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1.
PLoS One ; 19(7): e0306753, 2024.
Article in English | MEDLINE | ID: mdl-38980873

ABSTRACT

BACKGROUND: Hepatitis A virus (HAV) is the predominant cause of acute viral hepatitis worldwide; however, data on HAV antibody prevalence (seroprevalence) among migrant populations are limited. This study aimed to investigate HAV seroprevalence among Qatar's migrant craft and manual workers (CMWs), constituting approximately 60% of the country's population. METHODS: HAV antibody testing was conducted on stored serum specimens obtained from CMWs during a nationwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) population-based cross-sectional survey between July 26 and September 9, 2020. Associations with HAV infection were investigated through regression analyses. RESULTS: Of the 2,607 specimens with HAV antibody test results, 2,393 were positive, and 214 were negative. The estimated HAV seroprevalence among CMWs was 92.0% (95% CI: 90.9-93.1%). HAV seroprevalence was generally high but exhibited some variation, ranging from 70.9% (95% CI: 62.4-78.2%) among Sri Lankans to 99.8% (95% CI: 98.2-99.9%) among Pakistanis. The multivariable regression analysis identified age, nationality, and educational attainment as statistically significant factors associated with HAV infection. Relative to CMWs aged ≤29 years, the adjusted relative risk (ARR) was 1.06 (95% CI: 1.03-1.10) in CMWs aged 30-39 years and reached 1.15 (95% CI: 1.10-1.19) in those aged ≥50 years. In comparison to Indians, the ARR was lower among Sri Lankans, assessed at 0.81 (95% CI: 0.72-0.91), but higher among Nepalese at 1.07 (95% CI: 1.04-1.11), Bangladeshis at 1.10 (95% CI: 1.07-1.13), Pakistanis at 1.12 (95% CI: 1.09-1.15), and Egyptians at 1.15 (95% CI: 1.08-1.23). No evidence for differences was found by geographic location or occupation. CONCLUSIONS: HAV seroprevalence among Qatar's CMW population is very high, with over nine out of every ten individuals having been exposed to this infection, likely during childhood.


Subject(s)
Hepatitis A , Transients and Migrants , Humans , Qatar/epidemiology , Hepatitis A/epidemiology , Hepatitis A/blood , Female , Male , Adult , Seroepidemiologic Studies , Transients and Migrants/statistics & numerical data , Middle Aged , Cross-Sectional Studies , Prevalence , Young Adult , Hepatitis A virus/immunology , Adolescent , Hepatitis A Antibodies/blood , COVID-19/epidemiology , COVID-19/virology
2.
Metabolomics ; 20(4): 71, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38972029

ABSTRACT

BACKGROUND AND OBJECTIVE: Blood-based small molecule metabolites offer easy accessibility and hold significant potential for insights into health processes, the impact of lifestyle, and genetic variation on disease, enabling precise risk prevention. In a prospective study with records of heart failure (HF) incidence, we present metabolite profiling data from individuals without HF at baseline. METHODS: We uncovered the interconnectivity of metabolites using data-driven and causal networks augmented with polygenic factors. Exploring the networks, we identified metabolite broadcasters, receivers, mediators, and subnetworks corresponding to functional classes of metabolites, and provided insights into the link between metabolomic architecture and regulation in health. We incorporated the network structure into the identification of metabolites associated with HF to control the effect of confounding metabolites. RESULTS: We identified metabolites associated with higher and lower risk of HF incidence, such as glycine, ureidopropionic and glycocholic acids, and LPC 18:2. These associations were not confounded by the other metabolites due to uncovering the connectivity among metabolites and adjusting each association for the confounding metabolites. Examples of our findings include the direct influence of asparagine on glycine, both of which were inversely associated with HF. These two metabolites were influenced by polygenic factors and only essential amino acids, which are not synthesized in the human body and are obtained directly from the diet. CONCLUSION: Metabolites may play a critical role in linking genetic background and lifestyle factors to HF incidence. Revealing the underlying connectivity of metabolites associated with HF strengthens the findings and facilitates studying complex conditions like HF.


