SARS-CoV-2 infection triggers more potent antibody-dependent cellular cytotoxicity (ADCC) responses than mRNA-, vector-, and inactivated virus-based COVID-19 vaccines.

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.

Evaluation of psychological distress, burnout and structural empowerment status of healthcare workers during the outbreak of coronavirus disease (COVID-19): a cross-sectional questionnaire-based study.

BACKGROUND: In light of several recent studies, there is evidence that the coronavirus disease 2019 (COVID-19) pandemic has caused various mental health concerns in the general population, as well as among healthcare workers (HCWs). The main aim of this study was to assess the psychological distress, burnout and structural empowerment status of HCWs during the COVID-19 outbreak, and to evaluate its predictors. METHODS: This multi-center, cross-sectional web-based questionnaire survey was conducted on HCWs during the outbreak of COVID-19 from August 2020 to January 2021. HCWs working in hospitals from 48 different countries were invited to participate in an online anonymous survey that investigated sociodemographic data, psychological distress, burnout and structural empowerment (SE) based on Depression Anxiety and Stress Scale 21 (DASS-21), Maslach Burnout Inventory (MBI) and Conditions for work effectiveness questionnaire (CWEQ_II), respectively. Predictors of the total scores of DASS-21, MBI and CWEQ-II were assessed using unadjusted and adjusted binary logistic regression analysis. RESULTS: Out of the 1030 HCWs enrolled in this survey, all completed the sociodemographic section (response rate 100%) A total of 730 (70.9%) HCWs completed the DASS-21 questionnaire, 852 (82.6%) completed the MBI questionnaire, and 712 (69.1%) completed the CWEQ-II questionnaire. The results indicate that 360 out of 730 responders (49.3%) reported severe or extremely severe levels of stress, anxiety, and depression. Additionally, 422 out of 851 responders (49.6%) reported a high level of burnout, while 268 out of 712 responders (37.6%) reported a high level of structural empowerment based on the DASS-21, MBI, and CWEQ-II scales, respectively. In addition, the analysis showed that HCWs working in the COVID-19 areas experienced significantly higher symptoms of severe stress, anxiety, depression and higher levels of burnout compared to those working in other areas. The results also revealed that direct work with COVID-19 patients, lower work experience, and high workload during the outbreak of COVID-19 increase the risks of negative psychological consequences. CONCLUSION: Health professionals had high levels of burnout and psychological symptoms during the COVID-19 emergency. Monitoring and timely treatment of these conditions is needed.

Epigenetic age acceleration in surviving versus deceased COVID-19 patients with acute respiratory distress syndrome following hospitalization.

BACKGROUND: Aging has been reported as a major risk factor for severe symptoms and higher mortality rates in COVID-19 patients. Molecular hallmarks such as epigenetic alterations and telomere attenuation reflect the biological process of aging. Epigenetic clocks have been shown to be valuable tools for measuring biological age in various tissues and samples. As such, these epigenetic clocks can determine accelerated biological aging and time-to-mortality across various tissues. Previous reports have shown accelerated biological aging and telomere attrition acceleration following SARS-CoV-2 infection. However, the effect of accelerated epigenetic aging on outcome (death/recovery) in COVID-19 patients with acute respiratory distress syndrome (ARDS) has not been well investigated. RESULTS: In this study, we measured DNA methylation age and telomere attrition in 87 severe COVID-19 cases with ARDS under mechanical ventilation. Furthermore, we compared dynamic changes in epigenetic aging across multiple time points until recovery or death. Epigenetic age was measured using the Horvath, Hannum, DNAm skin and blood, GrimAge, and PhenoAge clocks, whereas telomere length was calculated using the surrogate marker DNAmTL. Our analysis revealed significant accelerated epigenetic aging but no telomere attrition acceleration in severe COVID-19 cases. In addition, we observed epigenetic age deceleration at inclusion versus end of follow-up in recovered but not in deceased COVID-19 cases using certain clocks. When comparing dynamic changes in epigenetic age acceleration (EAA), we detected higher EAA using both the Horvath and PhenoAge clocks in deceased versus recovered patients. The DNAmTL measurements revealed telomere attrition acceleration in deceased COVID-19 patients between inclusion and end of follow-up and a significant change in dynamic telomere attrition acceleration when comparing patients who recovered versus those who died. CONCLUSIONS: EAA and telomere attrition acceleration were associated with treatment outcomes in hospitalized COVID-19 patients with ARDS. A better understanding of the long-term effects of EAA in COVID-19 patients and how they might contribute to long COVID symptoms in recovered individuals is urgently needed.

