Background: The objective of our study was to evaluate baseline characteristics, COVID-19 infection and vaccine type and their association with stroke early after COVID-19 vaccination. Methods: In a retrospective cohort study, we estimated the 21-day post vaccination incidence of stroke among COVID-19 first dose vaccine recipients. We linked the Georgia Immunization Registry with the Georgia Coverdell Acute Stroke Registry and the Georgia State Electronic Notifiable Disease Surveillance System data to assess the relative risk of stroke by vaccine type. Results: About 5 million adult Georgians received at least one COVID-19 vaccine from December 1, 2020 to February 28, 2022: 54% received BNT162b2, 41% mRNA-1273 and 5% Ad26.COV2.S. Those with concurrent COVID infection within 21 days post vaccine had an increased risk of ischemic (OR=8.00, 95% CI: 4.18, 15.31) and hemorrhagic stroke (OR=5.23, 95% CI: 1.11, 24.64) with no evidence for interaction between vaccine type and concurrent COVID-19 infection. The 21-day post vaccination incidence of ischemic stroke was 8.14, 11.14, and 10.48 per 100,000 for BNT162b2, mRNA-1273 and Ad26.COV2.S recipients, respectively. After adjusting for age, race, gender, and COVID-19 infection status there was a 57% higher risk (OR=1.57, 95% CI: 1.02, 2.42) for ischemic stroke within 21 days of vaccination associated with the Ad26.COV2.S vaccine compared to BNT162b2. Conclusions: Concurrent COVID-19 infection had the strongest association with early ischemic and hemorrhagic stroke after first dose COVID-19 vaccination. The Ad26.COV2.S vaccine was associated with a higher risk of early post-vaccination ischemic stroke than BNT162b2.
Some individuals do not return to baseline health following SARS-CoV-2 infection, leading to a condition known as Long COVID. The underlying pathophysiology of Long COVID remains unknown. Given that autoantibodies have been found to play a role in severity of COVID infection and certain other post-COVID sequelae, their potential role in Long COVID is important to investigate. Here we apply a well-established, unbiased, proteome-wide autoantibody detection technology (PhIP-Seq) to a robustly phenotyped cohort of 121 individuals with Long COVID, 64 individuals with prior COVID-19 who reported full recovery, and 57 pre-COVID controls. While a distinct autoreactive signature was detected which separates individuals with prior COVID infection from those never exposed to COVID, we did not detect patterns of autoreactivity that separate individuals with Long COVID relative to individuals fully recovered from SARS-CoV-2 infection. These data suggest that there are robust alterations in autoreactive antibody profiles due to infection; however, no association of autoreactive antibodies and Long COVID was apparent by this assay.
Individual and societal reactions to an ongoing pandemic can lead to social dilemmas: In some cases, each individual is tempted to not follow an intervention, but for the whole society it would be best if they did. Now that in most countries the extent of regulations to reduce SARS-CoV-2 transmission is very small, interventions are driven by individual decision-making. Assuming that individuals act in their best own interest, we propose a framework in which this situation can be quantified, depending on the protection the intervention provides to a user and to others, the risk of getting infected, and the costs of the intervention. We discuss when a tension between individual and societal benefits arises and which parameter comparisons are important to distinguish between different regimes of intervention use.
Some individuals do not return to baseline health following SARS-CoV-2 infection, leading to a condition known as Long COVID. The underlying pathophysiology of Long COVID remains unknown. Given that autoantibodies have been found to play a role in severity of COVID infection and certain other post-COVID sequelae, their potential role in Long COVID is important to investigate. Here we apply a well-established, unbiased, proteome-wide autoantibody detection technology (PhIP-Seq) to a robustly phenotyped cohort of 121 individuals with Long COVID, 64 individuals with prior COVID-19 who reported full recovery, and 57 pre-COVID controls. While a distinct autoreactive signature was detected which separates individuals with prior COVID infection from those never exposed to COVID, we did not detect patterns of autoreactivity that separate individuals with Long COVID relative to individuals fully recovered from SARS-CoV-2 infection. These data suggest that there are robust alterations in autoreactive antibody profiles due to infection; however, no association of autoreactive antibodies and Long COVID was apparent by this assay.
