Contact tracing forms a crucial part of the public-health toolbox in mitigating and understanding emergent pathogens and nascent disease outbreaks. Contact tracing in the United States was conducted during the pre-Omicron phase of the ongoing COVID-19 pandemic. This tracing relied on voluntary reporting and responses, often using rapid antigen tests (with a high false negative rate) due to lack of accessibility to PCR tests. These limitations, combined with SARS-CoV-2s propensity for asymptomatic transmission, raise the question how reliable was contact tracing for COVID-19 in the United States? We answered this question using a Markov model to examine the efficiency with which transmission could be detected based on the design and response rates of contact tracing studies in the United States. Our results suggest that contact tracing protocols in the U.S. are unlikely to have identified more than 1.65% (95% uncertainty interval: 1.62%-1.68%) of transmission events with PCR testing and 0.88% (95% uncertainty interval 0.86%-0.89%) with rapid antigen testing. When considering an optimal scenario, based on compliance rates in East Asia with PCR testing, this increases to 62.7% (95% uncertainty interval: 62.6%-62.8%). These findings highlight the limitations in interpretability for studies of SARS-CoV-2 disease spread based on U.S. contact tracing and underscore the vulnerability of the population to future disease outbreaks, for SARS-CoV-2 and other pathogens.
Rationale: Persistent pulmonary sequelae are evident in many survivors of acute coronavirus disease 2019 (COVID-19) but the molecular mechanisms responsible are incompletely understood. Post-COVID radiological lung abnormalities comprise two broad categories, organising pneumonia and reticulation, interpreted as indicative of subacute inflammation and fibrosis, respectively. Whether these two patterns represent distinct pathologies, likely to require different treatment strategies is not known. Objectives: We sought to identify differences at molecular and cellular level, in the local immunopathology of post-COVID inflammation and fibrosis. Methods: We compared single-cell transcriptomic profiles and T cell receptor (TCR) repertoires of bronchoalveolar cells obtained from convalescent individuals with each radiological pattern of post-COVID lung disease (PCLD). Measurements and Main Results: Inflammatory and fibrotic PCLD single-cell transcriptomes closely resembled each other across all cell types. However, CD4 central memory T cells (TCM) and CD8 effector memory T cells (TEM) were significantly more abundant in inflammatory PCLD. A greater proportion of CD4 TCM also exhibited clonal expansion in inflammatory PCLD. High levels of clustering of similar TCRs from multiple donors was a striking feature of both PCLD phenotypes, consistent with tissue localised antigen-specific immune responses, but there was no enrichment for known SARS-CoV-2 reactive TCRs. Conclusions: There is no evidence that radiographic organising pneumonia and reticulation in PCLD are associated with differential immmunopathological pathways. Inflammatory radiology is characterised by greater bronchoalveolar T cell accumulation. Both groups show evidence of shared antigen-specific T cell responses, but the antigenic target for these T cells remains to be identified.
SARS-CoV-2 infection causes a multisystemic disease that affects numerous organs beyond the respiratory system. Thus, it is well known that COVID-19 is associated with a wide range of hematological disorders; however, it remains unclear how the SARS-CoV-2 virus is able to navigate from tissue to tissue. In this work, we performed a comprehensive analysis of the pleiotropic effects of a prototypical coronavirus in its natural host, the validated preclinical model of murine hepatitis virus (MHV). Throughout this study we compared our results with the real-world data from COVID-19 patients (including autopsies). Thus, the presence of viral RNA was only detected in less than 25% of the human serum samples, whereas all had multiple positive nasal swabs for SARS-CoV-2. Notably, we found viral RNA not only in lungs, but also in heart and kidney of deceased COVID-19 patients. Subsequently, we investigated the association between viral organotropism and clinical manifestations employing the MHV murine model. Results from RT-qPCR and viral infectivity showcased the presence of viral RNA and infectious particles in multiple organs including liver, lung, brain, heart, kidney, spleen and pancreas, and even the blood of infected mice. Surprisingly, when comparing plasma and red blood cells (RBCs)-enriched fraction, higher viral load levels were detected in RBCs, with decreased RBC count, and hematocrit and hemoglobin levels in infected mice. Next, we treated infected mice with hemin triggering more aggressive symptoms. Strikingly, when combining hemin treatment with chloroquine (a compound that known to interact with the heme group and induces a conformational change in its structure) the infection and its clinical manifestations were distinctly attenuated. Computational docking suggested that heme is able to bind to MHV Spike protein in a similar way to the one, experimentally observed for SARS-CoV-2. Overall, our results lead to a global perspective of COVID-19 beyond the canonical focus on the respiratory system, and strongly support the multi-organ extent of coronavirus infection through specific interactions with RBC hemoproteins.
