Background There is evidence of pre-established vulnerability in individuals that increases the risk of their progression to severe disease or death, though the mechanisms that cause this are still not fully understood. Previous research has demonstrated that a urinary peptide classifier (COV50) predicts disease progression and death from SARS-CoV-2 at an early stage, indicating that the outcome prediction may be partly due to already present vulnerabilities. The aim of this study is to examine the ability of COV50 to predict future non-COVID-19-related mortality, and evaluate whether the pre-established vulnerability can be generic and explained on a molecular level by urinary peptides. Methods Urinary proteomic data from 9193 patients (1719 patients sampled at intensive care unit (ICU) admission and 7474 patients with other diseases (non-ICU)) were extracted from the Human Urinary Proteome Database. The previously developed COV50 classifier, a urinary proteomics biomarker panel consisting of 50 peptides, was applied to all datasets. The association of COV50 scoring with mortality was evaluated. Results In the ICU group, an increase in the COV50 score of one unit resulted in a 20% higher relative risk of death (adj. HR 1.2 [95% CI 1.17-1.24]). The same increase in COV50 in non-ICU patients resulted in a higher relative risk of 61% (adj. HR 1.61 [95% CI 1.47-1.76]), in line with adjusted meta-analytic HR estimate of 1.55. The most notable and significant changes associated with future fatal events were reductions of specific collagen fragments, most of collagen alpha I(I). Conclusion The COV50 classifier is predictive of death in the absence of SARS-CoV-2 infection, suggesting that it detects pre-existing vulnerability. Prediction is based mainly on collagen fragments, possibly reflecting disturbances in the integrity of the extracellular matrix. These data may serve as basis for proteomics guided intervention aiming towards manipulating/improving collagen turnover, thereby reducing the risk of death.
BACKGROUND The current understanding of the long-term effectiveness of the BNT162b2 vaccine across diverse U.S. pediatric populations is limited. Using data from the PEDSnet collaboration, we assessed the effectiveness of BNT162b2 against various strains of the SARS-CoV-2 virus. METHODS We emulated three target trials to assess the real-world effectiveness of BNT162b2: adolescents aged 12 to 20 years during the Delta variant period (Target trial 1), children aged 5 to 11 years (Target trial 2) and adolescents aged 12 to 20 years during the Omicron variant period (Target trial 3). The outcomes included documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and two cardiac-related outcomes, myocarditis and pericarditis. We implemented a novel trial emulation pipeline accounting for possible misclassification bias in vaccine documentation in EHRs. RESULTS During the Delta period, the BNT162b2 vaccine demonstrated an overall effectiveness 98.4% against documented infection among adolescents, with no significant waning after receipt of the first dose. During the Omicron period, the overall effectiveness in preventing documented infection among children was estimated to be 74.3%. Higher levels of effectiveness of 75.5% and 84.9% were observed against moderate or severe COVID-19 and ICU admission with COVID-19, respectively. In the adolescent population, the overall effectiveness in preventing documented Omicron infection was 85.5%, with effectiveness of 84.8% against moderate or severe COVID-19, and 91.5% against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined after 4 months following the first dose and then stabilized. Across all three cohorts, the risk of cardiac outcomes was approximately 65% to 85% lower in the vaccinated group than that of the unvaccinated group. CONCLUSIONS Our study suggests that BNT162b2 is effective for various COVID-19-related outcomes in children and adolescents during Delta and Omicron periods, with lower cardiac risk. Waning effectiveness indicates potential need for future revaccination.
