Introduction: COVID-19 and tuberculosis (TB) exhibit similar symptomatic presentation and clinical parameters. Common underlying immunological mechanisms also highlight potential routes of immunopathogenic interaction between these diseases during co-infection. To explore immunological similarities, differences and interactions, single-cell RNA-seq (scRNA-seq) was performed on whole blood infected with Mycobacterium tuberculosis (Mtb), SARS-CoV-2, or both pathogens. Methods: Whole blood from four healthy adults, were subjected to ex vivo infection with Mtb and/or SARS-CoV-2 ancestral strain, or were maintained in an uninfected state, for 24 or 96 hours. At each timepoint, for each condition, the four biological replicates were captured, fixed and cryopreserved to be processed for scRNA-seq as a single batch. Following quality control filtering, genotype-based demultiplexing was performed to obtain data from each biological replicate for pseudobulk differential expression analysis. Results: Thirteen distinct clusters of cells were identified based on marker gene expression. Profound differences in the proportions of monocytes, T cells and neutrophils were observed between infection conditions and timepoints. The greatest divergence between pathogen responses occurred within myeloid cells at early timepoints of infection. Co-infection had the greatest synergistic effect 24 hours post-infection with 238 immunological pathways uniquely enriched, including IFN-γ and TNF production, whilst by 96 hours post-infection there was a large overlap of 182 shared pathways between Mtb, SARS-CoV-2 and co-infection. SARS-CoV-2-only infection resulted in widespread cell death by 96 hours post-infection, while Mtb-only and co-infected samples remained enriched for monocyte, T cell and NK cell signatures, sharing negative regulation of extrinsic apoptotic signalling. Distinct from Mtb, SARS-Co-V-2 had unique regulating of αβ T cell activation and differentiation at both time points. Conclusion: These data provide a high-resolution characterisation of distinct and overlapping immunological responses generated by SARS-CoV-2 and Mtb when a single infection or co-infection occurs. This sheds light on the potential effects of novel or existing host-directed therapies that target these pathways, which is particularly crucial for settings where dual presentation is common.
Wastewater surveillance has emerged as a valuable tool for monitoring infectious disease agents including SARS-CoV-2 and Mpox virus. However, detecting the Mpox virus in wastewater is particularly challenging due to its relatively low prevalence in the community. In this study, we detected Mpox virus in wastewater from a US-Mexico border city with a low prevalence of Mpox disease during February and March 2023 using real-time PCR assays targeting the C22L, F3L, and F8L genes. An increasing trend of viral concentration was observed 1~2 weeks earlier than when the Mpox case was reported. Further sequencing and epidemiological analysis provided supporting evidence for unreported Mpox infections in the city. This study showcases a combined approach with multiple molecular assays for efficient detection of the Mpox virus in wastewater in a low-prevalence area. The findings emphasize the value of wastewater surveillance as a timely identification tool for infectious diseases in low-prevalence areas, and the need for heightened vigilance to control the spread of infectious diseases in such settings.
The COVID-19 pandemic has resulted in a global public health crisis requiring immediate acute therapeutic solutions. To address this challenge, we developed a useful tool deep learning model using the graph-embedding convolution network (GECN) algorithm. Our approach identified COVID-19-related genes and potential druggable targets, including tyrosine kinase ABL1/2, pro-inflammatory cytokine CSF2, and pro-fibrotic cytokines IL-4 and IL-13. These target genes are implicated in critical processes related to COVID-19 pathogenesis, including endosomal membrane fusion, cytokine storm, and tissue fibrosis. Our analysis revealed that ABL kinase inhibitors, lenzilumab (anti-CSF2), and dupilumab (anti-IL4Rα) represent promising therapeutic solutions that can effectively block virus-host membrane fusion or attenuate hyperinflammation in COVID-19 patients. Compared to the traditional drug screening process, our GECN algorithm enables rapid analysis of disease-related human protein interaction networks and prediction of candidate drug targets from a large-scale knowledge graph in a cost-effective and efficient manner. Overall, Overall, our results suggest that the model has the potential to facilitate drug repurposing and aid in the fight against COVID-19.
