In late 2021, the Omicron SARS-CoV-2 variant spread rapidly worldwide. To track its emergence, and the continued evolution of SARS-CoV-2 while giving actionable epidemio- logical data that informs public health policy, we developed a high-throughput, automated, genotyping workflow that pairs flexible liquid handling with a re-configurable LIMS system. This workflow facilitated the real-time monitoring of the spread of BA.4 and BA.5, and by the time of its retirement, the system was responsible for typing c. 400,000 SARS-CoV-2 samples. When combined with a population-scale testing program, genotyping assays, can offer a rapid and cost-effective method of determining variants and horizon-scanning for changes in the pool of circulating mutations. Strategies to prepare diagnostics infrastructure for Pathogen X should consider the development of flexible systems with interchangeable components that can be rapidly re-configured to meet uncertain and changing requirements.
Since its emergence in late 2019, the SARS-CoV-2 virus has spread globally, causing the ongoing COVID-19 pandemic. In the fall of 2020, the Alpha variant (lineage B.1.1.7) was detected in England and spread rapidly, outcompeting the previous lineage. Yet, very little is known about the underlying modifications of the infection process that can explain this selective advantage. Here, we try to quantify how the Alpha variant differed from its predecessor on two phenotypic traits: the transmission rate and the duration of infectiousness. To this end, we analysed the joint epidemiological and evolutionary dynamics as a function of the Stringency Index, a measure of the amount of Non-Pharmaceutical Interventions. Assuming that these control measures reduce contact rates and transmission, we developed a two-step approach based on SEIR models and the analysis of a combination of epidemiological and evolutionary information. First, we quantify the link between Stringency Index and the reduction in viral transmission. Secondly, based on a novel theoretical derivation of the selection gradient in an SEIR model, we infer the phenotype of the Alpha variant from its frequency changes. We show that its selective advantage is more likely to result from a higher transmission than from a longer infectious period.
Mass gatherings frequently include close, prolonged interactions between people, which presents opportunities for infectious disease transmission. Over 20,000 pilgrims gathered at Namugongo Catholic and Protestant shrines to commemorate 2022 Uganda Martyr’s Day. We described syndromes suggestive of key priority diseases particularly COVID–19 and viral hemorrhagic fever (VHF) among visiting pilgrims during May 25−June 5, 2022. A suspected COVID–19 case was defined as ≥2 signs or symptoms of: fever >37.50C, flu, cough, and difficulty in breathing whereas a suspected VHF case was defined as fever >37.50C and unexplained bleeding among pilgrims who visited Namugongo Catholic and Protestant shrines from May 25 to June 5, 2022. Pilgrims were sampled systematically at entrances and demarcated zonal areas to participate in the survey. Additionally, we extracted secondary data on pilgrims who sought emergency medical services from Health Management Information System registers. Descriptive analysis was conducted to identify syndromes suggestive of key priority diseases based on signs and symptoms. Among 1,350 pilgrims interviewed, 767 (57%) were female. The mean age was 37.9 (±17.9) years. Nearly all pilgrims 1,331 (98.6%) were Ugandans. A total of 236 (18%) reported ≥1 case definition symptom and 25 (2%) reported ≥2 symptoms. Twenty-two (1.6%) were suspected COVID–19 cases and three (0.2%) were suspected VHF cases from different regions of Uganda. Among 5,582 pilgrims who sought medical care from tents, 538 (9.6%) had suspected COVID–19 and one had suspected VHF. Almost one in fifty pilgrims at the 2022 Uganda Martyrs’ commemoration had at least one symptom of COVID–19 or VHF. Overall, we identified 4 Viral Hemorrhagic Fever and 560 COVID-19 suspected cases during the 2022 Uganda Martyrs’ commemoration. Intensified syndromic surveillance and planned laboratory testing capacity at mass gatherings is important for early detection of public health emergencies that could stem from such events.
