We present Crykey, a computational tool for rapidly identifying cryptic mutations of SARS-CoV-2. Specifically, we identify co-occurring single nucleotide mutations on the same sequencing read, called linked-read mutations, that are rare or entirely missing in existing databases, and have the potential to represent novel cryptic lineages found in wastewater. While previous approaches exist for identifying cryptic linked-read mutations from specific regions of the SARS-CoV-2 genome, there is a need for computational tools capable of efficiently tracking cryptic mutations across the entire genome and for tens of thousands of samples and with increased scrutiny, given their potential to represent either artifacts or hidden SARS-CoV-2 lineages. Crykey fills this gap by identifying rare linked-read mutations that pass stringent computational filters to limit the potential for artifacts. We evaluate the utility of Crykey on >3,000 wastewater and >22,000 clinical samples; our findings are three-fold: i) we identify hundreds of cryptic mutations that cover the entire SARS-CoV-2 genome, ii) we track the presence of these cryptic mutations across multiple wastewater treatment plants and over a three years of sampling in Houston, and iii) we find a handful of cryptic mutations in wastewater mirror cryptic mutations in clinical samples and investigate their potential to represent real cryptic lineages. In summary, Crykey enables large-scale detection of cryptic mutations representing potential cryptic lineages in wastewater.
In this work the Luria and Delbruck Fluctuation Test was applied to the data of Morbidity and Mortality by COVID-19 in China from January 2020 to August 2023. Three types of data were used: es.statista.com, datosmacro.expansion.com and larepublica.co without modification, but trying to avoid and justify the anomalies and inconsistencies observed. The methods originally used to establish the interactions of two populations were evaluated: the viral population with that of its host and the drift of both organisms. Only the fluctuations of the weekly Variance of daily increase of Cases (Morbidity) and of the weekly Variance of daily increase of Deaths (Mortality) were studied. The results showed that the Fluctuation Test is applicable to the selected data from China and other data from India, Japan and South Korea, used as controls. The study was separated into two periods: a first initial period from January 2020 to September 2021 and a second final period from October 2021 to August 2023. Results were obtained for Morbidity and Mortality that relate the fluctuations of the first with the fluctuations of the second. However, it was possible to detect some anomalies and uncertainties that were possibly derived from inconsistencies in the original data. A repeated fluctuation was observed in the boreal winter in January, February and March of each one of the year studied. A clear decrease in fluctuation was detected in that period in 2021 that could be attributed to the strict confinement during the quarantine in China between 2020 and 2021. Massive, extensive and intensive vaccinations failed to completely eliminate the most important fluctuations. In this work we tried to correlate the appearance of some virus variants with the fluctuations. The most relevant results of said correlation are presented. With the results of this work, the animal origin cannot be confirmed nor can the human or laboratory origin of the SARS CoV-2 virus that caused the initial emerging infection, be ruled out. However, it was concluded that this method could be used to search for clues about its origin. One of these keys is the comparison of the result of the first important fluctuation in the boreal winter of 2020 in each of the countries studied as controls: India, Japan and South Korea. The comparison of this result with the first fluctuation of China for that same period could give clues about the origin of the virus.
Clinical data demonstrate an increased predisposition to cardiovascular disease (CVD) following severe COVID-19 infection. This may be driven by a dysregulated immune response associated with severe disease. Monocytes and vascular tissue resident macrophages play a critical role in atherosclerosis, the main pathology leading to ischemic CVD. Natural killer (NK) cells are a heterogenous group of cells that are critical during viral pathogenesis and are known to be dysregulated during severe COVID-19 infection. Their role in atherosclerotic cardiovascular disease has recently been described. However, the contribution of their altered phenotypes to atherogenesis following severe COVID-19 infection is unknown. We demonstrate for the first time that during and after severe COVID-19, circulating proinflammatory monocytes and activated NK cells act synergistically to increase uptake of oxidized low-density lipoprotein (Ox-LDL) into vascular tissue with subsequent foam cell generation leading to atherogenesis despite recovery from acute infection. Our data provide new insights, revealing the roles of monocytes/macrophages, and NK cells in COVID-19-related atherogenesis.
