cells, T follicular helper cells and antibody-secreting cells was similar in pregnant and non-pregnant women with COVID-19. Elevated levels of IL-1β, IFN-γ, IL-8, IL-18 and IL-33 were also found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, our study provides the first comprehensive map of longitudinal immunological responses to SARS-CoV-2 infection in pregnant women, providing insights into patient management and education during COVID-19 pregnancy.
During the COVID-19 pandemic authorities have been striving to obtain reliable predictions for the spreading dynamics of disease. We recently developed an in-homogeneous multi-“sub-populations” (multi-compartments: susceptible, exposed, pre-symptomatic, infectious, recovered) model, that accounts for the spatial in-homogeneous spreading of the infection and shown, for a variety of examples, how the epidemic curves are highly sensitive to location of epicenters, non-uniform population density, and local restrictions. In the present work we tested our model against real-life data from South Carolina during the period May 22 to July 22 (2020), that was available in the form of infection heat-maps and conventional epidemic curves. During this period, minimal restrictions have been employed, which allowed us to assume that the local reproduction number is constant in time. We accounted for the non-uniform population density in South Carolina using data from NASA, and predicted the evolution of infection heat-maps during the studied period. Comparing the predicted heat-maps with those observed, we find high qualitative resemblance. Moreover, the Pearson9s correlation coefficient is relatively high and does not get lower than 0.8, thus validating our model against real-world data. We conclude that our model accounts for the major effects controlling spatial in-homogeneous spreading of the disease. Inclusion of additional sub-populations (compartments), in the spirit of several recently developed models for COVID-19, can be easily performed within our mathematical framework.
Background: Pregnancy can be a stressful time and the COVID 19 pandemic has affected all aspects of life. This study aims to investigate the impact of the pandemic on population birth outcomes in Wales, rates of primary immunisations and examine expectant mothers experiences of pregnancy including self reported levels of stress and anxiety. Methods: Population level birth outcomes in Wales: Stillbirths, prematurity, birth weight and Caesarean section births before (2016 to 2019) and during (2020) the pandemic were compared using national level routine anonymised data held in the Secure Anonymised Information Linkage (SAIL) Databank. The first three scheduled primary immunisations were compared between 2019 and 2020. Self reported pregnancy experience: 215 expectant mothers (aged 16+) in Wales completed an online survey about their experiences of pregnancy during the pandemic. The qualitative survey data was analysed using codebook thematic analysis. Findings: There was no significant difference between annual outcomes including gestation and birth weight, stillbirths, and Caesarean sections for infants born in 2020 compared to years 2016 to 2019. There was an increase in late term births (>42 weeks gestation) during the first lockdown (OR: 1.28, p=0.019) and a decrease in moderate to late preterm births (32 to 36 weeks gestation) during the second lockdown (OR: 0.74, p=0.001). Fewer babies were born in 2020 (N=29,031) compared to years 2016 to 2019 (average N=32,582). All babies received their immunisations in 2020, but there were minor delays in the timings of vaccines. Those due at 8 weeks were 8% less likely to be on time (within 28 days) and at 16 weeks, they were 19% less likely to be on time. The pandemic had a negative impact on the mental health of 71% of survey respondents, who reported anxiety, stress and loneliness; this was associated with attending scans without their partner, giving birth alone, and minimal contact with midwives. Interpretation: The pandemic had a negative impact on mothers experiences of pregnancy; however, population level data suggests that this did not translate to adverse birth outcomes for babies born during the pandemic.
