Background: Different SARS-CoV-2 variants can differentially affect the prevalence of Post Covid-19 Condition (PCC). This prospective study assesses prevalence and severity of symptoms three months after an Omicron infection, compared to Delta, test-negative and population controls. This study also assesses symptomology after reinfection and breakthrough infections . Methods: After a positive SARS-CoV-2 test, cases were classified as Omicron or Delta based on ≥ 85% surveillance prevalence. Population controls were representatively invited and symptomatic test-negative controls enrolled after a negative SARS-CoV-2 test. Three months after enrolment, participants indicated point prevalence for 41 symptoms and severity of four symptoms. Permutation tests identified significantly elevated symptoms in cases compared to controls. PCC prevalence was estimated as the difference in prevalence of at least one elevated symptom in cases compared to population controls. Findings: At three months follow-up, five symptoms and severe dyspnea were significantly elevated in Omicron cases (n = 4138) compared to test-negative (n= 1672) and population controls (n= 2762). PCC prevalence was 10.4% for Omicron cases and 17.7% for Delta cases (n = 6855). Prevalence of severe fatigue and dyspnea were higher in reinfected compared to primary infected Omicron cases, while severity of symptoms did not significantly differ between Omicron cases with a booster or primary vaccination course. Interpretation: Three months after Omicron, prevalence of PCC is 41% lower than after Delta. Reinfection seems associated with more prevalent severe long-term symptoms compared to a first infection. A booster prior to infection does not seem to improve the outcome of long-term symptoms. Funding: The study is executed by the National Institute for Public Health and the Environment by order of the Ministry of Health, Welfare and Sport.
Strategies to improve the immunogenicity of COVID-19 vaccines are necessary to optimise their protection against disease. Fractional dosing by intradermal administration (ID) has been shown to be equally immunogenic as intramuscular (IM) for several vaccines, but the immunogenicity of ID inactivated whole-virus SARS-CoV-2 at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T cell responses of full-dose CoronaVac by ID over IM in adolescents. Participants aged 11-17 years received 2 doses IM or ID, followed by the 3rd dose 13-42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively. S IgG, S-RBD IgG, S IgG FcγRIIIa-binding, SNM-specific IL-2+CD4+, SNM-specific IL-2+CD8+, S-specific IL-2+CD8+, N-specific IL-2+CD4+, N-specific IL-2+CD8+ and M-specific IL-2+CD4+ responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test (sVNT), 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2+CD4+, interferon-γ+CD8+ and IL-2+CD8+ responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. More in the ID groups reported local, mild adverse reactions. This is the first study to demonstrate superior antibody and M-specific T cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve immunogenicity of inactivated vaccines.
Antibodies can have beneficial, neutral, or harmful effects so resolving an antibody repertoire to its target epitopes may explain heterogeneity in susceptibility to infectious disease. However, the three-dimensional nature of antibody-epitope interactions limits discovery of important targets. We describe and experimentally validated a novel computational method and synthetic biology pipeline for identifying epitopes that are structurally stable and functionally important and apply it to the SARS-CoV-2 proteome. We show patterns of epitope-binding antibodies associated with immunopathology, including a non-isotype switching IgM response to a Membrane protein epitope which is amongst the strongest immunological features associated with severe COVID-19 to date (adjusted OR 72.14, 95% CI: 9.71 - 1300.15). Consistent with a hypothesis that the mechanism driving the non-switching response was T independent B cell activation, we find that B cells secrete IgM and proliferate on exposure to virus-like particles lacking Spike. We also identified persistence (> 1 year) of this response in individuals with longCOVID particularly affected by fatigue and depression. These findings point to a previously unrecognized coronavirus host-pathogen interaction. We demonstrate that the Membrane epitope is a promising vaccine and monoclonal antibody target, which may complement spike-directed vaccination broadening immunological protection.