Harmful data shifts occur when the distribution of data used to train a clinical AI system differs significantly from the distribution of data encountered during deployment, leading to erroneous predictions and potential harm to patients. We evaluated the impact of data shifts on an early warning system (EWS) for in-hospital mortality that uses electronic health record (EHR) data from patients admitted to a general internal medicine service. We found model performance to differ across subgroups of clinical diagnoses, sex and age. To explore the robustness of the model, we evaluated potentially harmful data shifts across demographics, hospital types, seasons, times of hospital admission, and whether the patient was admitted from an acute care institution or nursing home, without relying on model performance. Interestingly, we found that models trained on community hospitals experience harmful data shifts when evaluated on academic hospitals, whereas the models trained on academic hospitals transfer well to the community hospitals. To improve model performance across hospital sites we employed transfer learning, a strategy that stores knowledge gained from learning one domain and applies it to a different but related domain. We found hospital type-specific models that leverage transfer learning, perform better than models that use all available hospitals. Furthermore, we monitored data shifts over time and identified model deterioration during the COVID-19 pandemic. Typically machine learning models remain locked after deployment, however, this can lead to model deterioration due to data shifts that occur over time. We used continual learning, the process of learning from a continual stream of data in a sequential manner, to mitigate data shifts over time and improve model performance. Overall, our study is a crucial step towards the deployment of clinical AI models, by providing strategies and workflows to ensure the safety and efficacy of these models in real-world settings.
Abstract Objective To assess the effectiveness of nirmatrelvir-ritonavir in the treatment of outpatients with mild to moderate COVID-19 who are at higher risk of developing severe illness, through a systematic review with meta-analyses of observational studies. Methods A systematic search was performed, in accordance with the Cochrane search methods, to identify observational studies that met the inclusion criteria. The outcomes of mortality and hospitalization were analyzed. Search was conducted on PubMed, EMBASE, and The Cochrane Library. Two reviewers independently screened references, selected the studies, extracted the data, assessed the risk of bias using ROBINS-I tool and evaluated the quality of evidence using the GRADE tool. This study followed the PRISMA reporting guideline. Results A total of 16 observational studies and 1,482,923 patients were finally included. The results of the meta-analysis showed that in comparison to standard treatment without antivirals, nirmatrelvir-ritonavir reduced the risk of death by 62% (OR= 0.38; 95% CI: 0.30-0.46; moderate certainty of evidence). In addition, a 53% reduction in the risk of hospital admission was observed (OR = 0.47; 95% CI: 0.36–0.60, with very low certainty of evidence). For the composite outcome of hospitalization and/or mortality, there was a 56% risk reduction (OR=0.44; 95% CI: 0.31-0.64, moderate certainty of evidence). Conclusion The results suggest that nirmatrelvir-ritonavir could be effective in reducing mortality and hospitalization. The results were valid in vaccinated or unvaccinated high-risk individuals with COVID-19. Data from ongoing and future trials may further advance our understanding of the effectiveness and safety of nirmatrelvir-ritonavir and help improve treatment guidelines for COVID-19.
