The SARS-CoV-2 Omicron variant has challenged the control of the COVID-19 49 pandemic even in highly vaccinated countries. While a second booster of mRNA 50 vaccines improved the immunity against SARS-CoV-2, the humoral and cellular 51 responses induced by a second booster of an inactivated SARS-CoV-2 vaccine have 52 not been studied. In the context of a phase 3 clinical study, we report that a second booster of CoronaVac 53 increased the neutralizing response against the ancestral 54 virus yet showed poor neutralization against the Omicron variant. Additionally, isolated PBMCs displayed equivalent activation of specific CD4+ 55 T cells and IFN-γ 56 production when stimulated with a mega-pool of peptides derived from the spike 57 protein of the ancestral virus or the Omicron variant. In conclusion, a second booster dose of CoronaVac 58 does not improve the neutralizing response against the 59 Omicron variant compared with the first booster dose, yet it helps maintaining a robust spike-specific CD4+ 60 T cell response.
Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms. Using measurements of ~4000 plasma proteins in two cohorts of patients hospitalized with COVID-19, we discovered and validated markers of COVID-associated AKI (stage 2 or 3) and long-term kidney dysfunction. In the discovery cohort (N= 437), we identified 413 higher plasma abundances of protein targets and 40 lower plasma abundances of protein targets associated with COVID-AKI (adjusted p <0.05). Of these, 62 proteins were validated in an external cohort (p <0.05, N =261). We demonstrate that COVID-AKI is associated with increased markers of tubular injury (NGAL) and myocardial injury. Using estimated glomerular filtration (eGFR) measurements taken after discharge, we also find that 25 of the 62 AKI-associated proteins are significantly associated with decreased post-discharge eGFR (adjusted p <0.05). Proteins most strongly associated with decreased post-discharge eGFR included desmocollin-2, trefoil factor 3, transmembrane emp24 domain-containing protein 10, and cystatin-C indicating tubular dysfunction and injury. Using clinical and proteomic data, our results suggest that while both acute and long-term COVID-associated kidney dysfunction are associated with markers of tubular dysfunction, AKI is driven by a largely multifactorial process involving hemodynamic instability and myocardial damage.
Background: The COVID-19 pandemic has had a devastating impact on the world over the past two years (2020-2021). One of the key questions about its future trajectory is the protection from subsequent infections and disease conferred by a previous infection, as the SARS-CoV-2 virus belongs to the coronaviruses, a group of viruses the members of which are known for their ability to reinfect convalescent individuals. Bulgaria, with high rates of previous infections combined with low vaccination rates and an elderly population, presents a somewhat unique context to study this question. Methods: We use detailed governmental data on registered COVID-19 cases to evaluate the incidence and outcomes of COVID-19 reinfections in Bulgaria in the period between March 2020 and early December 2021. Results: For the period analyzed, a total of 4,106 cases of individuals infected more than once were observed, including 31 cases of three infections and one of four infections. The number of reinfections increased dramatically during the Delta variant-driven wave of the pandemic towards the end of 2021. We observe a moderate reduction of severe outcomes (hospitalization and death) in reinfections relative to primary infections, and a more substantial reduction of severe outcomes in breakthrough infections in vaccinated individuals. Conclusions: In the available datasets from Bulgaria, prior infection appears to provide some protection from severe outcomes, but to a lower degree than the reduction in severity of breakthrough infections in the vaccinated compared to primary infections in the unvaccinated.