The SARS-CoV-2 pandemic has highlighted the need for devices capable of carrying out rapid differential detection of viruses that may manifest similar physiological symptoms yet demand tailored treatment plans. Seasonal influenza may be exacerbated by COVID-19 infections, increasing the burden on healthcare systems. In this work, we demonstrate a technology, based on liquid-gated graphene field-effect transistors, for rapid and ultraprecise detection and differentiation of influenza and SARS-CoV-2 surface protein. Most distinctively, our device consists of 4 onboard graphene field-effect electrolyte-gated transistors arranged in a quadruple architecture, where each quarter is functionalized individually (with either antibodies or chemically passivated control) but measured collectively. Our sensor platform was tested against a range of concentrations of viral surface proteins from both viruses with the lowest tested and detected concentration at ~50 ag/mL, or 88 zM for COVID-19 and 227 zM for Flu, which is 5-fold lower than the values reported previously on a similar platform. Unlike the classic Real-Time Polymerase Chain Reaction (RT-PCR) test, which has a turnaround time of a few hours, our technology presents an ultrafast response time of ~10 seconds even in complex media such as saliva. Thus, we have developed a multi-analyte, highly sensitive, and fault-tolerant technology for rapid diagnostic of contemporary, emerging, and future pandemics.
We measured brain injury markers, inflammatory mediators, and autoantibodies in 203 participants with COVID-19; 111 provided acute sera (1-11 days post admission) and 56 with COVID-19-associated neurological diagnoses provided subacute/convalescent sera (6-76 weeks post-admission). Compared to 60 controls, brain injury biomarkers (Tau, GFAP, NfL, UCH-L1) were increased in acute sera, significantly more so for NfL and UCH-L1, in patients with altered consciousness. Tau and NfL remained elevated in convalescent sera, particularly following cerebrovascular and neuroinflammatory disorders. Acutely, inflammatory mediators (including IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) were higher in participants with altered consciousness, and correlated with brain injury biomarker levels. Inflammatory mediators were lower than acute levels in convalescent sera, but levels of CCL2, CCL7, IL-1RA, IL-2Rα, M-CSF, SCF, IL-16 and IL-18 in individual participants correlated with Tau levels even at this late time point. When compared to acute COVID-19 patients with a normal GCS, network analysis showed significantly altered immune responses in patients with acute alteration of consciousness, and in convalescent patients who had suffered an acute neurological complication. The frequency and range of autoantibodies did not associate with neurological disorders. However, autoantibodies against specific antigens were more frequent in patients with altered consciousness in the acute phase (including MYL7, UCH-L1, GRIN3B, and DDR2), and in patients with neurological complications in the convalescent phase (including MYL7, GNRHR, and HLA antigens). In a novel low-inoculum mouse model of SARS-CoV-2, while viral replication was only consistently seen in mouse lungs, inflammatory responses were seen in both brain and lungs, with significant increases in CCL4, IFNγ, IL-17A, and microglial reactivity in the brain. Neurological injury is common in the acute phase and persists late after COVID-19, and may be driven by a para-infectious process involving a dysregulated host response.
Investigating the role of host genetic factors in COVID-19 severity and susceptibility can inform our understanding of the underlying biological mechanisms that influence adverse outcomes and drug development. Here we present a second updated genome-wide association study (GWAS) on COVID-19 severity and infection susceptibility to SARS-CoV-2 from the COVID-19 Host Genetic Initiative (data release 7). We performed a meta-analysis of up to 219,692 cases and over 3 million controls, identifying 51 distinct genome-wide significant loci—adding 28 loci from the previous data release. The increased number of candidate genes at the identified loci helped to map three major biological pathways involved in susceptibility and severity: viral entry, airway defense in mucus, and type I interferon.
Reports suggest that the potential long-lasting health consequences of SARS-CoV-2 infection may involve persistent dysregulation of some immune populations, but the potential clinical implications are unknown. In a nationwide cohort of 2,430,694 50+-year-olds, we compared the rates of non-Covid-19 infectious disease inpatient hospitalizations (of ≥5 hours) following the acute phase of SARS-CoV-2 infection in 930,071 individuals with rates among SARS-CoV-2 uninfected from 1 January 2021 to 10 December 2022. The post-acute phase of SARS-CoV-2 infection was associated with an incidence rate ratio of 0.90 (95% confidence interval 0.88-0.92) for any infectious disease hospitalization. Findings were similar for upper- (1.08, 0.97-1.20), lower respiratory tract (0.90, 0.87-0.93), influenza (1.04, 0.94-1.15), gastrointestinal (1.28, 0.78-2.09), skin (0.98, 0.93-1.03), urinary tract (1.01, 0.96-1.08), certain invasive bacterial (0.96, 0.91-0.1.01), and other (0.96, 0.92-1.00) infectious disease hospitalizations and in subgroups. Our study does not support an increased susceptibility to non-Covid-19 infectious disease hospitalization following SARS-CoV-2 infection.
