Summary Background The ReCOV is a recombinant trimeric two-component SARS-CoV-2 subunit vaccine adjuvanted with BFA03. We report the preliminary safety and immunogenicity results for the ReCOV. Methods This first in human, randomized, double-blind, placebo-controlled phase I study, was conducted at 2 study sites in New Zealand. Subjects were stratified into two age cohorts (18-55 years and 56-80 years old) and then randomly assigned in a 4:1 ratio to receive two 0.5 mL intramuscular doses of the ReCOV vaccine (20ug or 40ug, adjuvanted with BFA03 in each) or placebo, 21 days apart. The primary endpoints were incidence of solicited local and systemic adverse events (AEs) and unsolicited AEs after each dose; incidence of serious adverse events (SAEs) up to 30 days after the second dose; changes in clinical laboratory tests from baseline up to 7 days after each dose; and changes in vital signs from baseline up to 30 days after the second dose. The key secondary endpoints for immunogenicity were neutralizing antibody titers against SARS- CoV-2, S1 receptor binding domain (RBD) and N-terminal domain (NTD) IgG titers post-vaccination. The T cell-specific immune response elicited by ReCOV were also evaluated. The trial was registered with ClinicalTrials.gov (NCT04818801). Findings One hundred participants (50 for each age group) were randomized. The incidence of solicited local AEs in 20ug ReCOV, 40ug ReCOV, and pooled placebo group among younger adults were 60.0%, 70.0%, and 10.0%, respectively, while among older adults were 55.0%, 84.2%, and 10.0%, respectively. The incidence of solicited systemic AEs in 20ug ReCOV, 40ug ReCOV, and pooled placebo group among younger adults were 60.0%, 60.0%, and 30.0%, respectively, while among older adults were 50.0%, 52.6%, and 50.0%, respectively. All solicited AEs and unsolicited AEs were mild. No vaccination- related SAE, adverse events of special interest, and AE leading to early discontinuation were reported. ReCOV elicited SARS-CoV-2 neutralizing antibody after the first vaccination, which were increased further after the second vaccination irrespective of dose and age groups. The neutralizing antibody against wild-type SARS-CoV-2 peaked at 14 days post the second vaccination in both 20ug and 40ug ReCOV groups, with GMT of 1643.17 IU/mL and 1289.21 IU/mL among younger adults, and 1122.32 IU/mL and 680.31 IU/mL among older adults, respectively. Similarly, both anti-RBD and anti-NTD specific IgG were elicited after the first vaccination, and peaked at 14 days after the second vaccination. T helper 1 biased cellular responses were observed after ReCOV vaccinations. Interpretation Both 20 ugand 40ug ReCOV showed good safety profiles and elicited strong immune responses in the younger and the older adults. The results of this study support the accelerated development of ReCOV.
Objectives The COVID-19 pandemic has heightened the need to address loneliness and social isolation (and associated incidence of depression) amongst older adults. Between June and October 2020, the Behavioural Activation in Social IsoLation (BASIL) pilot study investigated the acceptability and feasibility of a remotely delivered brief psychological intervention (Behavioural Activation, BA) to prevent and reduce loneliness and depression in older people with long term conditions (LTCs) during the COVID-19 pandemic. Design An embedded qualitative study was conducted with semi-structured interviews to generate data that was first analysed inductively using thematic analysis and then deductively using the Theoretical Framework of Acceptability (TFA). Setting National Health Service and third sector organisations in England. Participants Sixteen older adults and 9 Support Workers (BSWs) participating in the BASIL pilot trial. Results Older adults and BSWs described a positive affective attitude towards the intervention linked to altruism, however the activity planning aspect of the intervention was limited due to COVID-19 restrictions. The intervention was understood by older adults & BSWs, although less understanding in older adults without low mood. A manageable burden was involved with delivering and participating in the intervention. For ethicality, older adults valued social contact and making changes, BSWs valued being able to observe those changes. Opportunity cost was low for BSWs & older adults. BA was perceived to be useful in the pandemic and likely to achieve its aims, (Perceived Effectiveness) especially if tailored to people with both low mood and LTCs. Self-efficacy developed over time and with experience for both BSWs and older adults. Conclusions Overall, the BASIL pilot study processes and BA intervention were found to be acceptable. Use of the TFA provided valuable insights into how the intervention was experienced and how the acceptability of study processes and the BA intervention could be enhanced ahead of the larger definitive trial (BASIL+).