Background The COVID-19 pandemic has brought unparalleled challenges for health systems worldwide, the impact of which has also been borne by the Healthcare Professionals (HCPs). Numerous studies have revealed the positive effects of Pranayama and Meditation on mental health. The effect of Pranayama in improving mental health of frontline HCP exposed to Covid-19 patients has not been studied. Aim & Objective: This quasi-randomized clinical trial was done to study the effect of especially designed Pranayama protocol on perceived stress, wellbeing and quality of life of frontline health care professionals who were exposed to COVID-19 patients in hospital settings. Methodology This study was done with 280 frontline healthcare professionals (HCP) assigned duties with COVID-19 patients during September-November, 2020 in 5 government hospitals and COVID-19 quarantine/isolation centres in New Delhi, India. The HCPs were first assessed for COVID-19 infection in the past using antibody test, and only those found negative were recruited. The enrolled respondents were randomly assigned to two arms an intervention arm where there were to practice 28 day Pranayama module (morning and evening sessions) under supervision of a trainer and a Control arm where the HCPs continued routine physical activity (walking jogging etc). Baseline and end-line (total: 250 HCPs) Psychological parameters of Perceived Stress, Well Being and Quality of Life were collected through self-reported questionnaires. Results The intervention (HCPs 123) and control (HCPs 127) groups (Total 250) were comparable in their demographic profile and baseline characteristics. Intervention with Pranayama module led to a significant reduction (Mean diff -2.46 P-value 0.028) in perceived stress score in the intervention group compared to the control group. The wellbeing index in Interventional group intervention showed a non-significant increase. The WHO Quality-of-life score increased in the intervention group as compared to the controls (mean difference 2.78, p-value: 0.17). Of its four components, the one for Psychological domain increased significantly (mean diff: 1.52, P-value: 0.019), while those for Physical domain and Environmental domains increased (mean diff: 0.64, P-value: 0.29 and mean diff: 0.68, p-value: 0.48) though not statistical significantly. Conclusion: The intervention of twice daily practice of the Pranayama module for 28 days in frontline HCPs performing COVID-19 duties had a noteworthy effect in lowering Perceived Stress, improving perceived Quality of life, especially its Psychological domains as measured through standardized questionnaires.
Background: There are few trials comparing homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. Methods: We conducted an open-label randomized trial in adults >=18 years of age who received two doses of inactivated vaccine (CoronaVac) or mRNA vaccine (BNT162b2) >=6 months earlier, randomised in 1:1 ratio to receive a third dose of either vaccine. We compared the reactogenicity, immunogenicity and cell-mediated immune responses, and assessed vaccine efficacy against infections during follow-up. Results: We enrolled 219 adults who previously received two doses of CoronaVac and randomised to CoronaVac (“CC-C”, n=101) or BNT162b2 (“CC-B”, n=118) third dose; and 232 adults who previously received BNT162b2 and randomised to CoronaVac (“BB-C”, n=118) or BNT162b2 (“BB-B”, n=114). There were more frequent reports of mild reactions in recipients of third-dose BNT162b2, which generally subsided within 7 days. Antibody responses against the ancestral virus, Omicron BA.1 and BA.2 subvariant by surrogate neutralization and PRNT50 were stronger for the recipients of a third dose of BNT162b2 over CoronaVac irrespective of prior vaccine type. CD4+ T cells boost only occurred in CoronaVac-primed arms. We did not identify differences in CD4+ and CD8+ T cell responses between arms. When Omicron BA.2 was circulating, we identified 58 infections with cumulative incidence of 15.3% and 15.4% in the CC-C and CC-B (p=0.93), and 16.7% and 14.0% in the BB-C and BB-B arms, respectively (p=0.56). Conclusions: Similar levels of incidence of infection in each arm suggest all third dose combinations may provide similar degrees of protection against prevalent Omicron BA.2 infection, despite very weak antibody responses to BA.2 in the recipients of a CoronaVac third dose. Further research is warranted to identify appropriate correlates of protection for inactivated COVID-19 vaccines.
Introduction Health system resilience is the ability to prepare, manage, and learn from a sudden and unpredictable extreme change which impacts health systems. Health systems globally have recently been affected by a number of catastrophic events, including natural disasters, and infectious disease epidemics. Understanding health system resilience has never been more essential until emerging global pandemics. Therefore, the application of resilience-enhancing strategies with existing frameworks needs to be assessed to identify the management gaps and give valuable recommendations from the lessons learnt from the global pandemic. Methodology The systematic review will be reported using the Preferred reporting items for systematic review and meta-analysis protocols guideline (PRISMA-P). Reporting data on health system building blocks and systematic searches on resilience enhancing strategies for the management of Public Health Emergencies of International Concerns (PHEIC) after the establishment of International Health Regulations (IHR) since managing PHEIC after the establishment of IHR in 2007 will be included. The search will be conducted in PubMed, Scopus, Web of Science, Google Scholar, and grey literature. Discussion Health system resilience is key to coping with catastrophic events, such as the economic crisis and COVID-19 pandemic. The mapping of available literature towards the application of resilience-enhancing strategies with existing frameworks needs to be assessed to identify the management gaps and give valuable recommendations from the lessons learnt from the global pandemic to improve the level of preparedness and response to similar public health emergencies in the future. Conclusion A protocol for a global review of health system resilience for pandemic management is described. This review will add to the body of knowledge about health systems enhancing research and policy formulation.