Aim: To assess the prevalence of post COVID-19 condition (PCC) on Bonaire and develop a practical risk scoring tool for PCC screening, using easily obtainable characteristics. Methods: A retrospective cohort study of symptomatic SARS-CoV-2 cases were randomly sampled from Bonaire their case-registry and telephone interviewed between 15-November-2021 and 4-December-2021. PCC patients had a PCR-positive SARS-CoV-2 test (1-March-2020 and 1-October-2021) and self-attributed at least one symptom lasting over four weeks to their infection. Multivariate logistic regression was used to derive a risk formula to develop a practical risk scoring tool. Results: Out of 414 cases, 160 (39%) were PCC patients. Fifty-three patients were unrecovered (median illness duration 250 days (IQR 34)). Of recovered patients, 35% experienced symptoms for at least 3 months after disease onset. PCC prevalence was highest among females (38%), 40-59 year-olds (40%), morbidly obese (31%) and hospitalized patients (80%). A PCC risk scoring tool using age, sex, presence of comorbidities, and acute phase hospitalization or GP visit had an area-under-the-curve (AUC) of 0.68 (95%CI 0.63-0.74). Adding smoking, alcohol use, BMI, education level, and number of acute phase symptoms increased the AUC to 0.79 (95%CI 0.74- 0.83). Subgroup analyses of non-hospitalized patients (n=362) resulted in similar AUCs. Conclusion: Thee estimated prevalence of PCC on Bonaire was 39%. Moreover, easily obtainable patient characteristics can be used to build a risk scoring tool for PCC with acceptable discriminatory power. After external validation, this tool could aid the development of healthcare interventions in low resource settings to identify patients at risk for PCC.
Nirmatrelvir/Ritonavir (NMV/r) is used for the treatment of COVID-19 infection. However, rebound COVID-19 infections can occur after taking NMV/r. We examined neutralizing antibodies to the SARS-CoV-2 spike protein before and after infection in people who did and did not take NMV/r to determine if NMV/r impedes the humoral immune response.
During the COVID-19 pandemic, contact tracing was used to identify individuals who had been in contact with a confirmed case so that these contacted individuals could be tested and quarantined to prevent further spread of the SARS-CoV-2 virus. Many countries developed mobile apps to find these contacted individuals faster. We evaluate the epidemiological effectiveness of the Dutch app CoronaMelder, where we measure effectiveness as the reduction of the reproduction number R. To this end, we use a simulation model of SARS-CoV-2 spread and contact tracing, informed by data collected during the study period (December 2020 - March 2021) in the Netherlands. We show that the tracing app caused a clear but small reduction of the reproduction number, and the magnitude of the effect was found to be robust in sensitivity analyses. The app could have been more effective if more people had used it, and if time intervals between symptom onset and reporting of contacts would have been shorter. The model used is novel as it accounts for the clustered nature of social networks and as it accounts for cases informally alerting their contacts directly after symptom onset, without involvement of health authorities or a tracing app.
Background: SARS-CoV-2 has been well studied in resource-rich areas but many questions remain about effects of infection in African populations, particularly in vulnerable groups such as pregnant women. Methods: We describe SARS-CoV-2 immunoglobulin (Ig) G and IgM antibody responses and clinical outcomes in mother-infant dyads enrolled in malaria chemoprevention trials in Uganda. Results: From December 2020 to February 2022, among 400 unvaccinated pregnant women, serologic assessments revealed that 128 (32%) were seronegative for anti-SARS-CoV-2 IgG and IgM at enrollment and delivery, 80 (20%) were infected either prior to or early in pregnancy, and 192 (48%) were infected or re-infected with SARS-CoV-2 during pregnancy. We observed preferential binding of plasma IgG to Wuhan-Hu-1-like antigens in individuals seroconverting up to early 2021, and to Delta variant antigens in a subset of individuals in mid-2021. Breadth of IgG binding to all variants improved over time. No participants experienced severe respiratory illness during the study. SARS-CoV-2 infection in early pregnancy was associated with lower median length-for-age Z-score at age 3 months compared with no infection or late pregnancy infection (-1.54 versus -0.37 and -0.51, p=0.009). Conclusion: Pregnant Ugandan women experienced high levels of SARS-CoV-2 infection without severe respiratory illness. Variant-specific serology testing demonstrated evidence of antibody affinity maturation at the population level. Early gestational SARS-CoV-2 infection was associated with shorter stature in early infancy.
