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Sumbul Bushra,1,* Duaa W Al-Sadeq,1,* Redwana Bari,1 Afifah Sahara,1 Amina Fadel,1 Nasser Rizk1,2 1Department of Biomedical Sciences, College of Health Sciences, QU-Health, Qatar University, Doha, Qatar; 2Biomedical Research Center (BRC), Qatar University, Doha, Qatar*These authors contributed equally to this workCorrespondence: Nasser Rizk, Department of Biomedical Sciences, College of Health Sciences, QU-Health, Qatar University, P.O. Box 2713, Doha, Qatar, Tel +974-4403-4786, Email nassrizk@qu.edu.qaBackground: The pathophysiology of diabetic retinopathy (DR) is multifaced. A low level of circulating adiponectin (APN) in type 2 diabetes is associated with microvasculature complications, and its role in the evolution of DR is complex.Aim: This study is designed to explore the potential impact of APN in the pathogenesis of DR, linking the changes in cellular and biological processes with the pathways, networks, and regulators involved in its actions.Methods: Human microvascular retinal endothelial cells (HMRECs) were exposed to 30mM glucose (HG) and treated with globular adiponectin (30μg/mL) for 24 hours. The cells were evaluated for reactive oxidative stress (ROS) and apoptosis. RT-PCR profile arrays were utilized to evaluate the profile of genes involved in endothelial functions, angiogenesis, extracellular matrix, and adhesion molecules for hyperglycemic HMRECs treated with adiponectin. In addition, the barrier function, leukocyte migration, and angiogenesis were evaluated. The differential expressed genes (DEGs) were outlined, and bioinformatic analysis was applied.Results: Adiponectin suppresses ROS production and apoptosis in HMRECs under HG conditions. Adiponectin improved migration and barrier functions in hyperglycemic cells. The bioinformatic analysis highlighted that the signaling pathways of integrin, HMGB1, and p38 AMPK, are mainly involved in the actions of APN on HMRECs. APN significantly affects molecular functions, including the adhesion of cells, chemotaxis, migration of WBCs, and angiogenesis. STAT3, NFKB, IKBKB, and mir-8 are the top upstream regulators, which affect the expressions of the genes of the data set, while TNF and TGFB1 are the top regulators.Conclusion: Adiponectin significantly counteracts hyperglycemia at various cellular and molecular levels, reducing its impact on the pathophysiological progression towards DR in vitro using HMRECs. Adiponectin ameliorates inflammatory response, oxidative stress, and endothelial barrier dysfunction using a causal network of NFBk complex, TNF, and HMGB1 and integrin pathways.Keywords: adiponectin, hyperglycemia, human microvascular retinal endothelial cells, diabetic retinopathy, bioinformatic analysis

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: We would like to declare that all Mindray kits used in this paper were provided as in-kind support for GKN lab., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2024. The Author(s).)

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., (© 2024 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Homocystinuria is a rare disease caused by mutations in the CBS gene that results in a deficiency of cystathionine β-synthase (CBS). CBS is an essential pyridoxal 5'-phosphate (PLP)-dependent enzyme in the transsulfuration pathway, responsible for combining serine with homocysteine to produce cystathionine, whose activity is enhanced by the allosteric regulator S-adenosylmethionine (SAM). CBS also plays a role in generating hydrogen sulfide (H2S), a gaseous signaling molecule with diverse regulatory functions within the vascular, nervous, and immune systems. In this study, we present the clinical and biochemical characterization of two novel CBS missense mutations that do not respond to pyridoxine treatment, namely c.689T > A (L230Q) and 215A > T (K72I), identified in a Chinese patient. We observed that the disease-associated K72I genetic variant had no apparent effects on the spectroscopic and catalytic properties of the full-length enzyme. In contrast, the L230Q variant expressed in Escherichia coli did not fully retain heme and when compared with the wild-type enzyme, it exhibited more significant impairments in both the canonical cystathionine-synthesis and the alternative H2S-producing reactions. This reduced activity is consistent with both in vitro and in silico evidence, which indicates that the L230Q mutation significantly decreases the overall protein's stability, which in turn, may represent the underlying cause of its pathogenicity., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Background: Cystathione beta-synthase (CBS) T236N is a novel mutation associated with pyridoxine non-responsiveness, which presents a significant difficulty in the medical treatment of homocystinuria. Reported severe phenotypes in homocystinuria patients highlight the urgent requirement to comprehend the molecular mechanisms underlying mutation pathogenicity for the advancement of the disease., Methodology: In this study, we used a multidisciplinary approach to investigate the molecular properties of bacterially expressed and purified recombinant CBS T236N protein, which we directly compared to those of the wild-type (CBS WT ) protein., Results: Our data revealed a profound impact of the p.T236N mutation on CBS enzymatic activity, with a dramatic reduction of ~96% compared to the CBS WT protein. Circular dichroism (CD) experiments indicated that the p.T236N mutation did not significantly alter the secondary structure of the protein. However, CD spectra unveiled distinct differences in the thermal stability of CBS WT and CBS T236N mutant protein species. In addition, chemical denaturation experiments further highlighted that the CBS WT protein exhibited greater thermodynamic stability than the CBS T236N mutant, suggesting a destabilizing effect of this mutation., Conclusions: Our findings provide an explanation of the pathogenicity of the p.T236N mutation, shedding light on its role in severe homocystinuria phenotypes. This study contributes to a deeper understanding of CBS deficiency and may improve the development of targeted therapeutic strategies for affected individuals.

