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Introduction. The frequency of multidrug-resistant organisms (MDROs) in hospitals and the risk of delaying effective treatment result in the culture of respiratory secretions for nearly all patients with suspected pneumonia. Culture delays contribute to over prescribing and use of broader spectrum antibiotics.Gap statement. The need for improved rapid diagnostics for early assessment of suspected hospital pneumonia.Aim. To validate a new metric, enhanced Gram stain (EGS), to provide a rapid diagnostic test of high diagnostic accuracy that could be assessed in clinical trials of the use of antibiotics in suspected pneumonia.Methodology. Ninety-two residual lower respiratory samples previously tested by culture and Gram stain were re-tested by 16S ribosomal DNA real-time polymerase chain reaction (16S qPCR) and reported as a combined metric with Gram stain termed EGS. The EGS was assessed for diagnostic accuracy, standard performance measurements and correlation against culture. For samples with discordance between culture and EGS, 16S ribosomal DNA whole operon sequencing (16S rDNA WOS) was used for test resolution. An amended EGS (A-EGS was reassessed against culture.Results. Gram stain, 16S qPCR, EGS and A-EGS had respective diagnostic accuracies of 77.01â%, 82.76â%, 84.04â% and 94.19â%. The same platforms had respective correlation with culture of r = 0.67, r = 0.71, r = 0.81 and r = 0.89. EGS had the highest negative predictive value (NPV) of 93.18â% (81.99â%-97.62â%). Adding an 16S qPCR result is achievable in most routine laboratories and, combined with Gram stain, could improve early decision-making in patients with suspected hospital pneumonia.Conclusion. EGS could improve early decision-making in patients with suspected hospital pneumonia and could be assessed in clinical trials. The 16S rDNA WOS results in the A-EGS also supported the use of pathogen genomic sequencing in early decision making of suspected pneumonia.
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Violeta de Genciana , Fenazinas , ARN Ribosómico 16S , Reacción en Cadena en Tiempo Real de la Polimerasa , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Sensibilidad y Especificidad , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/microbiología , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/microbiología , Neumonía/diagnóstico , Neumonía/microbiología , Bacterias/aislamiento & purificación , Bacterias/genética , Bacterias/clasificación , MasculinoRESUMEN
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.
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Hepatitis A , Migrantes , Humanos , Qatar/epidemiología , Hepatitis A/epidemiología , Hepatitis A/sangre , Femenino , Masculino , Adulto , Estudios Seroepidemiológicos , Migrantes/estadística & datos numéricos , Persona de Mediana Edad , Estudios Transversales , Prevalencia , Adulto Joven , Virus de la Hepatitis A/inmunología , Adolescente , Anticuerpos de Hepatitis A/sangre , COVID-19/epidemiología , COVID-19/virologíaRESUMEN
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.
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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.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , Inmunoglobulina A , Inmunoglobulina G , SARS-CoV-2 , Humanos , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Inmunoglobulina A/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , COVID-19/prevención & control , COVID-19/inmunología , Masculino , Femenino , Inmunización Secundaria/métodos , Adulto , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Persona de Mediana Edad , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Adulto Joven , Vacunación/métodos , Inmunogenicidad Vacunal , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Vacunas de ARNm/inmunología , Vacuna nCoV-2019 mRNA-1273/inmunología , Vacuna nCoV-2019 mRNA-1273/administración & dosificación , AncianoRESUMEN
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.
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Hepatitis B , Hepatitis C , Migrantes , Humanos , Qatar/epidemiología , Hepatitis B/epidemiología , Hepatitis B/virología , Hepatitis B/sangre , Femenino , Migrantes/estadística & datos numéricos , Hepatitis C/epidemiología , Adulto , Masculino , Prevalencia , Estudios Transversales , Persona de Mediana Edad , Hepacivirus/inmunología , Hepacivirus/aislamiento & purificación , Virus de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis B/inmunología , Adulto Joven , COVID-19/epidemiología , COVID-19/virología , Adolescente , Antígenos de Superficie de la Hepatitis B/sangre , Anticuerpos contra la Hepatitis C/sangreRESUMEN
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.
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Simulación del Acoplamiento Molecular , Unión Proteica , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas , Proteínas no Estructurales Virales , Proteínas de Motivos Tripartitos/metabolismo , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/química , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/metabolismo , Proteínas no Estructurales Virales/genética , Humanos , Ubiquitina-Proteína Ligasas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/química , Antivirales/farmacología , Antivirales/química , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A/inmunología , Fitoquímicos/farmacología , Fitoquímicos/química , Diseño de Fármacos , Evaluación Preclínica de MedicamentosRESUMEN
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.
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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.