Background: Widespread use of at-home COVID-19 tests hampers determination of community COVID-19 incidence. Using nationwide data available through the US National Wastewater Surveillance System, we examined the performance of two wastewater metrics in predicting high case and hospitalizations rates both before and after widespread use of at-home tests. Methods: We performed area under the receiver operating characteristic (ROC) curve analysis (AUC) for two wastewater metrics- viral concentration relative to the peak of January 2022 (9wastewater percentile9) and 15-day percent change in SARS-CoV-2 (9percent change9). Dichotomized reported cases (equal to or greater than 200 or <200 cases per 100,000) and new hospitalizations (equal to or greater than 10 or <10 per 100,000) were our dependent variables, stratified by calendar quarter. Using logistic regression, we assessed the performance of combining wastewater metrics. Results: Among 268 counties across 22 states, wastewater percentile detected high reported case and hospitalizations rates in the first quarter of 2022 (AUC 0.95 and 0.86 respectively) whereas the percent change did not (AUC 0.54 and 0.49 respectively). A wastewater percentile of 51% maximized sensitivity (0.93) and specificity (0.82) for detecting high case rates. A model inclusive of both metrics performed no better than using wastewater percentile alone. The predictive capability of wastewater percentile declined over time (AUC 0.84 and 0.72 for cases for second and third quarters of 2022). Conclusion: Nationwide, county wastewater levels above 51% relative to the historic peak predicted high COVID rates and hospitalization in the first quarter of 2022, but performed less well in subsequent quarters. Decline over time in predictive performance of this metric likely reflects underreporting of cases, reduced testing, and possibly lower virulence of infection due to vaccines and treatments.
Introduction: COVID-19 pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of immense global public health concern. RP7214, a novel, potent, oral, inhibitor of DHODH, has shown preclinical evidence in inhibiting viral replication and lung inflammation. Methods: This was a randomized, double-blind, placebo-controlled phase 2 study in patients with symptomatic mild SARS-CoV-2 infection, having at least one high-risk feature (e.g., hypertension, diabetes mellitus) for developing severe Covid-19 infection. The patients received RP7214 (400 mg BID) or a placebo for 14 days in a blinded fashion and were followed up to 30 days. Patients also received supportive therapy (e.g., antipyretics and antitussives for symptomatic relief) at the discretion of the investigator. The endpoints were Covid 19 related hospitalization rate by Day 15, SARS-CoV-2 viral load and clearance on Days 3,7 and 15, clinical symptoms improvement by Day 15, safety, and the immuno-modulatory effect of RP7214. Results: A total of 163 patients were treated in the study; 82 received RP7214 and 81 received placebo. Of the total patients, 44.2% had received Covid-19 vaccine prior to the study. The symptom onset was ≤ 3 days in 22.1%. None of the patients in the study required hospitalization. There was no difference in the mean change of viral load between RP7214 and placebo. In the subgroup analysis, in patients having symptom onset of ≤ 3 days, RP7214 significantly reduced viral load on Days 3 and 7, respectively. Similarly, in non-vaccinated patients with symptom onset of ≤ 3 days, RP7214 significantly reduced viral load on Day 3. Overall, there was a trend towards better viral load reduction in RP7214-treated patients with a baseline viral load of 5 log units or higher. For all other endpoints, there was no difference between RP7214 and placebo. Majority of the reported AEs were mild and not related either to study treatment. Conclusions: RP7214 at 400 mg BID dose level showed a statistically significant reduction in viral load at an early stage of the disease and in non-vaccinated patients. There was a trend towards better viral load reduction in RP7214-treated patients with a baseline viral load of 5 log units or higher. RP7214 showed a favorable safety profile. Further development of RP7214 in Covid 19 in a mild symptomatic population with co-morbidities and treated at an early stage of disease may show benefit. Keywords: RP7214; DHODH inhibitor; COVID-19; SARS-CoV-2.
It is quite well-documented that the COVID-19 pandemic disrupted cancer screening services in all countries, irrespective of their resources and healthcare settings. While quantitative estimates on reduction in volume of screening tests or diagnostic evaluation are readily available from the high-income countries, very little data is available from the low- and middle-income countries (LMICs). From the CanScreen5 global cancer screening data repository we identified six LMICs through purposive sampling based on the availability of cancer screening data at least for the years 2019 and 2020. These countries represented different human development index (HDI) categories and were from Asia (Bangladesh and Thailand), Africa (Morocco) and Latin America (Argentina and Colombia). The reduction in the volume of tests in 2020 compared to the previous years ranged from 14.1% in Bangladesh to 72.9% in Argentina (regional programme) for cervical screening, from 14.1% in Bangladesh to 52.2% in Morocco for breast cancer screening and 30.7% in Thailand for colorectal cancer screening. Number of colposcopies was reduced in 2020 compared to previous year by 88.9% in Argentina, 38.2% in Colombia, 27.4% in Bangladesh and 52.3% in Morocco. The reduction in detection rates of CIN 2 or worse lesions ranged from 20.7% in Morocco to 45.4% in Argentina. Reduction of breast cancer detection by 19.2% was reported from Morocco. No association of the impact of pandemic could be seen with HDI categories. Quantifying the impact of service disruptions in screening and diagnostic tests will allow the programmes to strategize how to ramp up services to clear the backlogs in screening and more crucially in further evaluation of screen-positives. The data can be used to estimate the impact on stage distribution and avoidable mortality from these common cancers.