Background: There are many COVID-19 vaccines currently available, however, Low- and middle-income countries (LMIC) still have large proportions of their populations un- vaccinated. Decision-makers must decide how to effectively allocate available vaccines (e.g. boosters or primary series vaccination, which age groups to target) but LMIC often lack the resources to undergo quantitative analyses of vaccine allocation, resulting in ad- hoc policies. We developed Covid19Vaxplorer (https://covid19vaxplorer.fredhutch.org/), a free, user-friendly online tool that simulates region-specific COVID-19 epidemics in con- junction with vaccination with the purpose of providing public health officials worldwide with a tool for vaccine allocation planning and comparison. Methods: We developed an age-structured mathematical model of SARS-CoV-2 trans- mission and COVID-19 vaccination. The model considers vaccination with up to three different vaccine products, primary series and boosters. We simulated partial immunity de- rived from waning of natural infection and vaccination. The model is embedded in an online tool, Covid19Vaxplorer that was optimized for its ease of use. By prompting users to fill information through several windows to input local parameters (e.g. cumulative and cur- rent prevalence), epidemiological parameters (e.g basic reproduction number, current social distancing interventions), vaccine parameters (e.g. vaccine efficacy, duration of immunity) and vaccine allocation (both by age groups and by vaccination status). Covid19Vaxplorer connects the user to the mathematical model and simulates, in real time, region-specific epidemics. The tool then produces key outcomes including expected numbers of deaths, hospitalizations and cases, with the possibility of simulating several scenarios of vaccine allocation at once for a side-by-side comparison.
Background: Immunocompromised (IC) individuals are at increased risk of COVID-19 infection-related severe outcomes. Moderna and Pfizer-BioNTech COVID-19 mRNA vaccines are available in Canada, and differences in vaccine effectiveness (VE) have been found between the two in IC individuals. The objective of this analysis was to compare the clinical and economic impact of a Moderna XBB.1.5 updated COVID-19 mRNA Fall 2023 vaccine to a Pfizer-BioNTech XBB.1.5 updated COVID-19 mRNA Fall 2023 vaccine in Canadian IC individuals aged ≥18 years. Methods: A static decision-analytic model estimated the number of COVID-19 infections, hospitalizations, deaths, and resulting quality-adjusted life years (QALYs) over a one-year time horizon (September 2023-August 2024) in the Canadian IC adult population (n=894,580). Costs associated with COVID-19 infection were estimated from health care and societal perspectives. The predicted VE of the updated Moderna vaccine was based on prior variant versions, which were well-matched to the circulating variant. Pfizer-BioNTech VE was calculated based on a meta-analysis of comparative effectiveness between both vaccines (relative risk for Moderna vaccine: infection=0.85 [95%CI 0.75-0.97], hospitalization=0.88 [95%CI 0.79-0.97]). The model combined VE estimates with COVID-19 incidence and probability of COVID-19 related severe outcomes. Sensitivity analyses tested the impact of uncertainty surrounding incidence, hospitalization and mortality rates, costs, and QALYs. Results: Given the expected higher VE against infection and hospitalizations with the Moderna Fall 2023 vaccine, its use is predicted to prevent an additional 2,411 infections (3.6%), 275 hospitalizations (3.7%), and 47 deaths (4.0%) compared to the Pfizer-BioNTech Fall 2023 vaccine, resulting in 330 QALYs gained, and savings of $7.4M in infection treatment costs, and $0.9M in productivity loss costs. Results were most sensitive to variations in VE parameters, specifically the relative risk of infection and hospitalizations between the vaccines, and waning rates. Conclusions: If the Moderna and Pfizer-BioNTech Fall 2023 vaccines protect against infection and hospitalizations similar to previous vaccines, using the Moderna Fall 2023 vaccine would result in substantial public health benefits in IC individuals, as well as provide health care and societal cost savings.
Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Panel to Support Home Use - Conditions: COVID-19; Influenza A; Influenza Type B
Interventions: Diagnostic Test: Panbio™ COVID-19/Flu A&B Panel
Sponsors: Abbott Rapid Dx
Recruiting
Building Engagement Using Financial Incentives Trial - Colorectal Cancer Screening - Conditions: Health Behavior; Colorectal Cancer; Influenza; COVID-19; Vaccine Hesitancy; Vaccine-Preventable Diseases; Healthcare Patient Acceptance
Interventions: Behavioral: Financial incentive for colorectal cancer screening; Behavioral: Financial incentive for flu shot; Behavioral: Financial incentive for COVID-19 shot
Sponsors: Tulane University; National Heart, Lung, and Blood Institute (NHLBI)
Not yet recruiting
Effects of Rehabilitation Combined With a Maintenance Program Compared to Rehabilitation Alone in Post-COVID-19 - Conditions: Post-COVID-19 Syndrome
Interventions: Procedure: Rehabilitation + maintenance program; Procedure: Rehabilitation only
Sponsors: Schön Klinik Berchtesgadener Land; Bavarian State Ministry of Health and Care (Funding); Deutsche Rentenversicherung Bund (German pension insurance) (Design); Betriebskrankenkassen Landesverband Bayern (Bavarian health insurance) (Design)
Not yet recruiting
Child and Adolescent Mental Health Literacy for Primary Schools Teachers. A Multicomponent Intervention - Conditions: Child Mental Health
Interventions: Behavioral: Child Mental Health Literacy Program
Sponsors: Universidad de Valparaiso
Recruiting
Brief Digital Intervention to Increase COVID-19 Vaccination Among Individuals With Anxiety or Depression - Conditions: Misinformation; Vaccine Hesitancy; Anxiety; Depression; COVID-19
Interventions: Behavioral: Attitudinal inoculation; Behavioral: Cognitive-behavioral therapy-informed intervention; Behavioral: Conventional public health messaging
Sponsors: City University of New York, School of Public Health; University of North Carolina, Chapel Hill
Not yet recruiting
A PhaseⅡ Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine - Conditions: SARS-CoV-2 Infection
Interventions: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated
Sponsors: CNBG-Virogin Biotech (Shanghai) Ltd.
Recruiting
Pilot Randomized Study of RD-X19 Tx Device in Subjects With PCC (Long Covid) in the Outpatient Setting - Conditions: Post COVID-19 Condition (PCC)
Interventions: Device: RDX-19
Sponsors: KNOWBio Inc.; NAMSA
Recruiting
CPAP Therapy Through a Helmet or a Full Face Mask in Patients With Acute Hypoxemic Respiratory Failure: Cross-over Study - Conditions: Pneumonia, Bacterial; Respiratory Failure; COVID-19 Pneumonia
Interventions: Diagnostic Test: Arterial blood gases; Diagnostic Test: Respiratory rate (RR); Diagnostic Test: Pulseoximeter; Diagnostic Test: Assessment of accessory respiratory muscles work; Diagnostic Test: Esophageal pressure measurement; Diagnostic Test: Discomfort Visual Analog Scale (VAS); Diagnostic Test: Noninvasive blood pressure; Diagnostic Test: Heart rate
Sponsors: I.M. Sechenov First Moscow State Medical University
Recruiting
Investigation of Efficacy and Safety of Electrical Signal Therapy Provided by Dr Biolyse® Device in COVID-19 Disease - Conditions: COVID-19 Pneumonia; Virus Diseases; COVID-19
Interventions: Device: Signal Therapy provided by Dr.Biolyse device; Other: Liquid Support Treatment
Sponsors: AVB Biotechnology
Recruiting
A Phase 1 Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine - Conditions: SARS-CoV-2 Infection
Interventions: Biological: Placebo; Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O) 10 μg; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O) 30 μg; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O) 60 μg
Sponsors: CNBG-Virogin Biotech (Shanghai) Ltd.; Shulan (Hangzhou) Hospital
Recruiting
SAFE Workplace Intervention for People With IDD - Conditions: Communicable Diseases; Prevention; Workplace Intervention
Interventions: Behavioral: SAFE Employment Training
Sponsors: Temple University; National Institute on Disability, Independent Living, and Rehabilitation Research
Recruiting
Effects of an EMDR Intervention on Traumatic and Obsessive Symptoms - Conditions: Adult ALL; Post-traumatic Stress Disorder; Obsessive-Compulsive Disorder; Disgust; Guilt; Shame
Interventions: Behavioral: EMDR
Sponsors: University of Pisa
Completed
Lithium Long COVID Dose-finding Study - Conditions: Long COVID
Interventions: Dietary Supplement: Lithium
Sponsors: State University of New York at Buffalo
Not yet recruiting
Pharmacokinetics and Safety of GST-HG171 Tablets in Subjects With Impaired and Normal Renal Function - Conditions: COVID-19 Pneumonia
Interventions: Drug: GST-HG171 Tablets
Sponsors: Fujian Akeylink Biotechnology Co., Ltd.