Third doses of COVID-19 vaccines were widely deployed following primary vaccine course waning and emergence of the Omicron-variant. We investigated protection from third-dose vaccines and previous infection against SARS-CoV-2 infection during Delta-variant and Omicron-variant (BA.1 & BA.2) waves in our frequently PCR-tested cohort of healthcare-workers. Relative effectiveness of BNT162b2 third doses and infection-acquired immunity was assessed by comparing the time to PCR-confirmed infection in boosted participants with those with waned dose-2 protection (≥254 days after dose-2). Follow-up time was divided by dominant circulating variant: Delta 07 September 2021 to 30 November 2021, Omicron 13 December 2021 to 28 February 2022. We used a Cox regression model with adjustment/stratification for demographic characteristics and staff-type. We explored protection associated with vaccination, infection and both. We included 19,614 participants, 29% previously infected. There were 278 primary infections (4 per 10,000 person-days of follow-up) and 85 reinfections (0.8/10,000 person-days) during the Delta period and 2467 primary infections (43/10,000 person-days) and 881 reinfections (33/10,000) during the Omicron period. Relative Vaccine Effectiveness (VE) 0-2 months post-3rd dose (V3) (3-doses BNT162b2) in the previously uninfected cohort against Delta infections was 63% (95% Confidence Interval (CI) 40%-77%) and was lower (35%) against Omicron infection (95% CI 21%-47%). For primary course ChAdOX1 recipients, BNT162b2 heterologous third doses were especially effective, with VE 0-2 months post-V3 over ≥68% higher for both variants. Third-dose protection waned rapidly against Omicron, with no significant difference between two and three BNT162b2 doses observed after 4-months. Previous infection continued to provide additional protection against Omicron (67% (CI 56%-75%) 3-6 months post-infection), but this waned to about 25% after 9-months, approximately three times lower than against Delta. Infection rates surged with Omicron emergence. Third doses of BNT162b2 vaccine provided short-term protection, with rapid waning against Omicron infections. Protection associated with infections incurred before Omicron was markedly diminished against the Omicron wave. Our findings demonstrate the complexity of an evolving pandemic with potential emergence of immune-escape variants and the importance of continued monitoring.
Introduction: During the COVID-19 pandemic, a digital transformation led to an expansion in telenursing practices and a shift in training to online learning. The aim of this study was to explore the impact of behavioral-related factors, based on both TAM and TPB variables, on the intention to use telenursing through videoconferencing and to compare the effect of frontal (before COVID-19) vs. online (during and after COVID-19) training in post-basic nursing courses on nursing attitudes to telenursing. Methods: A cross-sectional online survey was conducted in December 2022 among nurses working mainly at hospitals in Israel who underwent post-basic education training between January 2017 and December 2022. A multivariate ordinary least squares (OLS) regression analysis was used to investigate determinants of intention to use telenursing through videoconferencing Results: Nurses have a positive attitude towards telenursing technology via videoconferencing for remote patient care, regardless of whether they learned about it through face-to-face or online training. The ease of use and the perception of the technology9s importance by colleagues and supervisors were found to have the most significant impact on the attitude of both research groups towards the use of telelearning. Discussion: Successful implementation of new technology in healthcare requires organizational and collegial support. Therefore, managers should encourage the use of telenursing by providing appropriate training for nurses and the necessary resources and support.
