COVID-19 affects the population unequally with a higher impact on aged and immunosuppressed people. Hence, we assessed the effect of SARS-CoV-2 vaccination in immune compromised patients (older adults and oncohematologic patients), compared with healthy counterparts. While the acquired humoral and cellular memory did not predict subsequent infection 18 months after full immunization, spectral and computational cytometry revealed several subsets within the CD8+ T-cells, B-cells, NK cells, monocytes and CD45RA+CCR7- Tγδ cells differentially expressed in further infected and non-infected individuals not just following immunization, but also prior to that. Of note up to 7 subsets were found within the CD45RA+CCR7- Tγδ population with some of them being expanded and other decreased in subsequently infected individuals. Moreover, some of these subsets also predicted COVID-induced hospitalization in oncohematologic patients. Therefore, we hereby have identified several cellular subsets that, even before vaccination, strongly related to COVID-19 vulnerability as opposed to the acquisition of cellular and/or humoral memory following vaccination with SARS-CoV-2 mRNA vaccines.
Earlier global detection of novel SARS-CoV-2 variants gives governments more time to respond. However, few countries can implement timely national surveillance resulting in gaps in monitoring. The UK implemented large-scale community and hospital surveillance, but experience suggests it may be faster to detect new variants through testing UK arrivals for surveillance. We developed simulations of the emergence and importation of novel variants with a range of infection hospitalisation rates (IHR) to the UK. We compared time taken to detect the variant though testing arrivals at UK borders, hospital admissions, and the general community. We found that sampling 10 to 50% of arrivals at UK borders could confer a speed advantage of 3.5 to 6 weeks over existing community surveillance, and 1.5 to 5 weeks (depending on IHR) over hospital testing. We conclude that directing limited global capacity for surveillance to highly connected ports could speed up global detection of novel SARS-CoV-2 variants.
The COVID-19 pandemic infected many people worldwide with SARS-CoV2. Psychological distress is one of the sequelae reported to occur in many of those infected (Choutka et al., 2022). We investigated the association between personal experience of COVID-19 infection and psychological distress in Japan. A total of 18,560 persons participated in the original survey, conducted in December 2020. After excluding unreliable responses, data from 14,901 persons who participated in a follow-up survey in December 2022-were included in the analysis. Odds ratios (ORs) were estimated by univariate and multiple logistic regression analysis with history of COVID-19 infection as the independent variable and presence of psychological distress as the dependent variable. This results showed that the experience of COVID-19 infection is associated with psychological distress. Moreover, most cases of mental distress among those who experienced COVID-19 infection can be at least partly explained by a perception of unfair treatment.
The global devastation of the COVID-19 pandemic has led to calls for a revolution in heating, ventilation, and air conditioning (HVAC) systems to improve indoor air quality (IAQ), due to the dominant role of airborne transmission in disease spread. While simple guidelines have recently been suggested to improve IAQ mainly by increasing ventilation and filtration, this goal must be achieved in an energy-efficient and economical manner and include all air cleaning mechanisms. Here, we develop a simple protocol to directly, quantitatively, and optimally control transmission risk while minimizing energy cost. We collect a large dataset of HVAC and IAQ measurements in buildings and show how models of infectious aerosol dynamics and HVAC operation can be combined with sensor data to predict transmission risk and energy consumption. Using this data, we also verify that a simple safety guideline is able to limit transmission risk in full data-driven simulations and thus may be used to guide public health policy. Our results provide a comprehensive framework for quantitative control of transmission risk using all available air cleaning mechanisms in an indoor space while minimizing energy costs to aid in the design and automated operation of healthy, energy-efficient buildings.
Objective: To assess the evidence on the presence of antibodies that are cross-reactive with SARS-CoV-2 antigens in pre-pandemic samples from African populations. Methods: We performed a systematic review and meta-analysis of studies evaluating pre-pandemic African samples for anti-SARS-CoV-2 cross-reactive antibodies using pre-set assay-specific thresholds for seropositivity. Results: 24 articles with 146 datasets were eligible, including 3,194 positives among 27,269 measurements (11.7%) with large between-dataset heterogeneity. Positivity was similar for anti-N and anti-S antibodies (14% and 11%, respectively) and it was higher for anti-S1 (23%) and lower for anti-RBD antibodies (7%). Positivity was non-significantly higher for IgM than for IgG antibodies. Positivity was seen prominently in countries where malaria transmission occurs throughout and in datasets enriched in malaria cases (14%, 95% CI, 13-17%) versus 2%, 95% CI 1-3% in other datasets). Substantial SARS-CoV-2 reactivity was seen in high malaria burden with or without high dengue burden (15% and 12%, respectively), and not without high malaria burden (2% and 0%, respectively). Lower SARS-CoV-2 cross-reactivity was seen in countries and cohorts of high HIV seroprevalence, but this association was not validated in individual samples. Conclusions: Pre-pandemic samples from Africa show high levels of anti-SARS-CoV-2 seropositivity. Levels of cross-reactivity tracks especially with malaria prevalence.