Background: The Danish national SARS-CoV-2 mass test system was among the most ambitious worldwide. We describe its set-up and analyse differences in patterns of testing per demography and time period in relation to the three waves of SARS-CoV-2 transmission in Denmark. Methods: We included all reported PCR- and rapid antigen-tests performed between 27 February 2020 and 10 March 2022 among all residents aged 2 years or above. Descriptive statistics and Poisson regression models were used to analyse characteristics of individuals tested for SARS-CoV-2 using a national cohort study design. Results: A total of 63.7 million PCR-tests and 60.0 million antigen-tests were performed in the study period, testing 91.1% and 79.2% of the Danish population at least once by PCR or antigen, respectively. Female sex, younger age, Danish heritage and living in the capital area were all factors positively associated with the frequency of PCR-testing. The association between COVID-19 vaccination and PCR-testing changed from negative to positive over time. Conclusion: We provide details of the widely available, free-of-charge, national SARS-CoV-2 test system, which served to identify infected individuals, assist isolation of infectious individuals and contact tracing, and thereby mitigating the spread of SARS-CoV-2 in the Danish population. The test system was utilized by nearly the entire population at least once, and widely accepted across different demographic groups. However, demographic differences in the test uptake did exist and should be considered in order not to cause biases in studies related to SARS-CoV-2, e.g., studies of transmission and vaccine effectiveness.
Phase Ⅰ Clinical Trial of a Candidate COVID-19 Vaccine - Condition: COVID-19
Intervention: Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation
Sponsors: Wuhan BravoVax Co., Ltd.; National University Hospital, Singapore; Shanghai BravoBio Co., Ltd.
Not yet recruiting
Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care - Condition: COVID-19
Intervention: Drug: Plitidepsin
Sponsor: PharmaMar
Not yet recruiting
COVID-19 Self-testing Study - Condition: COVID-19
Intervention: Behavioral: SMARTest mobile app for COVID-19 self-testing
Sponsor: Columbia University
Recruiting
Incidence of COVID-19 Following Vaccination in Botswana Against SARS CoV 2 - Condition: COVID-19
Intervention: Drug: AZD 1222
Sponsors: Botswana Harvard AIDS Institute Partnership; AstraZeneca; Botswana Ministry of Health
Completed
Study Evaluating GS-5245 in Nonhospitalized Participants With COVID-19 - Condition: COVID-19
Interventions: Drug: GS-5245; Drug: GS-5245 Placebo
Sponsor: Gilead Sciences
Not yet recruiting
INFLUENCE OF HIGH FREQUENCY CHEST WALL OSCILLATION IN HOSPITALIZED PATIENTS WITH COVID-19 - Condition: COVID-19
Intervention: Device: HIGH FREQUENCY CHEST WALL OSCILLATION
Sponsor: Cairo University
Not yet recruiting
A Study To Assess The Efficacy and Safety of HH-120 Nasal Spray for the Treatment of Mild COVID-19 - Condition: COVID-19
Interventions: Drug: HH-120 nasal spray; Drug: Placebo Comparator
Sponsor: Huahui Health
Recruiting
Study of Flonoltinib Maleate Tablets in the Treatment of Severe Novel Coronavirus (COVID-19) Infection - Condition: COVID-19
Interventions: Drug: VV116+SOC; Drug: SOC
Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd
Recruiting
Study to Access the Efficacy and Safety of STI-1558 in Adult Subjects With Mild or Moderate (COVID-19) - Condition: COVID-19
Interventions: Drug: STI-1558; Drug: STI-1558 placebo
Sponsor: Zhejiang ACEA Pharmaceutical Co. Ltd.
