Objective This systematic review and meta-analysis aimed to quantitatively evaluate the effect of the COVID-19 pandemic on respiratory syncytial virus (RSV) associated bronchiolitis among hospitalised infants. Methods The study protocol was registered in the PROSPERO database (CRD42022314000) and was designed based on PRISMA guidelines updated in May 2020. The meta-analysis component was modified appropriately to synthesise the pooled proportion of infants having RSV-associated bronchiolitis before the COVID-19 pandemic in 2019 and during the pandemic with 95% confidence interval (CI). Results: The eight qualified studies for the meta-analysis were from Spain, Italy, France and China, including 109,186 symptomatic cases of bronchiolitis before the pandemic in 2019 and 61,982 cases in 2020-2021. The quantitative analysis included laboratory-confirmed RSV infection in 7691 infants with bronchiolitis reported before the pandemic in
Background: Antibodies are crucial for vaccine-mediated protection against many pathogens. Modifications to vaccine delivery that increase antibody magnitude, longevity, and/or quality are therefore of great interest for maximising efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6mo) - using AS01B-adjuvanted RH5.1 malaria antigen - substantially improves serum IgG durability as compared to monthly dosing (0-1-2mo; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing was unclear. Methods: Immunokinetics of PfRH5-specific Ig across multiple isotypes were compared between DFx and monthly regimen vaccinees. Peak responses were characterised in-depth with a systems serology platform including biophysical and functional profiling. Computational modelling was used to define the humoral feature set associated with DFx dosing. PfRH5-specific B cells were quantified by flow cytometry and sorted for single cell RNA sequencing (scRNA- seq). Differential gene expression between DFx and monthly dosing regimens was explored with Seurat, DESeq2 and gene set enrichment analysis. Results: DFx dosing increases the frequency of circulating PfRH5-specific B cells and longevity of PfRH5-specific IgG1, as well as other isotypes and subclasses. At the peak antibody response, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn-binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. At the same time point, scRNA-seq of PfRH5-specific B cells revealed enriched plasma cell and Ig / protein export signals in the monthly dosing group as compared to DFx vaccinees. Conclusions: DFx dosing of the RH5.1/AS01B vaccine had a profound impact on the humoral response. Our data suggest plausible mechanisms relating to improved FcRn-binding (known to improve Ig longevity) and a potential shift from short-lived to long-lived plasma cells. Recent reports of the positive impact of delayed boosting on SARS-CoV-2 vaccine immunogenicity highlight the broad relevance of these data.
Evidence from early observational studies suggested negative vaccine effectiveness for the SARS-CoV-2 Omicron variant. Using transmission modeling, we illustrated how increased contact between vaccinated individuals, vaccinated contact heterogeneity, paired with lower vaccine efficacies could produce negative measurements and how we can identify this mechanism via a key temporal signature.
In a population-based survey of NYC adults, we assessed positive SARS-CoV-2 tests (including via exclusive at- home testing) and possible cases among untested respondents. An estimated 27.4% (95%CI: 22.8%-32.0%) or 1.8 million adults (95%CI: 1.6-2.1 million) had SARS-CoV-2 infection. SARS-CoV-2 prevalence was high among groups that are more vulnerable to severe SARS-CoV-2 and death, including unvaccinated persons (21.7%, 95%CI 9.6%-33.8%) and those aged 65+ (17.8%, 95%CI 10.2-25.4%). Population-based representative surveys are an important adjunct surveillance tool to standard testing-based SARS-CoV-2 surveillance.
The antibody testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was used to detect the presence of antibodies in a private university setting. This serial cross-sectional study determined the seroprevalence of SARS-CoV-2 antibodies using qualitative and quantitative tests. Between June 2021 to December 2021, samples from 1,318 participants were tested, showing 47.80% of the study population yielding IgG antibodies to SARS-CoV-2 virus. A general increase in seroprevalence was observed from June to December 2021. However, a decreasing trend in IgG reactivity was found in vaccinated individuals over time. IgG antibody formation was observed across all brands of vaccines.
