Objective: To investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. Methods: Established patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response. Results: Although healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination. Conclusions: In two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.
Approval of emergency use of the Novel Coronavirus Disease 2019 (COVID-19) vaccines in many countries has brought hope to ending the COVID-19 pandemic sooner. Considering the limited vaccine supply in the early stage of COVID-19 vaccination programs in most countries, a highly relevant question to ask is: who should get vaccinated first? In this article we propose a network information-driven vaccination strategy where a small number of people in a network (population) are categorized, according to a few key network properties, into priority groups. Using a network-based SEIR model for simulating the pandemic progression, the network information-driven vaccination strategy is compared with a random vaccination strategy. Results for both large-scale synthesized networks and real social networks have demonstrated that the network information-driven vaccination strategy can significantly reduce the cumulative number of infected individuals and lead to a more rapid containment of the pandemic. The results provide insight for policymakers in designing an effective early-stage vaccination plan.
Despite declining SARS-CoV-2 incidence, continued epidemic monitoring is warranted. We collected SARS-CoV-2 test results from 150 drive-through testing centers across California from two observation periods: February 23rd-March 3rd 2021 and April 15th-April 30th 2021. We assessed SARS-CoV-2 positivity, stratified by Hispanic heritage among sociodemographic characteristics and potential exposures. We analyzed 114,789 test results (5.1% and 2.6% positive during the respective observation periods). Nearly half of all positive tests were among testers reporting a recent exposure (48.8% and 45.3% during the respective observation periods). Those findings may provide insight into evolving local transmission dynamics and support targeted public health strategies.
Abstract Objective Independent evaluation of the sensitivity of CE-marked SARS-CoV-2 antigen rapid diagnostic tests (Ag RDT) offered in Germany. Method The sensitivity of 122 Ag RDT was adressed using a common evaluation panel. Minimum sensitivity of 75% for panel members with CT<25 was used for differentiation of devices eligible for reimbursement in in the German healthcare system. Results The sensitivity of different SARS-CoV-2 Ag RDT varied over a wide range. The sensitivity limit of 75% for panel members with CT <25 was met by 96 of the 122 tests evaluated; 26 tests exhibited lower sensitivity, few of which were completely failing. Some devices exhibited high sensitivity, e.g. 100% for CT<30. Conclusion This comparative evaluation succeeded to distinguish less sensitive from better performing Ag RDT. Most of the Ag RDT evaluated appear to be suitable for fast identification of acute infections associated with high viral loads. Market access of SARS-CoV-2 Ag RDT should be based on minimal requirements for sensitivity and specificity.
Background More than one year into the COVID-19 pandemic, important data gaps remain on longitudinal prevalence of SARS-CoV-2 infection at the population level and in defined risk groups, efficacy of specific lockdown measures, and on (cost-)effective surveillance. Methods The ELISA (Luebeck Longitudinal Investigation of SARS-CoV-2 Infection) study invited adult inhabitants (n=~300,000) from the Luebeck area (Northern Germany) and enrolled 3051 participants (~1%); 1929 population-matched and 1645 with high-exposure based on profession. The one-year study period (03/2020-02/2021) covered massive influx of tourism in the summer, rise of infection rates in the fall/winter 2020/2021, and two lockdowns. Participants were screened seven times for SARS-CoV-2 infection using PCR and antibody testing and monitored with an app-based questionnaire (n=~91,000). Results Cohort (56% female; mean age: 45.6 years) retention was 75%-98%; 92 persons (3.5%) were antibody- and/or PCR-positive. Seropositivity was almost 2-fold higher in men and increased risk detected in several high-exposure groups (highest for nurses, followed by police, army, firemen, and students). In May 2020, 92% of the infections were missed by PCR testing; by February 2021, only 29% remained undiagnosed. Contact to COVID-19-affected was the most relevant risk factor. Other factors, such as frequent use of public transportation, shopping, close contacts at work, and extensive tourism in the summer did not impact infection rates. Conclusions We i) provide a model for effective, regional surveillance; ii) identify infection risk factors informing public health measures; iii) demonstrate that easing of lockdown measures appears safe at times of low prevalence in the presence of continuous monitoring.