A CRISPR-based approach using dead Cas9-sgRNA to detect SARS-CoV-2.

Rapid, highly specific, and robust diagnostic kits to detect viruses and pathogens are needed to control disease spread and transmission globally. Of the many different methods proposed to diagnose COVID-19 infection, CRISPR-based detection of nucleic acids tests are among the most prominent. Here, we describe a new way of using CRISPR/Cas systems as a rapid and highly specific tool to detect the SARS-CoV-2 virus using the in vitro dCas9-sgRNA-based technique. As a proof of concept, we used a synthetic DNA of the M gene, one of the SARS-CoV-2 virus genes, and demonstrated that we can specifically inactivate unique restriction enzyme sites on this gene using CRISPR/Cas multiplexing of dCas9-sgRNA-BbsI and dCas9-sgRNA-XbaI. These complexes recognize and bind to the target sequence spanning the BbsI and XbaI restriction enzyme sites, respectively, and protect the M gene from digestion by BbsI and/or XbaI. We further demonstrated that this approach can be used to detect the M gene when expressed in human cells and from individuals infected with SARS-CoV-2. We refer to this approach as dead Cas9 Protects Restriction Enzyme Sites, and believe that it has the potential to be applied as a diagnostic tool for many DNA/RNA pathogens.

The molecular mechanisms of apoptosis accompanied with the epigenetic regulation of the NY-ESO-1 antigen in non-small lung cancer cells treated with decitabine (5-aza-CdR).

Dysregulated epigenetic modifications are common in lung cancer but have been reversed using demethylating agent like 5-Aza-CdR. 5-Aza-CdR induces/upregulates the NY-ESO-1 antigen in lung cancer. Therefore, we investigated the molecular mechanisms accompanied with the epigenetic regulation of NY-ESO-1 in 5-Aza-CdR-treated NCI-H1975 cell line. We showed significant induction of the NY-ESO-1 protein (**p < 0.0097) using Cellular ELISA. Bisulfite-sequencing demonstrated 45.6% demethylation efficiency at the NY-ESO-1 gene promoter region and RT-qPCR analysis confirmed the significant induction of NY-ESO-1 at mRNA level (128-fold increase, *p < 0.050). We then investigated the mechanism by which 5-Aza-CdR inhibits cell proliferation in the NCI-H1975 cell line. Upregulation of the death receptors TRAIL (2.04-fold *p < 0.011) and FAS (2.1-fold *p < 0.011) indicate activation of the extrinsic apoptotic pathway. The upregulation of Voltage-dependent anion-selective channel protein 1 (1.9-fold), Major vault protein (1.8-fold), Bax (1.16-fold), and Cytochrome C (1.39-fold) indicate the activation of the intrinsic pathway. We also observed the differential expression of protein Complement C3 (3.3-fold), Destrin (-5.1-fold), Vimentin (-1.7-fold), Peroxiredoxin 4 (-1.6-fold), Fascin (-1.8-fold), Heme oxygenase-2 (-0.67-fold**p < 0.0055), Hsp27 (-0.57-fold**p < 0.004), and Hsp70 (-0.39-fold **p < 0.001), indicating reduced cell growth, cell migration, and metastasis. The upregulation of 40S ribosomal protein S9 (3-fold), 40S ribosomal protein S15 (4.2-fold), 40S ribosomal protein S18 (2.5-fold), and 60S ribosomal protein L22 (4.4-fold) implied the induction of translation machinery. These results reiterate the decisive role of 5-Aza-CdR in lung cancer treatment since it induces the epigenetic regulation of NY-ESO-1 antigen, inhibits cell proliferation, increases apoptosis, and decreases invasiveness.

High-temporal resolution profiling reveals distinct immune trajectories following the first and second doses of COVID-19 mRNA vaccines.