Objective: To measure the burden of the COVID-19 pandemic in 2020 at the subnational level by estimating excess mortality, defined as the increase in all-cause mortality relative to an expected baseline mortality level. Design: Statistical and demographic analyses of regional all-cause mortality data. Setting: The vital statistics systems of 21 European countries. Participants: The entire population of 561 spatial units in 21 European countries. Main Outcome Measures: Losses of life expectancy at ages 0 and 60 for males and females. Results: Evidence was found of a loss in life expectancy in 391 regions, while only three regions exhibit notable gains in life expectancy in 2020. For 12 regions, losses of life expectancy amounted to more than 2 years, and three regions showed losses greater than 3 years. Geographic clusters of high mortality were found in Northern Italia, Spain and Poland, while clusters of low mortality were found in Western France, Germany/Denmark and Norway/Sweden. Conclusions: Regional differences of loss of life expectancy are impressive, ranging from a loss of more than 4 years to a gain of 8 months. These findings provide a strong rationale for regional analysis, as national estimates hide significant regional disparities.
Evaluation of Safety & Efficacy of MIR 19 ® Inhalation Solution in Patients With Mild COVID-19 - Condition: COVID-19
Interventions: Drug: MIR 19 ®; Combination Product: Standard therapy
Sponsor: National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia
Completed
LACTYFERRIN™ Forte and ZINC Defense™ and Standard of Care (SOC) vs SOC in the Treatment of Non-hospitalized Patients With COVID-19 - Condition: COVID-19
Interventions: Drug: Sesderma LACTYFERRIN™ Forte and Sesderma ZINC Defense™; Drug: Placebo
Sponsors: Jose David Suarez, MD; Sesderma S.L.; Westchester General Hospital Inc. DBA Keralty Hospital Miami; MGM Technology Corp
Not yet recruiting
A Nasal Treatment for COVID-19 - Condition: COVID-19
Interventions: Drug: Optate; Drug: Placebo
Sponsor: Indiana University
Not yet recruiting
Effect of a Health Pathway for People With Persistent Symptoms Covid-19 - Condition: COVID-19
Interventions: Other: usual care and follow-up by a nurse; Other: Personalized Multifactorial Intervention (IMP)
Sponsor: Centre Hospitalier Universitaire de Saint Etienne
Not yet recruiting
RCT for Yinqiaosan-Maxingganshitang in the Treatment of COVID-19 - Condition: COVID-19
Interventions: Drug: Chinese Herb; Diagnostic Test: Placebo
Sponsor: Chinese University of Hong Kong
Not yet recruiting
A Study to Understand the Effect and Safety of the Study Medicine PF-07817883 in Adults Who Have Symptoms of COVID-19 But Are Not Hospitalized. - Condition: SARS-CoV-2 Infection
Interventions: Drug: PF-07817883; Drug: Placebo
Sponsor: Pfizer
Not yet recruiting
Traditional Chinese Medicine or Low-dose Dexamethasone in COVID-19 Pneumonia - Condition: COVID-19 Pneumonia
Interventions: Other: conventional western medicine treatment; Drug: Dexamethasone oral tablet; Other: Traditional Chinese medicine decoction
Sponsor: China-Japan Friendship Hospital
Recruiting
A Clinical Study on Safety and Effectiveness of Mesenchymal Stem Cell Exosomes for the Treatment of COVID-19. - Condition: COVID-19 Pneumonia
Intervention: Biological: Extracellular Vesicles from Mesenchymal Stem Cells
Sponsor: First Affiliated Hospital of Wenzhou Medical University
Recruiting
Inpatient COVID-19 Lollipop Study - Conditions: COVID-19; Diagnostic Test
Intervention: Device: Lollipop
Sponsor: University of Wisconsin, Madison
Not yet recruiting
Study of the Safety, Tolerability and Efficacy of NP-101 in Treating High Risk Participants Who Are Covid-19 Positive. - Condition: COVID-19
Interventions: Drug: NP-101; Other: Placebo
Sponsor: Novatek Pharmaceuticals
Recruiting
Effectiveness of Testofen Compared to Placebo on Long COVID Symptoms - Condition: Long Covid19
Interventions: Drug: Testofen; Drug: Microcrystalline cellulose
Sponsor: RDC Clinical Pty Ltd
Not yet recruiting
Care for Veterans Post-COVID - Condition: Post-Acute COVID-19 Syndrome
Interventions: Behavioral: Concordant Care Training; Behavioral: Education Packet Training
Sponsor: VA Office of Research and Development
Not yet recruiting
Complementary Self-help Strategies for Patients With Post-COVID Syndrome - Condition: Post-COVID-19 Syndrome
Interventions: Behavioral: Complementary self-help strategies in addition to treatment as usual; Other: Treatment as usual
Sponsor: Universität Duisburg-Essen
Not yet recruiting
Safety & Immunogenicity of RVM-V001/RVM-V002 or RVMV001+RVMV002 (Co Administered as Separate Injections) in Healthy Individuals - Conditions: Infectious Disease; COVID-19
Interventions: Biological: RVM-V001 30 µg; Biological: RVM-V002 30 µg; Biological: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration
Sponsor: RVAC Medicines (US), Inc.