Introduction - Adverse psychosocial Adverse psychosocial exposure is associated with increased proinflammatory gene expression and reduced type-1 interferon gene expression, a profile known as the conserved transcriptional response to adversity (CTRA). Little is known about CTRA activity in the context of cognitive impairment, although chronic inflammatory activation has been posited as one mechanism contributing to late-life cognitive decline. Methods - We studied 171 community-dwelling older adults from the Wake Forest Alzheimers Disease Research Center who answered questions via a telephone questionnaire battery about their perceived stress, loneliness, well-being, and impact of COVID-19 on their life, and who provided a self-collected dried blood spot sample. Of those, 148 had adequate samples for mRNA analysis, and 143 were included in the final analysis, which including participants adjudicated as having normal cognition (NC, n = 91) or mild cognitive impairment (MCI, n = 52) were included in the analysis. Mixed effect linear models were used to quantify associations between psychosocial variables and CTRA gene expression. Results - In both NC and MCI groups, eudaimonic well-being (typically associated with a sense of purpose) was inversely associated with CTRA gene expression whereas hedonic well-being (typically associated with pleasure seeking) was positively associated. In participants with NC, coping through social support was associated with lower CTRA gene expression, whereas coping by distraction and reframing was associated with higher CTRA gene expression. CTRA gene expression was not related to coping strategies for participants with MCI, or to either loneliness or perceived stress in either group. Discussion - Eudaimonic and hedonic well-being remain important correlates of molecular markers of stress, even in people with MCI. However, prodromal cognitive decline appears to moderate the significance of coping strategies as a correlate of CTRA gene expression. These results suggest that MCI can selectively alter biobehavioral interactions in ways that could potentially affect the rate of future cognitive decline and may serve as targets for future intervention efforts.
IBD is characterized by altered immune reactions and infections are thought to trigger the chronic inflammatory response in IBD. The gut represents a productive reservoir for SARS-CoV-2 and the aforementioned factors together with immunosuppression used to treat IBD are likely influencing the outcomes of IBD patients in COVID-19. We used large and small intestinal organoids from IBD patients and controls to comparatively assess the transcriptional response of the gut epithelium during SARS-CoV-2 infection. Our analysis showed that IBD epithelia exhibit reduced viral loads compared to controls associated with a reduced expression of SARS-CoV-2 entry factors including the host receptor ACE2. Moreover, several genes implicated in the epithelial response to viral infection are intrinsically altered in IBD likely counteracting viral propagation. Notably, differences between IBD phenotypes exist wherein ulcerative colitis represents with induced cell death pathways and an induction of IL-1β despite overall lower viral loads suggestive of increased epithelial stress in this IBD phenotype. Altogether our analysis shows that IBD epithelia are not more prone to SARS-CoV-2 infection but epithelia from ulcerative colitis and Crohn9s disease exhibit specific differences which might explain the differing COVID-19 outcomes between IBD phenotypes.
In this paper, we introduce a machine-learning approach to detecting COVID-19-positive cases from self-reported information. Specifically, the proposed method builds a tree-based binary classification model that includes a recursive feature elimination step. Based on Shapley values, the recursive feature elimination method preserves the most relevant features without compromising the detection performance. In contrast to previous approaches that use a limited set of selected features, the machine learning approach constructs a detection engine that considers the full set of features reported by respondents. Various versions of the proposed approach were implemented using three different binary classifiers: random forest (RF), light gradient boosting (LGB), and extreme gradient boosting (XGB). We consistently evaluate the performance of the implemented versions of the proposed detection approach on data extracted from the University of Maryland Global COVID-19 Trends and Impact Survey (UMD-CTIS) for four different countries: Brazil, Canada, Japan, and South Africa, and two periods: 2020 and 2021. We also compare the performance of the proposed approach to those obtained by state-of-the-art methods under various quality metrics: F1-score, sensitivity, specificity, precision, receiver operating characteristic (ROC), and area under ROC curve (AUC). It should be noted that the proposed machine learning approach outperformed state-of-the-art detection techniques in terms of the F1-score metric. In addition, this work shows the normalized daily case curves obtained by the proposed approach for the four countries. It should note that the estimated curves are compared to those reported in official reports. Finally, we perform an explainability analysis, using Shapley and relevance ranking of the classification models, to identify the most significant variables contributing to detecting COVID-19-positive cases. This analysis allowed us to determine the relevance of each feature and the corresponding contribution to the detection task.