A Phase 3 Randomized, Double-Blind Placebo Controlled, Multi-regional Trial to Evaluate the Efficacy and Safety of GT0918 for the Treatment of Mild to Moderate COVID-19 Male Patients - Condition: COVID-19
Intervention: Drug: GT0918 tablets or placebo
Sponsor: Suzhou Kintor Pharmaceutical Inc,
Not yet recruiting
Recombinant Hyperimmune Polyclonal Antibody (GIGA-2050) in COVID-19 Patients - Condition: COVID-19
Intervention: Drug: GIGA-2050
Sponsor: GigaGen, Inc.
Not yet recruiting
The Role of High Dose Co-trimoxazole in Severe Covid-19 Patients - Condition: COVID-19 Pneumonia
Interventions: Drug: Co-trimoxazole; Drug: Placebo
Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
Not yet recruiting
Breathing Effort in Covid-19 Pneumonia: Effects of Positive Pressure, Inspired Oxygen Fraction and Decubitus - Condition: COVID-19 Pneumonia
Intervention: Device: Esophageal catheter
Sponsor: San Luigi Gonzaga Hospital
Recruiting
The Effect of Vitamin D Supplementation on COVID-19 Recovery - Condition: Covid19
Interventions: Drug: Vit-D 0.2 MG/ML Oral Solution [Calcidol]; Drug: Physiological Irrigating Solution
Sponsors: University of Monastir; Loussaief Chawki; Nissaf Ben Alaya; Cyrine Ben Nasrallah; Manel Ben Belgacem; Hela Abroug; Imen Zemni; Manel Ben fredj; Wafa Dhouib
Completed
A Clinical Trial to Evaluate the Recombinant SARS-CoV-2 Vaccine (CHO Cell) for COVID-19 - Condition: COVID-19
Interventions: Biological: low-dose Recombinant SARS-CoV-2 Vaccine (CHO cell); Biological: high-dose Recombinant SARS-CoV-2 Vaccine (CHO cell); Biological: placebo
Sponsors: National Vaccine and Serum Institute, China; Lanzhou Institute of Biological Products Co., Ltd; Beijing Zhong Sheng Heng Yi Pharmaceutical Technology Co., Ltd.; Zhengzhou University
Recruiting
A Study to Evaluate the Safety and Effect of STC3141 Continuous Infusion in Subjects With Severe Corona Virus Disease 2019(COVID-19)Pneumonia - Condition: Severe COVID-19 Pneumonia
Intervention: Drug: STC3141
Sponsors: Grand Medical Pty Ltd.; Trium Clinical Consulting
Not yet recruiting
tDCS for Post COVID-19 Fatigue - Condition: Post Covid-19 Patients
Intervention: Device: Transcranial Direct Current Stimulation
Sponsor: Thorsten Rudroff
Recruiting
A Phase 2 Study of APX-115 in Hospitalized Patients With Confirmed Mild to Moderate COVID-19. - Condition: COVID-19
Interventions: Drug: APX-115; Drug: Placebo
Sponsors: Aptabio Therapeutics, Inc.; Covance
Not yet recruiting
Leveraging CHWs to Improve COVID-19 Testing and Mitigation Among CJIs Accessing a Corrections-focused CBO - Condition: Covid19
Intervention: Behavioral: Onsite Point-of-care
Sponsors: Montefiore Medical Center; The Fortune Society; University of Bristol
Not yet recruiting
Convalescent Plasma as Adjunct Therapy for COVID-19 - Condition: COVID-19
Intervention: Biological: Convalescent plasma treatment
Sponsors: National Institute of Health Research and Development, Ministry of Health Republic of Indonesia; Indonesian Red Cross; Eijkman Institute for Molecular Biology
Recruiting
Selenium as a Potential Treatment for Moderately-ill, Severely-ill, and Critically-ill COVID-19 Patients. - Condition: Covid19
Interventions: Drug: Selenium (as Selenious Acid); Other: Placebo
Sponsors: CHRISTUS Health; Pharco Pharmaceuticals
Not yet recruiting
Protecting Our Community: COVID-19 Testing - Conditions: SARS-CoV-2; Covid19
Intervention: Diagnostic Test: Home-based SARS-CoV-2 test kit
Sponsors: Montana State University; National Institute of General Medical Sciences (NIGMS); University of Washington; Fred Hutchinson Cancer Research Center; Salish Kootenai College
Recruiting
Estradiol and Progesterone in Hospitalized COVID-19 Patients - Condition: Covid19
Interventions: Other: Placebo injection and placebo pill; Drug: Estradiol Cypionate 5 MG/ML; Drug: Progesterone 200 MG Oral Capsule
Sponsor: Tulane University
Not yet recruiting
Safety, Tolerability and PK of Ensovibep (MP0420 - a New Candidate With Potential for Treatment of COVID-19) - Condition: COVID-19
Interventions: Drug: Ensovibep; Drug: Placebo
Sponsor: Molecular Partners AG
Recruiting
SARS-CoV-2 uses a multipronged strategy to impede host protein synthesis - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 19 pandemic¹. Coronaviruses developed varied mechanisms to repress host mRNA translation to allow the translation of viral mRNAs and concomitantly block the cellular innate immune response^(2,3). Although different SARS-CoV-2 proteins are implicated in host expression shutoff^(4-7), a comprehensive picture of the effects of SARS-CoV-2 infection on cellular gene expression is lacking….