Knowledge of the mechanisms underpinning the development of protective immunity conferred by mRNA vaccines is fragmentary. Here, we investigated responses to coronavirus disease 2019 (COVID-19) mRNA vaccination via high-temporal resolution blood transcriptome profiling. The first vaccine dose elicited modest interferon and adaptive immune responses, which peaked on days 2 and 5, respectively. The second vaccine dose, in contrast, elicited sharp day 1 interferon, inflammation, and erythroid cell responses, followed by a day 5 plasmablast response. Both post-first and post-second dose interferon signatures were associated with the subsequent development of antibody responses. Yet, we observed distinct interferon response patterns after each of the doses that may reflect quantitative or qualitative differences in interferon induction. Distinct interferon response phenotypes were also observed in patients with COVID-19 and were associated with severity and differences in duration of intensive care. Together, this study also highlights the benefits of adopting high-frequency sampling protocols in profiling vaccine-elicited immune responses.

Detection of Antinuclear Antibodies Targeting Intracellular Signal Transduction, Metabolism, Apoptotic Processes and Cell Death in Critical COVID-19 Patients.

Background and Objectives: The heterogeneity of the coronavirus disease of 2019 (COVID-19) lies within its diverse symptoms and severity, ranging from mild to lethal. Acute respiratory distress syndrome (ARDS) is a leading cause of mortality in COVID-19 patients, characterized by a hyper cytokine storm. Autoimmunity is proposed to occur as a result of COVID-19, given the high similarity of the immune responses observed in COVID-19 and autoimmune diseases. Here, we investigate the level of autoimmune antibodies in COVID-19 patients with different severities. Results: Initial screening for antinuclear antibodies (ANA) IgG using ELISA revealed that 1.58% (2/126) and 4% (5/126) of intensive care unit (ICU) COVID-19 cases expressed strong and moderate ANA levels, respectively. An additional sample was positive with immunofluorescence assays (IFA) screening. However, all the non-ICU cases (n=273) were ANA negative using both assays. Samples positive for ANA were further confirmed with large-scale autoantibody screening by phage immunoprecipitation-sequencing (PhIP-Seq). The majority of the ANA-positive samples showed "speckled" ANA pattern by microscopy and revealed autoantibody specificities that targeted proteins involved in intracellular signal transduction, metabolism, apoptotic processes, and cell death by PhIP-Seq; further denoting reactivity to nuclear and cytoplasmic antigens. Conclusion: Our results further support the notion of routine screening for autoimmune responses in COVID-19 patients, which might help improve disease prognosis and patient management. Further, results provide compelling evidence that ANA-positive individuals should be excluded from being donors for convalescent plasma therapy in the context of COVID-19.

In silico virtual screening of lead compounds for major antigenic sites in respiratory syncytial virus fusion protein.

Human respiratory syncytial virus (RSV) is a leading ubiquitous respiratory pathogen in newborn infants, young children, and the elderly, with no vaccine available to date. The viral fusion glycoprotein (RSV F) plays an essential role in the infection process, and it is a primary target of neutralizing antibodies, making it an attractive site for vaccine development. With this in view, there is a persistent need to identify selective antiviral drugs against RSV, targeting the major antigenic sites on the F protein. We aimed to conduct a robust in silico high-throughput drug screening of one million compounds to explore potential inhibitors that bind the major antigenic site Ø and site II on RSV F protein, which are the main target of neutralizing antibodies (NAb). We utilized the three-dimensional crystallographic structure of both antigenic site Ø on pre-F and antigenic II on post-F to screen for potential anti-RSV inhibitors. A library of one million small compounds was docked to explore lead binders in the major antigenic sites by using virtual lab bench CLC Drug Discovery. We also performed Quantitative Structure-Activity and Relationship (QSAR) for the lead best binders known for their antiviral activity. Among one million tested ligands, seven ligands (PubChem ID: 3714418, 24787350, 49828911, 24802036, 79824892, 49726463, and 3139884) were identified as the best binders to neutralizing epitopes site Ø and four ligands (PubChem ID: 865999, 17505357, 24802036, and 24285058) to neutralizing epitopes site II, respectively. These binders exhibited significant interactions with neutralizing epitopes on RSV F, with an average of six H bonds, docking energy of - 15.43 Kcal·mol-1, and minimum interaction energy of - 7.45 Kcal·mol-1. Using in silico virtual screening, we identified potential RSV inhibitors that bind two major antigenic sites on the RSV F protein. Using structure-based design and combination-based drug therapy, identified molecules could be modified to generate the next generation anti-RSV drugs. Supplementary Information: The online version contains supplementary material available at 10.1007/s42247-021-00213-6.

Predictive Biomarkers of Intensive Care Unit and Mechanical Ventilation Duration in Critically-Ill Coronavirus Disease 2019 Patients.