A Clinical Study to Evaluate the Efficacy and Safety of SIM0417 Orally Co-Administered With Ritonavir in Symptomatic Adult Participants With Mild to Moderate COVID-19 - Condition: COVID-19
Interventions: Drug: SIM0417; Drug: Placebo
Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Not yet recruiting
Self-management of Post COVID-19 Syndrome Using Wearable Biometric Technology - Condition: COVID-19
Intervention: Other: Self-management of post COVID-19 respiratory outcomes
Sponsor: University of Manitoba
Not yet recruiting
Clinical Study to Compare Efficacy and Safety of Casirivimab and Imdevimab Combination, Remdesivir and Favipravir in Hospitalized COVID-19 Patients - Condition: COVID-19
Interventions: Drug: Casirivimab and Imdevimab Drug Combination; Drug: Remdesivir; Drug: Favipiravir
Sponsor: Mansoura University Hospital
Completed
The Role of BCG Vaccine in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 Vaccines - Condition: COVID-19
Interventions: Biological: BCG (Bacillus Calmette-Guérin) vaccine; Other: Placebo
Sponsors: Oswaldo Cruz Foundation; University of Sao Paulo; Federal University of Juiz de Fora
Recruiting
Performance Evaluation of LumiraDx COVID-19 (SARS-CoV-2) Ag ULTRA Test (ASPIRE-2) - Condition: COVID-19
Interventions: Diagnostic Test: Nasal Swab; Diagnostic Test: Nasopharyngeal swab
Sponsor: LumiraDx UK Limited
Recruiting
Phase 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults. - Condition: COVID-19
Intervention: Drug: Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine, SARS-CoV-2 rS (CovovaxTM), BNT162b2 (Pfizer)
Sponsors: The Aurum Institute NPC; Coalition for Epidemic Preparedness Innovations
Recruiting
The Effects of a Sublingual Sprayable Microemulsion of Vitamin D on Inflammatory Markers in COVID-19 Patients - Conditions: COVID-19; Vitamin D Deficiency
Intervention: Dietary Supplement: Vitamin D 25 (OH) 12000 IU in the form of a sublingual sprayable microemulsion
Sponsor: Pauls Stradins Clinical University Hospital
Completed
UNAIR Inactivated COVID-19 Vaccine Phase III (Immunobridging Study) - Conditions: COVID-19 Pandemic; COVID-19 Vaccines
Interventions: Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg; Biological: CoronaVac Biofarma COVID-19 Vaccine
Sponsors: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia
Recruiting
Hydrogen-Oxygen Generator With Nebulizer for Rehabilitation Treatment of COVID-19 - Conditions: COVID-19; AMS-H-03; Hydrogen-oxygen Gas
Interventions: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Other: basic treatment
Sponsor: Shanghai Zhongshan Hospital
Recruiting
COVID Protection After Transplant - Sanofi GSK (CPAT-SG) Study - Conditions: COVID-19; Kidney Transplant
Intervention: Biological: Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine
Sponsors: National Institute of Allergy and Infectious Diseases (NIAID); PPD; Johns Hopkins University; Sanofi Pasteur, a Sanofi Company
Not yet recruiting
Canadian Adaptive Platform Trial for Long COVID - Condition: Long COVID, Post COVID Condition, Post Acute Sequelae of COVID-19
Interventions: Drug: Ibudilast; Dietary Supplement: Whey Protein Isolate; Drug: Pentoxifylline; Other: Placebo
Sponsor: University Health Network, Toronto
Not yet recruiting
Clinical Trial of Jinzhen Oral Liquid in Treating Children With COVID-19 Infection - Conditions: COVID-19; Child, Only