Critical Interactions Between the SARS-CoV-2 Spike Glycoprotein and the Human ACE2 Receptor - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells by binding its spike (S) glycoproteins to angiotensin-converting enzyme 2 (ACE2) receptors and causes the coronavirus disease 2019 (COVID-19). Therapeutic approaches to prevent SARS-CoV-2 infection are mostly focused on blocking S-ACE2 binding, but critical residues that stabilize this interaction are not well understood. By performing all-atom molecular dynamics (MD) simulations, we identified an extended network…
Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2 - Inhibitors of the protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and human ACE2 (hACE2), which acts as a ligand-receptor pair that initiates the viral attachment and cellular entry of this coronavirus causing the ongoing COVID-19 pandemic, are of considerable interest as potential antiviral agents. While blockade of such PPIs with small molecules is more challenging than that with antibodies, small-molecule inhibitors (SMIs) might offer alternatives that are less strain-…
A mini-review on Sofosbuvir and Daclatasvir treatment in COVID-19 - Sofosbovir and daclatasvir have been used successfully since 2013 for hepatitis C virus treatment .It has been shown by different studies that sofosbovir can inhibit RNA polymerase of other positive-strand RNA viruses including Flaviviridae and Togaviridae. Homology between HCV RNA polymerase and SARS-CoV-2 has also been established. The efficacy of sofosbuvir and daclatsvir as potential choices in treating patients with COVID-19 and their recovery can be hypothesized.
Thymoquinone: A Promising Natural Compound with Potential Benefits for COVID-19 Prevention and Cure - COVID-19 has caused a major global health crisis, as excessive inflammation, oxidation, and exaggerated immune response in some sufferers can lead to a condition known as cytokine storm, which may progress to acute respiratory distress syndrome (ARDs), which can be fatal. So far, few effective drugs have emerged to assist in the treatment of patients with COVID-19, though some herbal medicine candidates may assist in the fight against COVID-19 deaths. Thymoquinone (TQ), the main active…
Dengue virus-free defective interfering particles have potent and broad anti-dengue virus activity - Dengue virus (DENV) is spread from human to human through the bite of the female Aedes aegypti mosquito and leads to about 100 million clinical infections yearly. Treatment options and vaccine availability for DENV are limited. Defective interfering particles (DIPs) are considered a promising antiviral approach but infectious virus contamination has limited their development. Here, a DENV-derived DIP production cell line was developed that continuously produced DENV-free DIPs. The DIPs contained…
Identifying potential drug targets and candidate drugs for COVID-19: biological networks and structural modeling approaches - Background: Coronavirus (CoV) is an emerging human pathogen causing severe acute respiratory syndrome (SARS) around the world. Earlier identification of biomarkers for SARS can facilitate detection and reduce the mortality rate of the disease. Thus, by integrated network analysis and structural modeling approach, we aimed to explore the potential drug targets and the candidate drugs for coronavirus medicated SARS. Methods: Differentially expression (DE) analysis of CoV infected host genes (HGs)…
Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia - Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by binding of the viral Spike protein to host receptor angiotensin-converting enzyme 2 (ACE2), followed by fusion of viral and host membranes. Although antibodies that block this interaction are in emergency use as early coronavirus disease 2019 (COVID-19) therapies, the precise determinants of neutralization potency remain unknown. We discovered a series of antibodies that potently block ACE2 binding but…
Systematic functional analysis of SARS-CoV-2 proteins uncovers viral innate immune antagonists and remaining vulnerabilities - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades most innate immune responses but may still be vulnerable to some. Here, we systematically analyze the impact of SARS-CoV-2 proteins on interferon (IFN) responses and autophagy. We show that SARS-CoV-2 proteins synergize to counteract anti-viral immune responses. For example, Nsp14 targets the type I IFN receptor for lysosomal degradation, ORF3a prevents fusion of autophagosomes and lysosomes, and ORF7a interferes with…
Complement levels at admission as a reflection of Coronavirus Disease 19 (COVID-19) severity state - CONCLUSION: We found evidence of complement hyperactivation in COVID-19, associated with hyperinflammation and thrombotic microangiopathy. Complement inhibition should be further investigated for potential benefit in patients displaying a hyperinflammatory and microangiopathic phenotype. This article is protected by copyright. All rights reserved.