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., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Evidence on the effectiveness of vaccination-induced immunity compared to SARS-CoV-2 natural immunity is warranted to inform vaccination recommendations., Aim: In this study, we aimed to conduct a comparative assessment of antibody responses between vaccinated naïve (VN) and unvaccinated naturally infected individuals (NI) over 10 Months., Method: The study comprised fully-vaccinated naïve individuals (VN; n = 596) who had no history of SARS-CoV-2 infection, and received two doses of either BNT162b2 or mRNA-1273, and naturally infected individuals who had a documented history of SARS-CoV-2 infection and no vaccination record (NI cohort; n = 218). We measured the levels of neutralizing total antibodies (NtAbs), anti-S-RBD IgG, and anti-S1 IgA titers among VN and NI up to ∼10 months from administration of the first dose, and up to ∼7 months from SARS-CoV-2 infection, respectively. To explore the relationship between the antibody responses and time, Spearman's correlation coefficient was computed. Furthermore, correlations between the levels of NtAbs/anti-S-RBD IgG and NtAbs/anti-S1 IgA were examined through pairwise correlation analysis., Results: Up to six months, VN individuals had a significantly higher NtAb and anti-S-RBD IgG antibody responses compared to NI individuals. At the 7th month, there was a significant decline in antibody responses among VN individuals, but not NI individuals, with a minimum decrease of 3.7-fold (p < 0.001). Among VN individuals, anti-S1 IgA levels began to decrease significantly (1.4-fold; p = 0.007) after two months, and both NtAb and S-RBD IgG levels began to decline significantly (NtAb: 2.0-fold; p = 0.042, S-RBD IgG: 2.4-fold; p = 0.035) after three months. After 10 months, the most significant decline among VN individuals was observed for S-RBD-IgG (30.0-fold; P < 0.001), followed by NtAb (15.7-fold; P < 0.001) and S-IgA (3.7-fold; P < 0.001) (most stable). Moreover, after 5 months, there was no significant difference in the IgA response between the two groups., Conclusion: These findings have important implications for policymakers in the development of vaccination strategies, particularly in the consideration of booster doses to sustain long-lasting protection against COVID-19., Competing Interests: Declaration of Competing Interest There are no known conflicts of interest associated with this publication., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Limited data exists on herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections in migrant populations. This study investigated HSV-1 and HSV-2 seroprevalences and associations among craft and manual workers (CMWs) in Qatar who constitute 60% of Qatar's population., Methods: A national population-based cross-sectional seroprevalence survey was conducted on the CMW population, all men, between July 26 and September 9, 2020. 2,612 sera were tested for anti-HSV-1 IgG antibodies using HerpeSelect 1 ELISA IgG kits and for anti-HSV-2 IgG antibodies using HerpeSelect 2 ELISA IgG kits (Focus Diagnostics, USA). Univariable and multivariable logistic regression analyses were conducted to identify associations with HSV-1 and HSV-2 infections., Results: Serological testing identified 2,171 sera as positive, 403 as negative, and 38 as equivocal for HSV-1 antibodies, and 300 sera as positive, 2,250 as negative, and 62 as equivocal for HSV-2 antibodies. HSV-1 and HSV-2 seroprevalences among CMWs were estimated at 84.2% (95% CI 82.8-85.6%) and 11.4% (95% CI 10.1-12.6%), respectively. HSV-1 infection was associated with nationality, educational attainment, and occupation. HSV-2 infection was associated with age, nationality, and educational attainment., Conclusions: Over 80% of CMWs are infected with HSV-1 and over 10% are infected with HSV-2. The findings highlight the need for sexual health programs to tackle sexually transmitted infections among the CMW population., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: HIV and Syphilis are common STIs, which have become a concern and burden on healthcare systems, as many infections go untreated and lead to potentially serious complications. HIV is usually diagnosed with Western blot, PCR, and p24 antigen testing. Whereas, Syphilis is mainly diagnosed through clinical findings and serologic testing. The Medical Commission Department (MC) under MOPH is responsible for screening all newcomers to Qatar, aiming to keep the country free from serious infectious diseases., Objective: We aimed to evaluate the diagnostic efficiency of the protocols used in the MC for screening HIV and Syphilis infections., Methods: We conducted a retrospective study of samples analyzed by 4th Generation ARCHITECT® HIV Ag/Ab Combo and Rapid Plasma Reagin (RPR) between January to December 2019. ARCHITECT® HIV Ag/Ab Combo positive samples were confirmed by INNO-LIA™ HIVI/II and RT-PCR. RPR-reactive samples were confirmed by ARCHITECT® Syphilis Treponema pallidium Antibody (Syphilis TPA) assay., Results: For HIV, data were collected from 585,587 individuals, of which 595 (0.1%) were positive by the ARCHITECT® HIV Ag/Ab Combo (Analyzer A). When all initially positive sera were re-tested on newly collected blood samples using different ARCHITECT® HIV Ag/Ab Combo analyzer (analyzer B), 99.8% (594/595) of samples were also positive, suggesting high reproducibility. The positive predictive value (PPV) between ARCHITECT® HIV Ag/Ab Combo and the INNO-LIA™ HIVI/II confirmatory assay was 31.8%. The PPV between ARCHITECT® HIV Ag/Ab Combo and HIV-PCR assay was 26.8%. Retrospective data for Syphilis were collected from a total of 97,298 individuals who visited the MC, of which 198 (0.20%) were initially positive by RPR. The PPV between RPR and Syphilis TPA confirmatory assay was 36.6%., Conclusion: Despite the high rate of false positivity using ARCHITECT® HIV Ag/Ab Combo and RPR screening assays, both assays have proven to be highly effective as screening testing methods., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nasrallah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Waning protection against emerging SARS-CoV-2 variants by pre-existing antibodies elicited because of current vaccination or natural infection is a global concern. Whether this is due to the waning of immunity to SARS-COV-2 remains unclear., Aim: We aimed to investigate the dynamics of antibody isotype responses amongst vaccinated naïve (VN) and naturally infected (NI) individuals., Methods: We followed up antibody levels in COVID-19 messenger RNA (mRNA)-vaccinated subjects without prior infection (VN, n = 100) in two phases: phase-I (P-I) at ~ 1.4 and phase-II (P-II) at ~ 5.3 months. Antibody levels were compared with those of unvaccinated and naturally infected subjects (NI, n = 40) at ~ 1.7 (P-1) and 5.2 (P-II) months post-infection. Neutralizing antibodies (NTAb), anti-S-RBD-IgG, -IgM and anti-S-IgA isotypes were measured., Results: The VN group elicited significantly greater antibody responses (P < 0.001) than the NI group at P-I, except for IgM. In the VN group, a significant waning in antibody response was observed in all isotypes. There was about an ~ 4-fold decline in NTAb levels (P < 0.001), anti-S-RBD-IgG (~5-fold, P < 0.001), anti-S-RBD-IgM (~6-fold, P < 0.001) and anti-S1-IgA (2-fold, P < 0.001). In the NI group, a significant but less steady decline was notable in S-RBD-IgM (~2-fold, P < 0.001), and a much smaller but significant difference in NTAb (<2-fold, P < 0.001) anti-S-RBD IgG (<2-fold, P = 0.005). Unlike the VN group, the NI group mounted a lasting anti-S1-IgA response with no significant decline. Anti-S1-IgA, which were ~ 3-fold higher in VN subjects compared with NI in P-1 (P < 0.001), dropped to almost the same levels, with no significant difference observed between the two groups in P-II., Conclusion: Whereas double-dose mRNA vaccination boosted antibody levels, vaccinated individuals' 'boost' was relatively short-lived., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society of Travel Medicine.)

