Background: The effectiveness of inhaled corticosteroids to shorten time to symptom resolution or prevent hospitalization or death among outpatients with mild-to-moderate coronavirus 2019 (Covid-19) is unclear. Methods: ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial testing repurposed medications in outpatients with confirmed SARS-CoV-2 infection. Non-hospitalized adults aged >=30 years, experiencing >=2 symptoms of acute infection for <=7 days were randomized to inhaled fluticasone furoate 200 mcg once daily for 14 days or placebo. The primary outcome was time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Secondary outcomes included composites of hospitalization or death with or without urgent care or emergency department visit by day 28. Results: Of those eligible for the fluticasone arm, 656 were randomized to and received inhaled fluticasone; 621 received concurrent placebo. There was no evidence of improvement in time to recovery with fluticasone compared with placebo (hazard ratio [HR] 1.01, 95% credible interval [CrI] 0.91-1.12; posterior probability for benefit [HR>1]=0.56). Twenty-four participants (3.7%) in the fluticasone arm had urgent care or emergency department visits or were hospitalized compared with 13 (2.1%) in the pooled, concurrent placebo arm (HR 1.9, 95% CrI 0.8-3.5; posterior probability for benefit [HR<1]=0.03). Three participants in each arm were hospitalized, and no deaths occurred. Adverse events were uncommon in both arms. Conclusions: Treatment with inhaled fluticasone furoate for 14 days did not result in improved time to recovery among outpatients with Covid-19 in the United States during the delta and omicron variant surges.
Background: The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the United States with mild-to-moderate symptomatic coronavirus disease 2019 (COVID-19) is unknown. Objective: We evaluated the efficacy of ivermectin 400 mcg/kg daily for 3 days compared with placebo for the treatment of early mild-to-moderate COVID-19. Methods: ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial to evaluate repurposed therapies in outpatients with mild-to-moderate COVID-19. Non-hospitalized adults age >=30 years with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for <=7 days were randomized to receive ivermectin 400 mcg/kg daily for 3 days or placebo. The main outcome measure was time to sustained recovery, defined as achieving at least 3 consecutive days without symptoms. Secondary outcomes included a composite of hospitalization or death by day 28. Results: Of the 3457 participants who consented to be evaluated for inclusion in the ivermectin arm, 1591 were eligible for this study arm, randomized to receive ivermectin 400 mcg/kg (n=817) or placebo (n=774), and received study drug. Of those enrolled, 47% reported receiving at least 2 doses of SARS-CoV-2 vaccination. The posterior probability for any improvement in time to recovery was 0.91 (hazard ratio 1.07, 95% credible interval 0.96 to 1.17). The posterior probability of this benefit exceeding 24 hours was less than 0.01, as measured by the difference in mean time unwell. Hospitalizations or deaths were uncommon (ivermectin [n=10]; placebo [n=9]). Ivermectin at 400 mcg/kg was safe and without serious adverse events as compared with placebo (ivermectin [n=10]; placebo [n=9]). Conclusions: Ivermectin dosed at 400 mcg/kg daily for 3 days resulted in less than one day of shortening of symptoms and did not lower incidence of hospitalization or death among outpatients with COVID-19 in the United States during the delta and omicron variant time periods. Trial registration: ClinicalTrials.gov Identifier: NCT04885530.