Activation of Interleukin-1β Release and Pyroptosis by Transmissible Gastroenteritis Virus Is Dependent on the NOD-Like Receptor Protein 3 Inflammasome in Porcine Intestinal Epithelial Cell Line - Transmissible gastroenteritis virus (TGEV) is a coronavirus, which causes fatal severe diarrhea and leads to high mortality in newborn piglets. Inflammasomes are hub molecules that induce proinflammatory cytokine production and maturation to initiate innate immune defenses upon cellular infection. To date, the potential role of inflammasome in TGEV infection in porcine intestinal epithelial cells has not been elucidated. The present study aims to investigate the function of the inflammasome in…
Immune-Based Therapy for COVID-19 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel zoonotic virus identified as the cause of coronavirus disease 2019 (COVID-19) that has crossed species and infected humans. In order to develop new insights on the immune-based treatments against this disease, it is vital to understand the immunopathology of the COVID-19, implications of the immune response to SARS-CoV-2, and immune dysfunction in response to SARS-CoV-2. There is no approved drug for the treatment of…
Lipid-Modulating Agents for Prevention or Treatment of COVID-19 in Randomized Trials - Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multi-organ manifestations. Lipid modulating agents may be useful in treating patients with COVID-19. They may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglycerides portends worse outcome in patients with COVID-19. Upon a systematic…
A novel highly potent inhibitor of TMPRSS2-like proteases blocks SARS-CoV-2 variants of concern and is broadly protective against infection and mortality in mice - The COVID-19 pandemic caused by the SARS-CoV-2 virus remains a global public health crisis. Although widespread vaccination campaigns are underway, their efficacy is reduced against emerging variants of concern (VOCs) ^(1,2) . Development of host-directed therapeutics and prophylactics could limit such resistance and offer urgently needed protection against VOCs ^(3,4) . Attractive pharmacological targets to impede viral entry include type-II transmembrane serine proteases (TTSPs), such as…
Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity - COVID-19 can lead to life-threatening respiratory failure, with increased inflammatory mediators and viral load. Here, we perform single-cell RNA-sequencing to establish a high-resolution map of blood antigen-presenting cells (APCs) in 15 patients with moderate or severe COVID-19 pneumonia, at day 1 and day 4 post admission to intensive care unit or pulmonology department, as well as in 4 healthy donors. We generated a unique dataset of 81,643 APCs, including monocytes and rare dendritic cell…
IMPROVEMENTS RELATED TO PARTICLE, INCLUDING SARS-CoV-2, DETECTION AND METHODS THEREFOR - - link