Increasing evidence indicates that specific genetic variants influence the severity of outcomes after infection with COVID-19. However, it is not clear whether the effect of these genetic factors is independent of the risk due to more established non-genetic demographic and metabolic risk factors such as male sex, poor cardiometabolic health, and low socioeconomic status. We sought to identify interactions between genetic variants and non-genetic risk factors influencing COVID-19 severity via a genome-wide interaction study in the UK Biobank. Of 378,051 unrelated individuals of European ancestry, 2,402 were classified as having experienced severe COVID-19, defined as hospitalization or death due to COVID-19. Exposures included sex, cardiometabolic risk factors (obesity and type 2 diabetes [T2D], tested jointly), and multiple deprivation index. Multiplicative interaction was tested using a logistic regression model, conducting both an interaction test and a joint test of genetic main and interaction effects. Five independent variants reached genome- wide significance in the joint test, one of which also reached significance in the interaction test. One of these, rs2268616 in the PGF gene, showed stronger effects in males and in individuals with T2D. None of the five variants showed effects on a similarly-defined phenotype in a lookup in the COVID-19 Host Genetics Initiative. These results reveal potential additional genetic loci contributing to COVID-19 severity and demonstrate the value of including non- genetic risk factors in an interaction testing approach for genetic discovery.
Both SARS-CoV-2 infection and vaccination elicit potent immune responses, but the durability and scope of immune responses remain to be elucidated. Here, we performed multimodal single-cell profiling of peripheral blood of patients with acute COVID-19 and healthy volunteers before and after receiving the SARS-CoV-2 BNT162b2 mRNA vaccine to compare the immune responses elicited by the virus and by the vaccine. Phenotypic and transcriptional profiling of immune cells, coupled with reconstruction of B and T cell receptor repertoires, enabled us to characterize and compare the host responses to the virus and to defined viral antigens. In COVID-19 patients, immune responses were characterized by a highly augmented interferon response which was largely absent in vaccine recipients. Increased interferon signaling likely contributed to the dramatic upregulation of cytotoxic genes in the peripheral T cells and innate-like lymphocytes observed in COVID-19 patients. Analysis of B and T cell repertoires revealed that while the majority of clonal lymphocytes in COVID-19 patients were effector cells, in vaccine recipients clonal expansion was primarily restricted to circulating memory cells. Taken together, our analysis of immune responses to the mRNA vaccine reveals that despite the lack of dramatic inflammation observed during infection, the vaccine elicits a robust adaptive immune response.
Pulmonary Rehabilitation Post-COVID-19 - Condition: COVID-19
Intervention: Other: Exercise program (virtual/remote)
Sponsors: University of Manitoba; Health Sciences Centre Foundation, Manitoba; Health Sciences Centre, Winnipeg, Manitoba
Not yet recruiting
To Evaluate Efficacy & Safety of Proxalutamide in Hospitalized Covid-19 Subjects - Condition: Covid19
Interventions: Drug: GT0918; Drug: Standard of care; Drug: Matching placebo
Sponsors: Suzhou Kintor Pharmaceutical Inc,; IQVIA Biotech
Not yet recruiting
A Study of PF-07321332/Ritonavir in Non-hospitalized Low-Risk Adult Participants With COVID-19 - Condition: COVID-19
Interventions: Drug: PF-07321332; Drug: Ritonavir; Drug: Placebo
Sponsor: Pfizer
Not yet recruiting
Mix and Match Heterologous Prime-Boost Study Using Approved COVID-19 Vaccines in Mozambique - Condition: Covid19
Interventions: Biological: BBIBP-CorV - Inactivated SARS-CoV-2 vaccine (Vero cell); Biological: AZD1222 (replication-deficient Ad type 5 vector expressing full-length spike protein)
Sponsors: International Vaccine Institute; The Coalition for Epidemic Preparedness Innovations (CEPI); Instituto Nacional de Saúde (INS), Mozambique; University of Antananarivo; International Centre for Diarrhoeal Disease Research, Bangladesh; Harvard University; Heidelberg University
Not yet recruiting
Targeting de Novo Pyrimidine Biosynthesis by Leflunomide for the Treatment of COVID-19 Virus Disease - Condition: COVID-19