Background: Variability in the management of LBP has been extensively studied, however the degree to which this variability is associated with patient gender is less well understood. The purpose of this retrospective cohort study was to examine variability in the management of LBP associated with patient gender in commercially insured (CI) and Medicare Advantage (MA) cohorts before and after the COVID-19 pandemic. Methods: A US national sample of LBP episodes with a duration of less than 91 days experienced during 2019-2021 was analyzed. Independent variables included patient gender, whether an individual had CI or MA coverage, and the timing of LBP onset during pre-, early, and late COVID time periods. Dependent measures included the percent of individuals initially contacting eighteen types of health care provider (HCP) and receiving twenty-two types of health care services, and total episode cost. Measures associated with female patients were compared with a male patient baseline to examine patient gender related differences. Results: The study included 222,043 CI and 466,125 MA complete episodes of LBP. 114,322 (51.5%) of the CI and 281,597 (60.4%) of MA episodes were associated with female patients. Individual home address zip code population attributes were nearly identical in both CI and MA cohorts. During the pre-, early, and late COVID time periods, in both CI and MA cohorts, female patients were less likely than male patients to initially contact DCs (risk ratio (RR) CI pre-COVID 0.88, CI early COVID 0.90, CI late COVID 0.86, MA pre 0.70, MA early 0.70, MA late 0.73) and were more likely to initially contact rheumatologists (2.72, 2.62, 3.20, 2.15, 2.59, 2.08). In the CI cohort during the pre-, early, and late COVID time periods female patients more likely than male patients to initially contact physical therapists (PT) (RR pre-COVID 1.24, early COVID 1.17, late COVID 1.16) and licensed acupuncturists (LAC) (1.75, 1.53, 2.21). In both the CI and MA cohorts plain film radiology was the most provided service for both female (32-40% of episodes) and male (31-40%) patients. During all time periods in both CI and MA cohorts female patients were less likely than male patients to receive spinal surgery (risk ratio (RR) CI pre-COVID 0.53, CI early COVID 0.54, CI late COVID 0.53, MA pre- 0.45, MA early 0.46, MA late 0.42), prescription oral steroids (0.75, 0.73, 0.77, 0.82, 0.79, 0.83), and chiropractic manipulative therapy (CMT) (0.87, 0.89, 0.85, 0.70, 0.71, 0.73). In the CI cohort during all time periods female patients more likely than male patients to receive acupuncture (RR pre- 1.41, early 1.48, late 1.48). Conclusions: In both CI and MA cohorts, and compared to males, females with LBP were less likely to seek treatment from DCs and more likely to seek treatment from Rheumatologists. In the CI cohort females were more likely than males to seek treatment from PTs and LAcs. Females with LBP were less likely than males to undergo spinal surgery, receive a prescription oral steroid, or receive CMT.
Home food procurement (HFP), including gardening, is associated with food security and improved health behaviors and outcomes. In the beginning of the COVID-19 pandemic, HFP increased in many high-income countries; yet little evidence has demonstrated what impact HFP had on food security. Furthermore, existing HFP studies are largely qualitative from unrepresentative samples, limiting population-level understanding of HFP engagement and impact. Using data from a representative sample of residents (n=988) in northern New England in the United States conducted in Spring/Summer 2021, we explore the relationship between HFP engagement in the first year of the pandemic and changes in food security status. We employ matching techniques to compare food security outcomes in households with observably similar demographic and social characteristics, and examine food security outcomes in three periods among households who do and do not participate in HFP. Our results show that nearly 60% of respondents engaged in at least one kind of HFP in the first year of the COVID-19 pandemic, with food insecure households being more likely to do HFP. Food insecure households (both newly and chronically food insecure) were also more likely to do HFP activities for the first time or more intensely than they had previously. Newly food insecure households were the most likely to engage in HFP overall, especially gardening. Furthermore, HFP engagement early in the COVID-19 pandemic is associated with improved food security for food insecure households in the 9-12 months after the start of the pandemic, though these improvements were primarily associated with newly, not chronically, food insecure households. Future research about HFP should continue to explore multiple HFP strategies and their potentially myriad relationships to food security, diet, and health outcomes.