Rapid 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., (© 2022. The Author(s).)

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., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Background: Limited commercial LFA assays are available to provide a reliable quantitative measurement of the total binding antibody units (BAU/mL) against the receptor-binding domain of the SARS-CoV-2 spike protein (S-RBD). Aim: This study aimed to evaluate the performance of the fluorescence LFA FinecareTM 2019-nCoV S-RBD test along with its reader (Model No.: FS-113) against the following reference methods: (i) the FDA-approved GenScript surrogate virus-neutralizing assay (sVNT); and (ii) three highly performing automated immunoassays: BioMérieux VIDAS®3, Ortho VITROS®, and Mindray CL-900i®. Methods: Plasma from 488 vaccinees was tested by all aforementioned assays. Fingerstick whole-blood samples from 156 vaccinees were also tested by FinecareTM. Results and conclusions: FinecareTM showed 100% specificity, as none of the pre-pandemic samples tested positive. Equivalent FinecareTM results were observed among the samples taken from fingerstick or plasma (Pearson correlation r = 0.9, p < 0.0001), suggesting that fingerstick samples are sufficient to quantitate the S-RBD BAU/mL. A moderate correlation was observed between FinecareTM and sVNT (r = 0.5, p < 0.0001), indicating that FinecareTM can be used for rapid prediction of the neutralizing antibody (nAb) post-vaccination. FinecareTM BAU results showed strong correlation with VIDAS®3 (r = 0.6, p < 0.0001) and moderate correlation with VITROS® (r = 0.5, p < 0.0001) and CL-900i® (r = 0.4, p < 0.0001), suggesting that FinecareTM can be used as a surrogate for the advanced automated assays to measure S-RBD BAU/mL.

Background: A vast majority of the commercially available lateral flow immunoassay (LFIA) is used to detect SARS-CoV-2 antibodies qualitatively. Recently, a novel fluorescence-based lateral flow immunoassay (LFIA) test was developed for quantitative measurement of the total binding antibody units (BAUs) (BAU/mL) against SARS-CoV-2 spike protein receptor-binding domain (S-RBD)., Aim: This study aimed to evaluate the performance of the fluorescence LFIA Finecare TM 2019-nCoV S-RBD test along with its reader (Model No.: FS-113)., Methods: Plasma from 150 reverse trancriptase-PCR (RT-PCR)-confirmed positive individuals and 100 prepandemic samples were tested by Fincare TM to access sensitivity and specificity. For qualitative and quantitative validation of the FinCare TM measurements, BAU/mL results of FinCare TM were compared with results of 2 reference assays: the surrogate virus-neutralizing test (sVNT, GenScript Biotech, USA) and the VIDAS®3 automated assay (BioMérieux, France)., Results: Finecare TM showed 92% sensitivity and 100% specificity compared with PCR. Cohen's Kappa statistic denoted moderate and excellent agreement with sVNT and VIDAS®3, with values being 0.557 (95% CI: 0.32-0.78) and 0.731 (95% CI: 0.51-0.95), respectively. A strong correlation was observed between Finecare TM /sVNT (r = 0.7, p < 0.0001) and Finecare TM /VIDAS®3 (r = 0.8, p < 0.0001)., Conclusion: Finecare TM is a reliable assay and can be used as a surrogate to assess binding and neutralizing antibody response after infection or vaccination, particularly in none or small laboratory settings., Competing Interests: Conflict of interest GKN would like to declare that all test kits used in this study were provided as in-kind support for his laboratory to test seroprevalence of anti-SARS-CoV-2 and antibody response among vaccinated and infected individuals in Qatar., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The currently authorized mRNA COVID-19 vaccines, Pfizer-BNT162b2 and Moderna-mRNA-1273, offer great promise for reducing the spread of the COVID-19 by generating protective immunity against SARS-CoV-2. Recently, it was shown that the magnitude of the neutralizing antibody (NAbs) response correlates with the degree of protection. However, the difference between the immune response in naïve mRNA-vaccinated and previously infected (PI) individuals is not well studied. We investigated the level of NAbs in naïve and PI individuals after 1 to 26 (median = 6) weeks of the second dose of BNT162b2 or mRNA-1273 vaccination. The naïve mRNA-1273 vaccinated group ( n = 68) generated significantly higher (~2-fold, p ≤ 0.001) NAbs than the naïve BNT162b2 ( n = 358) group. The P -vaccinated group ( n = 42) generated significantly higher (~3-fold; p ≤ 0.001) NAbs levels than the naïve-BNT162b2 ( n = 426). Additionally, the older age groups produced a significantly higher levels of antibodies than the young age group (<30) ( p = 0.0007). Our results showed that mRNA-1273 generated a higher NAbs response than the BNT162b2 vaccine, and the PI group generated the highest level of NAbs response regardless of the type of vaccine.