The current study explored the impact of the Covid-19 pandemic on health-related behaviours in the United Kingdom. We conducted a repeated measures latent class analysis with five indicators of health-related behaviours; frequency of alcohol consumption, binge drinking, smoking, BMI and sleep, to identify distinct subgroups of individuals with similar patterns of change across three timepoints during the first 9 months of the pandemic. We hypothesised that various psychosocial risk factors, such as a history of adverse childhood experiences would predict membership in latent classes with a higher probability of engaging in risky health behaviours, and that protective factors, like social support, would be associated with membership in classes with less risky health behaviours. We identified 5 latent classes, and multinomial logistic regression analyses revealed multiple predictors of class membership. Our findings did not support the relationship between poor mental health and the adoption of risky health behaviours. Keywords: Repeated Measures Latent Class Analysis, Covid-19, Adverse Childhood Experiences, Health Related Behaviours
The 2022 FIFA World Cup was the first major multi-continental sporting Mass Gathering Event (MGE) of the post COVID-19 era to allow foreign spectators. Such large-scale MGEs can potentially lead to outbreaks of infectious disease and contribute to the global dissemination of such pathogens. Here we adapt previous work and create a generalisable model framework for assessing the use of disease control strategies at such events, in terms of reducing infections and hospitalisations. This framework utilises a combination of meta-populations based on clusters of people and their vaccination status, Ordinary Differential Equation integration between fixed time events, and Latin Hypercube sampling. We use the FIFA 2022 World Cup as a case study for this framework. Pre-travel screenings of visitors were found to have little effect in reducing COVID-19 infections and hospitalisations. With pre-match screenings of spectators and match staff being more effective. Rapid Antigen (RA) screenings 0.5 days before match day outperformed RT-PCR screenings 1.5 days before match day. A combination of pre-travel RT-PCR and pre-match RA testing proved to be the most successful screening-based regime. However, a policy of ensuring that all visitors had a COVID-19 vaccination (second or booster dose) within a few months before departure proved to be much more efficacious. The State of Qatar abandoned all COVID-19 related travel testing and vaccination requirements over the period of the World Cup. Our work suggests that the State of Qatar may have been correct in abandoning the pre-travel testing of visitors. However, there was a spike in COVID-19 cases and hospitalisations within Qatar over the World Cup. The research outlined here suggests a policy requiring visitors to have had a recent COVID-19 vaccination may have prevented the increase in COVID-19 cases and hospitalisations during the world cup.
The flu season is caused by a combination of different pathogens, including influenza viruses (IVS), that cause the flu, and non-influenza respiratory viruses (NIRVs), that cause common colds or influenza-like illness. These viruses have similar circulation patterns, and weather has been considered a main driver of their dynamics, with peaks in the winter and almost no circulation during the summer in temperate regions. However, after the emergence of SARS-CoV2, in 2019, the dynamics of these respiratory viruses were strongly perturbed worldwide: some infections almost disappeared, others were delayed or occurred “off-season”. This disruption raised questions regarding the dominant role of weather while also providing an unique opportunity to investigate the relevance of different driving factors on the epidemiological dynamics of IVs and NIRVs, including viral interactions, non-pharmacological individual measures (such as masking), or mobility. Here, we use epidemiological surveillance data on several respiratory viruses from Canada and the USA from 2016 to 2023, and tested the effects of weather and mobility in their dynamics before and after the COVID-19 pandemic. Using statistical modelling, we found evidence that whereas in the pre-COVID-19 pandemic period, weather had a strong effect and mobility a limited effect on dynamics; in the post-COVID-19 pandemic period the effect of weather was strongly reduced and mobility played a more relevant role. These results, together with previous studies, indicate that at least some of the behavioral changes resulting from the non-pharmacological interventions implemented during COVID-19 pandemic had a strong effect on the dynamics of respiratory viruses. Furthermore, our results support the idea that these seasonal dynamics are driven by a complex system of interactions between the different factors involved, which probably led to an equilibrium that was disturbed, and perhaps permanently altered, by the COVID-19 pandemic.