Recruiting
Preoperative Educational Videos on Maternal Stress Whose Children Received Congenital Heart Disease Surgery: During COVID-19 Panic - Conditions: COVID-19; Educational Videos; Maternal; Uncertainty; Anxiety; Depression; Congenital Heart Disease; Children
Interventions: Other: Preoperative educational videos plus routine education; Other: Preoperative routine education
Sponsors: Chung Shan Medical University
Completed
Exploring the disruption of SARS-CoV-2 RBD binding to hACE2 - The COVID-19 pandemic was declared due to the spread of the novel coronavirus, SARS-CoV-2. Viral infection is caused by the interaction between the SARS-CoV-2 receptor binding domain (RBD) and the human ACE2 receptor (hACE2). Previous computational studies have identified repurposed small molecules that target the RBD, but very few have screened drugs in the RBD-hACE2 interface. When studies focus solely on the binding affinity between the drug and the RBD, they ignore the effect of hACE2,…
Qinhuo Shanggan oral solution resolves acute lung injury by down-regulating TLR4/NF-κB signaling cascade and inhibiting NLRP3 inflammasome activation - Acute lung injury (ALI) is a common condition, particularly in the COVID-19 pandemic, which is distinguished by sudden onset of respiratory insufficiency with tachypnea, oxygen-refractory cyanosis, reduced lung compliance and diffuse infiltration of pulmonary alveoli. It is well-established that increasing activity of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling axis and the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation are associated…
A review: Mechanism and prospect of gastrodin in prevention and treatment of T2DM and COVID-19 - Gastrodin is an extract from the dried tuber of the Chinese herb Gastrodia elata (Tian ma), with anti-inflammatory, antioxidant, and antiviral properties. Recent studies have shown that, compared to commonly used diabetes drugs, gastrodin has antidiabetic effects in multiple ways, with characteristics of low cost, high safety, less side effects, protection of β-cell function, relieving insulin resistance and alleviating multiple complications. In addition, it is confirmed that gastrodin can…
Duvelisib for Critically Ill Patients With Coronavirus Disease 2019: An Investigator-Initiated, Randomized, Placebo-Controlled, Double-Blind Pilot Trial - CONCLUSIONS: In this pilot study, duvelisib did not significantly improve 28-day OS compared to placebo for severe COVID-19. Duvelisib appeared safe in this critically ill population and was associated with reduction in cytokines implicated in COVID-19 and acute respiratory distress syndrome, supporting further investigation.
Beneficial effects of the combination of BCc1 and Hep-S nanochelating-based medicines on IL-6 in hospitalized moderate COVID-19 adult patients: a randomized, double-blind, placebo-controlled clinical trial - CONCLUSIONS: In conclusion, the combination of BCc1 and Hep-S inhibits IL-6 as a highly important and well-known cytokine in COVID-19 pathophysiology and presents a promising view for immunomodulation that can manage CSS.
Safety of bempedoic acid in patients at high cardiovascular risk and with statin intolerance - CONCLUSIONS: Bempedoic acid was well-tolerated compared with placebo. Safety data from the long-term CLEAR Outcomes study reinforce the positive benefit-risk profile of bempedoic acid.
