The emergence of successive SARS-CoV-2 variants of concern (VOC) during 2020-22, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both pathogen biology and changing host characteristics - such as varying levels of immunity - can combine to influence replication and transmission of SARS-CoV-2 within and between hosts. Disentangling the role of variant and host in individual-level viral shedding of VOCs is essential to inform COVID-19 planning and response, and interpret past epidemic trends. Using data from a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening, we developed a Bayesian hierarchical model to reconstruct individual-level viral kinetics and estimate how different factors shaped viral dynamics, measured by PCR cycle threshold (Ct) values over time. Jointly accounting for both inter-individual variation in Ct values and complex host characteristics - such as vaccination status, exposure history and age - we found that age and number of prior exposures had a strong influence on peak viral replication. Older individuals and those who had at least five prior antigen exposures to vaccination and/or infection typically had much lower levels of shedding. Moreover, we found evidence of a correlation between the speed of early shedding and duration of incubation period when comparing different VOCs and age groups. Our findings illustrate the value of linking information on participant characteristics, symptom profile and infecting variant with prospective PCR sampling, and the importance of accounting for increasingly complex population exposure landscapes when analysing the viral kinetics of VOCs.
Introduction - Guidelines for diagnosing and managing Post-COVID syndrome have been rapidly developed. Consistency of the application of these guidelines in primary care is unknown. Electronic health records provide an opportunity to review the use of codes relating to Post-COVID syndrome. This paper explores the use of primary care records as a surrogate uptake measure for NICEs rapid guideline managing the long-term effects of COVID-19 by measuring the use of Post-COVID syndrome diagnosis and referral codes in the pathway. Method - With the approval of NHS England we used routine clinical data from the OpenSafely-EMIS/-TPP platforms. Counts of Post-COVID syndrome diagnosis and referral codes were generated from a cohort of all adults, establishing numbers of diagnoses and referrals following diagnosis. The relationship between Post-COVID syndrome diagnosis and referral codes was explored with reference to NICEs rapid guideline. Results - Of over 45 million patients, 69,220 (0.15%) had a Post-COVID syndrome diagnostic code, and 67,741 (0.15%) had a referral code. 78% of referral codes did not have an associated diagnosis code. 79% of diagnosis codes had no subsequent referral code. Only 18,633 (0.04%) had both. There were higher rates of both diagnosis and referral in those who were more deprived, female and some ethnic groups. Discussion - This study demonstrates variation in diagnosis and referral coding rates for Post-COVID syndrome across different patient groups. The results, with limited crossover of referral and diagnostic codes, suggest only one type of code is usually recorded. Recording one code limits the use of routine data for monitoring Post-COVID syndrome diagnosis and management, but suggests several areas for improvement in coding. Post-COVID syndrome coding, particularly diagnosis coding, needs to improve before administrators and researchers can use it to evaluate care pathways.
In recent years, hospital managers have reported increasing numbers of psychiatric hospital admissions in the Western Cape Province of South Africa, driven by poverty and substance use. We aimed to examine this trend, and the impact of the COVID-19 pandemic, as well as assess factors associated with linkage to ambulatory services following hospital discharge and repeat psychiatric admissions. Using electronic health data from the Provincial Health Data Centre, a consolidated routine service database, all psychiatric hospital admissions in the Western Cape public sector from 2015 to 2022 were analyzed, stratified by hospital level. Mixed effects logistic regression was used in this cohort study to determine the factors associated with successful linkage to ambulatory services within 30 days following hospital discharge, and repeat psychiatric admission within 30 and 90 days. We found that psychiatric hospital admissions, particularly at the district/acute level, were increasing prior to 2020 and an increasing proportion of diagnoses were substance related. 40% of admissions at the district level had not been seen at a primary health care facility in the year before the admission. Male patients and those with substance use disorders were less likely to be successfully linked to outpatient services following discharge. Successful linkage was one of the most protective factors against readmission within 90 days with an adjusted odds ratio of 0.76 (95%CI 0.73-0.79) and 0.45 (95%CI 0.42-0.49) at district/acute and specialized hospitals respectively. Improving linkage to ambulatory services by mental health patients post-discharge is likely to avert hospital readmissions.