Anosmia is common with respiratory virus infections, but loss of taste or chemesthesis is rare. Reports of true taste loss with COVID-19 were viewed skeptically until confirmed by multiple studies. Nasal menthol thresholds are elevated in some with prior COVID-19 infections, but data on oral chemesthesis are lacking. Many patients recover quickly, but precise timing and synchrony of recovery are unclear. Here, we collected broad sensory measures over 28 days, recruiting adults (18-45 years) who were COVID-19 positive or recently exposed (close contacts per U.S. CDC criteria at the time of the study) in the first half of 2021. Participants received nose clips, red commercial jellybeans (Sour Cherry and Cinnamon), and scratch-n-sniff cards (ScentCheckPro). Among COVID-19 cases who entered the study on or before Day 10 of infection, Gaussian Process Regression showed odor identification and odor intensity (two distinct measures of function) each declined relative to controls (close contacts who never developed COVID-19), but effects were larger for intensity than identification. To assess changes during early onset, we identified four COVID-19 cases who enrolled on or prior to Day 1 of their illness: this allowed for visualization of baseline ratings, loss, and recovery of function over time. Four controls were matched for age, gender, and race. Variables included sourness and sweetness (Sour Cherry jellybeans), oral burn (Cinnamon jellybeans), mean orthonasal intensity of four odors (ScentCheckPro), and perceived nasal blockage. Data were plotted over 28 days, creating panel plots for the eight cases and controls. Controls exhibited stable ratings over time. By contrast, COVID-19 cases showed sharp deviations over time. No single pattern of taste loss or recovery was apparent, implying different taste qualities might recover at different rates. Oral burn was transiently reduced for some before recovering quickly, suggesting acute loss may be missed in data collected after acute illness ends. Changes in odor intensity or odor identification were not explained by nasal blockage. Collectively, intensive daily testing shows orthonasal smell, oral chemesthesis and taste were each altered by acute COVID-19 infection, and this disruption was dyssynchronous for different modalities, with variable loss and recovery rates across modalities and individuals.
Estimation of the impact of vaccination and non-pharmaceutical interventions (NPIs) on COVID-19 incidence is complicated by several factors, including the successive emergence of SARS-CoV-2 variants of concern and changing population immunity resulting from vaccination and previous infection. We developed an age-structured multi-strain COVID-19 transmission model framework that could estimate the impact of vaccination and NPIs while accounting for these factors. We applied this approach to French Polynesia, which unlike many countries experienced multiple large COVID-19 waves from multiple variants over the course of the pandemic, interspersed with periods of elimination. We estimated that the vaccination programme averted 54.3% (95% CI 54.0-54.6%) of the 6840 hospitalisations and 60.2% (95% CI 59.9-60.5%) of the 1280 hospital deaths that would have occurred in a baseline scenario without any vaccination up to May 2022. Vaccination also averted an estimated 28.4% (95% CI 28.2-28.7%) of 193,000 symptomatic cases in the baseline scenario. We estimated the booster campaign contributed 3.4%, 2.9% and 3.3% to overall reductions in cases, hospitalisations and hospital deaths respectively. Our results suggested that removing, or altering the timings of, the lockdowns during the first two waves had non-linear effects on overall incidence owing to the resulting effect on accumulation of population immunity. Our estimates of vaccination and booster impact differ from those for other countries due to differences in age structure, previous exposure levels and timing of variant introduction relative to vaccination, emphasising the importance of detailed analysis that accounts for these factors.
Background: Leadership during the COVID-19 pandemic often manifested as a command-and-control style of leadership which had detrimental emotional impacts on staff particularly the nursing workforce. Organisational responsibility for staff wellbeing would be necessary in another pandemic and leadership emerged as a key indicator of the overall health of an organisation and its workforce. Leadership can have detrimental effects on staff wellbeing or it can greatly boost their ability to handle a crisis. We sought to explore the interrelationship between leadership and nurses wellbeing in an inner-city university hospital during the initial wave of the pandemic. Methods: Secondary analysis of interview data collected during a hospital-wide evaluation of barriers and facilitators to changes implemented to support the surge of COVID-19 related admissions during wave 1. Data were collected through semi-structured video interviews between May and July 2020. Interviews were analysed using Framework analysis Results: Thirty-one nurses participated including matrons (n=7), sisters (n=8) and specialist nursing roles (n=16). Three overarching themes were identified: impact on nurses, personal factors and organisational factors. The impact on nurses manifested as distress and fatigue. Coping and help-seeking behaviours were found to be the two personal factors which underpinned nurses wellbeing. The organisational factors that impacted nurses wellbeing included decision-making, duty and teamwork. Conclusions: The wellbeing of the workforce is pivotal to the health service, and it is mutually beneficial for patients, staff, and leaders. Addressing how beliefs and misconceptions around wellbeing are communicated, and accessing psychological support is a key priority to support nurses during pandemics.