Objective: This study compares decision trees on two COVID-19 symptom datasets to assess their performance and feature importance in predicting and understanding infection patterns. Methods: We created decision trees on Israeli and Swedish COVID-19 infection datasets. Performance metrics were used to assess their predictive capabilities, and feature importance analysis identified significant variables in the decision-making process. Results: The study observed different performance levels of decision trees on the COVID-19 datasets. The Swedish dataset achieved high accuracy and F1-score without hyperparameter tuning, while the Israeli dataset improved significantly with Extreme Gradient Boosting. Dataset characteristics impact the selection of an optimal decision tree algorithm. The key variable in both datasets was sore throat. Conclusion: This study compares decision trees on COVID-19 infection datasets, emphasizing the importance of dataset characteristics in selecting an optimal algorithm. Identifying significant features enhances understanding of infection patterns, benefiting decision-making and prediction accuracy in infectious disease analysis.
Background Mental health has always been under the shadow of everyone9s belief about their health. Concerns about mental health have already risen in the whole world. The COVID-19 pandemic has caused havoc worldwide, notably in the educational system. It has been difficult to quantify the influence of COVID-19 on the mental health of medical students in Bangladesh. Aims This study was conducted to assess medical students’ mental health status in Dhaka during COVID-19 pandemic. Methods This study was undertaken at Dhaka Medical College, Dhaka, Bangladesh and 359 medical students were the primary respondents for this study. Results Depression, anxiety and stress were found in around half of the study participants. Overall, three-fourth of the medical students had poor mental health status. The research study showed that depression, anxiety and stress were dependent on various socio-demographic and behavioral characteristics of medical students. Conclusion Poor mental health is still highly prevalent in the medical students. Different factors like age, gender, academic year, and physical exercise behavior have affected medical students9 mental health. This calls for attention towards the needs of the more vulnerable demographics and creating a welcoming environment for medical students.
Background: Complete reporting of seroepidemiologic studies is paramount to inform public health decision-making. The Reporting of Seroepidemiologic studies-SARS-CoV-2 (ROSES-S) guideline is a checklist that guides the reporting of SARS-CoV-2 seroepidemiological studies. Adherence of SARS-CoV-2 seroepidemiologic studies to the ROSES-S guideline has not yet been evaluated. Objectives: Evaluate SARS-CoV-2 seroepidemiologic study reporting by assessing adherence to the ROSES-S reporting guideline; determine whether publication of the ROSES-S guideline was associated with reporting completeness; and identify study characteristics associated with reporting completeness. Methods: A stratified random sample of SARS-CoV-2 seroepidemiologic studies was evaluated for adherence to the ROSES-S guideline. Study adherence to each reporting item was categorized as “reported”, “not reported”, or “not applicable”. Percent adherence per reporting item and the median and interquartile range (IQR) adherence were reported across all items and by item domain. Beta regression analyses examined if study characteristics were associated with changes in the overall adherence scores. Results: 199 studies were analyzed. Median adherence to reporting items was 48.1% (IQR 40.0%-55.2%) per study, with no significant changes before and after guideline publication. Article publication source (p<0.001), study risk of bias (p=0.001), and sampling method (p=0.004) were associated with adherence to the ROSES-S guideline. Conclusions: There was suboptimal reporting in SARS-CoV-2 seroepidemiologic studies, which was associated with key study characteristics. Publication of the ROSES-S guideline was not associated with changes in reporting practices. Given the importance of complete reporting for the utility of seroprevalence data, authors should improve reporting.
The COVID-19 pandemic began impacting Europe in early 2020, posing significant challenges for individuals requiring care. This group is particularly susceptible to severe COVID-19 infections and depends on regular health care services. In this article, we examine the situation of European care recipients aged 50 years and older 18 months after the pandemic outbreak and compare it to the initial phase of the pandemic. In the descriptive section, we illustrate the development of (unmet) care needs and access to health care throughout the pandemic. Additionally, we explore regional variations in health care receipt across Europe. In the analytical section, we shed light on the mid- and long-term health consequences of COVID-19-related restrictions on accessing health care services by making comparisons between care recipients and individuals without care needs. We conducted an analysis using data from the representative Corona Surveys of the Survey of Health, Ageing and Retirement in Europe (SHARE). Our study examines changes in approximately 3,400 care-dependent older Europeans (aged 50+) interviewed in 2020 and 2021, comparing them with more than 45,000 respondents not receiving care. The dataset provides a cross-national perspective on care recipients across 27 European countries and Israel. Our findings reveal that in 2021, compared to the previous year, difficulties in obtaining personal care from someone outside the household were significantly reduced in Western and Southern European countries. Access to health care services improved over the course of the pandemic, particularly with respect to medical treatments and appointments that had been canceled by health care institutions. However, even 18 months after the COVID-19 outbreak, a considerable number of treatments had been postponed either by respondents themselves or by health care institutions. These delayed medical treatments had adverse effects on the physical and mental health of both care receivers and individuals who did not rely on care.