Background. Fatigue has an adaptive function and serves as a temporary signal to rest and save energy often in response to immune activation. It may, however, also persist in a pathological condition incurring significant burden. While subjective symptoms and scientific consensus indicate that both physical and mental determinants of motivated behavior are affected in fatigue, the underlying processes are rarely examined using objective, task-based indicators. Methods. In three consecutive studies, including validation (N = 48) and reliability assessments (N = 27), we use an experimental task to jointly objectify reward learning and effort execution as two determinants of behavioral motivation. In addition, we tested how fatigue and its acute perturbation in response to immune activation after SARS- CoV-2 vaccination are linked to these task-based indicators of motivation in a longitudinal cross-over design (N = 55). Results. The validation study showed the utility of the experimental task for simultaneously assessing learning, effort exertion, and its regulation based on subjective confidence. The reliability assessment over a one-week period indicated that symptoms of fatigue and task behavior are highly reliable and that repetition effects have little impact on motivated behavior. Finally, in the vaccination trial, we found significant links between fatigue and task behavior. Baseline levels of fatigue predicted how effort is gauged in dependence of current confidence about reward outcomes, and state perturbations of fatigue in the context of the SARS-CoV-2 vaccination reduced confidence during learning. Importantly, task success was significantly lower in subjects who reported high fatigue at baseline and who additionally experienced stronger increase in fatigue in response to vaccination. Discussion. Our results demonstrate that the experimental task allows to jointly assess determinants of motivated behavior, and to link its constituent processes to subjective fatigue. This suggests that our understanding of fatigue and its perturbation due to acute immune activation can benefit from objective, task-based indicators of the underlying motivational mechanisms. Future studies could build on these findings to further deepen the understanding of neurobehavioral mechanisms underlying fatigue in the context of immune activation.
The immune-inflammatory response during the acute phase of COVID-19, as assessed using peak body temperature (PBT) and peripheral oxygen saturation (SpO2), predicts the severity of chronic fatigue, depression and anxiety (physio- affective) symptoms three to four months later. The present study was performed to characterize whether the effects of SpO2 and PBT on the physio-affective phenome of Long COVID are mediated by immune, oxidative and nitrosative stress (IO&NS) pathways. This study assayed SpO2 and PBT during acute COVID-19, and C-reactive protein (CRP), malondialdehyde (MDA), protein carbonyls (PCs), myeloperoxidase (MPO), nitric oxide (NO), zinc, and glutathione peroxidase (Gpx) in 120 Long COVID individuals and 36 controls. Cluster analysis showed that 31.7% of the Long COVID patients had severe abnormalities in SpO2, body temperature, increased oxidative toxicity (OSTOX) and lowered antioxidant defenses (ANTIOX), and increased total Hamilton Depression (HAMD) and Anxiety (HAMA) and Fibromylagia- Fatigue (FF) scores. Around 60% of the variance in the physio-affective phenome of Long COVID (a factor extracted from HAMD, HAMA and FF scores) was explained by OSTOX/ANTIOX ratio, PBT and SpO2. Increased PBT predicted increased CRP and lowered ANTIOX and zinc levels, while lowered SpO2 predicted lowered Gpx and increased NO production. Both PBT and SpO2 strongly predict OSTOX/ATIOX during Long COVID. In conclusion, the impact of acute COVID-19 on the physio-affective symptoms of Long COVID is partly mediated by OSTOX/ANTIOX, especially lowered Gpx and zinc, increased MPO and NO production and lipid peroxidation-associated aldehyde formation. Post-viral physio-affective symptoms have an inflammatory origin and are partly mediated by neuro-oxidative toxicity.
A novel automated mariPOC SARS-CoV-2 antigen test was evaluated in a Health care center laboratory among symptomatic and asymptomatic individuals seeking SARS-CoV-2 testing. According to the national testing strategy, RT-PCR was used as a reference method. A total of 962 subjects were included in this study, 4.8% (46/962) of their samples were SARS-CoV-2 RT-PCR positive, and 87% (40/46) of these were from symptomatics. Among the symptomatics, the overall sensitivity of the mariPOC SARS-CoV-2 test was 82.5% (33/40), though the sensitivity increased to 97.1% (33/34) in samples with a Ct value <30. The mariPOC SARS-CoV-2 test detected 2/6 PCR positive samples among the asymptomatics, four cases that remained antigen test negative had Ct values between 28 and 36. The specificity of the mariPOC SARS- CoV-2 test was 100% (916/916). The evaluation showed that the mariPOC SARS-CoV-2 rapid antigen test is very sensitive and specific for the detection of individuals who most probably are contagious.