Targeted surveillance allows public health authorities to implement testing and isolation strategies when diagnostic resources are limited. When transmission patterns are determined by social contact rates, the consideration of social network topologies in testing schemes is one avenue for targeted surveillance, specifically by prioritizing those individuals likely to contribute disproportionately to onward transmission. Yet, it remains unclear how to implement such surveillance and control when network data is unavailable, as is often the case in resource-limited settings. We evaluated the efficiency of a testing strategy that targeted individuals based on their degree centrality on a social network compared to a random testing strategy in the context of low testing capacity. We simulated SARS-CoV-2 dynamics on two contact networks from rural Madagascar and measured the epidemic duration, infection burden, and tests needed to end the epidemics. In addition, we examined the robustness of this approach when individuals9 true degree centralities were unknown and were instead estimated via readily-available socio-demographic variables (age, gender, marital status, educational attainment, and household size). Targeted testing reduced the infection burden by between 5 - 50% at low testing capacities, while requiring up to 28% fewer tests than random testing. Further, targeted tested remained more efficient when the true network topology was unknown and prioritization was based on socio-demographic characteristics, demonstrating the feasibility of this approach under realistic conditions. Incorporating social network topology into epidemic control strategies is an effective public health strategy for health systems suffering from low testing capacity and can be implemented via socio-demographic proxies when social networks are unknown.
Background: Hong Kong has enforced stringent travel restrictions particularly for inbound travellers since the emergence of SARS-CoV-2. Understanding the characteristics of imported COVID-19 cases is important for establishing evidence-based control measures. Methods: We conducted a retrospective cohort study to summarise the characteristics of cases classified as imported cases that were detected on or soon after arrival into Hong Kong from 13 November 2020 through to 31 January 2022, when all arriving persons were required to quarantine in a hotel or a designated quarantine facility. We analysed individual demographics, and clinical information including symptoms and disease severity, virus variants, and Ct values. Results: There were 2269 imported COVID-19 cases aged 0-85 years identified in Hong Kong. Almost half (48.6%) of the imported cases were detected on arrival. A shorter median delay from arrival to isolation was observed in Delta and Omicron cases (3 days) than cases infected with the ancestral strain and other variants (12 days; p<0.001) while lower Ct values at isolation were observed in cases infected with Omicron than the ancestral strain or other variants. No Omicron cases were detected beyond 14 days after arrival, and the cases (n=58, 2.6%) detected after 14 days of quarantine more frequently presented without symptoms at isolation and had a higher RT-PCR Ct-value during isolation. At least some of these cases were post-arrival infections. Conclusions: Testing inbound travellers at arrival and during on-arrival quarantine can detect imported cases early although it may not be sufficient to prevent all introductions of COVID-19 into the community. Public health measures should be adjusted in responses to the emergence of new variants of SARS-CoV-2 based on the epidemiologic evidence from continuous surveillance.
Background: The reliability of sequence-based inference of SARS-CoV-2 transmission is not clear. Sequence data from infections among household members can define the expected genomic diversity of a virus along a defined transmission chain. Methods: SARS-CoV-2 cases were identified prospectively among 2,369 participants in 706 households. Specimens with an RT-PCR cycle threshold less than or equal to 30 underwent whole genome sequencing. Intrahost single nucleotide variants (iSNV) were identified at greater than 5% frequency. Phylogenetic trees were used to evaluate the relationship of household and community sequences. Results: There were 178 SARS-CoV-2 cases in 706 households. Among 147 specimens sequenced, 106 yielded a whole genome consensus with coverage suitable for identifying iSNV. Twenty-six households had sequences from multiple cases within 14 days. Consensus sequences were indistinguishable among cases in 15 households, while 11 had greater than 1 consensus that differed by 1-2 mutations. Sequences from households and the community were often interspersed on phylogenetic trees. Identification of iSNV improved inference in 2 of 15 households with indistinguishable consensus sequences and 6 of 11 with distinct ones. Conclusions: In multiple infection households, whole genome consensus sequences differed by 0-1 mutations. Identification of shared iSNV occasionally resolved linkage, but the low genomic diversity of SARS-CoV-2 limits the utility of sequence-only transmission inference.