Abstract Purpose and motivation of this study: Angiotensin-converting enzyme inhibitors (ACEI) and Aldosterone receptor blockers (ARBs) are one most commonly used drugs for the treatment of cardiovascular disease among other comorbidities. As multiple studies have shown that covid virus binds to the ACE2 receptor for entry into the cell. ACEI and ARBs are shown to modulate the ACE2 receptor hence, it is important to see if there are any correlations between the use of medicine and the infectivity of COVID-19. The purpose of this study is to find if the use of ACEI /ARBs can in fact increase or decrease the spread of COVID-19. Method: This is a systemic review study during which all studies which helped us answer the question, of how the use of ACEI and ARBs can affect the transmission of the COVID-19 virus, were analyzed and reviewed to draw a conclusion about clinical safety and requirements of ACEI and ARBs in COVID-19 patients. Result: After a complete review of all the available data very conflicting results were found. Many studies showed an increase in the transmission of COVID-19 while others showed a decreased risk of COVID-19 transmission with ACEI and ARBs use. Both results were statistically significant. Conclusion: With these conflicting results the question we started with comes up again. Should we or should we not use ACEI & ARBs with covid patients? What should be the best clinical response with the use of ACEI & ARBs if it modulates transmission? To answer these, one must look not only at the statistically significant results of studies but also at the disease progression without ACEI & ARBs treatment regimes. Due to the small amount of data, there is currently no clear conclusive evidence to suggest that ACE inhibitors either increase or decrease the risk of COVID-19 transmission or the severity of the disease. Thus, more and larger studies should be developed to find a concrete answer. Until that these medicines should not be discontinued as the morbidities of cardiovascular diseases are high, and the use of ACEI and ARBs is central to the treatment.
Objectives: The COVID-19 has led to many studies of seroprevalence. A number of methods exist in the statistical literature to correctly estimate disease prevalence in the presence of diagnostic test misclassification, but these methods seem to be less known and not routinely used in the public health literature. We aimed to show how widespread the problem is in recent publications, and to quantify the magnitude of bias introduced when correct methods are not used. Methods: We examined a sample of recent literature to determine how often public health researcher did not account for test performance in estimates of seroprevalence. Using straightforward calculations, we estimated the amount of bias introduced when reporting the proportion of positive test results instead of using sensitivity and specificity to estimate disease prevalence. Results: Of the seroprevelance studies sampled, 87% failed to account for sensitivity and specificity. Expected bias is often more than is desired in practice, ranging from 1% to 10%. Conclusions: Researchers conducting studies of prevalence should correctly account for test sensitivity and specificity in their statistical analysis.
Vaccination remains the primary strategy for ending the COVID-19 pandemic. However, vaccination rates are still low in low-income countries. The primary goal of this study was to describe the status of COVID-19 vaccine acceptance and hesitancy among women in Guinea and to identify associated predictors. We conducted a cross-sectional study in five Guinean cities (Conakry, Mamou, Kindia, Kankan and N9zérékoré) across the four natural regions between Mar 22 and Aug 25 2021. Participants aged 18 were randomly recruited from the healthcare workers (HCWs) and the general population (GP). We used multivariate logistic regression to identify facilitators and barriers to acceptance of COVID-19 vaccination and a classification and regression tree (CART) to extract the profile of predictors. We included 2,208 women among the HCWs and 1,121 in the GP. Most HCWs (63%) were already vaccinated, compared to only 28% of GP. The main factors associated with acceptance of a COVID-19 vaccine in the HCWs were an absence of pregnancy ORA = 4.46 [CI95%: 3.08, 6.52] and positive subjective norms ORA = 2.34 [CI95%: 1.92, 2.84]. Regarding the GP, the main factors were the ability to receive the vaccine ORA = 5.20 [CI95%: 3.45, 8.01] and being adult ORA = 2.25 [CI95%: 1.34, 3.79] associated with acceptance of vaccination. Vaccination rates were higher in the HCWs. Favourable subjective norms and ability to receive the vaccine were facilitators of acceptance of COVID-19 vaccination, while youth and pregnancy were barriers to the approval of the COVID-19 vaccine.