Probiotic and Colchicine in COVID-19 - Condition: COVID-19
Interventions: Drug: Colchicine 0.5 MG; Dietary Supplement: Probiotic Formula; Other: Standard protocol
Sponsor: Ain Shams University
Completed
Community-engaged Optimization of COVID-19 Rapid Evaluation And TEsting Experiences - Conditions: COVID-19; COVID-19 Pandemic
Interventions: Behavioral: COVID-19 walk-up, on-site testing strategy; Behavioral: Community Health Worker (CHW) leading testing navigation and general preventive care reminders; Behavioral: No-cost self-testing kit vending machines
Sponsors: University of California, San Diego; San Ysidro Health Center
Not yet recruiting
Influence of Manual Diaphragm Release on Pulmonary Functions in Women With COVID-19 - Condition: COVID-19 Pneumonia
Interventions: Other: manual therapy; Other: breathing exercise and prone position alone
Sponsor: Cairo University
Completed
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm F (Montelukast) - Condition: Covid19
Interventions: Other: Placebo; Drug: Montelukast
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Recruiting
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm D (Ivermectin 600) - Condition: Covid19
Interventions: Drug: Ivermectin; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
ACTIV-6: COVID-19 Study of Repurposed Medications - Arm E (Fluvoxamine 100) - Condition: Covid19
Interventions: Drug: Fluvoxamine; Other: Placebo
Sponsors: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center
Completed
Study Evaluating SHEN26 Capsule in Patients With Mild to Moderate COVID-19 - Condition: COVID-19
Interventions: Drug: SHEN26 capsule; Drug: SHEN26 placebo
Sponsor: Shenzhen Kexing Pharmaceutical Co., Ltd.
Recruiting
A Clinical Trial of Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) in Booster Vaccination - Condition: COVID-19
Interventions: Biological: Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) (WSK-V101C); Biological: Recombinant COVID-19 vaccine(Sf9 Cell) (WSK-V101)
Sponsor: WestVac Biopharma Co., Ltd.
Not yet recruiting
A Phase Ⅲ Clinical Trial of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell) in Booster Vaccination - Condition: COVID-19
Interventions: Biological: High dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell); Biological: Low dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell); Biological: control group; Biological: Placebo group
Sponsor: WestVac Biopharma Co., Ltd.
Not yet recruiting
Impact Of Sensory Re-Education Paradigm On Sensation And Quality Of Life In Patients Post-Covid 19 Polyneuropathy - Condition: Post-COVID-19 Syndrome
Interventions: Other: sensory re-education training; Other: traditional treatment
Sponsor: Cairo University
Not yet recruiting
A Study to Investigate the Safety, Immunogenicity of a Bivalent mRNA Vaccine RQ3025 as a Booster Dose in Healthy Adults - Condition: COVID-19
Interventions: Biological: RQ3013; Biological: RQ3025
Sponsors: Affiliated Hospital of Yunnan University; Yunnan University; Kunming Medical University
Recruiting
A Study to Evaluate the Safety and Efficacy of COVID-19 Convalescent Plasma (CCP) Transfusion to Prevent COVID-19 in Adult Recipients Following Hematopoietic Stem Cell Transplantation - Conditions: COVID-19; Hematopoietic Stem Cell Transplantation
Intervention: Biological: COVID Convalescent Plasma
Sponsor: Institute of Hematology & Blood Diseases Hospital
Recruiting
Cupping Therapy on Immune System in Post Covid -19 - Condition: Covid-19 Patients
Interventions: Combination Product: Cupping therapy with convential medical treatment; Drug: Convential medical treatment
Sponsor: Cairo University
Completed
To Evaluate the Immunogenicity and Safety of Sequential Booster Immunization of Recombinant Novel Coronavirus Vaccine (CHO Cells) for SARS-CoV-2 - Condition: COVID-19
Intervention: Biological: Recombinant Novel Coronavirus vaccine (CHO Cells)
Sponsor: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd.