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Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , Inmunoglobulina A , Inmunoglobulina G , SARS-CoV-2 , Humanos , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Masculino , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Femenino , SARS-CoV-2/inmunología , Adulto , Vacuna nCoV-2019 mRNA-1273/inmunología , Persona de Mediana Edad , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Adulto Joven , Estudios de Seguimiento , Vacunación , Anciano , Inmunogenicidad Vacunal , Formación de Anticuerpos/inmunología , ChAdOx1 nCoV-19/inmunología , ChAdOx1 nCoV-19/administración & dosificación , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
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.
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COVID-19 , Metabolómica , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Humanos , COVID-19/mortalidad , COVID-19/sangre , COVID-19/metabolismo , Masculino , Persona de Mediana Edad , Femenino , Anciano , Metabolómica/métodos , Estudios Prospectivos , Metaboloma , Biomarcadores/sangre , Triptófano/metabolismo , Triptófano/sangre , Análisis de SupervivenciaRESUMEN
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.
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Vacuna nCoV-2019 mRNA-1273 , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Eficacia de las Vacunas , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Qatar/epidemiología , SARS-CoV-2/inmunología , Masculino , Vacuna nCoV-2019 mRNA-1273/inmunología , Persona de Mediana Edad , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Femenino , Adulto , Estudios de Casos y Controles , Adulto Joven , Adolescente , Anciano , Índice de Severidad de la Enfermedad , Vacunación/métodosRESUMEN
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.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Acrecentamiento Dependiente de Anticuerpo , COVID-19 , Inmunoglobulina G , Coronavirus del Síndrome Respiratorio de Oriente Medio , SARS-CoV-2 , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Anticuerpos Antivirales/sangre , SARS-CoV-2/inmunología , Inmunoglobulina G/sangre , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , COVID-19/inmunología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Persona de Mediana Edad , Masculino , Femenino , Pruebas de Neutralización , Adulto , Vacunas contra la COVID-19/inmunología , Antígenos Virales/inmunología , Animales , Anciano , Glicoproteína de la Espiga del Coronavirus/inmunología , VacunaciónRESUMEN
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.
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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.
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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.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , COVID-19/prevención & control , Vacuna BNT162 , SARS-CoV-2 , Sueroterapia para COVID-19 , Anticuerpos Neutralizantes , Citotoxicidad Celular Dependiente de Anticuerpos , Anticuerpos Antivirales , VacunaciónRESUMEN
The COVID-19 pandemic has highlighted the need to use infection testing databases to rapidly estimate effectiveness of prior infection in preventing reinfection ($P{E}_S$) by novel SARS-CoV-2 variants. Mathematical modeling was used to demonstrate a theoretical foundation for applicability of the test-negative, case-control study design to derive $P{E}_S$. Apart from the very early phase of an epidemic, the difference between the test-negative estimate for $P{E}_S$ and true value of $P{E}_S$ was minimal and became negligible as the epidemic progressed. The test-negative design provided robust estimation of $P{E}_S$ and its waning. Assuming that only 25% of prior infections are documented, misclassification of prior infection status underestimated $P{E}_S$, but the underestimate was considerable only when >50% of the population was ever infected. Misclassification of latent infection, misclassification of current active infection, and scale-up of vaccination all resulted in negligible bias in estimated $P{E}_S$. The test-negative design was applied to national-level testing data in Qatar to estimate $P{E}_S$ for SARS-CoV-2. $P{E}_S$ against SARS-CoV-2 Alpha and Beta variants was estimated at 97.0% (95% CI: 93.6-98.6) and 85.5% (95% CI: 82.4-88.1), respectively. These estimates were validated using a cohort study design. The test-negative design offers a feasible, robust method to estimate protection from prior infection in preventing reinfection.
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Swine influenza A viruses (SwIAVs) are pathogens of both veterinary and medical significance. Intranasal (IN) vaccination has the potential to reduce flu infection. We investigated the efficacy of split SwIAV H1N2 antigens adsorbed with a plant origin nanoparticle adjuvant [Nano11-SwIAV] or in combination with a STING agonist ADU-S100 [NanoS100-SwIAV]. Conventional pigs were vaccinated via IN and challenged with a heterologous SwIAV H1N1-OH7 or 2009 H1N1 pandemic virus. Immunologically, in NanoS100-SwIAV vaccinates, we observed enhanced frequencies of activated monocytes in the blood of the pandemic virus challenged animals and in tracheobronchial lymph nodes (TBLN) of H1N1-OH7 challenged animals. In both groups of the virus challenged pigs, increased frequencies of IL-17A+ and CD49d+IL-17A+ cytotoxic lymphocytes were observed in Nano11-SwIAV vaccinates in the draining TBLN. Enhanced frequency of CD49d+IFNγ+ CTLs in the TBLN and blood of both the Nano11-based SwIAV vaccinates was observed. Animals vaccinated with both Nano11-based vaccines had upregulated cross-reactive secretory IgA in the lungs and serum IgG against heterologous and heterosubtypic viruses. However, in NanoS100-SwIAV vaccinates, a slight early reduction in the H1N1 pandemic virus and a late reduction in the SwIAV H1N1-OH7 load in the nasal passages were detected. Hence, despite vast genetic differences between the vaccine and both the challenge viruses, IN vaccination with NanoS100-SwIAV induced antigen-specific moderate levels of cross-protective immune responses.