Clinical Performance Evaluation of the CareSuperb™ COVID-19 Antigen Home Test - Condition: COVID-19
Intervention: Device: CareSuperb COVID-19 Antigen Home Test Kit
Sponsor: AccessBio, Inc.
Recruiting
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
MP0420 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition: COVID-19
Interventions: Drug: MP0420; Drug: Placebo; Biological: Remdesivir
Sponsors: National Institute of Allergy and Infectious Diseases (NIAID); International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); University of Copenhagen; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; AIDS Clinical Trials Group; National Heart, Lung, and Blood Institute (NHLBI); US Department of Veterans Affairs; Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN); Molecular Partners AG; University of Minnesota
Active, not recruiting
AZD7442 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition: COVID-19
Interventions: Biological: AZD7442; Biological: Placebo; Biological: Remdesivir
Sponsors: National Institute of Allergy and Infectious Diseases (NIAID); International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); University of Copenhagen; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; AIDS Clinical Trials Group; National Heart, Lung, and Blood Institute (NHLBI); US Department of Veterans Affairs; Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN); AstraZeneca; University of Minnesota
Active, not recruiting
PF-07304814 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition: COVID-19
Interventions: Drug: PF-07304814; Drug: Placebo; Biological: Remdesivir
Sponsors: National Institute of Allergy and Infectious Diseases (NIAID); International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); University of Copenhagen; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; AIDS Clinical Trials Group; National Heart, Lung, and Blood Institute (NHLBI); US Department of Veterans Affairs; Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN); Pfizer; University of Minnesota
Suspended
VIR-7831 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition: COVID-19
Interventions: Biological: VIR-7831; Biological: Placebo; Biological: Remdesivir
Sponsors: National Institute of Allergy and Infectious Diseases (NIAID); International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); University of Copenhagen; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; AIDS Clinical Trials Group; National Heart, Lung, and Blood Institute (NHLBI); US Department of Veterans Affairs; Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN); Vir Biotechnology, Inc.; GlaxoSmithKline; University of Minnesota
Completed
BRII-196/BRII-198 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition: COVID-19
Interventions: Biological: BRII-196; Biological: BRII-198; Biological: Placebo; Biological: Remdesivir
Sponsors: National Institute of Allergy and Infectious Diseases (NIAID); International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); University of Copenhagen; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; AIDS Clinical Trials Group; National Heart, Lung, and Blood Institute (NHLBI); US Department of Veterans Affairs; Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN); Brii Biosciences Limited; University of Minnesota
Completed
LY3819253 (LY-CoV555) for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) - Condition: COVID-19
Interventions: Biological: LY3819253; Biological: Placebo; Biological: Remdesivir
Sponsors: National Institute of Allergy and Infectious Diseases (NIAID); International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); University of Copenhagen; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; AIDS Clinical Trials Group; National Heart, Lung, and Blood Institute (NHLBI); US Department of Veterans Affairs; Prevention and Early Treatment of Acute Lung Injury (PETAL); Cardiothoracic Surgical Trials Network (CTSN); Eli Lilly and Company; University of Minnesota
Completed
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
Short-term Effects of Transdermal Estradiol on Female COVID-19 Patients - Conditions: COVID-19; Hormone Replacement Therapy
Interventions: Drug: Climara 0.1Mg/24Hr Transdermal System; Other: Hydrogel patch
Sponsors: Istanbul University - Cerrahpasa (IUC); Turkish Menopause and Osteoporosis Society; Karakoy Rotary Club; Rebul Pharmacy
Completed
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
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
Teletechnology-assisted Home-based Exercise Program for Severe COVID-19 - Conditions: COVID-19; Telerehabilitation
Intervention: Behavioral: Teletechnology-assisted home-based pulmonary rehabilitation
Sponsor: National Taiwan University Hospital
Not yet recruiting
Multifaceted involvements of Paneth cells in various diseases within intestine and systemically - Serving as the guardians of small intestine, Paneth cells (PCs) play an important role in intestinal homeostasis maintenance. Although PCs uniquely exist in intestine under homeostasis, the dysfunction of PCs is involved in various diseases not only in intestine but also in extraintestinal organs, suggesting the systemic importance of PCs. The mechanisms under the participation of PCs in these diseases are multiple as well. The involvements of PCs are mostly characterized by limiting intestinal…