During the pandemic of COVID-19, wastewater-based epidemiology has become a powerful epidemic surveillance tool widely used around the world. However, the development and application of this technology in Chinese Mainland are relatively lagging. Herein, we report the first case of community circulation of SARS-CoV-2 lineages monitored by WBE in Chinese Mainland during the infection outbreak at the end of 2022 after the comprehensive relaxation of epidemic prevention policies. During the peak period of infection, six precious sewage samples were collected from the manhole in the student dormitory area of Wangjiang Campus of Sichuan University. According to the results RT-qPCR, the six sewage samples were all positive for SARS-CoV-2 RNA. Based on multiplex PCR amplicon sequencing, the local transmission of SARS-CoV-2 variants at that time was analyzed. The results show that the main virus lineages in sewage have clear evolutionary genetic correlations. Furthermore, the sampling time is very consistent with the timeline of concern for these virus lineages and consistent with the timeline for uploading the nucleic acid sequences of the corresponding lineages in Sichuan to the database. These results demonstrate the reliability of the sequencing results of SARS-CoV-2 nucleic acid in wastewater. Multiplex PCR amplicon sequencing is by far the most powerful analytical tool of WBE, enabling quantitative monitoring of virus lineage prevalence at the community level.
Objectives: This study aims to assess the progress of geographic, socioeconomic, and demographic disparities in Covid-19 vaccination coverage in Brazil over the first two years of the vaccination campaign. Methods: Data from the National Immunization Program Information System were used to estimate covid-19 vaccine coverage. Brazilian municipalities were divided into two groups based on their vaccine coverage for the booster dose. The first group comprised 20% of municipalities with the lowest coverage, while the second group (80% of municipalities) had higher coverage. The analysis was conducted separately for four age groups: 5-11, 12-17, 18-59, and 60+. Exploratory variables included socioeconomic and health services indicators. Crude and adjusted logistic regression models were used to estimate the probability of a municipality being among those with the worst vaccination coverage according to the categories of exploratory variables. Results: Between January/2021 and December/2022, Brazil administered 448.2 million doses of the covid-19 vaccine. The booster vaccination coverage varied from 24.8% among adolescents to 79.7% among the elderly. The difference between the group with the highest and lowest coverage increased during the national vaccination campaign. Municipalities with lower education levels, higher proportion of Black population, higher Gini index, and worse health service indicators had a greater likelihood of having lower vaccination coverage. Conclusions: High and increasing levels of inequality in Covid-19 vaccination were observed in Brazil across all age groups during the vaccination campaign in 2021-2022.
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
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
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
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
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
Phase 3 Study of Novavax Vaccine(s) as Booster Dose After mRNA Vaccines - Condition: COVID-19
Interventions: Biological: NVX-CoV2373; Biological: SARS-CoV-2 rS antigen/Matrix-M Adjuvant
Sponsor: Novavax
Active, not recruiting
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
Anti-SARS-CoV-2 Monoclonal Antibodies for Long COVID (COVID-19) - Conditions: Long COVID; Post-Acute Sequela of COVID-19; Post-Acute COVID-19
Interventions: Drug: AER002; Other: Placebo
Sponsors: Michael Peluso, MD; Aerium Therapeutics
Not yet recruiting
Dose Exploration Intramuscular/Intravenous Prophylaxis Pharmacokinetic Exposure Response Study - Condition: COVID-19
Interventions: Drug: AZD3152; Other: Placebo
Sponsor: AstraZeneca
Recruiting
Study to Assess Safety, Reactogenicity and Immunogenicity of the repRNA(QTP104) Vaccine Against SARS-CoV-2(COVID-19) - Conditions: COVID-19; SARS-CoV-2
Interventions: Biological: QTP104 1ug; Biological: QTP104 5ug; Biological: QTP104 25ug
Sponsor: Quratis Inc.