Background: Two mRNA vaccines, Pfizer-BNT162b2 and Moderna-mRNA-1273, obtained the Emergency Use Listing by WHO for preventing COVID-19. However, little is known about the difference in antibody responses induced by these two mRNA vaccines in naïve and previously infected (PI) individuals., Method: We investigated the levels of anti-S-RBD (total, IgG and IgA) levels in naïve and PI individuals, 1-13 (median = 6) weeks following the second dose of either vaccine. Results in the naïve-vaccinated group, the mRNA-1273 vaccine induced significantly higher levels of anti-S-RBD total antibodies (3.5-fold; P < 0.001), IgG (2-fold, P < 0.01) and IgA (2.1-fold, P < 0.001) as compared with the BNT162b2 vaccine. In addition, both vaccines produced significantly higher anti-S-RBD total antibody levels in the PI-group compared with naïve-vaccinated group. The PI group elicited a higher level of anti-S-RBD IgG than the naïve-BNT162b2 (P = 0.05), but not more than the naïve-mRNA-1273 (P = 0.9) group. Interestingly, the PI vaccinated group elicited a comparable level of IgA ratio to the naïve-mRNA-1273 group but significantly higher than the naïve-BNT162b2 group (1.6-fold, P < 0.001)., Conclusion: Our results showed that the PI-vaccinated group produces a higher level of antibodies than the naïve vaccinated group, particularly for those vaccinated with BNT162b2., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society of Travel Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Human 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., Methods: In 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., Results: Anti-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., Conclusion: The seroprevalence of HHV-6 in Qatar was found to be similar to rates reported in other parts of the world., Competing Interests: None declared., (© 2021 The Authors.)

Several studies have investigated the effect of repeated freeze-thaw (F/T) cycles on RNA detection for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, no data are available regarding the effect of repeated F/T cycles on SARS-CoV-2 antibody detection in serum. We investigated the effect of multiple F/T cycles on anti-SARS-CoV-2 IgG detection using an ELISA test targeting the nucleocapsid antibodies. Ten positive and 1 negative SARS-CoV-2 IgG sera from 11 participants, in replicates of 5, were subjected to a total of 16 F/T cycles and stored at 4 °C until tested by ELISA. Statistical analysis was performed to test for F/T cycle effect. None of the 10 positive sera became negative after 16 F/T cycles. There was no significant difference in the OD average reading between the first and last F/T cycles, except for one serum with a minimal decline in the OD. The random effect linear regression of log (OD) on the number of cycles showed no significant trend, with a slope consistent with zero (B=-0.0001; 95 % CI -0.0008; 0.0006; P -value=0.781). These results suggest that multiple F/T cycles had no effect on the ability of the ELISA assay to detect SARS-CoV-2 IgG antibodies.

Background : High-throughput assays that can infer neutralizing activity against SARS-CoV-2 are of great importance for assessing the immunity induced by natural infection and COVID-19 vaccines. We aimed to evaluate the performance and degree of correlation of three fully automated anti-SARS-CoV-2 immunoassays with neutralization activity using a surrogate virus-neutralizing test (sVNT) from GenScript, targeting the receptor-binding domain. Methods : 110 sera collected from PCR-confirmed asymptomatic COVID-19 individuals were tested for neutralizing antibodies (nAbs) using the sVNT. Positive samples were tested on three automated immunoassays targeting different viral antigens: Mindray CL-900i®, Abbott Architect, and Ortho VITROS®. The diagnostic sensitivity, specificity, agreement, and correlation with the sVNT were assessed. Receiver operating characteristic (ROC) curve analysis was performed to determine optimal thresholds for predicting the presence of neutralizing activity by each assay. Results : All three assays showed 100% specificities. The highest sensitivity was 99.0%, demonstrated by VITROS®, followed by 94.3%, for CL-900i®, and 81.0%, for Architect. Both VITROS® and CL-900i® had the strongest correlation with the sVNT (ρ = 0.718 and ρ = 0.712, respectively), while Architect showed a moderate correlation (ρ = 0.618). ROC curve analysis indicated that the manufacturer's recommended cutoff values are adequate for predicting the presence of nAbs and providing a strong correlation with the sVNT. Conclusion : VITROS® and CL-900i® serological assays, which detect antibodies against SARS-CoV-2 spike protein, could serve as reliable assays to predict neutralization activity after infection or vaccination., (© 2021 The Author(s). Published by BRI.)