Objective: To investigate SARS-COV-2 viral clearance and viral load kinetics in the course of infection in children aged 1-6 years in comparison with adults. Methods: Prospective cohort study of infected daycare children and staff and their close contacts in households from 11/2020-06/2021, comprising serial (self) sampling of upper respiratory tract specimen and testing for SARS-CoV-2 via PCR. Data on symptoms and exposure were used to determine the date of probable infection for each participant. We determined (a) viral clearance, and (b) viral load dynamics over time. Samples were taken from day 4-6 to day 16-18 after diagnosis of the index case in the respective daycare group (5 samples per participant). Results: We included 40 children (1-6 years) and 67 adults (18-77 years) with SARS-CoV-2 infection. Samples were available at a mean of 4.3 points of time per participant. Among the participants, the 12-day study period fell in different periods within the individual course of infection, ranging from day 5-17 to day 15-26 after assumed infection. Children reached viral clearance at a median of 20 days after assumed infection (95% CI 17-21 days, Kaplan Meier Analysis), adults at 23 days (95% CI 20-25 days, difference not significant). In both children and adults, viral load decreased over time with trajectories of the mean viral load not being statistically different between groups. Only small proportions of those tested positive had a viral load of >1 million copies/ml, which is considered the threshold for infectivity. Kaplan-Meier calculations show that from day 15 (95% CI 13-15), 50% of all participants that had a viral load no longer infectious or were negative. Conclusion: Children aged 1-6 and adults infected with SARS-CoV-2 (wild type and Alpha variant) did not differ significantly in terms of viral load kinetics and time needed to clear the virus. Therefore, containment measures are important also in the daycare settings as long as the pandemic continues.
Longitudinal immune response data following three-dose COVID-19 mRNA vaccination remain limited, particularly in older adults and those experiencing their first SARS-CoV-2 infection. We quantified wild-type- and Omicron-specific antibody concentrations and virus neutralization activity up to six months post-third-dose in COVID-19-naive adults aged 24-98 years. Among participants who remained COVID-19-naive, antibody concentrations were comparable between age groups over time. Omicron-specific neutralization declined more rapidly in older adults, and at six months was undetectable in 56% and 96% of COVID-19-naive younger and older adults, respectively. Post-vaccine SARS-CoV-2 breakthrough infections increased wild-type- and Omicron-specific responses above three-dose vaccination alone, illustrating beneficial hybrid immunity.
Sampling for prevalence estimation of infection is subject to bias by both oversampling of symptomatic individuals and error-prone tests. This results in na"ive estimators that can be very far from the truth. In this work, we present a method of prevalence estimation that removes the effect of testing errors and reduces the effect of oversampling symptomatic individuals. Moreover, this procedure considers stratified errors in which tests have different error rate profiles for symptomatic and asymptomatic individuals. The result is an easily implementable algorithm (for which code is provided) that produces better prevalence estimates than other methods, as demonstrated by simulation and on Covid-19 data from the Israeli Ministry of Health.
A Study to Measure the Amount of Study Medicine in Blood in Adult Participants With COVID-19 and Severe Kidney Disease - Condition: COVID-19
Intervention: Drug: PF-07321332 (nirmatrelvir)/ritonavir
Sponsor: Pfizer
Not yet recruiting
Cognitive Rehabilitation in Post-COVID-19 Condition - Condition: COVID-19
Intervention: Behavioral: Goal Management Training (GMT)