Intervention: Drug: leflunomide
Sponsor:
Ashford and St. Peter’s Hospitals NHS Trust
Active, not recruiting
Andrographis Paniculata vs Boesenbergia Rotunda vs Control in Asymptomatic COVID-19 - Condition: Covid19
Interventions: Drug: Andrographis Paniculata; Drug: Boesenbergia; Other: Standard supportive treatment
Sponsors: Mahidol University; Ministry of Health, Thailand
Not yet recruiting
Efficacy of PJS-539 for Adult Patients With COVID-19. - Conditions: Covid19; COVID-19 Pneumonia
Interventions: Drug: PJS-539 Dose 1; Drug: PJS-539 Dose 2; Drug: Placebo
Sponsors: Hospital do Coracao; Covicept
Not yet recruiting
Phase I/II Clinical Trial of Recombinant COVID-19 Vaccine (Sf9 Cells) in Children and Adolescents - Condition: COVID-19
Interventions: Biological: Recombinant COVID-19 vaccine (Sf9 cells); Other: Placebo control
Sponsors: WestVac Biopharma Co., Ltd.; West China Hospital
Not yet recruiting
COVID-19 Methylene Blue Antiviral Treatment - Condition: Covid19
Interventions: Drug: Methylene Blue; Drug: Saline nasal spray
Sponsors: Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences; Irkutsk State Medical University
Recruiting
Treatment of Covid-19 With a Herbal Compound, Xagrotin - Condition: Covid19
Intervention: Combination Product: Xagrotin
Sponsors:
Biomad AS; Directorate of health of Sulaimani, Iraq -KRG
Completed
Relaxation Exercise in Patients With COVID-19 - Condition: Covid19
Intervention: Other: Relaxation technique
Sponsor: Beni- Suef University
Completed
Trial of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector, Ad5-nCoV) in Adults Living With HIV - Condition: Covid19
Intervention: Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) (Ad5-nCoV)
Sponsors: Fundación Huésped; Canadian Center for Vaccinology; CanSino Biologics Inc.; Hospital Fernandez
Recruiting
Philippine Trial to Determine Efficacy and Safety of Favipiravir for COVID-19 - Condition: Covid19
Interventions: Combination Product: Favipiravir + Standard of Care; Procedure: Standard of Care
Sponsors: University of the Philippines; Department of Health, Philippines
Recruiting
Evaluation of the Effects of Bradykinin Antagonists on Pulmonary Manifestations of COVID-19 Infections (AntagoBrad- Cov Study). - Condition: Covid19
Interventions: Drug: C1 Inhibitor Human; Drug: Icatibant Injection; Other: Placebo
Sponsor: GCS Ramsay Santé pour l’Enseignement et la Recherche
Completed
Combination of Dietary Supplements Curcumin, Quercetin and Vitamin D for Early Symptoms of COVID-19 - Condition: Covid19
Interventions: Drug: Standard of care; Dietary Supplement: combination of curcumin, quercetin and Vitamin D
Sponsor: Ayub Teaching Hospital
Not yet recruiting
DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 M(pro) inhibitors - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration-approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific…
CuCl(2)-catalyzed inexpensive, faster and ligand/additive free synthesis of isoquinolin-1(2H)-one derivatives via the coupling-cyclization strategy: Evaluation of a new class of compounds as potential PDE4 inhibitors - In spite of possessing a wide range of pharmacological properties the anti-inflammatory activities of isoquinolin-1(2H)-ones were rarely known or explored earlier. PDE4 inhibitors on the other hand in addition to their usefulness in treating inflammatory diseases have been suggested to attenuate the cytokine storm in COVID-19 especially TNF-α. In our effort, a new class of isoquinolin-1(2H)-ones derivatives containing an aminosulfonyl moiety were designed and explored as potential inhibitors of…
Coronavirus disease-2019: A review on the disease exacerbation via cytokine storm and concurrent management - Setting up treatment strategies is the highest concern today to reduce the fatality of COVID-19. Due to a very new kind of virus attack, no specific treatment has been discovered to date. The most crucial way to dominate the disease severity is now the repurposing of drugs. In this review, we focused on the current treatment approaches targeting the crucial causative factors for the disease burden through cytokine storm or cytokine release syndrome. Several vaccines have been developed and have…
Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin - CONCLUSIONS: Clotting pathologies in both acute COVID-19 infection and in Long COVID/PASC might benefit from following a regime of continued anticlotting therapy to support the fibrinolytic system function.