Completed
Immunogenicity and Safety Study of SARS-CoV-2 DNA Vaccine (ICCOV) - Condition: COVID-19
Intervention: Biological: SARS-CoV-2 DNA Vaccine (ICCOV)
Sponsors: Immuno Cure 3 Limited; The University of Hong Kong
Recruiting
Accelerating drug target inhibitor discovery with a deep generative foundation model - Inhibitor discovery for emerging drug-target proteins is challenging, especially when target structure or active molecules are unknown. Here, we experimentally validate the broad utility of a deep generative framework trained at-scale on protein sequences, small molecules, and their mutual interactions-unbiased toward any specific target. We performed a protein sequence-conditioned sampling on the generative foundation model to design small-molecule inhibitors for two dissimilar targets: the…
ARF6 is a host factor for SARS-CoV-2 infection in vitro - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged beta-coronavirus that enter cells via two routes, direct fusion at the plasma membrane or endocytosis followed by fusion with the late endosome/lysosome. While the viral receptor, ACE2, multiple entry factors and the mechanism of fusion of the virus at the plasma membrane have been investigated extensively, viral entry via the endocytic pathway is less understood. By using a human hepatocarcinoma cell line, Huh-7,…
Irreversible Inactivation of SARS-CoV-2 by Lectin Engagement with Two Glycan Clusters on the Spike Protein - Host cell infection by SARS-CoV-2, similar to that by HIV-1, is driven by a conformationally metastable and highly glycosylated surface entry protein complex, and infection by these viruses has been shown to be inhibited by the mannose-specific lectins cyanovirin-N (CV-N) and griffithsin (GRFT). We discovered in this study that CV-N not only inhibits SARS-CoV-2 infection but also leads to irreversibly inactivated pseudovirus particles. The irreversibility effect was revealed by the observation…
Viral evasion of the interferon response at a glance - Re-emerging and new viral pathogens have caused significant morbidity and mortality around the world, as evidenced by the recent monkeypox, Ebola and Zika virus outbreaks and the ongoing COVID-19 pandemic. Successful viral infection relies on tactical viral strategies to derail or antagonize host innate immune defenses, in particular the production of type I interferons (IFNs) by infected cells. Viruses can thwart intracellular sensing systems that elicit IFN gene expression (that is, RIG-I-like…
Preventing Occludin Tight-Junction Disruption via Inhibition of microRNA-193b-5p Attenuates Viral Load and Influenza-induced Lung Injury - Virus-induced lung injury is associated with loss of pulmonary epithelial-endothelial tight junction integrity. While the alveolar-capillary membrane may be an indirect target of injury; viruses may interact directly and/or indirectly with miRs to augment their replication potential and evade the host antiviral defense system. Here we expose how the influenza virus (H1N1) capitalizes on host-derived interferon-induced, microRNA (miR)-193b-5p to target occludin and compromise antiviral defenses….
The impact of COVID-19 on the intention of third-child in China: an empirical analysis based on survey data - BACKGROUND: Against the grim background of declining intention to have children, the ravages of COVID-19 have pushed China and the world into a more complex social environment. To adapt to the new situation, the Chinese government implemented the three-child policy in 2021.