In their absence; intensive care nurses’ experiences of communicating and supporting relatives from a distance - CONCLUSION: Visiting restrictions in the ICU meant that ICU nurses missed vital information about their patients as a person, which might have had a negative effect on personalizing and centring the patient care. But using a combination of digital and audio tools helped nurses to guide the relatives to a clearer picture of the situation as a whole. The support that nurses were able to provide to relatives was often insufficient due to the visiting restriction and as a consequence, they…
Evaluation of experiences of the patients discharged from the COVID-19 intensive care unit: a qualitative research - Making arrangements by learning how intensive care patients feel due to a disease called as fatal worldwide can make it easier for patients to cope with the disease. For this reason, it is important for healthcare professionals to understand the patients who have been infected and discharged during the COVID-19 pandemic. The experiences of the patients may affect the perspective of the disease and cause different changes in the perception of it. This study, which was conducted based on this…
Fangchinoline inhibits SARS-CoV-2 and MERS-CoV entry - The COVID-19 pandemic caused by SARS-CoV-2, lead to mild to severe respiratory illness and resulted in 6.9 million deaths worldwide. Although vaccines are effective in preventing COVID-19, they may not be sufficient to protect immunocompromised individuals from this respiratory illness. Moreover, novel emerging variants of SARS-CoV-2 pose a risk of new COVID-19 waves. Therefore, identification of effective antivirals is critical in controlling SARS and other coronaviruses, such as MERS-CoV. We…
Antibody-mediated spike activation promotes cell-cell transmission of SARS-CoV-2 - The COVID pandemic fueled by emerging SARS-CoV-2 new variants of concern remains a major global health concern, and the constantly emerging mutations present challenges to current therapeutics. The spike glycoprotein is not only essential for the initial viral entry, but is also responsible for the transmission of SARS-CoV-2 components via syncytia formation. Spike-mediated cell-cell transmission is strongly resistant to extracellular therapeutic and convalescent antibodies via an unknown…
ceRNA Network Analysis Reveals Potential Key miRNAs and Target Genes in COVID-19-Related Chronic Obstructive Pulmonary Disease - The continued spread of SARS-CoV-2 has presented unprecedented obstacles to the worldwide public health system. Especially, individuals with chronic obstructive pulmonary disease (COPD) are at a heightened risk of contracting SARS-CoV-2 infection due to their pre-existing respiratory symptoms that are not well-managed. However, the viral mechanism of affecting the expression of host genes, COPD progression, and prognosis is not clear yet.This study integrated the differential expression…
Discovery of the covalent SARS-CoV-2 Mpro inhibitors from antiviral herbs via integrating target-based high-throughput screening and chemoproteomic approaches - The main proteases (M^(pro) ) are highly conserved cysteine-rich proteins that can be covalently modified by numerous natural and synthetic compounds. Herein, we constructed an integrative approach to efficiently discover covalent inhibitors of M^(pro) from complex herbal matrices. This work begins with biological screening of 60 clinically used antiviral herbal medicines, among which Lonicera japonica Flos (LJF) demonstrated the strongest anti-M^(pro) effect (IC(50) = 37.82 μg/mL). Mass…
An efficient eco-friendly, simple, and green synthesis of some new spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives as potential inhibitors of SARS-CoV-2 proteases: drug-likeness, pharmacophore, molecular docking, and DFT exploration - INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused a global health crisis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that can cause severe respiratory illness. There is no specific treatment for COVID-19, and the development of new drugs is urgently needed.
Lipid and cholesterols modulate the dynamics of SARS-CoV-2 viral ion channel ORF3a and its pathogenic variants - SARS-CoV-2 accessory protein, ORF3a is a putative ion channel which immensely contributes to viral pathogenicity by modulating host immune responses and virus-host interactions. Relatively high expression of ORF3a in diseased individuals and implication with inflammasome activation, apoptosis and autophagy inhibition, ratifies as an effective target for developing vaccines and therapeutics. Herein, we present the elusive dynamics of ORF3a-dimeric state using all-atoms molecular dynamics (MD)…
The anti-SARS-CoV-2 BNT162b2 vaccine suppresses mithramycin-induced erythroid differentiation and expression of embryo-fetal globin genes in human erythroleukemia K562 cells - The COVID-19 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) the ongoing coronavirus disease 2019 (COVID-19) pandemic. The SARS-CoV-2 Spike protein (S-protein) plays an important role in the early phase of SARS-CoV2 infection through efficient interaction with ACE2. The S-protein is produced by RNA-based COVID-19 vaccines, that were fundamental for the reduction of the viral spread within the population and the clinical severity of COVID-19. However, the S-protein has been…