Subject(s)
Heart Failure , Metabolomics , Heart Failure/metabolism , Humans , Metabolomics/methods , Male , Female , Prospective Studies , Middle Aged , Metabolome , Aged , Metabolic Networks and Pathways
3.
Adv Biol (Weinh) ; : e2400224, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963310

ABSTRACT

The maintenance and expansion of human neural stem cells (hNSCs) in 3D tissue scaffolds is a promising strategy in producing cost-effective hNSCs with quality and quantity applicable for clinical applications. A few biopolymers have been extensively used to fabricate 3D scaffolds, including hyaluronic acid, collagen, alginate, and chitosan, due to their bioactive nature and availability. However, these polymers are usually applied in combination with other biomolecules, leading to their responses difficult to ascribe to. Here, scaffolds made of chitosan, alginate, hyaluronic acid, or collagen, are explored for hNSC expansion under xeno-free and chemically defined conditions and compared for hNSC multipotency maintenance. This study shows that the scaffolds made of pure chitosan support the highest adhesion and growth of hNSCs, yielding the most viable cells with NSC marker protein expression. In contrast, the presence of alginate, hyaluronic acid, or collagen induces differentiation toward immature neurons and astrocytes even in the maintenance medium and absence of differentiation factors. The cells in pure chitosan scaffolds preserve the level of transmembrane protein profile similar to that of standard culture. These findings point to the potential of using pure chitosan scaffolds as a base scaffolding material for hNSC expansion in 3D.

4.
Vaccine ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38845303

ABSTRACT

BACKGROUND: Priming with two doses of AZD1222 (Oxford-AstraZeneca; ChAd) followed by a third mRNA vaccine boosting is considered in several countries, yet comparisons between heterologous and homologous booster efficacy remain unexplored. AIM: To evaluate and contrast the immunogenicity of homologous and heterologous boosting regimens. METHOD: The study examined antibody responses in 1113 subjects, comprising 895 vaccine-naïve individuals across different vaccination strategies (partial, primary series, heterologous booster, homologous booster) and 218 unvaccinated, naturally infected individuals. Assessments included neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA levels. RESULTS: The study found mRNA vaccines to exhibit superior immunogenicity in primary series vaccination compared to ChAd, with mRNA-1273 significantly enhancing NTAbs, TAbs, anti-S-RBD IgG, and anti-S1 IgA levels (p < 0.001). Both booster types improved antibody levels beyond primary outcomes, with no significant difference in TAbs and anti-S-RBD IgG levels between regimens. However, homologous mRNA boosters significantly outperformed heterologous boosters in enhancing NTAbs and anti-S1 IgA levels, with the BNT/BNT/BNT regimen yielding particularly higher enhancements (p < 0.05). CONCLUSION: The study concludes that although TAbs and anti-S-RBD IgG antibody levels are similar for both regimens, homologous mRNA boosting outperform heterologous regimen by enhancing anti-S1 IgA and neutralizing antibody levels.

5.
Vaccines (Basel) ; 12(6)2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38932376

ABSTRACT

This study focuses on the development and characterization of an intranasal vaccine platform using adjuvanted nanoparticulate delivery of swine influenza A virus (SwIAV). The vaccine employed whole inactivated H1N2 SwIAV as an antigen and STING-agonist ADU-S100 as an adjuvant, with both surface adsorbed or encapsulated in mannose-chitosan nanoparticles (mChit-NPs). Optimization of mChit-NPs included evaluating size, zeta potential, and cytotoxicity, with a 1:9 mass ratio of antigen to NP demonstrating high loading efficacy and non-cytotoxic properties suitable for intranasal vaccination. In a heterologous H1N1 pig challenge trial, the mChit-NP intranasal vaccine induced cross-reactive sIgA antibodies in the respiratory tract, surpassing those of a commercial SwIAV vaccine. The encapsulated mChit-NP vaccine induced high virus-specific neutralizing antibody and robust cellular immune responses, while the adsorbed vaccine elicited specific high IgG and hemagglutinin inhibition antibodies. Importantly, both the mChit-NP vaccines reduced challenge heterologous viral replication in the nasal cavity higher than commercial swine influenza vaccine. In summary, a novel intranasal mChit-NP vaccine platform activated both the arms of the immune system and is a significant advancement in swine influenza vaccine design, demonstrating its potential effectiveness for pig immunization.