Background: Thoracic CT imaging is widely used as a diagnostic method in the diagnosis of COVID-19 pneumonia. Radiological differential diagnosis and isolation of other viral agents causing pneumonia in patients gained importance, especially during the pandemic period. Aims: We aimed to investigate whether there is a difference between the CT imaging findings characteristically defined in COVID-19 pneumonia and the findings detected in pneumonia due to other viral agents, and which finding may be more effective in the diagnosis. Study Design: The study included 249 adult patients with pneumonia found in thorax CT examination and positive COVID-19 RT-PCR test and 94 patients diagnosed with non-COVID pneumonia (viral PCR positive, no bacterial/fungal agents were detected in other cultures) from the last 5 years before the pandemic. It was retrospectively analyzed using the PACS System. CT findings were evaluated by two radiologists with 5 and 20 years of experience who did not know to which group the patient belonged, and it was decided by consensus. Methods: Demographic data (age, gender, known chronic disease) and CT imaging findings (percentage of involvement, number of lesions, distribution preference, dominant pattern, ground-glass opacity distribution pattern, nodule, tree in bud sign, interstitial changes, crazy paving sign, reversed halo sign, vacuolar sign, halo sign, vascular enlargement, linear opacities, traction bronchiectasis, peribronchial wall thickness, air trapping, pleural retraction, pleural effusion, pericardial effusion, cavitation, mediastinal/hilar lymphadenopathy, dominant lesion size, consolidation, subpleural curvilinear opacities, air bronchogram, pleural thickening) of the patients were evaluated. CT findings were also evaluated with the RSNA consensus guideline and the CORADS scoring system. Data were divided into two main groups as non-COVID-19 and COVID-19 pneumonia and compared statistically with chi-square tests and multiple regression analysis of independent variables. Results: Two main groups; RSNA and CORADS classification, percentage of involvement, number of lesions, distribution preference, dominant pattern, nodule, tree in bud, interstitial changes, crazy paving, reverse halo vascular enlargement, peribronchial wall thickness, air trapping, pleural retraction, pleural/pericardial effusion, cavitation and mediastinal/hilar lymphadenopathy were compared, significant differences were found between the groups (p < 0.01). Multiple linear regression analysis of independent variables found a significant effect of reverse halo sign (β = 0.097, p <0.05) and pleural effusion (β = 10.631, p <0.05) on COVID-19 pneumonia. Conclusion: Presence of reverse halo and absence of pleural effusion was found to be efficient in the diagnosis of COVID-19 pneumonia.
Recently, the Centers for Diseases and Control released a nationwide health alert about an increase in hepatitis cases of unknown origin in children, raising concern about potential sequelae of COVID-19 infection. In this study, we test whether there was increased risk of elevated serum liver enzymes and bilirubin following COVID-19 infection in children. We performed a retrospective cohort study on a nation-wide database of patient electronic health records (EHRs) in the US. The study population comprise 796,369 children between the ages of 1-10 years including 245,675 who had contracted COVID-19 during March 11, 2020 - March 11, 2022 and 550,694 who contracted non-COVID other respiratory infection (ORI) during the same timeframe. Compared to children infected with other respiratory infections, children infected with COVID- 19 infection were at significantly increased risk for elevated AST or ALT (hazard ratio or HR: 2.52, 95% confidence interval or CI: 2.03-3.12) and total bilirubin (HR: 3.35, 95% CI: 2.16- 5.18). These results suggest acute and long-term hepatic sequelae of COVID-19 in pediatric patients. Further investigation is needed to clarify if post-COVID-19 related hepatic injury described in this study is related to the current increase in pediatric hepatitis cases of unknown origin.