Background: Registration in the Dutch national COVID-19 vaccination register requires consent from the vaccinee. This causes misclassification of non-consenting vaccinated persons as being unvaccinated. We quantified and corrected the resulting information bias in the estimation of vaccine effectiveness (VE). Methods: National data were used for the period dominated by the SARS-CoV-2 Delta variant (11 July to 15 November 2021). VE ((1-relative risk)*100%) against COVID-19 hospitalization and ICU admission was estimated for individuals 12-49, 50-69, and ≥70 years of age using negative binomial regression. Anonymous data on vaccinations administered by the Municipal Health Services were used to determine informed consent percentages and estimate corrected VEs by iterative data augmentation. Absolute bias was calculated as the absolute change in VE; relative bias as uncorrected / corrected relative risk. Results: A total of 8,804 COVID-19 hospitalizations and 1,692 COVID-19 ICU admissions were observed. The bias was largest in the 70+ age group where the non-consent proportion was 7.0% and observed vaccination coverage was 87%: VE of primary vaccination against hospitalization changed from 75.5% (95% CI 73.5-77.4) before to 85.9% (95% CI 84.7-87.1) after correction (absolute bias -10.4 percentage point, relative bias 1.74). VE against ICU admission in this group was 88.7% (95% CI 86.2-90.8) before and 93.7% (95% CI 92.2-94.9) after correction (absolute bias -5.0 percentage point, relative bias 1.79). Conclusions: VE estimates can be substantially biased with modest non-consent percentages for registration of vaccination. Data on covariate specific non-consent percentages should be available to correct this bias.
Objectives: To estimate the proportion of female university students reporting overeating (EO) in response to emotions during the COVID-19 university closures, and to investigate social and psychological factors associated with this response to stress. Design: Online survey gathered sociodemographic data, alcohol/drugs use disorders, boredom proneness and impulsivity using validated questionnaires, and EO using the Emotional Overeating Questionnaire (EOQ) assessing eating in response to six emotions (anxiety, sadness, loneliness, anger, fatigue, happiness), whose structure remains to be determined. Participants: Sample of 302 female students from Rennes University, France. Main Outcome Measure: Frequencies of emotional overeating. Analysis: The frequency of emotional overeating was expressed for each emotion as percentages. Exploratory Factor analyses (EFA) were used to determine EOQ structure and provide an index of all EOQ items used for further analysis. Linear regression models were used to explore relationships between EO and others covariates. Results: Nine in ten participants reported intermittent EO in the last 28 days, mostly during 6 to 12 days, in response to Anxiety (75.5%), Sadness (64.5%), Happiness (59.9%), Loneliness (57.9%), Tiredness (51.7%), and to a lesser extent to Anger (31.1%). EFA evidenced a one-factor latent variable reflecting “Distress-Induced Overeating” positively correlated with internal boredom proneness, tobacco use, attentional impulsivity, inability to resist emotional cues, and loss of control over food intake, and negatively with age and well-being. EO was unrelated to body mass index or substance abuse. Conclusion and Implications: Nine in ten female students reported emotional overeating during the COVID-19 university closure. This response to stress was related to eating tendencies typical of young women, but also to personality/behavioral patterns such as boredom and impulsivity proneness. Better understanding of the mechanisms underlying EO in response to stress and lack of external/social stimulation would improve preventive interventions.
Background Wastewater-based surveillance (WBS) on an institutional level was implemented during the COVID-19 pandemic, including carceral facilities. In this study of a mega-jail, we examined the relationship between COVID-19 diagnostic test results from jail residents and the PCR signal for SARS-CoV-2 detection in weekly samples of jail wastewater over a 28-week period. Methods This study in a Georgia Jail (average population ~2,700) was conducted October 2021-May 2022. Weekly on-site wastewater samples were collected (Moore Swabs) and tested for SARS-CoV-2 RNA using RTqPCR. The source of wastewater was identified using a tracer dye. The jail offered residents rapid antigen testing at entry. We conducted periodic mass screenings via RT-PCR of nasal swabs. We aggregated individual test data, calculated the Spearman correlation coefficient, and performed logistic regression to examine the relationship between the strength of the SARS-CoV-2 PCR signal (Ct value) in wastewater and the proportion of the jail population that tested positive for COVID-19. Results Overall, 3770 individual nasal specimens were collected; 3.4% were COVID-positive. Weekly diagnostic test positivity ranged from 0%-29.5%. Dye tests demonstrated that a single wastewater collection point was sufficiently representative of the jails aggregate viral load. Twenty-five wastewater samples were collected. RT-qPCR Ct values for wastewater samples with SARS-CoV-2 RNA ranged from 28.1-39.9. A strong inverse correlation was observed between diagnostic test positivity and Ct value (r= -0.67, p < 0.01). Conclusion WBS was shown to be an effective strategy for surveilling COVID-19 in a large jail. Strong partnerships with the jail administration are essential to the success of WBS surveillance.