Abstract One of the most significant challenges in the early combat against COVID-19 was the dif- ficulty in estimating the true magnitude of infections. Unreported infections drove up disease spread in numerous regions, made it very hard to accurately estimate the infectivity of the pathogen, therewith hampering our ability to react effectively. Despite the use of surveillance- based methods such as serological studies, identifying the true magnitude is still challenging today. This paper proposes an information theoretic approach for accurately estimating the number of total infections. Our approach is built on top of Ordinary Differential Equations (ODE) based models, which are commonly used in epidemiology and for estimating such infec- tions. We show how we can help such models to better compute the number of total infections and identify the parameterization by which we need the fewest bits to describe the observed dynamics of reported infections. Our experiments show that our approach leads to not only substantially better estimates of the number of total infections but also better forecasts of infec- tions than standard model calibration based methods. We additionally show how our learned parameterization helps in modeling more accurate what-if scenarios with non-pharmaceutical interventions. Our results support earlier findings that most COVID-19 infections were un- reported and non-pharmaceutical interventions indeed helped to mitigate the spread of the outbreak. Our approach provides a general method for improving epidemic modeling which is applicable broadly.
Objective: Vaccination is a vital cornerstone of public health, which has saved countless lives throughout history. Therefore, achieving high vaccination uptake rates is essential for successful vaccination programs. Unfortunately, vaccine uptake has been hindered by deferent factors and challenges. The objective of this study is to assess COVID-19 vaccine uptake and associated factors among the general population. Methods: This study is a descriptive cross-sectional study conducted in Basmaia city, Baghdad from June to October 2022. Data were collected through a semi-structured questionnaire using multi-stage random sampling. Statistical analysis was performed using descriptive statistics, chi-square analysis, Mann-Whitney test, and binary and multivariable logistic regression. Results: the prevalence of COVID-19 vaccine uptake was 70.4%. The most common reason for getting vaccinated was protection from the disease, while fear of side effects and not needing the vaccine were the main reasons for refusal. The study found that gender, age, education level, job title, risk perception, knowledge, and attitude towards the vaccine were significantly associated with COVID-19 vaccine uptake. Males were 2.273 times more likely to get vaccinated than females, and older age groups had higher odds of vaccination than younger age groups. Those with higher education levels were also more likely to receive the vaccine. Participants with higher risk perception, knowledge, and positive attitude towards the vaccine were more likely to get vaccinated. And found that mandatory vaccination policies may negatively impact uptake of subsequent vaccine doses. Conclusion: the study found a high prevalence of COVID-19 vaccine uptake, with gender, age, education level, and job title being significant factors associated with vaccine uptake. Additionally, mandatory vaccination policies may have a negative impact on the uptake of subsequent vaccine doses. Public health efforts should prioritize addressing these factors to increase vaccine uptake.
A Nasal Treatment for COVID-19 - Condition: COVID-19
Interventions: Drug: Optate; Drug: Placebo
Sponsor: Indiana University
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
Tailored COVID-19 Testing Support Plan for Francophone African Born Immigrants - Condition: COVID19 Testing
Interventions: Behavioral: FABI tailored COVID-19 testing pamphlet; Behavioral: Standard COVID-19 home-based test kit
Sponsors: Texas Woman’s University; National Institutes of Health (NIH)
Not yet recruiting
Complementary Self-help Strategies for Patients With Post-COVID-19 Syndrome - Condition: Post-COVID-19 Syndrome
Interventions: Behavioral: Complementary self-help strategies in addition to treatment as usual; Other: Treatment as usual
Sponsor: Universität Duisburg-Essen
Not yet recruiting
A Study to Understand the Effect and Safety of the Study Medicine PF-07817883 in Adults Who Have Symptoms of COVID-19 But Are Not Hospitalized. - Condition: SARS-CoV-2 Infection
Interventions: Drug: PF-07817883; Drug: Placebo
Sponsor: Pfizer
Not yet recruiting
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
Traditional Chinese Medicine or Low-dose Dexamethasone in COVID-19 Pneumonia - Condition: COVID-19 Pneumonia
Interventions: Other: conventional western medicine treatment; Drug: Dexamethasone oral tablet; Other: Traditional Chinese medicine decoction
Sponsor: China-Japan Friendship Hospital
Recruiting
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
Sponsors: First Affiliated Hospital of Wenzhou Medical University; REGEN-αGEEK (SHENZHEN) MEDICAL TECHNOLOGY CO., LTD.