Background: To determine the extent and nature of changes in infected patients healthcare utilization, we studied healthcare contact in the 1-4 weeks and 5-24 weeks following a COVID-19 diagnosis compared to propensity matched controls. Methods: Survival analysis was used for time to death and first clinical outcomes including clinical terminology concepts for post-viral illness, fatigue, embolism, respiratory conditions, mental and developmental conditions, fit note, or hospital attendance. Increased instantaneous risk for the occurrence of an outcome for positive individuals was quantified using hazard ratios (HR) from Cox Regression and absolute risk was quantified using relative risk (RR) from life table analysis. Results: Compared to matched individuals testing negative, surviving positive community-tested patients had a higher risk of post-viral illness (HR: 4.57, 95%CI: 1.77-11.80, p=0.002), fatigue (HR: 1.47, 95%CI: 1.24-1.75, p<0.001) and embolism (HR: 1.51, 95%CI: 1.13-2.02, p=0.005) at 5-24 weeks post- diagnosis. In the four weeks after COVID-19 higher rates of sick notes were being issued for community-tested (HR: 3.04, 95%CI: 0.88 to 10.50, p<0.079); the risk was reduced after four weeks, compared to controls. Overall healthcare attendance for anxiety, depression was less likely in those with COVID-19 in the first four weeks (HR: 0.83, 95%CI: 0.73-1.06, p=0.007). After four weeks, anxiety, depression is less likely to occur for the positive community-tested individuals (HR: 0.87, 95%CI: 0.77-1.00, p=0.048), but more likely for positive hospital-tested individuals (HR: 1.16, 95%CI: 1.00-1.45, p=0.053). Although statistical associations between positive infection and post-infection healthcare use are clear, the absolute use of healthcare is very. Conclusions: Community COVID-19 disease is associated with increased risks of post-viral illness, fatigue, embolism, depression, anxiety and respiratory conditions. Despite these elevated risks, the absolute healthcare burden is low. Either very small proportions of people experience adverse outcomes following COVID-19 or they are not presenting to healthcare. Trial registration: Data held in SAIL databank are anonymised and therefore, no ethical approval is required. All data in SAIL has the permission from the relevant Caldicott Guardian or Data Protection Officer and SAIL-related projects are required to obtain Information Governance Review Panel (IGRP) approval. The IGRP approval number for this study is 1259.
Clinical Performance Evaluation of the Bio-Self™ COVID-19 Antigen Home Test - Condition: COVID-19
Interventions: Device: Bio-Self COVID-19 Antigen Home Test; Device: Standard of Care COVID-19 Test; Diagnostic Test: RT-PCR Test
Sponsors: BioTeke USA, LLC; CSSi Life Sciences
Not yet recruiting
Immunogenicity and Safety of Fractional Booster Dose of COVID-19 Vaccines Available for Use in Pakistan/Brazil: A Phase 4 Dose-optimizing Trial - Condition: COVID-19
Interventions: Biological: Sinovac; Biological: AZD1222; Biological: BNT162b2
Sponsors: Albert B. Sabin Vaccine Institute; Aga Khan University; Oswaldo Cruz Foundation; Stanford University
Not yet recruiting
A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine as a Booster Dose in Population Aged 12-17 Years - Conditions: COVID-19; SARS-CoV-2 Infection
Interventions: Biological: SCTV01E; Biological: mRNA-1273
Sponsor: Sinocelltech Ltd.
Not yet recruiting
A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine in Population Aged ≥18 Years - Conditions: SARS-CoV-2 Infection; COVID-19
Interventions: Biological: SCTV01E; Biological: Comirnaty
Sponsor: Sinocelltech Ltd.