6.
Cureus ; 16(5): e60601, 2024 May.
Article in English | MEDLINE | ID: mdl-38894779

ABSTRACT

Aims Chronic obstructive pulmonary disease (COPD) is one of the most common causes of death worldwide. This study assesses the level of knowledge about COPD among undergraduate students that makes it different from other respiratory illnesses. Methods A cross-sectional study was conducted among undergraduate students at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS). The Bristol Chronic obstructive pulmonary disease Knowledge Questionnaire (BCKQ) was used to evaluate the knowledge about COPD, epidemiology, symptoms, exercise, smoking, and breathlessness domains. The questionnaire was distributed among the different male colleges. Results There were 304 respondents from five colleges. The overall BCKQ mean score was 15.16±4.52 (maximum 30). The mean score was highest for the Colleges of Pharmacy (18.89±2.17) and Medicine (18.00±3.84), and the College of Science and Health Professions had the lowest score (11.56±5.58). The highest overall means for the different domains (max=5) were for smoking (2.19±1.2), and epidemiology (2.83±1.27), while symptoms of COPD (2.23±1.06) and breathlessness (1.96±1.13) were the lowest among the domains. Conclusions There was a low level of understanding among undergraduate students in general, but the Colleges of Medicine and Pharmacy had better knowledge. On the other hand, the College of Science and Health Professions had a lower score. This indicates some areas for improvement in the education program. Appropriate development in the education program is recommended, such as increasing the awareness of symptoms of COPD and other aspects of the disease.

7.
Cureus ; 16(4): e59374, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38817488

ABSTRACT

Primary immunodeficiency (PID) Disorders include a variable group of diseases that are classified according to the functional defects encountered. Chronic granulomatous disease (CGD) is inherited as an X-linked recessive disorder in many cases, and it is the clinical model of disorders of phagocytosis. Skin and solid organs abscesses are the most common presenting symptoms; we will report the case of a four-day-old boy admitted to our hospital for a neck mass with purulent discharges associated with umbilical stump and circumcision site infection; the diagnosis of CGD was later confirmed by the Dihydrorhodamine (DHR) test that turned out to be positive.

8.
J Infect Public Health ; 17(7): 102448, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38815532

ABSTRACT

BACKGROUND: Influenza A virus causes severe respiratory illnesses, especially in developing nations where most child deaths under 5 occur due to lower respiratory tract infections. The RIG-I protein acts as a sensor for viral dsRNA, triggering interferon production through K63-linked poly-ubiquitin chains synthesized by TRIM25. However, the influenza A virus's NS1 protein hinders this process by binding to TRIM25, disrupting its association with RIG-I and preventing downstream interferon signalling, contributing to the virus's evasion of the immune response. METHODS: In our study we used structural-based drug designing, molecular simulation, and binding free energy approaches to identify the potent phytocompounds from various natural product databases (>100,000 compounds) able to inhibit the binding of NS1 with the TRIM25. RESULTS: The molecular screening identified EA-8411902 and EA-19951545 from East African Natural Products Database, NA-390261 and NA-71 from North African Natural Products Database, SA-65230 and SA- 4477104 from South African Natural Compounds Database, NEA- 361 and NEA- 4524784 from North-East African Natural Products Database, TCM-4444713 and TCM-6056 from Traditional Chinese Medicines Database as top hits. The molecular docking and binding free energies results revealed that these compounds have high affinity with the specific active site residues (Leu95, Ser99, and Tyr89) involved in the interaction with TRIM25. Additionally, analysis of structural dynamics, binding free energy, and dissociation constants demonstrates a notably stronger binding affinity of these compounds with the NS1 protein. Moreover, all selected compounds exhibit exceptional ADMET properties, including high water solubility, gastrointestinal absorption, and an absence of hepatotoxicity, while adhering to Lipinski's rule. CONCLUSION: Our molecular simulation findings highlight that the identified compounds demonstrate high affinity for specific active site residues involved in the NS1-TRIM25 interaction, exhibit exceptional ADMET properties, and adhere to drug-likeness criteria, thus presenting promising candidates for further development as antiviral agents against influenza A virus infections.


Subject(s)
Molecular Docking Simulation , Protein Binding , Tripartite Motif Proteins , Ubiquitin-Protein Ligases , Viral Nonstructural Proteins , Tripartite Motif Proteins/metabolism , Tripartite Motif Proteins/genetics , Tripartite Motif Proteins/chemistry , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/metabolism , Viral Nonstructural Proteins/genetics , Humans , Ubiquitin-Protein Ligases/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Transcription Factors/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Influenza A virus/drug effects , Influenza A virus/immunology , Phytochemicals/pharmacology , Phytochemicals/chemistry , Drug Design , Drug Evaluation, Preclinical
9.
Sci Rep ; 14(1): 11275, 2024 05 17.
Article in English | MEDLINE | ID: mdl-38760415

