19 research outputs found
Effectiveness of mRNA booster doses against the omicron variant
No full textSince its emergence in November, 2021, the omicron (B.1.1.529) variant of SARS-CoV-2 has rapidly spread and quickly overtaken the delta (B.1.617.2) variant as the most common cause of infection.1 Due to numerous spike mutations, the omicron variant showed increased transmissibility and reduced neutralisation by antibodies from prior infections compared with the wild-type virus and other variants of concern. Concurrently, breakthrough infections surged in populations with high vaccination rates, which expedited efforts to scale up booster vaccination
The spectrum of chromosomal translocations in the Arab world: ethnic-specific chromosomal translocations and their relevance to diseases
No full textChromosomal translocations (CTs) are the most common type of structural chromosomal abnormalities in humans. CTs have been reported in several studies in the Arab world, but the frequency and spectrum of these translocations are not well characterized. The aim of this study is to conduct a systematic review to estimate the frequency and spectrum of CTs in the 22 Arab countries. Four literature databases were searched: PubMed, Science Direct, Scopus, and Web of Science, from the time of inception until July 2021. A combination of broad search terms was used to collect all possible CTs reported in the Arab world. In addition to the literature databases, all captured CTs were searched in three chromosomal rearrangement databases (Mitelman Database, CytoD 1.0 Database, and the Atlas of Genetics and Cytogenetics in Oncology and Hematology), along with PubMed and Google Scholar, to check whether the CTs are unique to the Arabs or shared between Arabs and non-Arabs. A total of 9,053 titles and abstracts were screened, of which 168 studies met our inclusion criteria, and 378 CTs were identified in 15 Arab countries, of which 57 CTs were unique to Arab patients. Approximately 89% of the identified CTs involved autosomal chromosomes. Three CTs, t(9;22), t(13;14), and t(14;18), showed the highest frequency, which were associated with hematological malignancies, recurrent pregnancy loss, and follicular lymphoma, respectively. Complex CTs were commonly reported among Arabs, with a total of 44 CTs, of which 12 were unique to Arabs. This is the first study to focus on the spectrum of CTs in the Arab world and compressively map the ethnic-specific CTs relevant to cancer. It seems that there is a distinctive genotype of Arabs with CTs, of which some manifested with unique clinical phenotypes. Although ethnic-specific CTs are highly relevant to disease mechanism, they are understudied and need to be thoroughly addressed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00412-022-00775-2
Is preexisting immunity to seasonal coronaviruses limited to cross-reactivity with SARS-CoV-2? A seroprevalence cross-sectional study in north-eastern France
No full textIn light of the ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there remain unanswered questions regarding the humoral immune response and the breadth of cross-reactivity with preexisting seasonal human coronaviruses (HCoVs). Initially, the lack of preexisting immunity was believed to contribute to the virus's rampant spread. Several studies reported that the clinical manifestations of COVID-19 are age-dependent, with children appearing to be less susceptible to infection and severe disease [1]. This highlighted the potential cross-protective effect of preexisting immunity to seasonal HCoVs. However, reported data on cross-reactivity was contradictory, antigen-dependent, and mostly conducted on small sample sizes
Seroprevalence of influenza A H1N1 and influenza D viruses in ruminants in Qatar
No full textBackgroundInfluenza is among the most common viruses affecting humans and many animals worldwide. While influenza A (IAV) and D (IDV) viruses are associated with respiratory disease in humans and animals, respectively, their prevalence in the Middle East is unknown. MethodsHere, we assessed the seroprevalence of IDV and IAV/H1N1 in 331 ruminants (including camels, sheep, cattle, and goats) in Qatar. Sera samples were collected from ruminants in different farms and titrated by hemagglutination inhibition (HAI) assay. ResultsWe showed a high prevalence of IDV in all ruminants, ranging between 55 and 84 %, with the highest rates seen in sheep and cattle. The rates were much lower for IAV, ranging between 6 and 8 %, but were not detectable in goats. HAI titers of IDV-seropositive samples ranged between 20 and 2560, whereas IAV titers ranged between 20 and 640. ConclusionsOur study provides the first serological evidence of IDV and IAV/H1N1 in ruminants in Qatar. These results underscore the need for further investigation into the role of ruminants in influenza virus transmission.This work was funded by Qatar University, BRC Internal Funds 2020, and Qatar National Research Fund (QNRF), grant MME03-1128-210032
Evaluation of commercially available fully automated and ELISA-based assays for detecting anti-SARS-CoV-2 neutralizing antibodies