Recruiting
Inpatient COVID-19 Lollipop Study - Conditions: COVID-19; Diagnostic Test
Intervention: Device: Lollipop
Sponsor: University of Wisconsin, Madison
Not yet recruiting
Building Resilience During the COVID-19 Pandemic: a Randomized Controlled Trial - Conditions: Healthy; COVID-19; Distress, Emotional
Interventions: Behavioral: RASMUS Resilience Training; Behavioral: Progressive Muscle Relaxation
Sponsor: Medical University Innsbruck
Recruiting
Effectiveness of Testofen Compared to Placebo on Long COVID Symptoms - Condition: Long Covid19
Interventions: Drug: Testofen; Drug: Microcrystalline cellulose
Sponsor: RDC Clinical Pty Ltd
Not yet recruiting
Care for Veterans Post-COVID - Condition: Post-Acute COVID-19 Syndrome
Interventions: Behavioral: Concordant Care Training; Behavioral: Education Packet Training
Sponsor: VA Office of Research and Development
Not yet recruiting
Safety & Immunogenicity of RVM-V001/RVM-V002 or RVMV001+RVMV002 (Co Administered as Separate Injections) in Healthy Individuals - Conditions: Infectious Disease; COVID-19
Interventions: Biological: RVM-V001 30 µg; Biological: RVM-V002 30 µg; Biological: RVM-V001 (15 µg) + RVM-V002 (15 µg) co-administration
Sponsor: RVAC Medicines (US), Inc.
Recruiting
HH-120 Nasal Spray for Post-exposure Prevention of SARS-CoV-2 - Condition: COVID-19
Interventions: Drug: HH-120 Nasal Spray; Drug: Placebo
Sponsor: Huahui Health
Not yet recruiting
Addressing Vaccine Acceptance in Carceral Settings Through Community Engagement - Condition: COVID-19
Intervention: Behavioral: ADVANCE Steering Committee interventions
Sponsors: Yale University; National Institute on Minority Health and Health Disparities (NIMHD)
Recruiting
L-Tartaric Acid Inhibits Diminazene-induced Vasorelaxation in Isolated Rat Aorta - CONCLUSION: This investigation provides important experimental evidence of the efficacy of L-tartaric acid in inhibiting diminazene-induced vasorelaxation.
Deep learning-based network pharmacology for exploring the mechanism of licorice for the treatment of COVID-19 - Licorice, a traditional Chinese medicine, has been widely used for the treatment of COVID-19, but all active compounds and corresponding targets are still not clear. Therefore, this study proposed a deep learning-based network pharmacology approach to identify more potential active compounds and targets of licorice. 4 compounds (quercetin, naringenin, liquiritigenin, and licoisoflavanone), 2 targets (SYK and JAK2) and the relevant pathways (P53, cAMP, and NF-kB) were predicted, which were…
Discovery and characterization of the covalent SARS-CoV-2 3CLpro inhibitors from Ginkgo biloba extract via integrating chemoproteomic and biochemical approaches - CONCLUSION: Collectively, GBE50 and some constituents in this herbal product could strongly inhibit SARS-CoV-2 3CL^(pro) in dose- and time-dependent manner. Gallocatechin and sciadopitysin were identified as potent SARS-CoV-2 3CL^(pro) inhibitors, which offers promising lead compounds for the development of novel anti-SARS-CoV-2 drugs.
Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated that all SARS-CoV-2 VOCs possess the ability to suppress major histocompatibility complex class I (MHC-I) expression. We identified several viral…
Neurological damages in COVID-19 patients: Mechanisms and preventive interventions - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, causes coronavirus disease 2019 (COVID-19) which led to neurological damage and increased mortality worldwide in its second and third waves. It is associated with systemic inflammation, myocardial infarction, neurological illness including ischemic strokes (e.g., cardiac and cerebral ischemia), and even death through multi-organ failure. At the early stage, the virus infects the lung epithelial cells and is slowly…
The Unexpected Protective Role of Thrombosis in Sepsis-Induced Inflammatory Lung Injury Via Endothelial Alox15 - CONCLUSION: We have demonstrated that moderate levels of thrombosis protect against sepsis-induced inflammatory lung injury via endothelial Alox15. Overexpression of Alox5 inhibits severe pulmonary thrombosis-induced increase of ALI. Thus, activation of ALOX15 signaling represents a promising therapeutic strategy for treatment of ARDS, especially in sub-populations of patients with thrombocytopenia and/or severe pulmonary thrombosis.