ABSTRACT

Limited data exist on viral hepatitis among migrant populations. This study investigated the prevalence of current hepatitis B virus (HBV) infection and lifetime hepatitis C virus (HCV) infection among Qatar's migrant craft and manual workers (CMWs), constituting 60% of the country's population. Sera collected during a nationwide COVID-19 population-based cross-sectional survey on CMWs between July 26 and September 9, 2020, underwent testing for HBsAg and HCV antibodies. Reactive samples underwent confirmatory testing, and logistic regression analyses were employed to explore associations with HBV and HCV infections. Among 2528 specimens tested for HBV infection, 15 were reactive, with 8 subsequently confirmed positive. Three samples lacked sufficient sera for confirmatory testing but were included in the analysis through multiple imputations. Prevalence of current HBV infection was 0.4% (95% CI 0.2-0.7%). Educational attainment and occupation were significantly associated with current HBV infection. For HCV infection, out of 2607 specimens tested, 46 were reactive, and 23 were subsequently confirmed positive. Prevalence of lifetime HCV infection was 0.8% (95% CI 0.5-1.2%). Egyptians exhibited the highest prevalence at 6.5% (95% CI 3.1-13.1%), followed by Pakistanis at 3.1% (95% CI 1.1-8.0%). Nationality, geographic location, and occupation were significantly associated with lifetime HCV infection. HBV infection is relatively low among CMWs, while HCV infection falls within the intermediate range, both compared to global and regional levels.


Subject(s)
Hepatitis B , Hepatitis C , Transients and Migrants , Humans , Qatar/epidemiology , Hepatitis B/epidemiology , Hepatitis B/virology , Hepatitis B/blood , Female , Transients and Migrants/statistics & numerical data , Hepatitis C/epidemiology , Adult , Male , Prevalence , Cross-Sectional Studies , Middle Aged , Hepacivirus/immunology , Hepacivirus/isolation & purification , Hepatitis B virus/isolation & purification , Hepatitis B virus/immunology , Young Adult , COVID-19/epidemiology , COVID-19/virology , Adolescent , Hepatitis B Surface Antigens/blood , Hepatitis C Antibodies/blood
10.
Front Immunol ; 15: 1353903, 2024.
Article in English | MEDLINE | ID: mdl-38799469

ABSTRACT

Introduction: The global healthcare burden of COVID-19 pandemic has been unprecedented with a high mortality. Metabolomics, a powerful technique, has been increasingly utilized to study the host response to infections and to understand the progression of multi-system disorders such as COVID-19. Analysis of the host metabolites in response to SARS-CoV-2 infection can provide a snapshot of the endogenous metabolic landscape of the host and its role in shaping the interaction with SARS-CoV-2. Disease severity and consequently the clinical outcomes may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. Hence, the host metabolome can help predict potential clinical risks and outcomes. Methods: In this prospective study, using a targeted metabolomics approach, we studied the metabolic signature in 154 COVID-19 patients (males=138, age range 48-69 yrs) and related it to disease severity and mortality. Blood plasma concentrations of metabolites were quantified through LC-MS using MxP Quant 500 kit, which has a coverage of 630 metabolites from 26 biochemical classes including distinct classes of lipids and small organic molecules. We then employed Kaplan-Meier survival analysis to investigate the correlation between various metabolic markers, disease severity and patient outcomes. Results: A comparison of survival outcomes between individuals with high levels of various metabolites (amino acids, tryptophan, kynurenine, serotonin, creatine, SDMA, ADMA, 1-MH and carnitine palmitoyltransferase 1 and 2 enzymes) and those with low levels revealed statistically significant differences in survival outcomes. We further used four key metabolic markers (tryptophan, kynurenine, asymmetric dimethylarginine, and 1-Methylhistidine) to develop a COVID-19 mortality risk model through the application of multiple machine-learning methods. Conclusions: Metabolomics analysis revealed distinct metabolic signatures among different severity groups, reflecting discernible alterations in amino acid levels and perturbations in tryptophan metabolism. Notably, critical patients exhibited higher levels of short chain acylcarnitines, concomitant with higher concentrations of SDMA, ADMA, and 1-MH in severe cases and non-survivors. Conversely, levels of 3-methylhistidine were lower in this context.


Subject(s)
COVID-19 , Metabolomics , SARS-CoV-2 , Severity of Illness Index , Humans , COVID-19/mortality , COVID-19/blood , COVID-19/metabolism , Male , Middle Aged , Female , Aged , Metabolomics/methods , Prospective Studies , Metabolome , Biomarkers/blood , Tryptophan/metabolism , Tryptophan/blood , Survival Analysis
11.
BMC Chem ; 18(1): 99, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38734638