Not yet recruiting
Pirfenidone in Adult Hospitalized Patients With COVID-19 - Condition: COVID-19 Pneumonia
Interventions: Drug: Pirfenidone Oral Product; Drug: Pirfenidone placebo
Sponsor: Capital Medical University
Active, not recruiting
Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells in the Treatment of Long COVID-19 - Condition: Long COVID-19
Intervention: Biological: UC-MSCs
Sponsor: Shanghai East Hospital
Not yet recruiting
COVID-19 Molecular OTC At Home Test - Condition: COVID-19 Pandemic
Intervention: Diagnostic Test: Diagnostic Test: IN Vitro
Sponsor: 3EO Health
Not yet recruiting
The Effectiveness of a Health Education Intervention to Reduce Anxiety in Quarantined COVID-19 Patients - Condition: Health Education, COVID-19, Quarantine, Anxiety, Pandemic
Intervention: Other: health education intervention
Sponsor: University of Monastir
Completed
The Difference Between Non-invasive High-frequency Oscillatory Ventilation and Non-invasive Continuous Airway Pressure Ventilation in COVID-19 With Acute Hypoxemia - Conditions: COVID-19 Pneumonia; Non-invasive Ventilation
Interventions: Device: Non-invasive high-frequency oscillatory ventilation; Device: Non-invasive continuous positive airway pressure ventilation
Sponsor: Guangzhou Institute of Respiratory Disease
Not yet recruiting
Randomized-controlled Trial of Immunoadsorption (IA) in Patients With Chronic Fatigue Syndrome (CFS) Including Patients With Post-COVID-19 CFS (PACS-CFS) - Condition: ME/CSF Including CFS Related to Post-acute COVID-19 Syndrome (PACS)
Intervention: Device: Immunoadsorption
Sponsor: Charite University, Berlin, Germany
Not yet recruiting
Computational investigation on the antioxidant activities and on the Mpro SARS-CoV-2 non-covalent inhibition of isorhamnetin - In the present work, we report a computational study on some important chemical properties of the flavonoid isorhamnetin, used in traditional medicine in many countries. In the course of the study we determined the acid-base equilibria in aqueous solution, the possible reaction pathways with the •OOH radical and the corresponding kinetic constants, the complexing capacity of copper ions, and the reduction of these complexes by reducing agents such as superoxide and ascorbic anion by using…
The main protease of SARS-CoV-2 cleaves histone deacetylases and DCP1A, attenuating the immune defense of the interferon-stimulated genes - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), constitutes an emerging human pathogen of zoonotic origin. A critical role in protecting the host against invading pathogens is carried out by interferon-stimulated genes (ISGs), the primary effectors of the type I interferon (IFN) response. All coronaviruses studied thus far have to first overcome the inhibitory effects of the IFN/ISG system before establishing efficient viral…
Antibacterial and antiviral chitosan oligosaccharide modified cellulosic fibers with durability against washing and long-acting activity - The worldwide outbreak of SARS-CoV-2 has attracted extensive attention to antibacterial and antivirus materials. Cellulose is the most potential candidate for the preparation of green, environmentally friendly antibacterial and antiviral materials. Herein, modified cellulosic fibers with sustained antibacterial and antiviral performance was prepared by introducing chitosan oligosaccharide onto the fibers. The two-step method is proved to be more effective than the one-step method for enhanced…
Suppression of angiotensin converting enzyme 2, a host receptor for SARS-CoV-2 infection, using 5-aminolevulinic acid in vitro - Angiotensin converting enzyme 2 (ACE2), an entry receptor found on the surface of host cells, is believed to be detrimental to the infectious capability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Scientists have been working on finding a cure since its outbreak with limited success. In this study, we evaluated the potential of 5-aminolevulinic acid hydrochloride (ALA) in suppressing ACE2 expression of host cells. ACE2 expression and the production of intracellular…
Alkyne Derivatives of SARS-CoV-2 Main Protease Inhibitors Including Nirmatrelvir Inhibit by Reacting Covalently with the Nucleophilic Cysteine - Nirmatrelvir (PF-07321332) is a nitrile-bearing small-molecule inhibitor that, in combination with ritonavir, is used to treat infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Nirmatrelvir interrupts the viral life cycle by inhibiting the SARS-CoV-2 main protease (M^(pro)), which is essential for processing viral polyproteins into functional nonstructural proteins. We report studies which reveal that derivatives of nirmatrelvir and other M^(pro) inhibitors with a…
Identification of structural scaffold from interbioscreen (IBS) database to inhibit 3CLpro, PLpro, and RdRp of SARS-CoV-2 using molecular docking and dynamic simulation studies - A novel coronavirus SARS-CoV-2 has caused a worldwide pandemic and remained a severe threat to the entire human population. Researchers worldwide are struggling to find an effective drug treatment to combat this deadly disease. Many FDA-approved drugs from varying inhibitory classes and plant-derived compounds are screened to combat this virus. Still, due to the lack of structural information and several mutations of this virus, initial drug discovery efforts have limited success. A…
Mini-review: Angiotensin- converting enzyme 1 (ACE1) and the impact for diseases such as Alzheimer’s disease, sarcopenia, cancer, and COVID-19 - Ageing has been associated with comorbidities, systemic low-grade of inflammation, and immunosenescence. Hypertension is the most common morbidity and anti-hypertensives are used for more than 50%. Angiotensin-converting enzyme 1 inhibitors (ACEi) and angiotensin II receptor blockers (ARB) control blood pressure but also seem to play a role in comorbidities such as Alzheimer’s disease, sarcopenia and cancer. The impact of anti-hypertensives in comorbidities is due to the expression of…
Role of innate and acquired resilience in behavioral system, mental health, and internet addiction among Japanese adolescents in the COVID-19 pandemic - BACKGROUND: This study examines mediation models in which behavioral inhibition and activation systems (BIS/BAS) impact internet addiction through mental health and the moderating roles of innate and acquired resilience in the models.