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Background: The rapid growth of Qatar in the last two decades has attracted a large influx of immigrant craft and manual workers (CMWs) seeking employment in jobs associated with food handling, domestic service, and construction. Nearly 60 % of Qatar's population are expatriates CMWs, including many from hyperendemic countries for HEV. Thus, estimating the seroprevalence of HEV in Qatar and understanding its epidemiology is essential for public health efforts to control HEV transmission in Qatar. Methods: Blood samples from 2670 CMWs were collected between 2020 and 2021. All samples were tested for HEV-IgG antibodies. Positive HEV-IgG samples were tested for HEV-IgM antibodies, and those positives were also tested for viral antigens using an HEV-Ag ELISA kit and HEV-RNA by RT-PCR to confirm current HEV infections. Results: The seroprevalence of HEV-IgG was 27.3 % (729/2670; 95 % CI: 25.6-29.0). Of those HEV-IgG positive, 8.23 % (60/729; 95 % CI: 6.30-10.5) were HEV-IgM positive. Of the IgM-positive samples, 2 were HEV-RNA positive (3.39 %; 95 % CI: 0.40-11.7), and 1 was HEV-Ag positive (1.69 %; 95 % CI: 0.04-9.09). In addition, HEV-IgG seroprevalence was associated with age and nationality, with the highest seroprevalence in participants from Egypt (IgG 60.0 %; IgM 5.56 %), Pakistan (IgG 59.0 %; IgM 2.24 %), Nepal (IgG 29.3 %; IgM 2.70 %), Bangladesh (IgG 27.8 %; IgM 2.45 %), and India (IgG 23.9 %; IgM 2.43 %). Conclusion: In this study, we showed that the seroprevalence of HEV among CMWs was slightly higher than what was previously reported among the urban population in Qatar (2013-2016).
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BACKGROUND: We investigated the contribution of age, coexisting medical conditions, sex, and vaccination to incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe, critical, or fatal COVID-19 in older adults since pandemic onset. METHODS: A national retrospective cohort study was conducted in the population of Qatar aged ≥50 years between February 5, 2020 and June 15, 2023. Adjusted hazard ratios (AHRs) for infection and for severe coronavirus disease 2019 (COVID-19) outcomes were estimated through Cox regression models. RESULTS: Cumulative incidence was 25.01% (95% confidence interval [CI]: 24.86-25.15%) for infection and 1.59% (95% CI: 1.55-1.64%) for severe, critical, or fatal COVID-19 after a follow-up duration of 40.9 months. Risk of infection varied minimally by age and sex but increased significantly with coexisting conditions. Risk of infection was reduced with primary-series vaccination (AHR: 0.91, 95% CI: 0.90-0.93) and further with first booster vaccination (AHR: 0.75, 95% CI: 0.74-0.77). Risk of severe, critical, or fatal COVID-19 increased exponentially with age and linearly with coexisting conditions. AHRs for severe, critical, or fatal COVID-19 were 0.86 (95% CI: 0.7-0.97) for one dose, 0.15 (95% CI: 0.13-0.17) for primary-series vaccination, and 0.11 (95% CI: 0.08-0.14) for first booster vaccination. Sensitivity analysis restricted to only Qataris yielded similar results. CONCLUSION: Incidence of severe COVID-19 in older adults followed a dynamic pattern shaped by infection incidence, variant severity, and population immunity. Age, sex, and coexisting conditions were strong determinants of infection severity. Vaccine protection against severe outcomes showed a dose-response relationship, highlighting the importance of booster vaccination for older adults.
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COVID-19 , Humanos , Anciano , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Estudios de Cohortes , Estudios Retrospectivos , Vacunación , ComorbilidadRESUMEN
Laboratory evidence suggests a possibility of immune imprinting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the differences in the incidence of SARS-CoV-2 reinfection in a cohort of persons who had a primary Omicron infection, but different vaccination histories using matched, national, retrospective, cohort studies. Adjusted hazard ratio for reinfection incidence, factoring adjustment for differences in testing rate, was 0.43 [95% confidence interval (CI): 0.39 to 0.49] comparing history of two-dose vaccination to no vaccination, 1.47 (95% CI: 1.23 to 1.76) comparing history of three-dose vaccination to two-dose vaccination, and 0.57 (95% CI: 0.48 to 0.68) comparing history of three-dose vaccination to no vaccination. Divergence in cumulative incidence curves increased markedly when the incidence was dominated by BA.4/BA.5 and BA.2.75* Omicron subvariants. The history of primary-series vaccination enhanced immune protection against Omicron reinfection, but history of booster vaccination compromised protection against Omicron reinfection. These findings do not undermine the public health utility of booster vaccination.