Background The COVID-19 pandemic has spurred large-scale, inter-institutional research efforts. To enable these efforts, the German Corona Consensus (GECCO) dataset has been developed previously as a harmonized, interoperable collection of the most relevant data elements for COVID-19-related patient research. As GECCO has been developed as a compact core dataset across all medical fields, the focused research within particular medical domains demanded the definition of extension modules that include those data elements that are most relevant to the research performed in these individual medical specialties. Main body We created GECCO extension modules for the immunization, pediatrics, and cardiology domains with respect to the pandemic requests. The data elements included in each of these modules were selected in a consensus-based process by working groups of medical experts from the respective specialty to ensure that the contents are aligned with the research needs of the specialty. The selected data elements were mapped to international standardized vocabularies and data exchange specifications were created using HL7 FHIR profiles on the appropriate resources. All steps were performed in close interdisciplinary collaboration between medical domain experts, medical information scientists and FHIR developers. The profiles and vocabulary mappings were syntactically and semantically validated in a two-stage process. In that way, we defined dataset specifications for a total number of 23 (immunization), 59 (pediatrics), and 50 (cardiology) data elements that augment the GECCO core dataset. We created and published implementation guides and example implementations as well as dataset annotations for each extension module. Conclusions We here present extension modules for the GECCO core dataset that contain data elements most relevant to COVID-19-related patient research in immunization, pediatrics and cardiology. These extension modules were defined in an interdisciplinary, iterative, consensus-based approach that may serve as a blueprint for the development of further dataset definitions and GECCO extension modules. The here developed GECCO extension modules provide a standardized and harmonized definition of specialty-related datasets that can help to enable inter-institutional and cross-country COVID-19 research in these specialties.
The Covid-19 pandemic resulted in significant challenges to the provision of face-to-face clinics in geriatric perioperative care (G-POC). There are no studies evaluating the use of telemedicine in this population. A pilot study at North Bristol NHS Trust demonstrated that delivery of GPOC clinics via video consultation was feasible, but did not record outcome measures to demonstrate effectiveness and was not compared to face to face clinic. This study aims to provide proof of concept examining the outcomes of virtual G-POC consultations, compared to a face-to-face clinic, using standardised perioperative outcomes. It will test the feasibility of the intervention with a view to developing a randomised controlled trial.
Public health indicators typically used for COVID-19 surveillance can be biased or lag changing community transmission patterns. The United States city of Chicago opportunistically investigated whether sentinel surveillance of recently symptomatic individuals receiving outpatient diagnostic testing for SARS-CoV-2 could accurately assess the instantaneous reproductive number R(t) and provide early warning of changes in transmission. Patients tested at community-based diagnostic testing sites between September 2020 and June 2021, and reporting symptom onset within four days preceding their test, formed the sentinel population. R(t) calculated from sentinel cases agreed well with R(t) from other indicators. Retrospectively, trends in sentinel cases did not precede trends in COVID-19 hospital admissions by any identifiable lead time. In deployment, sentinel surveillance held an operational recency advantage of nine days over hospital admissions. The promising performance of opportunistic sentinel surveillance suggests that deliberately designed outpatient sentinel surveillance would provide robust early warning of increasing transmission.
The Role of Glutathione Deficiency and MSIDS Variables in Long COVID-19 - Condition: COVID-19
Intervention: Dietary Supplement: NAC (N-acetyl cysteine) , Alpha lipoic acid (ALA), liposomal glutathione (GSH)
Sponsors: University of California, Irvine; Hudson Valley Healing Arts Center
Not yet recruiting
Study to Evaluate the Efficacy of IN STI-9199 in Treating Symptomatic COVID-19 in Outpatient Adults and Adolescents - Condition: COVID-19
Interventions: Drug: STI-9199; Drug: Placebo
Sponsor:
Sorrento Therapeutics, Inc.