Aloin A inhibits SARS CoV-2 replication by targeting its binding with ACE2 - Evidence from modeling-supported molecular dynamics simulation - The current study aimed to expand on the recently published results and assess the inhibitory efficacy of aloin A against SARS CoV-2. In vitro testing of aloin A against SARS CoV-2 proteases (i.e., M^(Pro) and PL^(Pro)) showed weak to moderate activity (IC(50) = 68.56 ± 1.13 µM and 24.77 ± 1.57 µM, respectively). However, aloin A was able to inhibit the replication of SARS CoV-2 in Vero E6 cells efficiently with an IC(50) of 0.095 ± 0.022 µM. Depending on the reported poor permeability of aloin…
SARS-CoV-2 NSP7 inhibits type I and III IFN production by targeting the RIG-I/MDA5, TRIF, and STING signaling pathways - SARS-CoV-2 is a poor inducer of innate antiviral immunity, and the underlying mechanism still needs further investigation. Here, we reported that SARS-CoV-2 NSP7 inhibited the production of type I and III IFNs by targeting the RIG-I/MDA5, TLR3-TRIF, and cGAS-STING signaling pathways. SARS-CoV-2 NSP7 suppressed the expression of IFNs and IFN-stimulated genes induced by poly (I:C) transfection and infection with Sendai virus or SARS-CoV-2 virus-like particles. NSP7 impaired type I and III IFN…
Modulation of transient receptor potential (TRP) channels by plant derived substances used in over-the-counter cough and cold remedies - CONCLUSIONS: The literature suggests that these plant derived substances have multifaceted actions and can interact with the TRP ‘cough’ receptors. The plant derived substances used in cough and cold medicines have the potential to target multiple symptoms experienced during a cold.
Potential antiviral effects of pantethine against SARS-CoV-2 - SARS-CoV-2 interacts with cellular cholesterol during many stages of its replication cycle. Pantethine was reported to reduce total cholesterol levels and fatty acid synthesis and potentially alter different processes that might be involved in the SARS-CoV-2 replication cycle. Here, we explored the potential antiviral effects of pantethine in two in vitro experimental models of SARS-CoV-2 infection, in Vero E6 cells and in Calu-3a cells. Pantethine reduced the infection of cells by SARS-CoV-2 in…
Liposome-based high-throughput and point-of-care assays toward the quick, simple, and sensitive detection of neutralizing antibodies against SARS-CoV-2 in patient sera - The emergence of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in 2019 caused an increased interest in neutralizing antibody tests to determine the immune status of the population. Standard live-virus-based neutralization assays such as plaque-reduction assays or pseudovirus neutralization tests cannot be adapted to the point-of-care (POC). Accordingly, tests quantifying competitive binding inhibition of the angiotensin-converting enzyme 2 (ACE2) receptor to the…
Effect of acetic acid inactivation of SARS-CoV-2 - Effective measures are needed to prevent the spread and infectivity of SARS-CoV-2 that causes COVID-19. Chemical inactivation may help to prevent the spread and transmission of this and other viruses. Hence, we tested the SARS-CoV-2 antiviral activity of acetic acid, the main component of vinegar, in vitro. Inactivation and binding assays suggest that acetic acid is virucidal. We found that 6% acetic acid, a concentration typically found in white distilled vinegar, effectively inactivated…
Protease-Responsive Potential-Tunable AIEgens for Cell Selective Imaging of TMPRSS2 and Accurate Inhibitor Screening - Transmembrane protease serine 2 (TMPRSS2) is a plasma membrane protease that activates both spike protein of coronaviruses for cell entry and oncogenic signaling pathways for tumor progression. TMPRSS2 inhibition can reduce cancer invasion and metastasis and partially prevent the entry of SARS-CoV-2 into host cells. Thus, there is an urgent need for both TMPRSS2-selective imaging and precise screening of TMPRSS2 inhibitors. Here, we report a TMPRSS2-responsive surface-potential-tunable…