To assess the association between sleep and seroconversion after receipt of two doses of inactivated severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) vaccines in pregnant women. The serum level of immunoglobulin (Ig)G antibodies against the nucleic acids of SARS-CoV-2 was measured. Logistic regression was used to analyze the association between sleep and seroconversion. After two doses of SARS-CoV-2 vaccine, 41.2% of the study cohort reached seroconversion. Analysis revealed that pregnant women with poor quality of sleep had a lower serum level of IgG antibodies (P = 0.008, 95%CI = 0.285–0.826) and that sleeping late at night (SLaN) may be a risk factor for a low serum level of IgG antibodies (P = 0.025, 95%CI = 0.436–0.946). Besides sleep, age and the time since vaccination were important influences on seroconversion. A stratified analysis revealed that the effects of sleep quality and SLaN on seroconversion occurred mainly in pregnant women aged <35 years. Thus, sleep quality and SLaN can affect the serum level of IgG antibodies in pregnant women after vaccination with inactivated SARS-CoV-2.
Background Current primary care cognitive assessment tools are either crude or time-consuming instruments that can only detect cognitive impairment when it is well established. This leads to unnecessary or late referrals to memory services, by which time the disease may have already progressed into more severe stages. Due to the COVID-19 pandemic, some memory services have adapted to the new environment by shifting to remote assessments of patients to meet service user demand. However, the use of remote cognitive assessments has been inconsistent, and there has been little evaluation of the outcome of such a change in clinical practice. Emerging research has highlighted computerised cognitive tests, such as the Integrated Cognitive Assessment (ICA), as the leading candidates for adoption in clinical practice. This is true both during the pandemic and in the post-COVID-19 era as part of healthcare innovation. Objectives The Accelerating Dementias Pathways Technologies (ADePT) Study was initiated in order to address this challenge and develop a real-world evidence basis to support the adoption of ICA as an inexpensive screening tool for the detection of cognitive impairment and improving the efficiency of the dementia care pathway. Methods Ninety-nine patients aged 55-90 who have been referred to a memory clinic by a general practitioner (GP) were recruited. Participants completed the ICA either at home or in the clinic along with medical history and usability questionnaires. The GP referral and ICA outcome were compared with the specialist diagnosis obtained at the memory clinic. Participants were given the option to carry out a retest visit where they were again given the chance to take the ICA test either remotely or face-to-face. Results The primary outcome of the study compared GP referral with specialist diagnosis of MCI/dementia. Of those the GP referred to memory clinics, 78% were necessary referrals, with ~22% unnecessary referrals, or patients who should have been referred to other services as they had disorders other than MCI/dementia. In the same population the ICA was able to correctly identify cognitive impairment in ~90% of patients, with approximately 9% of patients being false negatives. From the subset of unnecessary GP referrals, the ICA classified ~72% of those as not having cognitive impairment, suggesting that these unnecessary referrals may not have been made if the ICA was in use. Conclusions The results from this study demonstrate the potential of the ICA as a screening tool, which can be used to support accurate referrals from primary care settings, along with the work conducted in memory clinics and in secondary care.