Intervention: Drug: Jinzhen oral liquid or Jinhuaqinggan granules
Sponsor: The Affiliated Hospital of Qingdao University
Recruiting
Smartphone Intervention for Overdose and COVID-19 - Conditions: Substance Use Disorders; Overdose; COVID-19
Intervention: Device: iThrive WI Intervention
Sponsors: University of Wisconsin, Madison; National Institute on Drug Abuse (NIDA)
Not yet recruiting
Phase 2 Study of the Safety and Immunogenicity of COVID-19 and Influenza Combination Vaccine - Conditions: COVID-19; Influenza
Interventions: Drug: CIC Vaccine; Drug: qNIV Vaccine; Drug: SARS-CoV-2 rS Vaccine; Drug: Influenza Vaccine
Sponsor: Novavax
Not yet recruiting
Study to Assess Efficacy and Safety of Treamid for Patients With Reduced Exercise Tolerance After COVID-19 - Conditions: SARS-CoV-2 Infection; Lung Fibrosis
Interventions: Drug: Treamid; Drug: Treamid twice a day; Drug: Treamid once a day; Drug: Placebo
Sponsor: PHARMENTERPRISES LLC
Not yet recruiting
Nonstructural Protein 1 of Variant PEDV Plays a Key Role in Escaping Replication Restriction by Complement C3 - Zoonotic coronaviruses represent an ongoing threat to public health. The classical porcine epidemic diarrhea virus (PEDV) first appeared in the early 1970s. Since 2010, outbreaks of highly virulent PEDV variants have caused great economic losses to the swine industry worldwide. However, the strategies by which PEDV variants escape host immune responses are not fully understood. Complement component 3 (C3) is considered a central component of the three complement activation pathways and plays a…
Anti-viral organic coatings for high touch surfaces based on smart-release, Cu2+ containing pigments - Viruses such as SARS-CoV-2 can remain viable on solid surfaces for up to one week, hence fomites are a potential route of exposure to infectious virus. Copper has well documented antiviral properties that could limit this problem, however practical deployment of copper surfaces has been limited due to the associated costs and the incompatibility of copper metal in specific environments and conditions. We therefore developed an organic coating containing an intelligent-release Cu^(2+) pigment…
The motivations and their conditions which drive students to seek higher education in a foreign country - This article summarizes a vast literature tracing the plethora of motivations of international students to study abroad. We detail the push factors (i.e., personal goals) and pull factors (i.e., attracting elements) for this decision to pursue higher education overseas. To elaborate, the push factors are around the attainment and/or increase of three main capitals: human, financial and psychological. Pull factors are around the attracting capacity of three main entities: the destination country,…
Exploring the mechanism of action of Xuanfei Baidu granule (XFBD) in the treatment of COVID-19 based on molecular docking and molecular dynamics - CONCLUSION: For the first time, it was found that the important active chemical components in XFBD, such as I-SPD, Pachypodol and Vestitol, reduce inflammatory response and apoptosis by inhibiting the activation of NLRP3, and reduce the production of inflammatory factors and chemotaxis of inflammatory cells by inhibiting the activation of CSF2. Therefore, XFBD can effectively alleviate the clinical symptoms of COVID-19 through NLRP3 and CSF2.