Recruiting
HH-120 Nasal Spray for Post-exposure Prevention of SARS-CoV-2 - Condition: COVID-19
Interventions: Drug: HH-120 Nasal Spray; Drug: Placebo
Sponsor: Huahui Health
Not yet recruiting
Chemical Composition of Honeysuckle (Lonicerae japonicae) Extracts and Their Potential in Inhibiting the SARS-CoV-2 Spike Protein and ACE2 Binding, Suppressing ACE2, and Scavenging Radicals - Honeysuckle (Lonicerae japonicae) has been used in functional tea products. The chemical compositions of the water and ethanol extracts of honeysuckle were examined in the present study, along with their potential in inhibiting SARS-CoV-2 spike protein binding to ACE2, suppressing ACE2 activity, and scavenging reactive free radicals. Thirty-six compounds were tentatively identified from the honeysuckle extracts using HPLC-MS/MS, with ten reported for the first time in honeysuckle. Both…
Surfactin-like lipopeptides from Bacillus clausii efficiently bind to spike glycoprotein of SARS-CoV-2 - The coronavirus disease 2019 (COVID-19) rapidly spread across the globe, infecting millions and causing hundreds of deaths. It has been now around three years but still, it remained a serious threat worldwide, even after the availability of some vaccines. Bio-surfactants are known to have antiviral activities and might be a potential alternative for the treatment of SARS-CoV-2 infection. In the present study, we have isolated and purified, a surfactin-like lipopeptide produced by a probiotic…
Repurposing immune boosting and anti-viral efficacy of Parkia bioactive entities as multi-target directed therapeutic approach for SARS-CoV-2: exploration of lead drugs by drug likeness, molecular docking and molecular dynamics simulation methods - The COVID-19 pandemic has caused adverse health (severe respiratory, enteric and systemic infections) and environmental impacts that have threatened public health and the economy worldwide. Drug repurposing and small molecule multi-target directed herbal medicine therapeutic approaches are the most appropriate exploration strategies for SARS-CoV-2 drug discovery. This study identified potential multi-target-directed Parkia bioactive entities against SARS-CoV-2 receptors (S-protein, ACE2,…
Attitudes and concerns regarding booster dose of COVID-19 vaccine among Egyptian patients with autoimmune and rheumatic diseases: a cross-sectional survey study - CONCLUSIONS: There is a low acceptability rate of booster dose of COVID-19 vaccine among Egyptian patients with ARD diseases. Public health workers and policymakers need to make sure that all ARD patients get clear messages about accepting the COVID-19 booster dose.
Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy? - Despite the need for novel, effective therapeutics for the COVID-19 pandemic, no curative regimen is yet available, therefore patients are forced to rely on supportive and nonspecific therapies. Some SARS-CoV-2 proteins, like the 3 C-like protease (3CLpro) or the major protease (Mpro), have been identified as promising targets for antiviral drugs. The Mpro has major a role in protein processing as well as pathogenesis of the virus, and could be a useful therapeutic target. The antiviral drug…
Efficacy of pentasodium diethylenetriamine pentaacetate in ameliorating anosmia post COVID-19 - CONCLUSION: This study confirmed the efficacy of DTPA in treating post-COVID-19 anosmia.