Paradoxical effects of cigarette smoke and COPD on SARS-CoV-2 infection and disease - CONCLUSIONS: ACE2 levels were decreased in both bronchial and alveolar epithelial cells from COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-exposure potently inhibited SARS-CoV-2 replication in vitro. These findings urge to investigate further the controversial effects of CS and COPD on SARS-CoV-2 infection.
Brief report: Tempol, a novel antioxidant, inhibits both activated T cell and antigen presenting cell derived cytokines in-vitro from COVID-19 patients - COVID-19 is characterized by a dysregulation of inflammatory cytokines ultimately resulting a cytokine storm that can result in significant morbidity and mortality. We developed an in-vitro assay using activated peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide (LPS) or CD3 + CD28 to examine secretion of cytokines from antigen presenting cells (APCs) and T cells, respectively, in donor patients with a history of COVID-19 (convalescent) and uninfected negative…
The early interferon catches the SARS-CoV-2 - Interferons establish innate antiviral immunity. Two recent papers in JEM by Lopez et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20211211) and Cheemarla et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210583) show that an appropriate supply of antiviral interferon enables epithelial cells of the nasopharyngeal mucosa to inhibit SARS-CoV-2 growth and that interferon-induced mucosal genes serve as biomarkers of infection.
Analysis of the avian coronavirus spike protein reveals heterogeneity in the glycans present - Infectious bronchitis virus (IBV) is an economically important coronavirus, causing damaging losses to the poultry industry worldwide as the causative agent of infectious bronchitis. The coronavirus spike (S) glycoprotein is a large type I membrane protein protruding from the surface of the virion, which facilitates attachment and entry into host cells. The IBV S protein is cleaved into two subunits, S1 and S2, the latter of which has been identified as a determinant of cellular tropism. Recent…
Reviewing the physiology, pharmacology and therapeutic uses of ketamine - Ketamine is a synthetic drug with unique properties which started to be used therapeutically in humans in the 1970s and is now widely used in all fields of nursing. Ketamine acts on the central nervous system, primarily through inhibiting N-methyl-D-aspartate receptors. However, the precise understanding of its mechanisms of action remains elusive in many respects. Ketamine is frequently used as an anaesthetic in medical and surgical procedures and as an analgesic in children and adults. It is…
Drug Repurposing for the SARS-CoV-2 Papain-Like Protease - As the pathogen of COVID-19, SARS-CoV-2 encodes two essential cysteine proteases that process the pathogen’s two large polypeptide products pp1a and pp1ab in the human cell host to form 15 functionally important, mature nonstructural proteins. One of the two enzymes is papain-like protease or PL Pro . It possesses deubiquitination and deISGylation activities that suppress host innate immune responses toward SARS-CoV-2 infection. To repurpose drugs for PL Pro , we experimentally screened…
Experimental and CFD evaluation of Ozone Efficacy against Coronavirus and Enteric Virus Contamination on Public Transport Surfaces - The limited information about the routes of the transmission of SARS-CoV-2 within the ongoing pandemic scenario mobilized the administration, industry and academy to develop sanitation and disinfection systems for public and private spaces. Ozone has been proposed as an effective disinfection method against enveloped and non-enveloped viruses, including viruses with similar morphology to SARS-CoV-2. Due to this efficacy, numerous gaseous and aqueous phase ozone applications have emerged…
The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models - The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure the dimerization of angiotensin-converting enzyme 2 (ACE2), the primary receptor for the virus. This screen identified fenofibric acid, the active metabolite of fenofibrate. Fenofibric acid also destabilized the receptor-binding domain (RBD) of the viral…
Effectivity of mesenchymal stem cells for bleomycin-induced pulmonary fibrosis: a systematic review and implication for clinical application - Pulmonary fibrosis (PF) is a chronic, progressive, fibrotic interstitial disease of the lung with poor prognosis and without effective treatment currently. Data from previous coronavirus infections, such as the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome, as well as current clinical evidence from the Coronavirus disease 2019 (COVID-19), support that SARS-CoV-2 infection may lead to PF, seriously impacting patient prognosis and quality of life. Therefore,…
Effects of the COVID-19 pandemic on family planning services - PURPOSE OF REVIEW: The COVID-19 pandemic has highlighted existing healthcare disparities worldwide and has challenged access to family planning (FP) services.