Objectives: The United States confronted a “triple-demic” of influenza, respiratory syncytial virus, and COVID-19 in the winter of 2022, resulting in increased respiratory infections and a higher demand for medical supplies. It is urgent to analyze each epidemic and their co-occurrence in space and time to identify hotspots and provide insights for public health strategy. Methods: We used retrospective space-time scan statistics to retrospect the situation of COVID-19, influenza, and RSV in 51 US states from October 2021 to February 2022, and then applied prospective space-time scan statistics to monitor spatiotemporal variations of each individual epidemic, respectively and collectively from October 2022 to February 2023. Results: Our analysis indicated that compared to the winter of 2021, COVID-19 cases decreased while influenza and RSV infections increased significantly during the winter of 2022. We revealed that a twin-demic high-risk cluster of influenza and COVID-19 but no triple-demic clusters emerged during the winter of 2021. We further identified a large high-risk cluster of triple-demic in the central US from late November, with COVID-19, influenza, and RSV having relative risks of 1.14, 1.90, and 1.59, respectively. The number of states at high risk for multiple-demic increased from 15 in October 2022 to 21 in January 2023. Conclusion: Our study provides a novel spatiotemporal perspective to explore and monitor the transmission patterns of the triple epidemic, which could inform public health authorities9 resource allocation to mitigate future outbreaks.
The Standard of Care Combined With Glucocorticoid in Elderly People With Mild or Moderate COVID-19 - Condition: COVID-19
Intervention: Drug: Glucocorticoid
Sponsor: Huashan Hospital
Not yet recruiting
Investigation of the Effect on Cognitive Skills of COVID-19 Survivors - Condition: COVID-19
Intervention: Other: green walking and intelligence gam
Sponsors: Bayburt University; Karadeniz Technical University
Completed
Conducting Clinical Trials of the Medicine “Rutan Tablets 0.1g” No. 10 in the Complex Therapy of COVID-19 - Condition: Patients With COVID-19
Interventions: Drug: The drug “Rutan 0.1”.; Other: Basic treatment
Sponsor: Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan
Completed
The Effect of Special Discharge Training in the COVID-19 - Condition: COVID-19 Pneumonia
Intervention: Other: COVID-19 Discharge Education
Sponsor: Kilis 7 Aralik University
Completed
Evaluation of Safety, Tolerability, Reactogenicity, Immunogenicity of Baiya SARS-CoV-2 Vax 2 as a Booster for COVID-19 - Conditions: COVID-19 Vaccine; COVID-19
Interventions: Biological: 50 μg Baiya SARS-CoV-2 Vax 2; Other: Placebo
Sponsor: Baiya Phytopharm Co., Ltd.
Not yet recruiting
Arginine Replacement Therapy in COVID-19 - Condition: COVID-19
Intervention: Drug: Arginine Hydrochloride
Sponsor: Emory University
Not yet recruiting
Effectiveness of a Second COVID-19 Vaccine Booster in Chinese Adults - Condition: COVID-19
Interventions: Biological: Intramuscularly administered Ad5-nCoV vaccine; Biological: Aerosolized Ad5-nCoV; Biological: DelNS1-2019-nCoV-RBD-OPT1; Biological: SYS6006
Sponsor: Jiangsu Province Centers for Disease Control and Prevention
Not yet recruiting
Physiotherapy in Mutated COVID-19 Patients - Condition: COVID-19 Pandemic
Intervention: Behavioral: Physiotherapy
Sponsor: Giresun University
Completed
Studying the Efficiency of the Natural Preparation Rutan in Children in the Treatment of COVID-19, ARVI - Condition: COVID-19 Respiratory Infection
Interventions: Drug: Rutan 25 mg; Other: Control group
Sponsor: Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan
Completed
A Pilot Study Evaluating the Efficacy of the Vielight Neuro RX Gamma in the Treatment of Post COVID-19 Cognitive Impairment - Condition: Post COVID-19 Cognitive Impairment
Interventions: Device: Vielight Neuro RX Gamma active device; Device: Vielight Neuro RX Gamma sham device
Sponsor: Vielight Inc.