Not yet recruiting
A Study to Evaluate the Safety and Immunogenicity of Omicron COVID-19 Vaccine (Vero Cell), Inactivated in Population 18 Years Old of Age and Above - Condition: COVID-19
Intervention: Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated
Sponsors: China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Shulan (Hangzhou) Hospital
Recruiting
Study on Sequential Immunization of Omicron Inactivated COVID-19 Vaccine and Prototype Inactivated COVID-19 Vaccine in Population Aged 18 Years Old and Above - Condition: COVID-19
Interventions: Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated; Biological: COVID-19 Vaccine (Vero Cell), Inactivated
Sponsors:
China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Hunan Provincial Center for Disease Control and Prevention
Recruiting
Neuro-inflammation and Post-infectious Fatigue in Individuals With and Without COVID-19 - Condition: COVID-19
Intervention: Radiation: [18F]DPA-714 positron emission tomography (PET) scan
Sponsors: Amsterdam UMC, location VUmc; ZonMw: The Netherlands Organisation for Health Research and Development
Enrolling by invitation
Phase II Safety Single-arm Study of CDK4/6 Inhibition With Palbociclib in Hospitalized, Moderate COVID-19 Cases to Prevent Thromboinflammation - Condition: COVID-19
Intervention: Drug: Palbociclib
Sponsor: biotx.ai GmbH
Active, not recruiting
Phase I Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older - Condition: COVID-19
Interventions: Biological: COVID-19 mRNA vaccine; Biological: Placebo
Sponsor: CanSino Biologics Inc.
Not yet recruiting
Phase II Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older - Condition: COVID-19
Interventions: Biological: COVID-19 mRNA vaccine; Biological: Placebo
Sponsor: CanSino Biologics Inc.
Not yet recruiting
THEMBA II T-Cell Vaccine: Vaccination With saRNA COVID-19 Vaccines - Condition: COVID-19
Interventions: Biological: AAHI-SC2 Vaccine; Biological: AAHI- SC3 Vaccine; Biological: EUA or approved vaccine
Sponsor: ImmunityBio, Inc.
Recruiting
To Evaluate SSD8432/Ritonavir in Adults With COVID-19 - Condition: COVID-19
Interventions: Drug: SSD8432 dose; Drug: SSD8432 placebo
Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Not yet recruiting
The Use of Chinese Herbal Medicine and Vitamin C by Hospital Care Workers in HK to Prevent COVID-19 - Condition: COVID-19
Intervention: Drug: Chinese herbal medicine
Sponsor:
Hong Kong Baptist University
Not yet recruiting
Evaluation of SSD8432 and Ritonavir in Adult Subjects With COVID-19 Placebo-Controlled, Phase II Clinical Study - Condition: COVID-19
Interventions: Drug: SSD8432 dose1; Drug: SSD8432 dose2; Drug: SSD8432Placebo
Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Not yet recruiting
To Evaluate SSD8432/ Ritonavir in Adults With COVID-19 - Condition: COVID-19 Patients
Interventions: Drug: SSD8432 dose 1/Ritonavir; Drug: SSD8432 dose 2
Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Not yet recruiting
Safety, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine - Condition: COVID-19 Pandemic
Interventions: Biological: A Lyophilized COVID-19 mRNA Vaccine; Biological: Placebo
Sponsor: Wuhan Recogen Biotechnology Co., Ltd.