A COMPREHENSIVE DISINFECTION SYSTEM DURING PANDEMIC FOR PERSONAL ITEMS AND PROTECTIVE EQUIPMENT (PPE) TO SAFEGUARD PEOPLE - The current Covid-19 pandemic has led to an enormous demand for gadgets / objects for personal protection. To prevent the spread of virus, it is important to disinfect commonly touched objects. One of the ways suggested is to use a personal UV-C disinfecting box that is “efficient and effective in deactivating the COVID-19 virus. The present model has implemented the use of a UV transparent material (fused silica quartz glass tubes) as the medium of support for the objects to be disinfected to increase the effectiveness of disinfection without compromising the load bearing capacity. Aluminum foil, a UV reflecting material, was used as the inner lining of the box for effective utilization of the UVC light emitted by the UVC lamps. Care has been taken to prevent leakage of UVC radiation out of the system. COVID-19 virus can be inactivated in 5 minutes by UVC irradiation in this disinfection box - link
UBIQUITOUS COMPUTING SYSTEM FOR MENTAL HEALTH MONITORING OF PERSON DURING THE PANDEMIC OF COVID-19 - - link
USE OF IMINOSUGAR COMPOUND IN PREPARATION OF ANTI-SARS-COV-2 VIRUS DRUG - - link
逆转录酶突变体及其应用 - 本发明提供一种MMLV逆转录酶突变体,在野生型MMLV逆转录酶氨基酸序列(如SEQ ID No.1序列所示)中进行七个氨基酸位点的突变,氨基酸突变位点为:R205H;V288T;L304K;G525D;S526D;E531G;E574G。该突变体可以降低MMLV逆转录酶对Taq DNA聚合酶的抑制作用,大大提高了一步法RT‑qPCR的灵敏度。 - link
Compositions and methods for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection - - link
用于检测新型冠状病毒的试纸和试剂盒 - 本发明涉及生物技术和免疫检测技术领域,具体涉及一种用于检测新型冠状病毒的试纸和试剂盒。所述试纸或试剂盒含有抗体1和/或抗体2,所述抗体1的重、轻链可变区的氨基酸序列分别如SEQ ID NO:1‑2所示,所述抗体2的重、轻链可变区的氨基酸序列分别如SEQ ID NO:3‑4所示。本发明对于大批量的新型冠状病毒样本,包括新型冠状病毒突变(英国、南非)与非突变株的人血清、鼻咽拭子等样本的检测有普遍检测意义,避免突变株的漏检。 - link
Die Erfindung betrifft ein Fahrgastleitsystem zum Leiten von mit einem Fahrzeug (1) mit wenigstens zwei Türen (2.L, 2.R) transportieren Fahrgästen (3), mit wenigstens einem Sensor (4) zur Überwachung der Fahrgäste (3), wenigstens einem Anzeigemittel (5) zur Ausgabe von Leitinformationen, wenigstens einem Aktor zum Öffnen oder Verriegeln einer Tür (2.L, 2.R) und wenigstens einer Recheneinheit (7). Das erfindungsgemäße Fahrgastleitsystem ist dadurch gekennzeichnet, dass die Recheneinheit (7) dazu eingerichtet ist durch Auswertung vom wenigstens einen Sensor (4) erzeugter Sensordaten zu erkennen an welcher Tür (2.L, 2.R) des Fahrzeugs (1) Fahrgäste (3) ein- und/oder aussteigen möchten und wenigstens eine Tür (2.L, 2.R) für einen Ausstieg festzulegen und/oder wenigstens eine Tür (2.L, 2.R) für einen Einstieg festzulegen, sodass eine Anzahl an Begegnungen von sich durch das Fahrzeug (1) bewegender Fahrgäste (3) und/oder aus dem Fahrzeug (1) aussteigenden und/oder in das Fahrzeug (1) einsteigenden Fahrgästen (3) minimiert wird.
Vorrichtung zum Desinfizieren, der Körperpflege oder dergleichen mittels einer flüssigen oder cremigen Substanz (20), dadurch gekennzeichnet, dass die Vorrichtung mit einem elektrisch betriebenen Erinnerungs-Modul und einem Vorratsbehälter (10) für die Substanz (20) versehen ist, die Substanz (20) in dosierter Menge zur Ausgabeöffnung (9) gefördert wird und die Vorrichtung dazu geeignet ist, am Körper oder der Kleidung einer Person getragen zu werden.
Die Erfindung betrifft ein Verfahren zur laborbasierten Überprüfung und/oder weiteren Ausdifferenzierung einer im Schnelltestverfahren erhaltenen Diagnose einer Infektionskrankheit, wobei im Rahmen des Schnelltestverfahrens eine flüssige Patientenprobe auf ein Objekt aus einem porösen Material aufgetragen wird und wobei dieses Objekt nach Trocknung der flüssigen Patientenprobe an das diagnostische Labor übermittelt wird. Im Labor werden dann die eingetrockneten Probenreste aus dem porösen Material ausgelöst und analysiert.