Extracorporeal Photopheresis as a Possible Therapeutic Approach to Adults With Severe and Critical COVID-19 - Condition: COVID-19
Intervention: Procedure: Extracorporeal photopheresis
Sponsor: Del-Pest Central Hospital - National Institute of Hematology and Infectious Diseases
Recruiting
A Clinical Trial on Booster Immunization of Two COVID-19 Vaccines Constructed From Different Technical Routes - Condition: COVID-19
Interventions: Biological: Prototype and Omicron BA.4/5 Bivalent Recombinant COVID-19 Vaccine(Adenovirus Type 5 Vector) For Inhalation; Biological: Bivalent COVID-19 mRNA Vaccine; Biological: Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) For Inhalation
Sponsors: Zhongnan Hospital; Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China
Recruiting
Evaluation of Safety, Tolerability, Reactogenicity, Immunogenicity of Baiya SARS-CoV-2 Vax 2 as a Booster for COVID-19 - Conditions: COVID-19 Vaccine; COVID-19
Interventions: Biological: 50 μg Baiya SARS-CoV-2 Vax 2; Other: Placebo
Sponsor: Baiya Phytopharm Co., Ltd.
Not yet recruiting
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm B (Fluvoxamine) - Condition: Covid19
Interventions: Drug: Fluvoxamine; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
Physiotherapy in Mutated COVID-19 Patients - Condition: COVID-19 Pandemic
Intervention: Behavioral: Physiotherapy
Sponsor: Giresun University
Completed
Safety Study of COVID19 Vaccine on the Market - Condition: COVID-19
Intervention: Biological: Recombinant new coronavirus vaccine (CHO cell)
Sponsors: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention; Guizhou Center for Disease Control and Prevention; Hainan Center for Disease Control & Prevention
Recruiting
Evaluation of Home Use COVID-19 Frequent Antigen Testing and Data Reporting - Condition: COVID-19 Respiratory Infection
Intervention: Diagnostic Test: SARS CoV-2 antigen tests
Sponsors: IDX20 Inc; National Institute on Minority Health and Health Disparities (NIMHD)
Recruiting
Pycnogenol® in Post-COVID-19 Condition - Conditions: Post COVID-19 Condition; Long COVID
Interventions: Drug: Pycnogenol®; Drug: Placebo
Sponsor: University of Zurich
Not yet recruiting
Efficacy of Bailing Capsule on Pulmonary Fibrosis After COVID-19 - Conditions: Pulmonary Fibrosis; COVID-19 Pneumonia
Intervention: Drug: Bailing capsule
Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Not yet recruiting
To Explore the Regulatory Effect of Combined Capsule FMT on the Levels of Inflammatory Factors in Peripheral Blood of Patients With COVID-19 During Treatment. - Conditions: Fecal Microbiota Transplantation; COVID-19 Infection
Intervention: Procedure: Fecal microbiota transplantation
Sponsor: Shanghai 10th People’s Hospital
Completed
Mitoquinone/Mitoquinol Mesylate as Oral and Safe Postexposure Prophylaxis for Covid-19 - Conditions: SARS-CoV Infection; COVID-19
Interventions: Drug: Mitoquinone/mitoquinol mesylate; Other: Placebo
Sponsor: University of Texas Southwestern Medical Center
Not yet recruiting
Evaluating Emetine for Viral Outbreaks (EVOLVE) - Condition: COVID-19
Interventions: Drug: Emetine Hydrochloride; Drug: Placebo
Sponsors: Johns Hopkins University; Nepal Health Research Council; Bharatpur Hospital Chitwan; Stony Brook University; Rutgers University
Not yet recruiting
Phase 3 Study of Novavax Vaccine(s) as Booster Dose After mRNA Vaccines - Condition: COVID-19
Interventions: Biological: NVX-CoV2373; Biological: SARS-CoV-2 rS antigen/Matrix-M Adjuvant
Sponsor: Novavax
Active, not recruiting
Anti-SARS-CoV-2 Monoclonal Antibodies for Long COVID (COVID-19) - Conditions: Long COVID; Post-Acute Sequela of COVID-19; Post-Acute COVID-19
Interventions: Drug: AER002; Other: Placebo
Sponsors: Michael Peluso, MD; Aerium Therapeutics
Not yet recruiting
Study to Assess Safety, Reactogenicity and Immunogenicity of the repRNA(QTP104) Vaccine Against SARS-CoV-2(COVID-19) - Conditions: COVID-19; SARS-CoV-2
Interventions: Biological: QTP104 1ug; Biological: QTP104 5ug; Biological: QTP104 25ug
Sponsor: Quratis Inc.