Background: There is an urgent need to elucidate the epidemiology of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and characterize its potential impact. Investing in characterising the SARS-CoV2 will help plan and improve the response to the pandemic. Furthermore, it will help identify the most efficient ways of managing the pandemic, avoiding public health policies and interventions that may be unduly restrictive of normal activity or unnecessarily costly. This paper describes the design and reports findings of a population based epidemiological study undertaken to characterise SARS-CoV2 in Qatar using limited resources in a timely manner., Methods: Asymptomatic individuals ≥10 years registered with Qatar's publicly funded primary health provider were eligible. A stratified random sampling technique was utilized to identify the study sample. Participants were invited to an appointment where they completed a questionnaire and provided samples for polymerase chain reaction and Immunoglobulin M and G immunoassay tests. Data collected were analyzed to calculate point and period prevalence by sociodemographic, lifestyle and clinical characteristics., Results: Of 18,918 individuals invited for the study, 2084 participated (response rate 10.8%). The overall point prevalence and period prevalence were estimated to be 1.6% (95% CI 1.1-2.2) and 14.6% (95% CI 13.1-16.2) respectively. Period prevalence of SARS-CoV2 infection was not considerably different across age groups (9.7-19.8%). It was higher in males compared to females (16.2 and 12.7% respectively). A significant variation was observed by nationality (7.1 to 22.2%) and municipalities (6.9-35.3%)., Conclusions: The study provides an example of a methodologically robust approach that can be undertaken in a timely manner with limited resources. It reports much-needed epidemiological data about the spread of SARS-CoV2. Given the low prevalence rates, majority of the population in Qatar remains susceptible. Enhanced surveillance must continue to be in place, particularly due to the large number of asymptomatic cases observed. Robust contact tracing and social distancing measures are key to prevent future outbreaks.

Background: The rapid growth of Qatar in the last two decades has attracted a large influx of immigrant workers who mostly come from HEV-hyperendemic countries. Thus, we aim to investigate the prevalence of HEV among acute non-A-C hepatitis patients in Qatar; and to evaluate the performance of four dominant commercial serological assays for HEV diagnosis., Methods: 259 patients with non-A-C hepatitis were tested using the Wantai HEV-IgM, HEV-IgG, HEV-Ag ELISA kits, and the MP Biomedical HEV-Total Ab ELISA kit. ALT levels were tested and HEV RNA (viral loads) was performed using Taqman AmpliCube HEV RT-PCR kit (Mikrogen, Neuried, Germany). The performance of each kit was assessed according to the RT-PCR results., Results: HEV-RNA was detected in 23.1% of the samples. Most of these HEV-RNA-positive cases belonged to non-Qatari residents from the Indian subcontinent; India, Pakistan, etc. HEV-Ag, HEV-IgM, HEV-IgG, HEV-Total Ab were detected in 5.56%, 8.65%, 32.1%, and 34.2% of all tested samples, respectively. Elevated ALT levels were highly correlated with the HEV-Ag, HEV-IgM, HEV-RNA but not with the HEV-IgG and HEV-Total Ab. Although HEV-Ag was very specific (100%), yet its sensitivity was poor (36.7%). HEV-IgM demonstrated the best second marker for diagnosis of acute HEV after RT-PCR as jugged by the overall performance parameters: specificity (96.2%), sensitivity (71.4%), PPV (83.3%), NPP (92.7%), agreement with RT-PCR (91.0%), and Kappa-value (0.71)., Conclusion: Our study demonstrated a high prevalence of HEV virus in Qatar, mostly among immigrants from the Indian subcontinent. The HEV-IgM represents the best marker for detecting the acute HEV infection, where RT-PCR cannot be performed.