No full textRapid and accurate measurement of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-specific neutralizing antibodies (nAbs) is paramount for monitoring immunity in infected and vaccinated subjects. The current gold standard relies on pseudovirus neutralization tests which require sophisticated skills and facilities. Alternatively, recent competitive immunoassays measuring anti-SARS-CoV-2 nAbs are proposed as a quick and commercially available surrogate virus neutralization test (sVNT). Here, we report the performance evaluation of three sVNTs, including two ELISA-based assays and an automated bead-based immunoassay for detecting nAbs against SARS-CoV-2. The performance of three sVNTs, including GenScript cPass, Dynamiker, and Mindray NTAb was assessed in samples collected from SARS-CoV-2 infected patients (n = 160), COVID-19 vaccinated individuals (n = 163), and pre-pandemic controls (n = 70). Samples were collected from infected patients and vaccinated individuals 2–24 weeks after symptoms onset or second dose administration. Correlation analysis with pseudovirus neutralization test (pVNT) and immunoassays detecting anti-SARS-CoV-2 binding antibodies was performed. Receiver operating characteristic (ROC) curve analysis was generated to assess the optimal threshold for detecting nAbs by each assay. All three sVNTs showed an excellent performance in terms of specificity (100%) and sensitivity (100%, 97.0%, and 97.1% for GenScript, Dynamiker, and Mindray, respectively) in samples collected from vaccinated subjects. GenScript demonstrated the strongest correlation with pVNT (r = 0.743, R(2) = 0.552), followed by Mindray (r = 0.718, R(2) = 0.515) and Dynamiker (r = 0.608, R(2) = 0.369). Correlation with anti-SARS-CoV-2 binding antibodies was variable, but the strongest correlations were observed between anti-RBD IgG antibodies and Mindray (r = 0.952, R(2) = 0.907). ROC curve analyses demonstrated excellent performance for all three sVNT assays in both groups, with an AUC ranging between 0.99 and 1.0 (p < 0.0001). Also, it was shown that the manufacturer's recommended cutoff values could be modified based on the tested cohort without significantly affecting the sVNT performance. The sVNT provides a rapid, low-cost, and scalable alternative to conventional neutralization assays for measuring and expanding nAbs testing across various research and clinical settings. Also, it could aid in evaluating actual protective immunity at the population level and assessing vaccine effectiveness to lay a foundation for boosters' requirements
Simple drag prediction strategies for an Autonomous Underwater Vehicle’s hull shape
No full textThe range of an AUV is dictated by its finite energy source and minimising the energy consumption is required to maximise its endurance. One option to extend the endurance is by obtaining the optimum hydrodynamic hull shape with balancing the trade-off between computational cost and fluid dynamic fidelity. An AUV hull form has been optimised to obtain low resistance hull. Hydrodynamic optimisation of hull form has been carried out by employing five parametric geometry models with a streamlined constraint. Three Genetic Algorithm optimisation procedures are applied by three simple drag predictions which are based on the potential flow method. The results highlight the effectiveness of considering the proposed hull shape optimisation procedure for the early stage of AUV hull desig
SARS-CoV-2 infection triggers more potent antibody-dependent cellular cytotoxicity (ADCC) responses than mRNA-, vector-, and inactivated virus-based COVID-19 vaccines
No full textNeutralizing 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.We thank the virology research center at the National Institute of Health (VRC-NIH) for providing the plasmids used to generate SARS-CoV-2 pseudoviruses and for providing HEK293T cells. We also thank the UREP students who assisted in the blood samples collection and coordination: Tala Jamaleddin, Huda Abdul Hameed, Amira Elsharafi, Fatima AlHamaydeh, Bushra Abu Halawa, Hadiya Khalid, Nasrin Cusman, Maram Ali, Hamas Fouda, Salma Mohamud, and Reham Kamal. This study was supported by partial funds from grant #NPRP11S-1212-170092 awarded to Dr. Yassine. GKN would like to acknowledge that this work was made possible by WHO grant number COVID-19-22-43; QUCG-BRC-23/24-170, and grant number UREP29-026-3-004 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the authors' responsibility
Antibody-dependent enhancement of SARS-CoV-2, the impact of variants and vaccination
No full textThis study characterized antibody-dependent enhancement (ADE) in serum samples from individuals exposed to SARS-CoV-2 via infection or vaccination and evaluated its association with SARS-CoV-2 variants (Wuhan and Omicron), MERS-CoV, and NL63. ADE assays were performed on sera from SARS-CoV-2-infected patients (n = 210) with varying disease severity and vaccinated individuals (n = 225) who received adenovirus vector, inactivated virus or mRNA vaccines. ADE was assessed using pseudoviruses (PVs) in BHK cells expressing FcgRIIa. Neutralizing antibody levels, total IgG, IgG subclasses, and complement activation were analyzed using ELISA and neutralization assays. ADE was observed in 6.2% of infection samples (primarily severe cases) and 5.3% of vaccinated samples (adenovirus-vector and inactivated virus groups). ADE-positive samples showed reduced neutralizing activity, while total IgG and IgG subclasses did not differ significantly between ADE-positive and negative samples. Complement activation was elevated in severe cases but did not correlate clearly with ADE. Notably, MERS-CoV PV induced ADE in a subset of infected samples, but no ADE was detected for NL63. ADE was observed in SARS-CoV-2-infected individuals, particularly in severe cases, and in those vaccinated with adenovirus-vector and inactivated virus vaccines, but not with mRNA vaccines. Cross-reactivity leading to ADE was detected for MERS-CoV but not for NL63. ADE was associated with reduced neutralizing antibody activity and elevated complement activation in severe infections, though the specific role of complement in ADE remains unclear. These findings highlight the need to investigate the mechanisms underlying ADE and its implications for vaccine design and post-infection immunity against respiratory viruses