Not yet recruiting
Home-based Exercise Program in Patients With the Post-COVID-19 Condition - Conditions: Long COVID; Post-acute COVID-19 Syndrome
Intervention: Other: Home- based physical training
Sponsor: University of Sao Paulo
Not yet recruiting
How SARS-CoV-2 dodges immune surveillance and facilitates infection: an analytical review - INTRODUCTION: Effective treatments for the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are limited. The virus has evolved strategies to evade the immune system or hijack immune responses to facilitate infection and escape immune surveillance. Mechanistically, SARS-CoV-2 takes advantage of TLR4 and cytokine-induced integrins to promote its entrance into the cell. Furthermore, the activation of pattern recognition receptors (PRR)-mediated signaling pathways is…
Screening for inhibitors against SARS-CoV-2 and its variants - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, generating new variants that pose a threat to global health; therefore, it is imperative to obtain safe and broad-spectrum antivirals against SARS-CoV-2 and its variants. To this end, we screened compounds for their ability to inhibit viral entry, which is a critical step in virus infection. Twenty compounds that have been previously reported to inhibit SARS-CoV-2 replication were tested by using pseudoviruses…
Nitric-oxide enriched plasma-activated water inactivates 229E coronavirus and alters antiviral response genes in human lung host cells - The ongoing pandemic caused by the novel coronavirus, SARS-CoV-2, is influencing global health. Moreover, there is a major threat of future coronaviruses affecting the entire world in a similar, or even more dreadful, manner. Therefore, effective and biocompatible therapeutic options against coronaviruses are urgently needed. To address this challenge, medical specialists require a well-informed and safe approach to treating human coronaviruses (HCoVs). Herein, an environmental friendly approach…
Aerosol Transmission of the Pandemic SARS-CoV-2 and Influenza A Virus Was Blocked by Negative Ions - The pandemic of respiratory diseases, such as coronavirus disease 2019 (COVID-19) and influenza, has imposed significant public health and economic burdens on the world. Wearing masks is an effective way to cut off the spread of the respiratory virus. However, due to cultural differences and uncomfortable wearing experiences, not everyone is willing to wear masks; there is an urgent need to find alternatives to masks. In this study, we tested the disinfection effect of a portable ionizer on…
Glycopeptide Antibiotic Teicoplanin Inhibits Cell Entry of SARS-CoV-2 by Suppressing the Proteolytic Activity of Cathepsin L - Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), public health worldwide has been greatly threatened. The development of an effective treatment for this infection is crucial and urgent but is hampered by the incomplete understanding of the viral infection mechanisms and the lack of specific antiviral agents. We previously reported that teicoplanin, a glycopeptide antibiotic that has been commonly used in the…
Novel Insights Into the Sulfated Glucuronic Acid-Based Anti-SARS-CoV-2 Mechanism of Exopolysaccharides From Halophilic Archaeon Haloarcula hispanica - The pandemic caused by SARS-CoV-2 is the most widely spread disease in the 21st century. Due to the continuous emergence of variants across the world, it is necessary to expand our understanding of host-virus interactions and explore new agents against SARS-CoV-2. In this study, it was found exopolysaccharides (EPSs) from halophilic archaeon Haloarcula hispanica ATCC33960 can bind to the spike protein of SARS-CoV-2 with the binding constant K(D) of 2.23 nM, block the binding of spike protein to…
Antiviral phytocompounds “ellagic acid” and “(+)-sesamin” of Bridelia retusa identified as potential inhibitors of SARS-CoV-2 3CL pro using extensive molecular docking, molecular dynamics simulation studies, binding free energy calculations, and bioactivity prediction - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected billions and has killed millions to date. Studies are being carried out to find therapeutic molecules that can potentially inhibit the replication of SARS-CoV-2. 3-chymotrypsin-like protease (3CL pro) involved in the polyprotein cleavage process is believed to be the key target for viral replication, and hence is an attractive target for the discovery of antiviral molecules. In the present study, we aimed to identify…