Complanatuside alleviates inflammatory cell damage induced by pro-inflammatory cytokines in skin keratinocytes - Cytokine-mediated inflammatory response is considered a cause of skin lesion in COVID-19 patients. Complanatuside is a flavonol glycoside isolated from Astragalus complanatus. Flavonoids from Astragalus complanatus were reported to have anti-inflammatory and anticancer activities but the potential protective effect of complanatuside on cytokine-induced inflammatory damage in skin keratinocytes is not known. The aim of this study is to explore the inhibitory effect of complanatuside on…
Probiotic-Based Bacteriocin: Immunity Supplementation Against Viruses. An Updated Review - Viral infections are a major cause of severe, fatal diseases worldwide. Recently, these infections have increased due to demanding contextual circumstances, such as environmental changes, increased migration of people and product distribution, rapid demographic changes, and outbreaks of novel viruses, including the COVID-19 outbreak. Internal variables that influence viral immunity have received attention along with these external causes to avert such novel viral outbreaks. The gastrointestinal…
Synthesis, characterization, DFT, antioxidant, antibacterial, pharmacokinetics and inhibition of SARS-CoV-2 main protease of some heterocyclic hydrazones - Three hydrazone derivatives have been synthesized using condensation reaction of 4-hydrazinylbenzoic acid with three aromatic aldehydes namely: thiophene-2-carbaldehyde, thiophene-3-carbaldehyde and 2-furaldehyde in ethanol at 78 °C reflux. The synthesized molecules have been characterized using spectroscopic and physicochemical methods including UV-Vis, IR, ¹H NMR, ^(13)C NMR, ^(15)N NMR and melting point determination. Optimized molecular structures, UV-Vis and IR spectra modeling, the…
Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion - Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure…
Self-assembling short immunostimulatory duplex RNAs with broad spectrum antiviral activity - The current COVID-19 pandemic highlights the need for broad-spectrum antiviral therapeutics. Here we describe a new class of self-assembling immunostimulatory short duplex RNAs that potently induce production of type I and type III interferon (IFN-I and IFN-III). These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique sequence motif (sense strand: 5’-C, antisense strand: 3’-GGG) that mediates…
Immunogenicity and immune-persistence of the CoronaVac or Covilo inactivated COVID-19 Vaccine: a 6-month population-based cohort study - CONCLUSION: Antibodies that were elicited by these two inactivated COVID-19 vaccines appeared to wane following their peak after the second vaccine dose, but they persisted at detectable levels through 6 months after the second vaccine dose, and the effectiveness of these antibodies against the Delta variant of SARS-CoV-2 was lower than their effectiveness against wildtype SARS-CoV-2, which suggests that attention must be paid to the protective effectiveness, and its persistence, of COVID-19…
Circulating microRNA signatures associated with disease severity and outcome in COVID-19 patients - CONCLUSIONS: We discovered circulating miRNAs associated with COVID-19 severity and mortality. The identified DE miRNAs provided clues on COVID-19 pathogenesis, highlighting signatures of impaired interferon and antiviral responses, inflammation, organ damage and cardiovascular failure as associated with severe disease and death.
Papain-like protease of SARS-CoV-2 inhibits RLR signaling in a deubiquitination-dependent and deubiquitination-independent manner - The newly emerged severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) can result in dysregulated interferon (IFN) responses that contribute to disease severity. The papain-like protease of SARS-CoV-2 (SCoV2-PLpro) has been previously reported to attenuate IFN responses, but the underlying mechanism is not fully understood. In this study, we found that SCoV2-PLpro potently suppressed IFN production and signaling induced by Sendai virus as well as RIG-I-like receptor (RLR)…
Ginsenoside Rg5 allosterically interacts with P2RY12 and ameliorates deep venous thrombosis by counteracting neutrophil NETosis and inflammatory response - CONCLUSIONS: Rg5 could attenuate experimental DVT by counteracting NETosis and inflammatory response in neutrophils via P2RY(12), which may pave the road for its clinical application in the prevention of DVT-related disorders.
Natural inhibitors of SARS-CoV-2 main protease: structure based pharmacophore modeling, molecular docking and molecular dynamic simulation studies - Main protease (M^(pro)) plays a key role in replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was designed for finding natural inhibitors of SARS-CoV-2 M^(pro) by in silico methods. To this end, the co-crystal structure of M^(pro) with telaprevir was explored and receptor-ligand pharmacophore models were developed and validated using pharmit. The database of “ZINC Natural Products” was screened, and 288 compounds were filtered according to pharmacophore…
Inhibition of MEK signaling prevents SARS-CoV2-induced lung damage and improves survival of infected mice - Coronavirus disease 2019 (COVID-19) is the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over 500 million confirmed cases of COVID-19 have been recorded, with 6 million deaths. Thus, reducing the COVID-19-related medical burden is an unmet need. Despite a vaccine that is successful in preventing COVID-19-caused death, effective medication to relieve COVID-19-associated symptoms and alleviate disease progression is still in high demand. In particular, one in…