ABSTRACT

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to over six million deaths worldwide. In human immune system, the type 1 interferon (IFN) pathway plays a crucial role in fighting viral infections. However, the ORF8 protein of the virus evade the immune system by interacting with IRF3, hindering its nuclear translocation and consequently downregulate the type I IFN signaling pathway. To block the binding of ORF8-IRF3 and inhibit viral pathogenesis a quick discovery of an inhibitor molecule is needed. Therefore, in the present study, the interface between the ORF8 and IRF3 was targeted on a high-affinity carbon nanotube by using computational tools. After analysis of 62 carbon nanotubes by multiple docking with the induced fit model, the top five compounds with high docking scores of - 7.94 kcal/mol, - 7.92 kcal/mol, - 7.28 kcal/mol, - 7.19 kcal/mol and - 7.09 kcal/mol (top hit1-5) were found to have inhibitory activity against the ORF8-IRF3 complex. Molecular dynamics analysis of the complexes revealed the high compactness of residues, stable binding, and strong hydrogen binding network among the ORF8-nanotubes complexes. Moreover, the total binding free energy for top hit1-5 was calculated to be - 43.21 ± 0.90 kcal/mol, - 41.17 ± 0.99 kcal/mol, - 48.85 ± 0.62 kcal/mol, - 43.49 ± 0.77 kcal/mol, and - 31.18 ± 0.78 kcal/mol respectively. These results strongly suggest that the identified top five nanotubes (hit1-5) possess significant potential for advancing and exploring innovative drug therapies. This underscores their suitability for subsequent in vivo and in vitro experiments, marking them as promising candidates worthy of further investigation.

12.
Influenza Other Respir Viruses ; 18(5): e13290, 2024 May.
Article in English | MEDLINE | ID: mdl-38706402

ABSTRACT

BACKGROUND: Priming with ChAdOx1 followed by heterologous boosting is considered in several countries. Nevertheless, analyses comparing the immunogenicity of heterologous booster to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between homologous primary vaccination regimens and heterologous prime-boost vaccination using BNT162b2 or mRNA-1273. METHODS: We matched vaccinated naïve (VN) individuals (n = 673) with partial vaccination (n = 64), primary vaccination (n = 590), and primary series plus mRNA vaccine heterologous booster (n = 19) with unvaccinated naturally infected (NI) individuals with a documented primary SARS-CoV-2 infection (n = 206). We measured the levels of neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA titers. RESULTS: Homologous primary vaccination with ChAdOx1 not only showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune responses compared to primary BNT162b2 or mRNA-1273 vaccination regimens (p < 0.05) but also showed ~3-fold less anti-S1 IgA response compared to infection-induced immunity (p < 0.001). Nevertheless, a heterologous booster led to an increase of ~12 times in the immune response when compared to two consecutive homologous ChAdOx1 immunizations. Furthermore, correlation analyses revealed that both anti-S-RBD IgG and anti-S1 IgA significantly contributed to virus neutralization among NI individuals, particularly in symptomatic and pauci-symptomatic individuals, whereas among VN individuals, anti-S-RBD IgG was the main contributor to virus neutralization. CONCLUSION: The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity particularly in patients who received primary vaccination with ChAdOx1.


Subject(s)
2019-nCoV Vaccine mRNA-1273 , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , Immunization, Secondary , Immunoglobulin A , Immunoglobulin G , SARS-CoV-2 , Humans , BNT162 Vaccine/immunology , BNT162 Vaccine/administration & dosage , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19/immunology , Male , Immunoglobulin G/blood , Immunoglobulin G/immunology , Female , SARS-CoV-2/immunology , Adult , 2019-nCoV Vaccine mRNA-1273/immunology , Middle Aged , Immunoglobulin A/blood , Immunoglobulin A/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Young Adult , Follow-Up Studies , Vaccination , Aged , Immunogenicity, Vaccine , Antibody Formation/immunology , ChAdOx1 nCoV-19/immunology , ChAdOx1 nCoV-19/administration & dosage , Spike Glycoprotein, Coronavirus/immunology
14.
Crit Rev Anal Chem ; : 1-18, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38593048

ABSTRACT

Electrochemical sensors have been the subject of much research and development as of late, with several publications detailing new designs boasting enhanced performance metrics. That is, without a doubt, because such sensors stand out from other analytical tools thanks to their excellent analytical characteristics, low cost, and ease of use. Their progress has shown a trend toward seeking out novel useful nano structure materials. A variety of nanostructure metal oxides have been utilized in the creation of potentiometric sensors, which are the subject of this article. For screen-printed pH sensors, metal oxides have been utilized as sensing layers due to their mixed ion-electron conductivity and as paste-ion-selective electrode components and in solid-contact electrodes. Further significant uses include solid-contact layers. All the metal oxide uses mentioned are within the purview of this article. Nanoscale metal oxides have several potential uses in the potentiometry method, and this paper summarizes such uses, including hybrid materials and single-component layers. Potentiometric sensors with outstanding analytical properties can be manufactured entirely from metal oxides. These novel sensors outperform the more traditional, conventional electrodes in terms of useful characteristics. In this review, we looked at the potentiometric analytical properties of different building solutions with various nanoscale metal oxides.