Not yet recruiting
Evaluate the Safety and Immunogenicity of Ad5 COVID-19 Vaccines for Booster Use in Children Aged 6-17 Years. - Condition: COVID-19
Interventions: Biological: 1 Nebulized inhalation for booster groups; Biological: 2 Nebulized inhalation for booster groups; Biological: 3 Nebulized inhalation for booster groups; Biological: 4 Nebulized inhalation for booster groups; Biological: 5 Intramuscular injection for booster groups; Biological: 6 Intramuscular injection for booster groups; Biological: 7 Intramuscular injection for booster groups; Biological: 8 Intramuscular injection for booster groups; Biological: 9 Intramuscular injection for booster groups; Biological: 10 Intramuscular injection for booster groups; Biological: 11 Nebulized inhalation for booster groups; Biological: 12 Nebulized inhalation for booster groups; Biological: 13 Nebulized inhalation for booster groups; Biological: 14 Nebulized inhalation for booster groups; Biological: 15 Intramuscular injection for booster groups; Biological: 16 Intramuscular injection for booster groups; Biological: 17 Intramuscular injection for booster groups; Biological: 18 Intramuscular injection for booster groups; Biological: 19 Intramuscular injection for booster groups; Biological: 20 Intramuscular injection for booster groups; Biological: 21 Nebulized inhalation for primary groups; Biological: 22 Nebulized inhalation for primary groups; Biological: 23 Nebulized inhalation for primary groups; Biological: 24 Nebulized inhalation for primary groups
Sponsor:
Seventh Medical Center of PLA General Hospital
Not yet recruiting
A First-In-Human Phase 1b Study of AmnioPul-02 in COVID-19 - Condition: COVID-19
Intervention: Drug: AmnioPul-02
Sponsor: Amniotics AB
Not yet recruiting
Immunogenicity，Safety and Cross - Immune Response With the Strains of the Booster Immunization Using an Inactivated COVID-19 Vaccine - Condition: COVID-19
Intervention: Biological: Inactivated COVID-19 Vaccine
Sponsor: Sinovac Research and Development Co., Ltd.
Not yet recruiting
Aerobic Exercise and Covid-19 Survivors With Post-Intensive Care Syndrome (Pics) - Conditions: COVID-19; Post Intensive Care Syndrome
Interventions:
Other: Aerobic Exercise Training; Other: Home Plan
Sponsor: Riphah International University
Not yet recruiting
Efficacy and Safety of JT001 (VV116) Compared With Paxlovid - Condition: COVID-19
Interventions: Drug: JT001; Drug: Paxlovid
Sponsor:
Vigonvita Life Sciences
Recruiting
Interleukine 6 (IL6) Assay for Predicting Failure of Spontaneous Breathing in Patients With COVID-19 Acute Respiratory Distress Syndrome - Condition: COVID-19 Acute Respiratory Distress Syndrome
Interventions:
Biological: IL6 assessment; Biological: CRP and PCT assessment
Sponsor:
Centre Hospitalier Henri Duffaut - Avignon
Recruiting
A Single Arm Phase-IV Study to Determine Reactogenicity and Immunogenicity of Delayed COVID-19 Vaccine Schedule in Children - Conditions: Vaccine Reaction; COVID-19; Children, Only
Intervention:
Biological: BNT162b2 Pfizer-BioNTech/Comirnaty
Sponsors: KK Women’s and Children’s Hospital; Duke- NUS Graduate Medical School
Recruiting
Use of Continuous Glucose Monitors in Coronavirus Disease 2019 ICU and Potential Inpatient Settings - Conditions: Covid19; Diabetes Mellitus
Intervention: Device: continuous glucose monitoring
Sponsor: Tanureet K Arora
Completed
Pilot Trial on Immunosuppression Modulation to Increase SARS-CoV-2 Vaccine Response in Kidney Transplant Recipients - Condition: COVID-19
Interventions: Other: Immunosuppression reduction; Other: No immunosuppression reduction
Sponsor: Medical University of Vienna
Active, not recruiting
ABNCoV2 Vaccine in Adult Subjects Previously Vaccinated for SARS-CoV-2 - Condition: COVID-19 Disease
Interventions: Biological: ABNCoV2; Biological: Comirnaty
Sponsor: Bavarian Nordic
Not yet recruiting
Bivalirudin Versus Enoxaparin in Critically Ill COVID-19 Patients - Conditions: Acute Respiratory Failure; SARS CoV 2 Infection; Anticoagulants