Synthesis, molecular docking, and binding Gibbs free energy calculation of β-nitrostyrene derivatives: Potential inhibitors of SARS-CoV-2 3CL protease - The outbreak of novel coronavirus disease 2019 (COVID-19), caused by the novel coronavirus (SARS-CoV-2), has had a significant impact on human health and the economic development. SARS-CoV-2 3CL protease (3CLpro) is highly conserved and plays a key role in mediating the transcription of virus replication. It is an ideal target for the design and screening of anti-coronavirus drugs. In this work, seven β-nitrostyrene derivatives were synthesized by Henry reaction and β-dehydration reaction, and…
Engineering Nanomolar Potent Protein-based Inhibitors for Papain-like Protease Guided by Residue Correlation Network - We developed a rational protocol with a minimal number of mutated residues to create highly potent and selective protein-based inhibitors. Guided by an interaction and dihedral correlation network of ubiquitin (Ub) and MERS coronaviral papain-like protease (PLpro) complex, our designed ubiquitin variant (UbV) with 3 mutated residues (A46F, K48E, and E64Y) resulted in a ~3,500-fold increase in functional inhibition as compared with the wildtype Ub (wtUb). Further optimization with C-terminal R74N…
Development of monoclonal antibody-based blocking ELISA for detecting SARS-CoV-2 exposure in animals - The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to public health. Besides humans, SARS-CoV-2 can infect several animal species. Highly sensitive and specific diagnostic reagents and assays are urgently needed for rapid detection and implementation of strategies for prevention and control of the infection in animals. In this study, we initially developed a panel of monoclonal antibodies (mAbs) against SARS-CoV-2 nucleocapsid (N)…
Cell Surface Nucleocapsid Protein Expression: A Betacoronavirus Immunomodulatory Strategy - We recently reported that SARS-CoV-2 Nucleocapsid (N) protein is abundantly expressed on the surface of both infected and neighboring uninfected cells, where it enables activation of Fc receptor-bearing immune cells with anti-N antibodies (Abs) and inhibits leukocyte chemotaxis by binding chemokines (CHKs). Here, we extend these findings to N from the seasonal human coronavirus (HCoV)-OC43, which is also robustly expressed on the surface of infected and non-infected cells by binding…
Totally-green cellulosic fiber with prominent sustained antibacterial and antiviral properties for potential use in spunlaced non-woven fabric production - The worldwide spread of COVID-19 has put a higher requirement for personal medical protective clothing, developing protective clothing with sustained antibacterial and antiviral performance is the priority for safe and sustaining application. For this purpose, we develop a novel cellulose based material with sustained antibacterial and antiviral properties. In the proposed method, the chitosan oligosaccharide (COS) was subjected to a guanylation reaction with dicyandiamide in the presence of…
Risk perception of compound emergencies: A household survey on flood evacuation and sheltering behavior during the COVID-19 pandemic - Compound hazards are derived from independent disasters that occur simultaneously. Since the outbreak of COVID-19, the coupling of low-probability high-impact climate events has introduced a novel form of conflicting stressors that inhibits the operation of traditional logistics developed for single-hazard emergencies. The competing goals of hindering virus contagion and expediting massive evacuation have posed unique challenges for community safety. Yet, how a community perceives associated…
Ginsenosides, potential TMPRSS2 inhibitors, a trade-off between the therapeutic combination for anti-PD-1 immunotherapy and the treatment of COVID-19 infection of LUAD patients - Background: Acting as a viral entry for coronavirus to invade human cells, TMPRSS2 has become a target for the prevention and treatment of COVID-19 infection. Before this, TMPRSS2 has presented biological functions in cancer, but the roles remain controversial and the mechanism remains unelucidated. Some chemicals have been reported to be inhibitors of TMPRSS2 and also demonstrated other pharmacological properties. At this stage, it is important to discover more new compounds targeting TMPRSS2,…
Efficient CRISPR-Cas13d-Based Antiviral Strategy to Combat SARS-CoV-2 - The current SARS-CoV-2 pandemic forms a major global health burden. Although protective vaccines are available, concerns remain as new virus variants continue to appear. CRISPR-based gene-editing approaches offer an attractive therapeutic strategy as the CRISPR-RNA (crRNA) can be adjusted rapidly to accommodate a new viral genome sequence. This study aimed at using the RNA-targeting CRISPR-Cas13d system to attack highly conserved sequences in the viral RNA genome, thereby preparing for future…
Repurposing Astragalus Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects - The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health. In an effort to develop novel anti-coronavirus therapeutics and achieve prophylactics, we used gene set enrichment analysis (GSEA) for drug screening and identified that Astragalus polysaccharide (PG2), a mixture of polysaccharides purified from Astragalus membranaceus, could effectively reverse COVID-19 signature genes….
Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID - The COVID-19 pandemic has caused havoc all around the world. The causative agent of COVID-19 is the novel form of the coronavirus (CoV) named SARS-CoV-2, which results in immune system disruption, increased inflammation, and acute respiratory distress syndrome (ARDS). T cells have been important components of the immune system, which decide the fate of the COVID-19 disease. Recent studies have reported an important subset of T cells known as regulatory T cells (Tregs), which possess…
Ex Vivo Immune Responsiveness to SARS-CoV-2 Omicron BA.5.1 Following Vaccination with Unmodified mRNA-Vaccine - (1) Background: The high incidence of SARS-CoV-2 infection in vaccinated persons underscores the importance of individualized re-vaccination. PanIg antibodies that act against the S1/-receptor binding domain quantified in serum by a routine diagnostic test (ECLIA, Roche) can be used to gauge the individual ex vivo capacity of SARS-CoV-2 neutralization. However, that test is not adapted to mutations in the S1/-receptor binding domain, having accumulated in SARS-CoV-2 variants. Therefore, it might…
Comparison of Immunogenicity and Reactogenicity of Five Primary Series of COVID-19 Vaccine Regimens against Circulating SARS-CoV-2 Variants of Concern among Healthy Thai Populations - To compare immunogenicity and reactogenicity of five COVID-19 vaccine regimens against wild-type SARS-CoV-2 and variants of concern (VoCs) among Thai populations, a prospective cohort study was conducted among healthy participants aged ≥18 years who had never been infected with COVID-19 and were scheduled to get one of the five primary series of COVID-19 vaccine regimens, including CoronaVac/CoronaVac, AZD1222/AZD1222, CoronaVac/AZD1222, AZD1222/BNT162b2, and BNT162b2/BNT162b2. Anti-receptor…
Immunogenicity and Safety of the Third Booster Dose with mRNA-1273 COVID-19 Vaccine after Receiving Two Doses of Inactivated or Viral Vector COVID-19 Vaccine - The changes in the severe acute respiratory syndrome coronavirus 2 and the tapering of immunity after vaccination have propelled the need for a booster dose vaccine. We aim to evaluate B and T cell immunogenicity and reactogenicity of mRNA-1273 COVID-19 vaccine (100 µg) as a third booster dose after receiving either two doses of inactivated COVID-19 vaccine (CoronaVac) or two doses of viral vector vaccine (AZD1222) in adults not previously infected with COVID-19. The anti-receptor-binding-domain…
Binding of SARS-CoV-2 Structural Proteins to Hemoglobin and Myoglobin Studied by SPR and DR LPG - One of the first clinical observations related to COVID-19 identified hematological dysfunctions. These were explained by theoretical modeling, which predicted that motifs from SARS-CoV-2 structural proteins could bind to porphyrin. At present, there is very little experimental data that could provide reliable information about possible interactions. The surface plasmon resonance (SPR) method and double resonance long period grating (DR LPG) were used to identify the binding of S/N protein and…