Activity of nsp14 Exonuclease from SARS-CoV-2 towards RNAs with Modified 3’-Termini - The COVID-19 pandemic has shown the urgent need for new treatments for coronavirus infections. Nucleoside analogs were successfully used to inhibit replication of some viruses through the incorporation into the growing DNA or RNA chain. However, the replicative machinery of coronaviruses contains nsp14, a non-structural protein with a 3’→5’-exonuclease activity that removes misincorporated and modified nucleotides from the 3’ end of the growing RNA chain. Here, we studied the efficiency of…
Effective inhibition of HCoV-OC43 and SARS-CoV-2 by phytochemicals in vitro and in vivo - Several coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human coronavirus OC43 (HCoV-OC43) can cause respiratory infections in humans. To address the need for reliable anti-coronavirus therapeutics, we screened 16 active phytochemicals selected from medicinal plants used in traditional applications for respiratory-related illnesses. An initial screen was completed using HCoV-OC43. The phytochemicals lycorine (LYC), capsaicin (CAP), rottlerin (RTL),…
Generation of host-directed and virus-specific antivirals using targeted protein degradation promoted by small molecules and viral RNA mimics - Targeted protein degradation (TPD), as exemplified by proteolysis-targeting chimera (PROTAC), is an emerging drug discovery platform. PROTAC molecules, which typically contain a target protein ligand linked to an E3 ligase ligand, recruit a target protein to the E3 ligase to induce its ubiquitination and degradation. Here, we applied PROTAC approaches to develop broad-spectrum antivirals targeting key host factors for many viruses and virus-specific antivirals targeting unique viral proteins….
A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein - The ongoing COVID-19 pandemic has had great societal and health consequences. Despite the availability of vaccines, infection rates remain high due to immune evasive Omicron sublineages. Broad-spectrum antivirals are needed to safeguard against emerging variants and future pandemics. We used messenger RNA (mRNA) display under a reprogrammed genetic code to find a spike-targeting macrocyclic peptide that inhibits SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Wuhan strain infection…
Specific nasopharyngeal Corynebacterium strains serve as gatekeepers against SARS-CoV-2 infection - The SARS-CoV-2 virus is still causing a worldwide problem. The virus settles primarily on the nasal mucosa, and the infection and its course depend on individual susceptibility. Our aim was to investigate the nasopharynx composition’s role in the individual susceptibility. During the first phase of SARS-CoV-2 pandemic, nasopharyngeal microbiome samples of close contact unvaccinated patients were investigated by 16S rRNA analysis and by culturing. The whole genome of cultured Corynebacteria was…
Research progress on pharmacological effects and mechanisms of cepharanthine and its derivatives - Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid compound found in plants of the Stephania genus, which has biological functions such as regulating autophagy, inhibiting inflammation, oxidative stress, and apoptosis. It is often used for the treatment of inflammatory diseases, viral infections, cancer, and immune disorders and has great clinical translational value. However, there is no detailed research on its specific mechanism and dosage and administration methods, especially clinical…
A mutation in the coronavirus nsp13-helicase impairs enzymatic activity and confers partial remdesivir resistance - Coronaviruses (CoVs) encode nonstructural proteins 1-16 (nsps 1-16) which form replicase complexes that mediate viral RNA synthesis. Remdesivir (RDV) is an adenosine nucleoside analog antiviral that inhibits CoV RNA synthesis. RDV resistance mutations have been reported only in the nonstructural protein 12 RNA-dependent RNA polymerase (nsp12-RdRp). We here show that a substitution mutation in the nsp13-helicase (nsp13-HEL A335V) of the betacoronavirus murine hepatitis virus (MHV) that was…
Efficacy and safety of MAS825 (anti-IL-1ꞵ/IL-18) in COVID-19 patients with pneumonia and impaired respiratory function - MAS825, a bispecific IL-1⍰/IL-18 monoclonal antibody, could improve clinical outcomes in COVID19 pneumonia by reducing inflammasome-mediated inflammation. Hospitalized nonventilated patients with COVID-19 pneumonia (n=138) were randomized (1:1) to receive MAS825 (10 mg/kg single i.v.) or placebo in addition to standard of care (SoC). The primary endpoint was the composite Acute Physiology and Chronic Health Evaluation II (APACHE II) score on Day 15 or on day of discharge (whichever was earlier)…
Targeting the cGAS-STING pathway as an inflammatory crossroad in coronavirus disease 2019 (COVID-19) - Context and objective: The emerging pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has imposed significant mortality and morbidity on the world. An appropriate immune response is necessary to inhibit SARS-CoV-2 spread throughout the body.Results: During the early stages of infection, the pathway of stimulators of interferon genes (STING), known as the cGAS-STING pathway, has a significant role in the induction of the…