Introduction: Detection of early metabolic changes in critically-ill coronavirus disease 2019 (COVID-19) patients under invasive mechanical ventilation (IMV) at the intensive care unit (ICU) could predict recovery patterns and help in disease management. Methods: Targeted metabolomics of serum samples from 39 COVID-19 patients under IMV in ICU was performed within 48 h of intubation and a week later. A generalized linear model (GLM) was used to identify, at both time points, metabolites and clinical traits that predict the length of stay (LOS) at ICU (short ≤ 14 days/long >14 days) as well as the duration under IMV. All models were initially trained on a set of randomly selected individuals and validated on the remaining individuals in the cohort. Further validation in recently published metabolomics data of COVID-19 severity was performed. Results: A model based on hypoxanthine and betaine measured at first time point was best at predicting whether a patient is likely to experience a short or long stay at ICU [area under curve (AUC) = 0.92]. A further model based on kynurenine, 3-methylhistidine, ornithine, p-cresol sulfate, and C24.0 sphingomyelin, measured 1 week later, accurately predicted the duration of IMV (Pearson correlation = 0.94). Both predictive models outperformed Acute Physiology and Chronic Health Evaluation II (APACHE II) scores and differentiated COVID-19 severity in published data. Conclusion: This study has identified specific metabolites that can predict in advance LOS and IMV, which could help in the management of COVID-19 cases at ICU.

Level of maternal respiratory syncytial virus (RSV) F antibodies in hospitalized children and correlates of protection.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory infection among children and no vaccine is available. The stabilized form of the fusion (F) protein - pre-F - is a leading vaccine candidate to target different populations, including pregnant women. This study aimed to determine the magnitude and nature of RSV-directed maternal antibodies (matAbs) in hospitalized children with RSV infection. METHODS: Sixty-five paired blood samples were collected from RSV-infected children aged <6 months and their corresponding mothers. All pairs were screened for levels of pre-F and post-F antibodies using ELISA. The neutralizing antibodies (NAbs) in both groups were measured in vitro against mKate RSV-A2 using H28 cells. RESULTS: It was found that 14% of matAbs (log2 12.8) were present in infants at hospitalization, with an average log2 EP titer of 10.2 directed to both F-protein conformations. Additionally, 61.4% of maternal NAbs (log2 EC50 = 9.4) were detected in infants (log2 EC50 = 8.7), which were mostly pre-F exclusive (81%). Pre-F antibodies in children showed a positive correlation with matAbs titers and negative correlations with age and bronchiolitis score. CONCLUSIONS: The maintenance of neutralizing activity in infants relative to maternal titers was greater than the maintenance of antibody binding based on ELISA, suggesting that higher-potency antibodies may have a longer half-life than weakly neutralizing antibodies.

Prevalence and Phylogenetic Analysis of Parvovirus (B19V) among Blood Donors with Different Nationalities Residing in Qatar.

Human parvovirus (B19V) is the causative agent of erythema infectiosum in children and is linked to a wide range of clinical manifestations. Studies related to B19V prevalence in the Middle East and North Africa (MENA) region and other parts of Asia are very scarce. The objectives of this study were to estimate the seroprevalence (anti-B19V IgM and IgG), the viremia rate (B19V DNA), and the circulating genotypes of B19V among blood donors in Qatar. METHODS: Donors' blood samples (n = 5026) from different nationalities, mainly from the MENA region and South East Asia, were collected from 2014-2016. Samples were tested for the B19V DNA using RT-PCR. Furthermore, 1000 selected samples were tested to determine the seroprevalence of B19V antibodies using enzyme-linked immunosorbent assay (ELISA). Genotyping was performed on 65 DNA positive samples by sequencing of nested PCR fragments (NS1-VP1u region, 927 nt). RESULTS: Only 1.4% (70/5026) of the samples had detectible B19V DNA in their blood. B19V DNA prevalence statistically decreased with age (p = 0.03). Anti-B19V IgG was detected in 60.3% (561/930) of the tested samples, while only 2.1% (20/930) were IgM-positive and 1.2% (11/930) were both IgM- and IgG-positive. B19V genotyping showed a predominance of Genotype 1 (100%). Sequence analysis of the NS1-VP1u region revealed 139 mutation sites, some of which were amino acid substitutions. CONCLUSION: Our results indicated a relatively high seroprevalence of B19V in Qatar. Most importantly, B19 DNA was detected among Qatari and non-Qatari blood donors. Therefore, blood banks in Qatar might need to consider screening for B19V, especially when transfusion is intended for high-risk populations, including immunocompromised patients.