Sponsors: Lovisenberg Diakonale Hospital; University of Oslo; Icahn School of Medicine at Mount Sinai; University of Toronto; UiT The Arctic University of Norway; Oslo University Hospital
Not yet recruiting
EFFECTS OF INSPIRATORY MUSCLE TRAINING IN POST-COVID-19 PATIENTS - Condition: Covid19
Interventions: Other: TREATMENT GROUP (TG); Other: CONTROL GROUP (CG)
Sponsor: University Vila Velha
Completed
Long-term Effects of SARS-CoV-2 on the Central Nervous System and One-year Follow-up of “Long COVID-19” Patients - Condition: Long Covid19
Intervention: Diagnostic Test: Perfusion brain scintigraphy imaging
Sponsor: Brugmann University Hospital
Recruiting
Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome - Condition: Post-COVID-19 Syndrome
Interventions: Drug: Temelimab 54mg/kg; Drug: Placebo
Sponsor: GeNeuro SA
Not yet recruiting
Physiotherapy in Post COVID-19 Syndrome Patients - Condition: Post-COVID-19 Syndrome
Interventions: Other: Cognitive behavioral principles-based treatment program; Other: Control intervention
Sponsor: Universidad de Granada
Recruiting
Active Cycle Of Breathing Technique Verses Breathing Exercises In Post ICU COVID-19 Patients - Condition: Post Covid-19 Patients
Interventions: Other: Chest physiotherapy with breathing exercises and ACBT; Other: Chest physiotherapy with breathing exercises
Sponsor: Riphah International University
Recruiting
Addressing Vaccine Hesitancy and Increasing COVID-19 Vaccine Uptake Among African American Young Adults in the South - Conditions: COVID-19; Vaccine Uptake
Intervention: Behavioral: Tough Talks COVID
Sponsors: University of North Carolina, Chapel Hill; University of Alabama at Birmingham; National Institute on Minority Health and Health Disparities (NIMHD)
Not yet recruiting
rSIFN-co Among Healthy Subjects and Subjects With Mild or Asymptomatic COVID-19 - Conditions: COVID-19; SARS-CoV-2
Interventions: Drug: rSIFN-co Nasal Spray; Drug: Placebo Nasal Spray
Sponsor: Sichuan Huiyang Life Science and Technology Corporation
Recruiting
Evaluation of Safety and Immunogenicity of the Recombinant ZR202-CoV and ZR202a-CoV Vaccines in Adults. - Conditions: SARS-CoV-2 Infection; COVID-19
Interventions: Biological: ZR202-CoV; Biological: ZR202a-CoV; Biological: Comirnaty®
Sponsor: Shanghai Zerun Biotechnology Co.,Ltd
Recruiting
The Effect of Pilates on Biopsychosocial Characteristics in the Covid-19 Pandemic - Conditions: COVID-19; Healthy; Sedentary; Exercise; Pilates
Interventions: Behavioral: Sedantary; Behavioral: Exercise therapy
Sponsor: Medipol University
Recruiting
Immunogenicity and Safety of BBIBP-Corv Coadministered With PPV23 and IIV4 in Hemodialysis Population - Conditions: Hemolysis; COVID-19
Interventions: Biological: coadministration; Biological: COVID-19 vaccine; Biological: IIV4+PPV23
Sponsors: China National Biotec Group Company Limited; Hunan Provincial Center for Disease Control and Prevention; Sichuan Center for Disease Control and Prevention; Guizhou Center for Disease Control and Prevention; Xiangya Hospital of Central South University; Beijing Institute of Biological Products Co Ltd.; Chengdu Institute of Biological Products Co.,Ltd.; Shanghai Institute Of Biological Products
Not yet recruiting
Safety and Immunogenicity Study of a Booster Dose of the Investigational CV0501 mRNA COVID-19 Vaccine in Adults at Least 18 Years Old - Condition: SARS-CoV-2
Interventions: Biological: CV0501 (3 μg); Biological: CV0501 (6 μg); Biological: CV0501 (12 μg); Biological: CV0501 (25 μg); Biological: CV0501 (50 μg); Biological: CV0501 (75 μg); Biological: CV0501 (100 μg); Biological: CV0501 (150 μg); Biological: CV0501 (200 μg)
Sponsor: GlaxoSmithKline
Not yet recruiting
This Trial is a Clinical Performance Validation Study That Will Evaluate the Clinical Agreement of the Sky Medical™ Rapid Antigen Test Comparing the Antigen Rapid Test to RT-PCR - Conditions: COVID-19; Sars-CoV-2 Infection