15.
J Med Virol ; 96(5): e29628, 2024 May.
Article in English | MEDLINE | ID: mdl-38682568

ABSTRACT

This study evaluated the potential for antibody-dependent enhancement (ADE) in serum samples from patients exposed to Middle East respiratory syndrome coronavirus (MERS-CoV). Furthermore, we evaluated the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on ADE in individuals with a MERS infection history. We performed ADE assay in sera from MERS recovered and SARS-CoV-2-vaccinated individuals using BHK cells expressing FcgRIIa, SARS-CoV-2, and MERS-CoV pseudoviruses (PVs). Further, we analyzed the association of ADE to serum IgG levels and neutralization. Out of 16 MERS patients, nine demonstrated ADE against SARS-CoV-2 PV, however, none of the samples demonstrated ADE against MERS-CoV PV. Furthermore, out of the seven patients exposed to SARS-CoV-2 vaccination after MERS-CoV infection, only one patient (acutely infected with MERS-CoV) showed ADE for SARS-CoV-2 PV. Further analysis indicated that IgG1, IgG2, and IgG3 against SARS-CoV-2 S1 and RBD subunits, IgG1 and IgG2 against the MERS-CoV S1 subunit, and serum neutralizing activity were low in ADE-positive samples. In summary, samples from MERS-CoV-infected patients exhibited ADE against SARS-CoV-2 and was significantly associated with low levels of neutralizing antibodies. Subsequent exposure to SARS-CoV-2 vaccination resulted in diminished ADE activity while the PV neutralization assay demonstrated a broadly reactive antibody response in some patient samples.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Antibody-Dependent Enhancement , COVID-19 , Immunoglobulin G , Middle East Respiratory Syndrome Coronavirus , SARS-CoV-2 , Humans , Middle East Respiratory Syndrome Coronavirus/immunology , Antibodies, Viral/blood , SARS-CoV-2/immunology , Immunoglobulin G/blood , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , COVID-19/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Middle Aged , Male , Female , Neutralization Tests , Adult , COVID-19 Vaccines/immunology , Antigens, Viral/immunology , Animals , Aged , Spike Glycoprotein, Coronavirus/immunology , Vaccination
16.
Vaccine ; 42(14): 3307-3320, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38616439

ABSTRACT

BACKGROUND: Vaccines were developed and deployed to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to characterize patterns in the protection provided by the BNT162b2 and mRNA-1273 mRNA vaccines against a spectrum of SARS-CoV-2 infection symptoms and severities. METHODS: A national, matched, test-negative, case-control study was conducted in Qatar between January 1 and December 18, 2021, utilizing a sample of 238,896 PCR-positive tests and 6,533,739 PCR-negative tests. Vaccine effectiveness was estimated against asymptomatic, symptomatic, severe coronavirus disease 2019 (COVID-19), critical COVID-19, and fatal COVID-19 infections. Data sources included Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalization, and death. RESULTS: Effectiveness of two-dose BNT162b2 vaccination was 75.6% (95% CI: 73.6-77.5) against asymptomatic infection and 76.5% (95% CI: 75.1-77.9) against symptomatic infection. Effectiveness against each of severe, critical, and fatal COVID-19 infections surpassed 90%. Immediately after the second dose, all categories-namely, asymptomatic, symptomatic, severe, critical, and fatal COVID-19-exhibited similarly high effectiveness. However, from 181 to 270 days post-second dose, effectiveness against asymptomatic and symptomatic infections declined to below 40%, while effectiveness against each of severe, critical, and fatal COVID-19 infections remained consistently high. However, estimates against fatal COVID-19 often had wide 95% confidence intervals. Analogous patterns were observed in three-dose BNT162b2 vaccination and two- and three-dose mRNA-1273 vaccination. Sensitivity analyses confirmed the results. CONCLUSION: A gradient in vaccine effectiveness exists and is linked to the symptoms and severity of infection, providing higher protection against more symptomatic and severe cases. This gradient intensifies over time as vaccine immunity wanes after the last vaccine dose. These patterns appear consistent irrespective of the vaccine type or whether the vaccination involves the primary series or a booster.