In vivo testing of novel nitric oxide-releasing nanoparticles for alleviating heart failure using the zebrafish embryo model
No full textHeart failure (HF) is a multifactorial, heterogeneous systemic disease that is considered one of the leading causes of death and morbidity worldwide. It is well-known that endothelial dysfunction (ED) plays an important role in cardiac disease etiology. A reduction in the bioavailability of nitric oxide (NO) in the bloodstream leads to vasoconstriction and ED. Many studies indicated diminishment of peripheral arteries vasodilation that is mediated by the endothelium in the of patients with chronic HF. With the advancement of nanomedicine, nanotechnology can provide adequate solutions for delivering exogenous NO with the aid of nanoparticles (NPs) to treat ED. The properties of superparamagnetic iron oxide nanoparticles (SPIONs) enable both passive and active delivery of drugs. This prompted us to investigate the efficacy of our newly-developed hydrogel nanoparticles (NO-RPs) for the delivery and sustained release of NO gas to alleviate cardiac failure and inflammation in the heart failure zebrafish model. The hydrogel NO-RPs incorporate SPIONS and NO precursor. The sustainend release of NO in the NO-RPs (4200 s), overcomes the problem of the short half life of NO in vivo which is expected to ameliorate the reduced NO bioavailabilty, and its consequences in endothelial and cardiac dysfunction. Zebrafish embryos were used as the animal model in this study to determine the effect of SPIONs-loaded NO-RPs on the cardiovascular system. Cardiac failure was induced in 24hpf embryos by exposure to aristolochic acid (AA)(0.25, 0.5 μM) for 8 h, followed by the SPIONs-loaded NO-RPs (0.25, 0.5 mg/ml) for 48 h, experimental groups included: control group which is healthy non treated zebrafish embryos, AA injured zebrafish embryos (HF) model,and NO-RP treated HF zebrafish embryos. Survival rate was assessed at 72hpf. Cardiac function was also evaluated by analyzing cardiac parameters including heartbeat, major blood vessels primordial cardinal vein and dorsal aorta (PCV &DA) diameter, blood flow velocity in PCV & DA vessels, cardiac output, and PCV & DA shear stresses. All cardiac parameters were analyzed with the aid of MicroZebraLab blood flow analysis software from Viewpoint. In addition, we studied the molecular effects of the developed NO-RPs on the mRNA expression of selected pro-inflammatory markers: IL-6, and Cox-2. Our findings demonstrated that the NO-RPs improved the survival rate in the heart failure zebrafish model and reversed heart failure by enhancing blood flow perfusion in Zebrafish embryos, significantly. In addition, RT-PCR results showed that the NO-RPs significantly reduced the expression of pro-inflammatory markers (lL-6&COX-2) in the heart failure zebrafish model. Our study confirmed that the developed SPIONs-loaded NO-RPs are effective tool to alleviate cardiac failure and inflammation in the HF zebrafish model.Other Information Published in: Nitric Oxide License: http://creativecommons.org/licenses/by/4.0/See article on publisher's website: https://dx.doi.org/10.1016/j.niox.2024.01.007</p
Human herpes simplex virus-6 (HHV-6) detection and seroprevalence among Qatari nationals and immigrants residing in Qatar
No full textBackgroundHuman herpes simplex virus-6 (HHV-6) is the causative agent of exanthema subitum. Transmission mainly occurs through salivary secretions, yet blood transfusions and organ transplantations have also been reported as routes of transmission. Studies of seroprevalence of HHV-6 in the Middle East and North Africa (MENA) region and other parts of Asia are scarce. As such, this study aimed to estimate the seroprevalence of HHV-6 among healthy blood donors in Qatar. MethodsIn total, 620 healthy blood donors from different nationalities residing in Qatar, mainly from the MENA region and Southeast Asia, were tested using a commercial anti-HHV-6 immunoglobulin G (IgG) enzyme-linked immunosorbent assay kit. In addition, HHV-6 DNA from randomly selected samples was tested and quantified using quantitative reverse transcriptase polymerase chain reaction. ResultsAnti-HHV-6 IgG was detected in 71.7% (445/620) [95% confidence interval (CI) 68.2–75.3%] of the tested samples, while 24.3% (61/251) (95% CI 20.0–29.6%) had detectable HHV-6 viraemia. Only 22.5% of individuals with positive IgG status had detectable HHV-6 DNA in their blood, indicating a weak association between viraemia and IgG positivity (P=0.08). Furthermore, no significant difference was associated between HHV-6 viraemia and demographic characteristics, except for nationality. ConclusionThe seroprevalence of HHV-6 in Qatar was found to be similar to rates reported in other parts of the world.This work was made possible by collaborative grant number M-QJRC-2020-5 from Qatar University