Not yet recruiting
To Explore the Regulatory Effect of Combined Capsule FMT on the Levels of Inflammatory Factors in Peripheral Blood of Patients With COVID-19 During Treatment. - Conditions: Fecal Microbiota Transplantation; COVID-19 Infection
Intervention: Procedure: Fecal microbiota transplantation
Sponsor: Shanghai 10th People’s Hospital
Completed
Use of a Hypochlorous Acid Spray Solution in the Treatment of COVID-19 Patients : COVICONTROL Study . - Condition: SARS CoV 2 Infection
Interventions: Other: Spray with Hypochlorous Acid Group; Other: Spray with Placebo Group
Sponsor: University of Monastir
Recruiting
Telerehabilitation Program and Detraining in Patients With Post-COVID-19 Sequelae - Condition: COVID-19 Acute Respiratory Distress Syndrome
Intervention: Other: Telerehabilitation program
Sponsor: Campus docent Sant Joan de Déu-Universitat de Barcelona
Completed
COVID-19 Vaccine Uptake Amongst Underserved Populations in East London - Conditions: COVID-19; Influenza; Vaccination Refusal
Intervention: Device: Patient Engagement tool
Sponsors: Queen Mary University of London; Social Action for Health
Not yet recruiting
REVERSE-Long COVID-19 With Baricitinib Pilot Study - Condition: Post-Acute COVID-19 Syndrome
Intervention: Drug: Baricitinib 4 MG
Sponsors: Vanderbilt University Medical Center; Emory University; University of California, San Francisco; University of Minnesota; Vanderbilt University; Yale University
Not yet recruiting
Immunosuppressants exert differential effects on pan-coronavirus infection and distinct combinatory antiviral activity with molnupiravir and nirmatrelvir - CONCLUSIONS: Different immunosuppressants have distinct effects on coronavirus replication, with 6-TG, MPA, tofacitinib and filgotinib possessing pan-coronavirus antiviral activity. The combinations of MPA, 6-TG, tofacitinib and filgotinib with antiviral drugs exerted an additive or synergistic antiviral activity. Thus, these findings provide an important reference for optimal management of immunocompromised patients infected with coronaviruses.
Myricetin possesses the potency against SARS-CoV-2 infection through blocking viral-entry facilitators and suppressing inflammation in rats and mice - CONCLUSION: Our findings showed that myricetin inhibited HCoV-229E and SARS-CoV-2 replication in vitro, blocked SARS-CoV-2 virus entry facilitators and relieved inflammation through the RIPK1/NF-κB pathway, suggesting that this flavonol has the potential to be developed as a therapeutic agent against COVID-19.
Promoting cognitive health: a virtual group intervention for community-living older adults - CONCLUSIONS: The synchronous virtual group intervention was shown to be feasible for the elderly in the community who participated in the study.
SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19 - The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden. Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia (VITT) are both associated with thrombosis and thrombocytopenia; however, the underlying mechanisms remain inadequately understood. Both infection and vaccination utilize the spike protein receptor-binding domain (RBD) of SARS-CoV-2. We found that intravenous injection of recombinant RBD caused significant…
HSPA5 Promotes Attachment and Internalization of Porcine Epidemic Diarrhea Virus through Interaction with the Spike Protein and the Endo-/Lysosomal Pathway - Porcine epidemic diarrhea virus (PEDV) has caused huge economic losses to the global pig industry. The swine enteric coronavirus spike (S) protein recognizes various cell surface molecules to regulate viral infection. In this study, we identified 211 host membrane proteins related to the S1 protein by pulldown combined with liquid-chromatography tandem mass spectrometry (LC-MS/MS) analysis. Among these, heat shock protein family A member 5 (HSPA5) was identified through screening as having a…
Evaluation of the Inhibition Potency of Nirmatrelvir against Main Protease Mutants of SARS-CoV-2 Variants - SARS-CoV-2 continues to pose a threat to public health. Main protease (M^(pro)) is one of the most lucrative drug targets for developing specific antivirals against SARS-CoV-2 infection. By targeting M^(pro), peptidomimetic nirmatrelvir is able to inhibit viral replication of SARS-CoV-2 and reduce the risk for progression to severe COVID-19. However, multiple mutations in the gene encoding M^(pro) of emerging SARS-CoV-2 variants raise a concern of drug resistance. In the present study, we…
Culture and pandemic control at cross-roads: navigating the burial guidelines for COVID-19-related deaths in a Ghanaian setting - CONCLUSIONS: Insensitivity to socio-cultural practices compromised the implementation of the COVID-19 pandemic control interventions, particularly, the COVID-19-related death and burial protocols. Some compromises that were not sanctioned by the protocols were reached to allow health officials and families respectfully bury their dead. These findings call for the need to prioritize the incorporation of sociocultural practices in future pandemic prevention and management strategies.