Subject(s)
2019-nCoV Vaccine mRNA-1273 , BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Vaccine Efficacy , Humans , COVID-19/prevention & control , COVID-19/immunology , BNT162 Vaccine/immunology , BNT162 Vaccine/administration & dosage , Qatar/epidemiology , SARS-CoV-2/immunology , Male , 2019-nCoV Vaccine mRNA-1273/immunology , Middle Aged , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Female , Adult , Case-Control Studies , Young Adult , Adolescent , Aged , Severity of Illness Index , Vaccination/methods
17.
J Med Virol ; 96(3): e29527, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38511514

ABSTRACT

Neutralizing antibodies (NAbs) are elicited after infection and vaccination and have been well studied. However, their antibody-dependent cellular cytotoxicity (ADCC) functionality is still poorly characterized. Here, we investigated ADCC activity in convalescent sera from infected patients with wild-type (WT) severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or omicron variant compared with three coronavirus disease 2019 (COVID-19) vaccine platforms and postvaccination breakthrough infection (BTI). We analyzed ADCC activity targeting SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in convalescent sera following WT SARS-CoV-2-infection (n = 91), including symptomatic and asymptomatic infections, omicron-infection (n = 8), COVID-19 vaccination with messenger RNA- (mRNA)- (BNT162b2 or mRNA-1273, n = 77), adenovirus vector- (n = 41), and inactivated virus- (n = 46) based vaccines, as well as post-mRNA vaccination BTI caused by omicron (n = 28). Correlations between ADCC, binding, and NAb titers were reported. ADCC was elicited within the first month postinfection and -vaccination and remained detectable for ≥3 months. WT-infected symptomatic patients had higher S-specific ADCC levels than asymptomatic and vaccinated individuals. Also, no difference in N-specific ADCC activity was seen between symptomatic and asymptomatic patients, but the levels were higher than the inactivated vaccine. Notably, omicron infection showed reduced overall ADCC activity compared to WT SARS-CoV-2 infection. Although post-mRNA vaccination BTI elicited high levels of binding and NAbs, ADCC activity was significantly reduced. Also, there was no difference in ADCC levels across the four vaccines, although NAbs and binding antibody titers were significantly higher in mRNA-vaccinated individuals. All evaluated vaccine platforms are inferior in inducing ADCC compared to natural infection with WT SARS-CoV-2. The inactivated virus-based vaccine can induce N-specific ADCC activity, but its relevance to clinical outcomes requires further investigation. Our data suggest that ADCC could be used to estimate the extra-neutralization level against COVID-19 and provides evidence that vaccination should focus on other Fc-effector functions besides NAbs. Also, the decreased susceptibility of the omicron variant to ADCC offers valuable guidance for forthcoming efforts to identify the specific targets of antibodies facilitating ADCC.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , COVID-19/prevention & control , BNT162 Vaccine , SARS-CoV-2 , COVID-19 Serotherapy , Antibodies, Neutralizing , Antibody-Dependent Cell Cytotoxicity , Antibodies, Viral , Vaccination
18.
One Health ; 18: 100708, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38496338

ABSTRACT

Rodents are known reservoirs for a diverse group of zoonotic pathogens that can pose a threat to human health. Therefore, it is crucial to investigate these pathogens to institute prevention and control measures. To achieve this, the current study was conducted to investigate the frequency of different parasites in commensal rodents in Qatar. A total of 148 rodents, including Rattus norvegicus, Rattus rattus, and Mus musculus were captured using traps placed in different habitats such as agricultural and livestock farms, residential areas, and other localities. Blood, feces, ectoparasite, and visceral organs were collected for gross, microscopic, immunological, and molecular analysis. The study identified 10 different parasites, including Capillaria annulosa, Eimeria spp., Giardia spp., Hymenolepis diminuta, Mastophorus muris, Ornithonyssus bacoti, Taenia taeniaeformis, Toxoplasma gondii, Trypanosoma lewisi, and Xenopsylla astia. Overall, 62.2% of the rodents tested positive for at least one parasite species. Helminths were found to be the most prevalent parasites (46.0%), followed by ectoparasites (31.8%), and protozoa (10.1%). However, individually, X. astia was the most prevalent (31.8%), whereas C. annulosa was the least common (0.7%). The prevalence of X. astia and H. diminuta significantly differed between habitats (p < 0.05). The sequence analysis of Hymenolepis spp. was closely related to the previously reported H. diminuta in Iran, China, and Mexico. In conclusion, the study identified a diverse range of rodent-borne parasites that are important to public health, with most of them being recorded for the first time among commensal rodents in Qatar.