Active, not recruiting
The PRMT5/WDR77 complex restricts hepatitis E virus replication - Hepatitis E virus (HEV) is one of the main pathogenic agents of acute hepatitis in the world. The mechanism of HEV replication, especially host factors governing HEV replication is still not clear. Here, using HEV ORF1 trans-complementation cell culture system and HEV replicon system, combining with stable isotope labelling with amino acids in cell culture (SILAC) and mass spectrometry (MS), we aimed to identify the host factors regulating HEV replication. We identified a diversity of host…
Gasdermin D-mediated pyroptosis: mechanisms, diseases, and inhibitors - Gasdermin D (GSDMD)-mediated pyroptosis and downstream inflammation are important self-protection mechanisms against stimuli and infections. Hosts can defend against intracellular bacterial infections by inducing cell pyroptosis, which triggers the clearance of pathogens. However, pyroptosis is a double-edged sword. Numerous studies have revealed the relationship between abnormal GSDMD activation and various inflammatory diseases, including sepsis, coronavirus disease 2019 (COVID-19),…
Anti-SARS-CoV-2 Activity of Adamantanes In Vitro and in Animal Models of Infection - Coronavirus disease 2019 (COVID-19) has had devastating effects worldwide, with particularly high morbidity and mortality in outbreaks on residential care facilities. Amantadine, originally licensed as an antiviral agent for therapy and prophylaxis against influenza A virus, has beneficial effects on patients with Parkinson’s disease and is used for treatment of Parkinson’s disease, multiple sclerosis, acquired brain injury, and various other neurological disorders. Recent observational data…
In silico evidence implicating novel mechanisms of Prunella vulgaris L. as a potential botanical drug against COVID-19-associated acute kidney injury - COVID-19-associated acute kidney injury (COVID-19 AKI) is an independent risk factor for in-hospital mortality and has the potential to progress to chronic kidney disease. Prunella vulgaris L., a traditional Chinese herb that has been used for the treatment of a variety of kidney diseases for centuries, could have the potential to treat this complication. In this study, we studied the potential protective role of Prunella vulgaris in COVID-19 AKI and explored its specific mechanisms applied by…
Analyzing immune responses to varied mRNA and protein vaccine sequences - In response to the COVID-19 pandemic, different types of vaccines, such as inactive, live-attenuated, messenger RNA (mRNA), and protein subunit, have been developed against SARS-CoV-2. This has unintentionally created a unique scenario where heterologous prime-boost vaccination against a single virus has been administered to a large human population. Here, we aimed to analyze whether the immunization order of vaccine types influences the efficacy of heterologous prime-boost vaccination,…
Recent topics in the pathophysiology and treatment of immune thrombocytopenic purpura - Increased and impaired platelet productions via immunological abnormalities are the main pathophysiological mechanisms of primary immune thrombocytopenia (ITP). Recent studies have revealed that platelet removal from circulation involves not only Fc receptor-mediated phagocytosis of immunoglobulin G autoantibodies-bound platelets but also complement-dependent mechanism and platelet glycoprotein desialylation. Understanding the molecular mechanism of ITP pathophysiology has helped develop many…
Prospective evaluation of the efficacy, safety, and optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock (ASTONISH): a double-blind, randomised, controlled, phase 2b trial - BACKGROUND: Activation of the triggering receptor expressed on myeloid cells-1 (TREM-1) pathway is associated with septic shock outcomes. Data suggest that modulation of this pathway in patients with activated TREM-1 might improve survival. Soluble TREM-1 (sTREM-1), a potential mechanism-based biomarker, might facilitate enrichment of patient selection in clinical trials of nangibotide, a TREM-1 modulator. In this phase 2b trial, we aimed to confirm the hypothesis that TREM1 inhibition might…
Isolation of Anti-SARS-CoV-2 Natural Products Extracted from Mentha canadensis and the Semi-synthesis of Antiviral Derivatives - Traditional herbal medicine offers opportunities to discover novel therapeutics against SARS-CoV-2 mutation. The dried aerial part of mint (Mentha canadensis L.) was chosen for bioactivity-guided extraction. Seven constituents were isolated and characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS). Syringic acid and methyl rosmarinate were evaluated in drug combination treatment. Ten amide derivatives of methyl rosmarinate were synthesized, and the dodecyl (13) and…