Which ones, when and why should renin-angiotensin system inhibitors work against COVID-19? - The article describes the possible pathophysiological origin of COVID-19 and the crucial role of renin-angiotensin system (RAS), providing several “converging” evidence in support of this hypothesis. SARS-CoV-2 has been shown to initially upregulate ACE2 systemic activity (early phase), which can subsequently induce compensatory responses leading to upregulation of both arms of the RAS (late phase) and consequently to critical, advanced and untreatable stages of COVID-19 disease. The main and…
Anti-Sars-Cov-2 Neutralizing Antibodies - - link
Expression Vector for Anti-Sars-Cov-2 Neutralizing Antibodies - - link
DEVELOPMENT OF CNN SCHEME FOR COVID-19 DISEASE DETECTION USING CHEST RADIOGRAPH - - link
SARS-COV-2 BINDING PROTEINS - - link
A PROCESS FOR PREPARING MONTELUKAST SODIUM FOR TREATING COVID 19 PATIENTS - - link
IDENTIFICATION OF ANTI-COVID 19 AGENT SOMNIFERINE AS INHIBITOR OF MPRO & ACE2-RBD INTERACTION - - link
Deep Learning Based System For Detection of Covid-19 Disease of Patient At Infection Risk. - - link
자외선살균등 - 본 발명은 사람의 의복이나 사용한 마스크 등에 부착하여 있다 호흡기로 유입되어 감염을 유발할 수 있는 COVID-19와 같은 유해균류를 간편하게 살균하기 위한 휴대용 자와선살균등에 관한 것이다. 반감기가 길고 인체에 유해한 오존을 발생하지 않으면서 탁월한 살균능력이 있는 250~265nm(최적은 253.7nm) 파장의 자외선을 발광하는 자외선램프를 본 발명의 막대형의 자외선살균등 광원으로 사용하고 비광원부를 손으로 잡고 의복이나 사용한 마스크 등 유해균류가 부착되었을 것으로 의심되는 곳에 자외선을 조사하여 간편하게 유해균류를 살균하므로써 감염을 예방하기 위한 휴대용 자외선살균등에 관함 것이다. - link
Protein chip and kit for detecting the SARS-CoV-2 S antigen - - link
一种新冠病毒疫苗的表达载体及其构建方法、应用和疫苗 - 本发明适用于生物技术领域，提供了一种新冠病毒疫苗的表达载体及其构建方法、应用和疫苗，该表达载体的构建方法包括以下步骤：将表达新冠病毒S蛋白与NP蛋白的核苷酸序列使用2A肽进行连接，合成融合基因；在融合基因的两端分别包含两个酶切位点，并装载到质粒，得到重组质粒；对重组质粒进行双酶切，切胶回收目的基因片段；对原始的质粒进行双酶切，切胶回收载体片段；将目的基因片段和载体片段进行连接，得到所述表达载体。本发明实施例通过同时表达冠状病毒S蛋白受体结合区与NP蛋白，使该表达载体感染的细胞不但可以诱导抗体反应还能诱导T细胞反应，从而有效诱导体液免疫和细胞免疫，为受试者提供更强的免疫保护。 - link