Active, not recruiting
Effects of Individual Tailored Physical Exercise in Patients With POTS After COVID-19 - a Randomized Controlled Study - Conditions: Postural Orthostatic Tachycardia Syndrome; COVID-19; Post COVID-19 Condition; Post-Acute COVID-19 Syndrome
Intervention: Other: Individual tailored exercise
Sponsors: Karolinska Institutet; Karolinska University Hospital
Enrolling by invitation
Immunogenicity and safety of COVID-19 BNT162b2 booster vaccine in end-stage kidney disease patients receiving haemodialysis in Yogyakarta, Indonesia: a cohort prospective study - CONCLUSIONS: The majority of ESKD patients on haemodialysis mounted a good antibody response to the BNT162b2 booster vaccination with tolerable adverse events.
Capture and neutralization of SARS-CoV-2 and influenza virus by algae-derived lectins with high-mannose and core fucose specificities - We first investigated the interactions between several algae-derived lectins and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We created lectin columns using high-mannose (HM)-type glycan-specific lectins OAA and KAA-1 or core fucose-specific lectin hypninA-2 and conducted binding experiments with SARS-CoV-2. The results showed that these lectins were capable of binding to the virus. Furthermore, when examining the neutralization ability of nine different lectins, it was found…
Inflammation inhibitory activity of green tea, soybean, and guava extracts during Sars-Cov-2 infection through TNF protein in cytokine storm - Coronavirus disease is caused by the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) known as COVID-19. COVID-19 has caused the deaths of 6,541,936 people worldwide as of September 27th, 2022. SARS-CoV-2 severity is determined by a cytokine storm condition, in which the innate immune system creates an unregulated and excessive production of pro-inflammatory such IL-1, IL-6, NF Kappa B, and TNF alpha signaling molecules known as cytokines. The patient died due to respiratory…
Long Time Scale Ensemble Methods in Molecular Dynamics: Ligand-Protein Interactions and Allostery in SARS-CoV-2 Targets - We subject a series of five protein-ligand systems which contain important SARS-CoV-2 targets, 3-chymotrypsin-like protease (3CLPro), papain-like protease, and adenosine ribose phosphatase, to long time scale and adaptive sampling molecular dynamics simulations. By performing ensembles of ten or twelve 10 μs simulations for each system, we accurately and reproducibly determine ligand binding sites, both crystallographically resolved and otherwise, thereby discovering binding sites that can be…
SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis - Viral infection-induced cell death has long been considered as a double-edged sword in the inhibition or exacerbation of viral infections. Patients with severe Coronavirus Disease 2019 (COVID-19) are characterized by multiple organ dysfunction syndrome and cytokine storm, which may result from SARS-CoV-2-induced cell death. Previous studies have observed enhanced ROS level and signs of ferroptosis in SARS-CoV-2 infected cells or specimens of patients with COVID-19, but the exact mechanism is not…
Utilization of Marine Seaweeds as a Promising Defense Against COVID-19: a Mini-review - COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which mainly affects the respiratory system. It has been declared as a “pandemic” in March 2020 by the World Health Organization due to the high spreading rate. SARS-CoV-2 binds with the angiotensin-converting enzyme 2 (ACE2) receptors on the cell surface which leads to the downregulation of ACE2 and upregulation of angiotensin-converting enzyme (ACE) receptors. The elevated level of…
Identification of Host Proteins Interacting with IBV S1 Based on Tracheal Organ Culture - Infectious bronchitis virus (IBV) belongs to the gamma-coronavirus genus of Coronaviridae and causes serious infectious diseases in the poultry industry. However, only a few IBV strains can infect avian passage cell lines, seriously hindering the progress of basic research on IBV pathogenesis. Whereas IBV field strains can replicate in tracheal ring organ culture (TOC) without any previous adaptation in chicken embryos or primary cells. In this study, to investigate the potential use of TOC as…