Computational design of medicinal compounds to inhibit RBD-hACE2 interaction in the Omicron variant: unveiling a vulnerable target site - The COVID-19 pandemic, caused by SARS-CoV-2, has globally affected both human health and economy. Several variants with a high potential for reinfection and the ability to evade immunity were detected shortly after the initial reported case of COVID-19. A total of 30 mutations in the spike protein (S) have been reported in the SARS-CoV-2 (BA.2) variant in India and South Africa, while half of these mutations are in the receptor-binding domain and have spread rapidly throughout the world. Drug…
In silico screening, ADMET analysis and MD simulations of phytochemicals of Onosma bracteata Wall. as SARS CoV-2 inhibitors - Being attracted with their cardiotonic, antidiabetic, cough relieving activity, treatment of fever, absorbent, anti-asthmatic, etc. activities reported in ancient Ayurvedic literature, phytochemicals of Onosma bracteata wall should be evaluated for their activity against SARS-CoV-2 virus. The main objective of this study is to identify a hit molecule for the inhibition of entry, replication, and protein synthesis of SARS CoV-2 virus into the host. To achieve given objective, computational…
In silico Antivirus Repurposing and its Modification to Organoselenium Compounds as SARS-CoV-2 Spike Inhibitors - <b>Background and Objective:</b> The COVID-19, which has been circulating since late 2019, is caused by SARS-CoV-2. Because of its high infectivity, this virus has spread widely throughout the world. Spike glycoprotein is one of the proteins found in SARS-CoV-2. Spike glycoproteins directly affect infection by forming ACE-2 receptors on host cells. Inhibiting glycoprotein spikes could be one method of treating COVID-19. In this study, the antivirus marketed as a database will be…
PACT inhibits the replication of SARS-CoV-2 through the blockage of GSK-3β-N-nsp3 cascade - The protein activator of protein kinase R (PKR) (PACT) has been shown to play a crucial role in stimulating the host antiviral response through the activation of PKR, retinoic acid-inducible gene I, and melanoma differentiation-associated protein 5. Whether PACT can inhibit viral replication independent of known mechanisms is still unrevealed. In this study, we show that, like many viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks GSK-3β to facilitate its replication….
Evaluation of SARS-CoV-2 isolation in cell culture from nasal/nasopharyngeal swabs or saliva specimens of patients with COVID-19 - It has been revealed that SARS-CoV-2 can be efficiently isolated from clinical specimens such as nasal/nasopharyngeal swabs or saliva in cultured cells. In this study, we examined the efficiency of viral isolation including SARS-CoV-2 mutant strains between nasal/nasopharyngeal swab or saliva specimens. Furthermore, we also examined the comparison of viral isolation rates by sample species using simulated specimens for COVID-19. As a result, it was found that the isolation efficiency of…
A Facile Strategy to Construct Anti-Swelling, Antibacterial and Antifogging Coatings for Protection of Medical Goggles - During the COVID-19 pandemic, traditional medical goggles are not only easy to attach bacteria and viruses in long-term exposure, but also easy to fogged up, which increases the risk of infection and affects productivity. Bacterial adhesion and fog can be significantly inhibited through the hydrogel coatings, owing to their super hydrophilic properties. But on the one hand, hydrophilic hydrogel coatings are easy to absorb water and swell in wet environment, resulting in reduced mechanical…
Secreted ORF8 induces monocytic pro-inflammatory cytokines through NLRP3 pathways in patients with severe COVID-19 - Despite extensive research, the specific factor associated with SARS-CoV-2 infection that mediates the life-threatening inflammatory cytokine response in patients with severe COVID-19 remains unidentified. Herein we demonstrate that the virus-encoded Open Reading Frame 8 (ORF8) protein is abundantly secreted as a glycoprotein in vitro and in symptomatic patients with COVID-19. ORF8 specifically binds to the NOD-like receptor family pyrin domain-containing 3 (NLRP3) in CD14^(+) monocytes to…