Rational Design of Covalent Kinase Inhibitors by an Integrated Computational Workflow (Kin-Cov) - Covalent kinase inhibitors (CKIs) hold great promise for drug development. However, examples of computationally guided design of CKIs are still scarce. Here, we present an integrated computational workflow (Kin-Cov) for rational design of CKIs. The design of the first covalent leucine-zipper and sterile-α motif kinase (ZAK) inhibitor was presented as an example to showcase the power of computational workflow for CKI design. The two representative compounds, 7 and 8, inhibited ZAK kinase with…
Essential Oil Derived from Underutilized Plants Cymbopogon khasianus Poses Diverse Biological Activities against “Aspergillosis” and “Mucormycosis” - Palmrosa essential oil (PEO) from Cymbopogon khasianus, is used as complementary and traditional medicine worldwide. The present study aimed at compositional profiling of PEO and molecular docking of PEO bioactive compound geraniol against fungal enzymes chitin synthase (CS), UDP-glycosyltransferase (UDPG) and glucosamine-6-phosphate synthase (GPS), as apposite sites for drug designing against “Aspergillosis” and “Mucormycosis” and in vitro confirmation. Compositional profile of PEO was…
Detection of SARS-CoV-2 Antibodies: Comparison of Enzyme Immunoassay, Surrogate Neutralization and Virus Neutralization Test - CONCLUSIONS: sVNT appeared to be a reliable method for the assessment COVID-19 serology in patients with high antibody levels, while false-negative results were frequently observed in patients with low NT titers.
Elucidating Atomistic Insight into the Dynamical Responses of the SARS-CoV-2 Main Protease for the Binding of Remdesivir Analogues: Leveraging Molecular Mechanics To Decode the Inhibition Mechanism - To combat mischievous coronavirus disease followed by continuous upgrading of therapeutic strategy against the antibody-resistant variants, the molecular mechanistic understanding of protein-drug interactions is a prerequisite in the context of target-specific rational drug development. Herein, we attempt to decipher the structural basis for the inhibition of SARS-CoV-2 main protease (M^(pro)) through the elemental analysis of potential energy landscape and the associated thermodynamic and…
Risk connectedness between crude oil, gold and exchange rates in China: Implications of the COVID-19 pandemic - This study examined the risk connectedness and its asymmetry between oil, gold, and foreign exchange under the realized volatility, spillover index framework, and high-frequency data during the COVID-19 pandemic. It was found that: (1) At the beginning of the pandemic outbreak, the total volatility spillover in the system declined, which may indicate that the pandemic cuts the trading activities in the financial markets by inhibiting personnel mobility, then, the spillover experienced a…
Prognostic immune markers identifying patients with severe COVID-19 who respond to tocilizumab - CONCLUSIONS: We found that tocilizumab has pleiotropic effects and that clinical response to this drug remain heterogenous. Our data suggest that it is possible to identify patients who will respond to treatment and that the administration of tocilizumab is able to restore the immune balance through the re-establishment of different cell populations affected by SARS-COV-2 infection, highlighting the importance of temporal examination of the pathological features from the diagnosis.
Immunogenicity of NVX-CoV2373 in PREVENT-19: A Phase 3, Randomized, Placebo-Controlled Trial in Adults in the United States and Mexico - CONCLUSIONS: NVX-CoV2373 elicited robust humoral immune responses against ancestral SARS-CoV-2 virus 2 weeks following the second vaccination in adult PREVENT-19 participants, consistent with previously reported high vaccine efficacy. PREVENT-19 ClinicalTrials.gov number, NCT04611802.
Hydroxychloroquine and azithromycin alter the contractility of living porcine heart slices - The cardiotoxicity risk of hydroxychloroquine (HCQ) and azithromycin (AZM) has been the subject of intensive research triggered by safety concerns in COVID-19 patients. HCQ and AZM have been associated with QT interval prolongation and drug-induced arrhythmias, however other cardiotoxicity mechanisms remain largely unexplored. Our group has pioneered the living heart slice preparation, an ex-vivo platform that maintains native cardiac tissue architecture and physiological electrical and…