Nutrition Literacy among Adolescents and Its Association with Eating Habits and BMI in Tripoli, Lebanon.

(1) Background: Adolescence is a period of increased autonomy and independent decision making; it determines health behaviors that can persist into the future. Individual factors like food choices and unhealthy lifestyle have an essential role in the development and prevention of obesity among adolescents and are associated with the nutrition literacy of parents and other adults. While the association of parents' nutrition literacy with adolescent BMI has been addressed, there is still a scarcity of studies that examine the effect of adolescents' nutrition literacy on their eating habits and body mass index (BMI) status. (2) Methods: A cross-sectional study was conducted that included 189 adolescents (68 with overweight and obesity and 121 with normal weight) aged between 14-19 years from four private schools in Tripoli, Lebanon. A self-administered questionnaire that included the Nutrition Literacy Assessment Instrument (NLAI) and the Adolescent Food Habits Checklist (AFHC) was used. Anthropometrics were measured using standardized procedures. The association between nutrition literacy, food habits and BMI was assessed using a chi squared test for independence and Poisson regression analysis where suitable. (3) Results: Results indicated no association between all five components of nutrition literacy and body mass index categories. Furthermore, there was no association between the Adolescent Food Habits Checklist and overweight or obese BMI status (RR = 0.947, 95%CI: 0.629-1.426) (p = 0.796). No association was observed between nutrition literacy and food habits, except for an inverse association with macronutrients literacy. (4) Conclusions: In conclusion, the study indicated that there was no association between the components of nutrition literacy with body mass index or with food habits, except for macronutrient literacy.

Performance evaluation of five ELISA kits for detecting anti-SARS-COV-2 IgG antibodies.

OBJECTIVES: To evaluate and compare the performances of five commercial ELISA assays (EDI, AnshLabs, Dia.Pro, NovaTec, and Lionex) for detecting anti-SARS-CoV-2 IgG. METHODS: Seventy negative control samples (collected before the COVID-19 pandemic) and samples from 101 RT-PCR-confirmed SARS-CoV-2 patients (collected at different time points from symptom onset: ≤7, 8-14 and >14 days) were used to compare the sensitivity, specificity, agreement, and positive and negative predictive values of each assay with RT-PCR. A concordance assessment between the five assays was also conducted. Cross-reactivity with other HCoV, non-HCoV respiratory viruses, non-respiratory viruses, and nuclear antigens was investigated. RESULTS: Lionex showed the highest specificity (98.6%; 95% CI 92.3-99.8), followed by EDI and Dia.Pro (97.1%; 95% CI 90.2-99.2), NovaTec (85.7%; 95% CI 75.7-92.1), then AnshLabs (75.7%; 95% CI 64.5-84.2). All ELISA kits cross-reacted with one anti-MERS IgG-positive sample, except Lionex. The sensitivity was low during the early stages of the disease but improved over time. After 14 days from symptom onset, Lionex and NovaTec showed the highest sensitivity at 87.9% (95% CI 72.7-95.2) and 86.4% (95% CI 78.5-91.7), respectively. The agreement with RT-PCR results based on Cohen's kappa was as follows: Lionex (0.89) > NovaTec (0.70) > Dia.Pro (0.69) > AnshLabs (0.63) > EDI (0.55). CONCLUSION: The Lionex and NovaLisa IgG ELISA kits, demonstrated the best overall performance.

Hepatitis B Virus Molecular Epidemiology, Host-Virus Interaction, Coinfection, and Laboratory Diagnosis in the MENA Region: An Update.

Hepatitis B virus (HBV) is an enveloped partial double-stranded DNA virus that can cause acute and chronic hepatitis. According to the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), 257 million people are living with HBV. Moreover, 20,900 acute hepatitis B cases were reported in 2016. Hepatitis B is highly prevalent in the African, Western Pacific, Eastern Mediterranean, South-East Asia, and European regions, respectively. Due to the high mutational rate of HBV and lack of reverse transcriptase proofreading activity, ten different genotypes with different geographical distributions have been identified. HBV pathogenesis and severity of infection depend on several host and viral factors, particularly, the genetic variability of both the host and virus. Although HBV infection is a global health concern, there is a lack of adequate studies and reports in the Middle East and North Africa (MENA) region. Here, we provide a review on HBV epidemiology, pathogenesis, host-pathogen interactions, coinfection with selected viruses, and laboratory diagnosis, focusing on studies conducted in the MENA region to determine the current situation of the HBV infection and outline the future study areas.