ORF8 protein of SARS-CoV-2 reduces male fertility in mice - As one of the most rapidly evolving proteins of the genus Betacoronavirus, ORF8’s function and potential pathological consequence in vivo are still obscure. In this study, we show that the secretion of ORF8 is dependent on its N-terminal signal peptide sequence and can be inhibited by ROS scavenger and ER-Golgi transportation inhibitor in cultured cells. To trace the effect of its possible in vivo secretion，we examined the plasma samples of COVID-19 convalescent patients and found that the…
Recommendations for the management of drug-drug interactions between the COVID-19 antiviral nirmatrelvir/ritonavir (Paxlovid® ) and comedications - The Covid-19 antiviral nirmatrelvir/ritonavir (NMV/r) (Paxlovid^(®) ) has been granted authorization or approval in several countries for the treatment of patients with mild to moderate COVID-19 at high risk of progression to severe disease and with no requirement for supplemental oxygen. NMV/r will be primarily administered outside the hospital setting as a 5-day course oral treatment. The ritonavir component boosts plasma concentrations of nirmatrelvir through the potent and rapid inhibition…
Molecular Interactions and Inhibition of the SARS-CoV-2 Main Protease by a Thiadiazolidinone Derivative - We report molecular interactions and inhibition of the main protease (M^(Pro) ) of SARS-CoV-2, a key enzyme involved in the viral life cycle. By using a thiadiazolidinone (TDZD) derivative as a chemical probe, we explore conformational dynamics of M^(Pro) via docking protocols and molecular dynamics (MD) simulations in all-atom detail. We reveal local and global dynamics of M^(Pro) in the presence of this inhibitor and confirm the inhibition of the enzyme with an IC(50) value of 1.39 ± 0.22 μM,…
Conducting the RBD of SARS-CoV-2 Omicron Variant with Phytoconstituents from Euphorbia dendroides to Repudiate the Binding of Spike Glycoprotein Using Computational Molecular Search and Simulation Approach - (1) Background: Natural constituents are still a preferred route for counteracting the outbreak of COVID-19. Essentially, flavonoids have been found to be among the most promising molecules identified as coronavirus inhibitors. Recently, a new SARS-CoV-2 B.1.1.529 variant has spread in many countries, which has raised awareness of the role of natural constituents in attempts to contribute to therapeutic protocols. (2) Methods: Using various chromatographic techniques, triterpenes (1-7),…
Flavonoids as Potential Anti-Inflammatory Molecules: A Review - Hydroxylated polyphenols, also called flavonoids, are richly present in vegetables, fruits, cereals, nuts, herbs, seeds, stems, and flowers of numerous plants. They possess numerous medicinal properties such as antioxidant, anti-cancer, anti-microbial, neuroprotective, and anti-inflammation. Studies show that flavonoids activate antioxidant pathways that render an anti-inflammatory effect. They inhibit the secretions of enzymes such as lysozymes and β-glucuronidase and inhibit the secretion of…
Antiinflammation Derived Suzuki-Coupled Fenbufens as COX-2 Inhibitors: Minilibrary Construction and Bioassay - A small fenbufen library comprising 18 compounds was prepared via Suzuki Miyara coupling. The five-step preparations deliver 9-17% biphenyl compounds in total yield. These fenbufen analogs exert insignificant activity against the IL-1 release as well as inhibiting cyclooxygenase 2 considerably. Both the para-amino and para-hydroxy mono substituents display the most substantial COX-2 inhibition, particularly the latter one showing a comparable activity as celecoxib. The most COX-2 selective and…
Semi-Synthesis of N-Aryl Amide Analogs of Piperine from Piper nigrum and Evaluation of Their Antitrypanosomal, Antimalarial, and Anti-SARS-CoV-2 Main Protease Activities - Piper nigrum, or black pepper, produces piperine, an alkaloid that has diverse pharmacological activities. In this study, N-aryl amide piperine analogs were prepared by semi-synthesis involving the saponification of piperine (1) to yield piperic acid (2) followed by esterification to obtain compounds 3, 4, and 5. The compounds were examined for their antitrypanosomal, antimalarial, and anti-SARS-CoV-2 main protease activities. The new 2,5-dimethoxy-substituted phenyl piperamide 5 exhibited the…
Novel Inhibitors of 2’-O-Methyltransferase of the SARS-CoV-2 Coronavirus - The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2’-O-methyltransferase (nsp16) enzyme that is crucial for effective translation of viral RNA and virus replication. For methylation of substrates, nsp16 utilizes S-adenosyl methionine (SAM). Binding of a small molecule in the protein site where SAM…