Propolis effects in periodontal disease seem to affect coronavirus disease: a meta-analysis - This meta-analysis aimed to investigate the effects of propolis on the severity of coronavirus disease symptoms by reducing periodontal disease. PubMed, EMBASE, SciELO, Web of Science, and SCOPUS databases were systematically searched. Studies have been conducted analyzing propolis’s effects on COVID-19 and periodontitis. The study was conducted according to the PRISMA statement and registered in PROSPERO. Risk of Bias (RoB) assessment and meta-analysis of clinical studies were performed (Review…
Reduced serological response to COVID-19 booster vaccine is associated with reduced B cell memory in patients with Inflammatory Bowel Disease; VARIATION (VAriability in Response in IBD AgainsT SARS-COV-2 ImmunisatiON) - CONCLUSIONS: Patients with IBD have an attenuated response to three doses of SARS-CoV-2 vaccine. Physicians should consider patients with higher anti-TNF drug levels and/or zinc deficiency as potentially at higher risk of attenuated response to vaccination.
Comprehensive structural analysis reveals broad-spectrum neutralizing antibodies against SARS-CoV-2 Omicron variants - The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread around the world. Mutant strains of SARS-CoV-2 are constantly emerging. At present, Omicron variants have become mainstream. In this work, we carried out a systematic and comprehensive analysis of the reported spike protein antibodies, counting the epitopes and genotypes of these antibodies. We further comprehensively analyzed the impact of Omicron mutations on antibody epitopes and classified these antibodies according to their…
Phosphatidylglycerol-specific phospholipase C from Amycolatopsis sp. NT115 strain: purification, characterization, and gene cloning - Recently, phosphatidylglycerol (PG) focused on its important role in chloroplast photosynthesis, mitochondrial function of the sperm, an inhibitory effect on SARS-CoV-2 ability to infect naïve cells and reducing lung inflammation caused by COVID-19. To develop an enzymatic PG determination method as the high-throughput analysis of PG, a PG-specific phospholipase C (PG-PLC) was found in the culture supernatant of Amycolatopsis sp. NT115. PG-PLC (54 kDa by SDS-PAGE) achieved the maximal activity…
Antiviral Activity of Cell Membrane-Bound Amphiphilic Polymers - We demonstrate that cholesterol-modified polyethylene glycol has antiviral activity, exerted by anchoring to plasma membranes and sterically inhibiting viruses from entering cells. These polymers distribute sparsely on cell membranes even at binding saturation. However, the polymers have sufficient elastic repulsion energy to repel various kinds of viruses with sizes larger than the mean distances between anchored polymers, including SARS-CoV-2 pseudoparticles. Our strategy can be applied to…
Effects of Omicron Infection and Changes in Serum Antibody Response to Wild-Type, Delta, and Omicron After a Booster Dose With BNT163b2 Vaccine in Korean Healthcare Workers - CONCLUSION: Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination. Further studies are needed to understand the characteristics of immunogenicity in these populations.
Cyanometabolites: molecules with immense antiviral potential - Cyanometabolites are active compounds derived from cyanobacteria that include small low molecular weight peptides, oligosaccharides, lectins, phenols, fatty acids, and alkaloids. Some of these compounds may pose a threat to human and environment. However, majority of them are known to have various health benefits with antiviral properties against pathogenic viruses including Human immunodeficiency virus (HIV), Ebola virus (EBOV), Herpes simplex virus (HSV), Influenza A virus (IAV) etc….
Heat shock protein 90 facilitates SARS-CoV-2 structural protein-mediated virion assembly and promotes virus-induced pyroptosis - Inhibition of heat shock protein 90 (Hsp90), a prominent molecular chaperone, effectively limits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but little is known about any interaction between Hsp90 and SARS-CoV-2 proteins. Here, we systematically analyzed the effects of the chaperone isoforms Hsp90α and Hsp90β on individual SARS-CoV-2 viral proteins. Five SARS-CoV-2 proteins, namely nucleocapsid (N), membrane (M), and accessory proteins Orf3, Orf7a, and Orf7b were…
CCL12 induces trabecular bone loss by stimulating RANKL production in BMSCs during acute lung injury - In the last three years, the capacity of health care systems and the public health policies of governments worldwide were challenged by the spread of SARS-CoV-2. Mortality due to SARS-CoV-2 mainly resulted from the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Moreover, millions of people who survived ALI/ARDS in SARS-CoV-2 infection suffer from multiple lung inflammation-induced complications that lead to disability and even death. The lung-bone axis refers…