19.
Front Med (Lausanne) ; 11: 1363045, 2024.
Article in English | MEDLINE | ID: mdl-38529118

ABSTRACT

Introduction: Reinfections are increasingly becoming a feature in the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, accurately defining reinfection poses methodological challenges. Conventionally, reinfection is defined as a positive test occurring at least 90 days after a previous infection diagnosis. Yet, this extended time window may lead to an underestimation of reinfection occurrences. This study investigated the prospect of adopting an alternative, shorter time window for defining reinfection. Methods: A longitudinal study was conducted to assess the incidence of reinfections in the total population of Qatar, from February 28, 2020 to November 20, 2023. The assessment considered a range of time windows for defining reinfection, spanning from 1 day to 180 days. Subgroup analyses comparing first versus repeat reinfections and a sensitivity analysis, focusing exclusively on individuals who underwent frequent testing, were performed. Results: The relationship between the number of reinfections in the population and the duration of the time window used to define reinfection revealed two distinct dynamical domains. Within the initial 15 days post-infection diagnosis, almost all positive tests for SARS-CoV-2 were attributed to the original infection. However, surpassing the 30-day post-infection threshold, nearly all positive tests were attributed to reinfections. A 40-day time window emerged as a sufficiently conservative definition for reinfection. By setting the time window at 40 days, the estimated number of reinfections in the population increased from 84,565 to 88,384, compared to the 90-day time window. The maximum observed reinfections were 6 and 4 for the 40-day and 90-day time windows, respectively. The 40-day time window was appropriate for defining reinfection, irrespective of whether it was the first, second, third, or fourth occurrence. The sensitivity analysis, confined to high testers exclusively, replicated similar patterns and results. Discussion: A 40-day time window is optimal for defining reinfection, providing an informed alternative to the conventional 90-day time window. Reinfections are prevalent, with some individuals experiencing multiple instances since the onset of the pandemic.

20.
J Environ Manage ; 353: 120206, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38325287

ABSTRACT

Wastewater irrigation for vegetable cultivation is greatly concerned about the presence of toxic metals in irrigated soil and vegetables which causes possible threats to human health. This study aimed to ascertain the accumulation of heavy metals (HMs) in edible parts of vegetables irrigated with different stages of textile dyeing wastewater (TDW). Bio-concentration factor (BCF), Estimated daily intake (EDI), and target hazard quotient (THQ) were computed to estimate human health risks and speculate the hazard index (HI) of adults and children with the consumption of HMs contaminated vegetables at recommended doses. Five vegetables (red amaranth, Indian spinach, cauliflower, tomato, and radish) in a pot experiment were irrigated with groundwater (T1) and seven stages of TDW (T2∼T8) following a randomized complete block design (RCBD) with three replications. Among the TDW stages, T8, T7, T4, and T5 exhibited elevated BCF, EDI, THQ, and HI due to a rising trend in the accumulation of Pb, Cd, Cr, and Ni heavy metals in the edible portion of the red amaranth, followed by radish, Indian spinach, cauliflower, and tomato. The general patterns of heavy metal (HM) accumulation, regarded as vital nutrients for plants, were detected in the following sequence: Zn > Mn/Cu > Fe. Conversely, toxic metals were found to be Cd/Cr > Ni > Pb, regardless of the type of vegetables. Principal Component Analysis (PCA) identified T8, T7, and T4 of TDW as the primary contributors to the accumulation of heavy metals in the vegetables examined. Furthermore, the analysis of the heavy metals revealed that the BCF, THQ, and HI values for all studied metals were below 1, except for Pb. This suggests that the present consumption rates of different leafy and non-leafy vegetables, whether consumed individually or together, provide a low risk in terms of heavy metal exposure. Nevertheless, the consumption of T8, T7, and T4 irrigated vegetables, specifically Indian spinach alone or in combination with red amaranth and radish, by both adults and children, at the recommended rate, was found to pose potential health risks. On the other hand, T2, T3, and T6 irrigated vegetables were deemed safe for consumption. These findings indicated that the practice of irrigating the vegetables with T8, T7, and T4 stages of TDW has resulted in a significant buildup of heavy metals in the soils and edible parts of vegetables which are posing health risks to adults and children. Hence, it is imperative to discharge the T8, T7, and T4 stages of TDW after ETP to prevent the contamination of vegetables and mitigate potential health risks.


Subject(s)
Metals, Heavy , Soil Pollutants , Solanum lycopersicum , Adult , Child , Humans , Cadmium , Environmental Monitoring , Food Contamination/analysis , Lead , Metals, Heavy/analysis , Risk Assessment , Soil , Soil Pollutants/analysis , Vegetables , Wastewater
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