Interventions:
Drug: Enoxaparin Sodium; Drug: Bivalirudin
Sponsor: University Magna Graecia
Not yet recruiting
A VSV-based assay quantifies coronavirus Mpro/3CLpro/Nsp5 main protease activity and chemical inhibition - Protease inhibitors are among the most powerful antiviral drugs. However, for SARS-CoV-2 only a small number of protease inhibitors have been identified thus far and there is still a great need for assays that efficiently report protease activity and inhibition in living cells. Here, we engineer a safe VSV-based system to report both gain- and loss-of- function of coronavirus main protease (M^(pro)/3CLpro/Nsp5) activity in living cells. We use SARS-CoV-2 3CLpro in this system to confirm…
2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart - 2-Deoxy-D-glucose (2DG) has recently received emergency approval for the treatment of COVID-19 in India, after a successful clinical trial. SARS-CoV-2 infection of cultured cells is accompanied by elevated glycolysis and decreased mitochondrial function, whereas 2DG represses glycolysis and stimulates respiration, and restricts viral replication. While 2DG has pleiotropic effects on cell metabolism in cultured cells it is not known which of these manifests in vivo. On the other hand, it is known…
Virtual communication curbs creative idea generation - COVID-19 accelerated a decade-long shift to remote work by normalizing working from home on a large scale. Indeed, 75% of US employees in a 2021 survey reported a personal preference for working remotely at least one day per week¹, and studies estimate that 20% of US workdays will take place at home after the pandemic ends². Here we examine how this shift away from in-person interaction affects innovation, which relies on collaborative idea generation as the foundation of commercial and…
SARS-CoV-2 variants C.1.2 and B.1.621 (Mu) partially evade neutralization by antibodies elicited upon infection or vaccination - Rapid spread of SARS-CoV-2 variants C.1.2 and B.1.621 (Mu variant) in Africa and the Americas, respectively, as well as a high number of mutations in the viral spike proteins raised concerns that these variants might pose an elevated threat to human health. Here, we show that C.1.2 and B.1.621 spike proteins mediate increased entry into certain cell lines but do not exhibit increased ACE2 binding. Further, we demonstrate that C.1.2 and B.1.621 are resistant to neutralization by bamlanivimab but…
Virus-host interaction networks as new antiviral drug targets for IAV and SARS-CoV-2 - Currently, SARS-CoV-2, especially the Omicron strain, is ravaging the world and even co-infecting human beings with IAV, which is a serious threat to human public health. As of yet, no specific antiviral drug has been discovered for SARS- CoV-2. Therefore, there is an urgent need to explore antiviral drug targets for SARS-CoV-2 and develop effective clinical drugs. This requires a deeper understanding of the SARS-CoV-2 replication cycle and the molecular mechanisms of SARS-CoV-2-host interaction…
Potential of sphingosine-1-phosphate in preventing SARS-CoV-2 infection by stabilizing and protecting endothelial cells: Narrative review - Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, resulting in over 250 million infections and >5 million deaths. Most antiviral drugs and vaccines have shown limited efficacy against SARS-CoV-2. Clinical data revealed that except for the large number of self-healing mild cases, moderate and severe cases mostly survived after supportive treatment but not specific drug administration or vaccination. The endothelial system is…
Lichen planus drugs re-purposing as potential anti COVID-19 therapeutics through molecular docking and molecular dynamics simulation approach - CONCLUSION: EGCG can be a potential inhibitor drug which can bind with ACE-2 receptor thus inhibiting the interaction of mainly M^(pro) protein and spike glycoprotein of SARS-CoV-2.