Spectrum of mutations of cystic fibrosis in the 22 Arab countries: A systematic review.

Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, with various clinical manifestations that affect pulmonary, digestive, exocrine and male reproductive functions as well as the bones and kidneys. This study aimed to reveal the spectrum of CFTR gene mutations in Arab CF patients and their corresponding clinical phenotypes among the 22 Arab countries. We searched four literature databases (PubMed, Science Direct, Web of Science and Scopus) from their times of inception to January 2018. All possible search terms were used to encompass the different clinical phenotypes, disease incidences, CFTR mutations, ages and consanguinity rates of CF patients in the 22 Arab countries. Our search strategy identified 678 articles; of these, 72 were eligible for this systematic review. We retrieved data from 18 Arab countries; only 1766 Arab patients with CF were identified, even after additional searches using Google and Google Scholar. The search uncovered a wide spectrum of mutations, some of which are shared with other ethnic groups and some unique to Arab patients. Although the clinical phenotypes of Arab patients were typical of CF, several distinct phenotypes were reported. Despite the rarity of genetic epidemiological studies of CF patients among the 22 Arab nations, the disease is frequently reported in Arab countries where consanguineous marriage is common. Therefore, significant attention should be paid to this problem by implementing carrier and premarital screening, newborn screening and genetic counselling.

Human respiratory syncytial virus: pathogenesis, immune responses, and current vaccine approaches.

Respiratory syncytial virus continues to pose a serious threat to the pediatric populations worldwide. With a genomic makeup of 15,200 nucleotides, the virus encodes for 11 proteins serving as envelope spikes, inner envelope proteins, and non-structural and ribonucleocapsid complexes. The fusion (F) and attachment (G) surface glycoproteins are the key targets for neutralizing antibodies. The highly variable G with altered glycosylations and the conformational alternations of F create challenges for vaccine development. The metastable F protein is responsible for RSV-host cell fusion and thus infectivity. Novel antigenic sites were identified on this form following its stabilization and solving its crystal structure. Importantly, site ø displays neutralizing activity exceeding those of post-F-specific and shared antigenic sites, such as site II which is the target for Palivizumab therapeutic antibody. Induction of high neutralizing antibody responses by pre-F immunization in animal models promoted it as a major vaccine candidate. Since RSV infection is more serious at age extremities and in individuals with undermining health conditions, vaccines are being developed to target these populations. Infants below three months of age have a suppressive immune system, making vaccines' immunogenicity weak. Therefore, a suggested strategy to protect newborns from RSV infection would be through passive immunity of maternal antibodies. Hence, pregnant women at their third trimester have been selected as an ideal target for vaccination with RSV pre-F vaccine. This review summarizes the different modes of RSV pathogenesis and host's immune response to the infection, and illustrates on the latest updates of vaccine development and vaccination approaches.

Prevalence and molecular profiling of Epstein Barr virus (EBV) among healthy blood donors from different nationalities in Qatar.

BACKGROUND: The Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis. EBV is highly prevalent lymphotropic herpesvirus and has been linked to several malignancies. Transmission is generally by oral secretions, but can be through blood transfusions and organ transplantations. This study aimed to determine the seroprevalence, viremia rates, and circulating genotypes of EBV in healthy blood donors in Qatar. METHODS: Blood samples from 673 blood donors of different nationalities residing in Qatar (mainly Qatar, Egypt, Syria, Jordan, Pakistan, and India) were collected and tested for anti-EBV capsid (VCA; IgG & IgM), nuclear (EBNA; IgG), and early (EA-D; IgG) antigens. Avidity testing was determined when active infection was suspected. DNA was extracted from the buffy coat and subjected to EBV-DNA quantification using qRT-PCR. Genotyping was performed using nested-PCR targeting EBV-EBNA2 gene, and phylogeny by sequence analysis of the LMP-1 gene. RESULTS: 97.9% (673/659) of the samples were seropositive as indicated by the presence VCA-IgG, while 52.6% (354/673) had detectible EBV-DNA. EBV seroprevalence and viremia rates increased significantly with age. Genotyping of 51 randomly selected samples showed predominance of Genotype 1 (72.5%, 37/51) as compared to genotype 2 (3.5%), and mixed infections were detected in 4% of the samples. Sub-genotyping for these samples revealed that the Mediterranean strain was predominant (65.3%), followed by B95.8 prototype and North Carolina strains (12.2% each), and China1 strain (6%). CONCLUSION: As a first study to evaluate EBV infection in highly diverse population in Qatar, where expatriates represent more than 85% of the population, our results indicated high seroprevalence and viremia rate of EBV in different nationalities, with genotype 1 and Mediterranean strain being predominant. Clinical significance of these finding have not been investigated and shall be evaluated in future studies.