Intervention: Diagnostic Test: Sky Medical™ Rapid Antigen Test
Sponsor: Sky Medical Supplies & Equipments, LLC
Recruiting
The Effect Of Distraction Methods On Fear And Anxiety In Children Before The Covid 19 Test - Conditions: Anxiety; Fear
Interventions: Behavioral: The Kaleidescope; Behavioral: The visual illusion cards
Sponsor: Ondokuz Mayıs University
Completed
Author Correction: Structure basis for inhibition of SARS-CoV-2 by the feline drug GC376 - No abstract
Single-injection COVID-19 subunit vaccine elicits potent immune responses - Current vaccination schedules, including COVID-19 vaccines, require multiple doses to be administered. Single injection vaccines eliciting equivalent immune response are highly desirable. Unfortunately because unconventional release kinetics are difficult to achieve it still remains a huge challenge. Herein a single-injection COVID-19 vaccine was designed using a highly programmable release system based on dynamic layer-by-layer (LBL) films. The antigen, S1 subunit of SARS-CoV-2 spike protein,…
An Exploration of Resiliency Among Nurse Educators During the COVID-19 Pandemic - CONCLUSION: Resilience and related characteristics have the potential to assist nurse educators in adapting successfully to stressful circumstances. It is crucial that schools of nursing develop programs to enhance or develop resilience among nurse educators. Support and training in the area of online education are also of paramount importance.
The long term vaccine-induced anti-SARS-CoV-2 immune response is impaired in quantity and quality under TNFα blockade - CONCLUSIONS: We show a reduced SARS-CoV-2 neutralising capacity in patients under TNFα blockade. In this cohort, the plasma cell response appears to be less specific and show stronger bystander activation. While these effects were observable after the first two vaccinations and with older VOC, the differences in responses to BA.2 were enhanced. This article is protected by copyright. All rights reserved.
Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial - CONCLUSION: Administration of zilucoplan to COVID-19 patients in this proof-of-concept randomized trial was well tolerated under antibiotic prophylaxis. While not reaching statistical significance, indicators of respiratory function (PaO(2)/FiO(2)) and clinical outcome (mortality and 6-min walk test) suggest that C5 inhibition might be beneficial, although this requires further research in larger randomized studies.
Targeting autophagy regulation in NLRP3 inflammasome-mediated lung inflammation in COVID-19 - Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated, which results in a cytokine storm at the late stage of COVID-19. Autophagy regulation is involved in the infection and replication of SARS-CoV-2 at the early stage and the inhibition of NLRP3 inflammasome-mediated lung inflammation at the late…
Therapeutic drug monitoring and dosage adjustments of immunosuppressive drugs when combined with nirmatrelvir/ritonavir in patients with COVID-19 - Nirmatrelvir/ritonavir (Paxlovid®) consists of a peptidomimetic inhibitor (Nirmatrelvir) of the SARS-CoV-2 main protease and a pharmacokinetic enhancer (Ritonavir). It is approved for the treatment of mild-to-moderate COVID-19. This combination of nirmatrelvir and ritonavir can mediate significant and complex drug-drug interactions (DDIs), primarily due to the ritonavir component. Indeed, ritonavir inhibits the metabolism of nirmatrelvir through cytochrome P450 3A (CYP3A) leading to higher…
Selective serotonin reuptake inhibitor (SSRI) antidepressants reduce COVID-19 infection: prospects for use - CONCLUSION: If successful, these drugs can substantially reduce hospitalization and mortality rates, as well as allow for fully outpatient treatment for mild-to-moderate infections. Thus, repositioning SSRIs can provide benefits when faced with a rapidly evolving pandemic such as COVID-19.