Transcription Factor Driven Gene Regulation in COVID-19 Patients - SARS-CoV-2 and its many variants have caused a worldwide emergency. Host cells colonised by SARS-CoV-2 present a significantly different gene expression landscape. As expected, this is particularly true for genes that directly interact with virus proteins. Thus, understanding the role that transcription factors can play in driving differential regulation in patients affected by COVID-19 is a focal point to unveil virus infection. In this regard, we have identified 19 transcription factors which…
Genes Involved in miRNA Biogenesis Are Not Downregulated in SARS-CoV-2 Infection - miRNAs, small non-coding RNAs that regulate gene expression, are involved in various pathological processes, including viral infections. Virus infections may interfere with the miRNA pathway through the inhibition of genes involved in miRNA biogenesis. A reduction in the number and the levels of miRNAs expressed in nasopharyngeal swabs of patients with severe COVID-19 was lately observed by us, pointing towards the potential of miRNAs as possible diagnostic or prognostic biomarkers for…
In Silico and In Vitro Evaluation of Some Amidine Derivatives as Hit Compounds towards Development of Inhibitors against Coronavirus Diseases - Coronaviruses, including SARS-CoV-2, SARS-CoV, MERS-CoV and influenza A virus, require the host proteases to mediate viral entry into cells. Rather than targeting the continuously mutating viral proteins, targeting the conserved host-based entry mechanism could offer advantages. Nafamostat and camostat were discovered as covalent inhibitors of TMPRSS2 protease involved in viral entry. To circumvent their limitations, a reversible inhibitor might be required. Considering nafamostat structure and…
The Dimeric Peptide (KKYRYHLKPF)2K Shows Broad-Spectrum Antiviral Activity by Inhibiting Different Steps of Chikungunya and Zika Virus Infection - Chikungunya virus (CHIKV) and Zika virus (ZIKV) are important disease-causing agents worldwide. Currently, there are no antiviral drugs or vaccines approved to treat these viruses. However, peptides have shown great potential for new drug development. A recent study described (p-BthTX-I)(2)K [(KKYRYHLKPF)(2)K], a peptide derived from the Bothropstoxin-I toxin in the venom of the Bothrops jararacussu snake, showed antiviral activity against SARS-CoV-2. In this study, we assessed the activity of…
GRP78 Inhibitor YUM70 Suppresses SARS-CoV-2 Viral Entry, Spike Protein Production and Ameliorates Lung Damage - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic, has given rise to many new variants with increased transmissibility and the ability to evade vaccine protection. The 78-kDa glucose-regulated protein (GRP78) is a major endoplasmic reticulum (ER) chaperone that has been recently implicated as an essential host factor for SARS-CoV-2 entry and infection. In this study, we investigated the efficacy of YUM70, a small molecule inhibitor of…
IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein - Less than a year after the global emergence of the coronavirus SARS-CoV-2, a novel vaccine platform based on mRNA technology was introduced to the market. Globally, around 13.38 billion COVID-19 vaccine doses of diverse platforms have been administered. To date, 72.3% of the total population has been injected at least once with a COVID-19 vaccine. As the immunity provided by these vaccines rapidly wanes, their ability to prevent hospitalization and severe disease in individuals with…
Long COVID and Hybrid Immunity among Children and Adolescents Post-Delta Variant Infection in Thailand - This study aimed to assess long COVID, and describe immunogenicity against Omicron variants following BNT162b2 vaccination. A prospective cohort study was conducted among children (aged 5-11) and adolescents (aged 12-17) who had SARS-CoV-2 infection from July to December 2021 (Delta predominant period). Long COVID symptoms were assessed by questionnaires at 3 months after infection. Immunogenicity was evaluated by using a surrogate virus-neutralizing antibody test (sVNT) against the Omicron…
Natural Product-Based Screening for Lead Compounds Targeting SARS CoV-2 Mpro - Drugs that cure COVID-19 have been marketed; however, this disease continues to ravage the world without becoming extinct, and thus, drug discoveries are still relevant. Since M^(pro) has known advantages as a drug target, such as the conserved nature of the active site and the absence of homologous proteins in the body, it receives the attention of many researchers. Meanwhile, the role of traditional Chinese medicine (TCM) in the control of epidemics in China has also led to a focus on natural…