Concomitant occurrence of primary hyperparathyroidism (PHPT) due to mediastinal parathyroid adenoma and sublingual thyroid gland: the role of parathyroid technetium-99m-MIBI scintigraphy.

The concomitant appearance of a sublingual thyroid and primary hyperparathyroidism due to parathyroid mediastinal adenoma is not common. This co-occurrence can lead to a misdiagnosis by morphological imaging methods alone. This case emphasizes the role of 99mTc-MIBI scintigraphy in the detection of parathyroid ectopic adenoma in a patient with an ectopic thyroid gland. This more accurate location of parathyroid scintigraphy is of great benefit to the surgeon for surgical excision.

Seroprevalence of hepatitis E virus among blood donors in Qatar (2013-2016).

BACKGROUND: Hepatitis E virus (HEV) is an RNA virus transmitted mainly through zoonotic transmission or fecal-oral route. More than 80% of Qatar's population are expatriates, including many coming from hyperendemic countries; thus, it is important to estimate the seroprevalence and to compare between different nationalities. The results can be useful in alerting blood banks to the importance of HEV screening. STUDY DESIGN AND METHODS: Samples from 5854 blood donations provided by Hamad Medical Corporation were tested in the period between June 2013 to June 2016. Samples were tested for the presence of anti-HEV immunoglobulin (Ig)G and IgM antibodies and viral RNA using real-time polymerase chain reaction (PCR). Descriptive statistics, bivariate analysis, and multivariate logistic regression were used. RESULTS: Anti-HEV seroprevalence was 20.7%. A total of 1198 and 38 donations tested positive for IgG and IgM antibodies, respectively. Of the IgM-positive donations four tested positive by PCR. A significant association was detected between HEV seroprevalence with age and nationality. CONCLUSION: The seroprevalence of anti-HEV was high in Qatar. Since HEV IgM and RNA were detected, this suggests the possibility of HEV transmission by transfusion. Blood banks in Qatar and the region should consider screening for HEV, especially when transfusion is intended to pregnant women or immunocompromised patients.

Poorly differentiated thyroid carcinoma: a retrospective clinicopathological study.

Poorly differentiated thyroid carcinoma (PDTC) is an independent thyroid cancer histotype. In spite of its scarcity, it represents the main cause of death from non-anaplastic follicular cell-derived thyroid cancer. However, given the newness of this entity, few data are available on its clinical behaviour and no explicit consensus sets its treatment. To report the experience of a tertiary medical centre in morocco with PDTC over a period of 7 years. Retrospective study selecting all patients treated for thyroid carcinoma in Nuclear Medicine Department of a tertiary medical centre in Casablanca over seven years period. Patient's files were reviewed for background data, clinico-pathological characteristics, treatment and outcome. Seven patients were included in the study. Patient's average age was 60 years old (30-81) including six women and one man. All patients underwent a total thyroidectomy completed by cervical lymph node dissection in 57% of cases. Mean primary tumour size was 4cm (1-9cm). Patients were classified pT3 in 70% of cases, pT1 and pT2 in 15% each. Vascular invasion was found in 85% of cases. Pathological subtypes found were "insular carcinoma" in 85% of cases. Radioiodine therapy (RIT) was indicated in all cases. Follow-up period ranged between 10 months and 6 years. It showed a complete remission in 57% of cases, persistent disease in 28% of cases and a progressive disease in 15% of cases with a local recurrence. To date, the survival rate is 85%. PDTC is an aggressive thyroid cancer histotype. Treatment remains surgical followed by RIT if the tumour is radioavid. Multimodality therapy is indicated depending on the case and close monitoring is always indicated given the high risk of relapse.