Targeting Doublecortin-Like Kinase 1 (DCLK1)-Regulated SARS-CoV-2 Pathogenesis in COVID-19 - Host factors play critical roles in SARS-CoV-2 infection-associated pathology and the severity of COVID-19. In this study, we systematically analyzed the roles of SARS-CoV-2-induced host factors, doublecortin-like kinase 1 (DCLK1), and S100A9 in viral pathogenesis. In autopsied subjects with COVID-19 and pre-existing chronic liver disease, we observed high levels of DCLK1 and S100A9 expression and immunosuppressive (DCLK1(+)S100A9(+)CD206^(+)) M2-like macrophages and N2-like neutrophils in…
Broad-spectrum antiviral activity of Spatholobus suberectus Dunn against SARS-CoV-2, SARS-CoV-1, H5N1, and other enveloped viruses - The current COVID-19 pandemic caused by SARS-Cov-2 is responsible for more than 6 million deaths globally. The development of broad-spectrum and cost-effective antivirals is urgently needed. Medicinal plants are renowned as a complementary approach in which antiviral natural products have been established as safe and effective drugs. Here, we report that the percolation extract of Spatholobus suberectus Dunn (SSP) is a broad-spectrum viral entry inhibitor against SARS-CoV-1/2 and other enveloped…
Zinc pyrithione is a potent inhibitor of PLPro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication - Zinc pyrithione (1a), together with its analogues 1b-h and ruthenium pyrithione complex 2a, were synthesised and evaluated for the stability in biologically relevant media and anti-SARS-CoV-2 activity. Zinc pyrithione revealed potent in vitro inhibition of cathepsin L (IC(50)=1.88 ± 0.49 µM) and PL^(Pro) (IC(50)=0.50 ± 0.07 µM), enzymes involved in SARS-CoV-2 entry and replication, respectively, as well as antiviral entry and replication properties in an ex vivo system derived from primary human…
Not “My” crisis: Social identity and followers’ crisis responses to COVID-19 - Operationalizing social group identification as political partisanship, we examine followers’ (i.e., US residents’) affective experiences and behavioral responses during the initial COVID-19 outbreak in the United States (March to May 2020). In Study 1, we conducted content analyses on major news outlets’ coverage of COVID-19 (N = 4319) to examine media polarization and how it plays a role in shaping followers’ perceptions of the pandemic and leadership. News outlets trusted by Republicans…
Oridonin Inhibits SARS-CoV-2 by Targeting Its 3C-Like Protease - Oridonin Inhibits SARS-CoV-2 Oridonin, a natural product extracted from Rabdosia rubescens, possesses a wide range of pharmacological properties, including anti-inflammatory, anti-cancer, anti-microbial, neuroprotection, immunoregulation, etc. In article number 2100124, Baisen Zhong, Litao Sun, and co-workers demonstrate that Oridonin targets the SARS-CoV-2 3CL protease by covalently binding to cysteine145 in its active pocket to exert an anti-SARS-CoV-2 effect, which provides a novel candidate…
‘In most supermarkets food does not cost £3 per day …’ The impact of the school food voucher scheme during COVID-19 - Households with children eligible for Free School Meals are at risk of food insecurity. This paper reports on a rapid-response study that investigated the impact of the school food voucher scheme during the COVID-19 crisis on young people, families and schools. It pays close attention to the reliance of the state on the goodwill of society and its citizens in feeding those most in need. The Capabilities Approach is used to highlight factors that inhibited and restricted the use of the vouchers…
Synthesis, crystal structure elucidation, DFT analysis, drug-likeness and ADMET evaluation and molecular docking studies of triazole derivatives: Binary inhibition of spike protein and ACE2 receptor protein of COVID-19 - The recent incidence of terrible acute respiratory syndrome coronavirus 2 (SARS CoV-2) has presently experienced some noteworthy mutations since its discovery in 2019 in Wuhan, China. The present research work focuses on the synthesis of three triazole derivatives (BMTPP, BMTTP, and BMTIP) and their inhibition activities against SARS-Cov-2 spike and ACE2 receptor proteins. The crystal structure for BMTTP was determined by the SCXRD method and optimized geometrical parameters for the three…