Massively Parallel Profiling of RNA-targeting CRISPR-Cas13d - Type VI CRISPR enzymes cleave target RNAs and are widely used for gene regulation, RNA tracking, and diagnostics. However, a systematic understanding of their RNA binding specificity and cleavage activation is lacking. Here, we describe RNA c hip- h ybridized a ssociation- m apping p latform (RNA-CHAMP), a massively parallel platform that repurposes next-generation DNA sequencing chips to measure the binding affinity for over 10,000 RNA targets containing structural perturbations, mismatches,…
Immune and ionic mechanisms mediating the effect of dexamethasone in severe COVID-19 - CONCLUSION: Our findings suggest that dexamethasone attenuates inflammatory cytokine release via Kv1.3 suppression, and this mechanism contributes to dexamethasone-mediated immunosuppression in severe COVID-19.
Transporter Inhibition Profile for the Antivirals Tilorone, Quinacrine and Pyronaridine - Pyronaridine, tilorone and quinacrine are cationic molecules that have in vitro activity against Ebola, SARS-CoV-2 and other viruses. All three molecules have also demonstrated in vivo activity against Ebola in mice, while pyronaridine showed in vivo efficacy against SARS-CoV-2 in mice. We have recently tested these molecules and other antivirals against human organic cation transporters (OCTs) and apical multidrug and toxin extruders (MATEs). Quinacrine was found to be an inhibitor of OCT2,…
The therapeutic effect and mechanism of parthenolide in skeletal disease, cancers, and cytokine storm - Parthenolide (PTL or PAR) was first isolated from Magnolia grandiflora and identified as a small molecule cancer inhibitor. PTL has the chemical structure of C15H20O3 with characteristics of sesquiterpene lactones and exhibits the biological property of inhibiting DNA biosynthesis of cancer cells. In this review, we summarise the recent research progress of medicinal PTL, including the therapeutic effects on skeletal diseases, cancers, and inflammation-induced cytokine storm. Mechanistic…
Immune-mediated liver injury following COVID-19 vaccination - Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019 (COVID-19) vaccination protocols. All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations, e.g., BNT162b2, mRNA-1273, and ChAdOx1-S, can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like…
Happily Distant or Bitter Medicine? The Impact of Social Distancing Preferences, Behavior, and Emotional Costs on Subjective Wellbeing During the Epidemic - To inhibit the spread of COVID-19 Public health officials stress, and governments often require, restrictions on social interaction (“social distancing”). While the medical benefits are clear, important questions remain about these measures’ downsides: How bitter is this medicine? Ten large non-probability internet-based surveys between April and November 2020, weighted statistically to reflect the US population in age, education, and religious background and excluding respondents who even…
5-alpha reductase inhibitors use in prostatic disease and beyond - 5-alpha reductase inhibitors (5-ARIs) are commonly used and widely available, with benefits observed from their effect on androgen signalling. Their effect relies on the inhibition of the 5-alpha reductase enzyme which aids in the conversion of testosterone to dihydrotestosterone. 5-ARIs have increasing clinical relevance outside of benign prostatic hyperplasia (BPH). Such development requires clinicians to have an updated review to guide clinical practices. This review details the pharmacology…
Suramin binds and inhibits infection of SARS-CoV-2 through both spike protein-heparan sulfate and ACE2 receptor interactions - SARS-CoV-2 receptor binding domains (RBDs) interact with both the ACE2 receptor and heparan sulfate on the surface of host cells to enhance SARS-CoV-2 infection. We show that suramin, a polysulfated synthetic drug, binds to the ACE2 receptor and heparan sulfate binding sites on the RBDs of wild-type, Delta, and Omicron variants. Specifically, heparan sulfate and suramin had enhanced preferential binding for Omicron RBD, and suramin is most potent against the live SARS-CoV-2 Omicron variant…
Metabolic dysregulation impairs lymphocyte function during severe SARS-CoV-2 infection - Cellular metabolic dysregulation is a consequence of SARS-CoV-2 infection that is a key determinant of disease severity. However, how metabolic perturbations influence immunological function during COVID-19 remains unclear. Here, using a combination of high-dimensional flow cytometry, cutting-edge single-cell metabolomics, and re-analysis of single-cell transcriptomic data, we demonstrate a global hypoxia-linked metabolic switch from fatty acid oxidation and mitochondrial respiration towards…