Ayurvedic formulations: Potential COVID-19 therapeutics? - CONCLUSION: The most commonly used Ayurvedic treatments for management of respiratory symptoms associated with SARS- CoV-2 infection appear to have prophylactic and/or therapeutic properties. It would be of particular interest to assess synergistic and concomitant systemic effects and antiviral activities of individual phytoconstituents and their combinations in the Ayurvedic treatments.
Photo-Cross-Linked Probe-Modified Magnetic Particles for the Selective and Reliable Recovery of Nucleic Acids - Polymerase chain reaction (PCR) assays are used to diagnose various infectious diseases such as Coronavirus disease 2019 by detecting the nucleic acids of the pathogen. However, in practice, the yield of the extraction process and the inhibition of the reverse transcription reaction and PCR by foreign substances reduce the sensitivity and may yield false negative results. The sensitivity of the PCR test can be improved by using technologies that can reliably capture the target nucleic acid and…
An antibody targeting the N-terminal domain of SARS-CoV-2 disrupts the spike trimer - The protective human antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus focuses on the spike (S) protein which decorates the virion surface and mediates cell binding and entry. Most SARS-CoV-2 protective antibodies target the receptor-binding domain or a single dominant epitope (‘supersite’) on the N terminal domain (NTD). Here, using the single B cell technology LIBRA-seq, we isolated a large panel of NTD-reactive and SARS- CoV-2 neutralizing antibodies…
Gain-of-Signal Assays for Probing Inhibition of SARS-CoV-2 Mpro/3CLpro in Living Cells - The main protease, M^(pro), of SARS-CoV-2 is required to cleave the viral polyprotein into precise functional units for virus replication and pathogenesis. Here, we report quantitative reporters for M^(pro) function in living cells in which protease inhibition by genetic or chemical methods results in robust signal readouts by fluorescence (enhanced green fluorescent protein [eGFP]) or bioluminescence (firefly luciferase). These gain-of-signal systems are scalable to high- throughput platforms…
Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2 - The global spread of SARS-CoV-2 led to major economic and health challenges worldwide. Revealing host genes essential for infection by multiple variants of SARS-CoV-2 can provide insights into the virus pathogenesis, and facilitate the development of novel therapeutics. Here, employing a genome-scale CRISPR screen, we provide a comprehensive data-set of cellular factors that are exploited by wild type SARS-CoV-2 as well as two additional recently emerged variants of concerns (VOCs), Alpha and…
Transcriptional regulation and small compound targeting of ACE2 in lung epithelial cells - Angiotensin-converting enzyme 2 (ACE2) is the receptor of COVID-19 pathogen SARS-CoV-2, but the transcription factors (TFs) that regulate the expression of the gene encoding ACE2 (ACE2) have not been systematically dissected. In this study we evaluated TFs that control ACE2 expression, and screened for small molecule compounds that could modulate ACE2 expression to block SARS-CoV-2 from entry into lung epithelial cells. By searching the online datasets we found that 24 TFs might be ACE2…
SARS-CoV-2-specific immune responses in elderly and immunosuppressed participants and patients with hematologic disease or checkpoint inhibition in solid tumors: study protocol of the prospective, observational CoCo immune study - BACKGROUND: Immunocompromised people (ICP) and elderly individuals (older than 80 years) are at increased risk for severe coronavirus infections. To protect against serious infection with SARS-CoV-2, ICP are taking precautions that may include a reduction of social contacts and participation in activities which they normally enjoy. Furthermore, for these people, there is an uncertainty regarding the effectiveness of the vaccination. The COVID-19 Contact (CoCo) Immune study strives to…
SARS-CoV2 wild type and mutant specific humoral and T cell immunity is superior after vaccination than after natural infection - CONCLUSION: Antibody neutralisation of the delta mutant was reduced compared to wt, as assessed in a novel inhibition assay with a finger prick blood drop. Strong CD4 T cell responses were present against wt and mutant SARS-CoV2 variants, including the delta (B.1.617.2) strain, in fully vaccinated individuals, whereas they were partly weaker 1 year after natural infection. Hence, immune responses after vaccination are stronger compared to those after naturally occurring infection, pointing out…