Performance of three automated commercial serological IgG-based assays was investigated for assessing SARS-CoV-2 "ever" (past or current) infection in a population-based sample in a high exposure setting. PCR and serological testing was performed on 394 individuals. SARS-CoV-2-IgG seroprevalence was 42.9% (95% CI 38.1-47.8%), 40.6% (95% CI 35.9-45.5%), and 42.4% (95% CI 37.6-47.3%) using the CL-900i, VidasIII, and Elecsys assays, respectively. Between the three assays, overall, positive, and negative percent agreements ranged between 93.2-95.7%, 89.3-92.8%, and 93.8-97.8%, respectively; Cohen's kappa statistic ranged from 0.86 to 0.91; and 35 specimens (8.9%) showed discordant results. Among all individuals, 12.5% (95% CI 9.6-16.1%) had current infection, as assessed by PCR. Of these, only 34.7% (95% CI 22.9-48.7%) were seropositive by at least one assay. A total of 216 individuals (54.8%; 95% CI 49.9-59.7%) had evidence of ever infection using antibody testing and/or PCR during or prior to this study. Of these, only 78.2%, 74.1%, and 77.3% were seropositive in the CL-900i, VidasIII, and Elecsys assays, respectively. All three assays had comparable performance and excellent agreement, but missed at least 20% of individuals with past or current infection. Commercial antibody assays can substantially underestimate ever infection, more so when infection rates are high.

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.

Objective: To estimate the age- and nationality-specific West Nile virus (WNV) seroprevalence in select Middle East and North Africa (MENA) populations residing in Qatar., Methods: Sera were collected from male blood donors attending Hamad Medical Corporation. A total of 1,948 sera were tested for anti-WNV antibodies using Serion ELISA classic IgG and IgM kits., Results: Overall, seroprevalence estimates of WNV-specific IgG and IgM antibodies were 10.4% and 3.3%, respectively. Country-specific WNV-specific IgG seroprevalence was estimated to be 37.0% (34/92) in Sudanese, 33.0% in Egyptians (66/200), 13.0% (26/200) in Indians, 10.6% (11/104) in Iranians, 10.2% (14/137) in Yemenis, 9.2% (18/195) in Pakistanis, 7.0% (14/199) in Jordanians, 5.4% (6/111) in Filipinos, 2.5% (5/200) in Palestinians, 2.5% (5/200) in Syrians, 1.5% (3/200) in Qataris, and 0.9% (1/110) in Lebanese. Seroprevalence of WNV-specific IgM was lowest in Iranians (0/77), Lebanese (0/108), and Filipinos (0/107) at 0.0%, and was highest in Sudanese at 10.0% (8/80). While there seemed to be apparent trends in the prevalence of WNV-IgM and WNV-IgG antibodies, none of these trends were found to be statistically significant., Conclusion: The findings support the circulation of WNV in human populations in different countries of the MENA region. Seroprevalence was highest in Sudanese and Egyptians and lowest in Qataris and nationals of the Levant. The findings call for further animal, vector, and human studies, such as studying the actual prevalence of the viral RNA in blood donors to assess the risk of viral transmission through blood donation and for a better characterization of the epidemiology of this infection in this part of the world., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

To support the deployment of serology assays for population screening during the COVID-19 pandemic, we compared the performance of three fully automated SARS-CoV-2 IgG assays: Mindray CL-900i ® (target: spike [S] and nucleocapsid [N]), BioMérieux VIDAS ® 3 (target: receptor-binding domain [RBD]) and Diasorin LIAISON ® XL (target: S1 and S2 subunits). A total of 111 SARS-CoV-2 RT-PCR- positive samples collected at ≥ 21 days post symptom onset, and 127 pre-pandemic control samples were included. Diagnostic performance was assessed in correlation to RT-PCR and a surrogate virus-neutralizing test (sVNT). Moreover, cross-reactivity with other viral antibodies was investigated. Compared to RT-PCR, LIAISON ® XL showed the highest overall specificity (100%), followed by VIDAS ® 3 (98.4%) and CL-900i ® (95.3%). The highest sensitivity was demonstrated by CL-900i ® (90.1%), followed by VIDAS ® 3 (88.3%) and LIAISON ® XL (85.6%). The sensitivity of all assays was higher in symptomatic patients (91.1-98.2%) compared to asymptomatic patients (78.4-80.4%). In correlation to sVNT, all assays showed excellent sensitivities (92.2-96.1%). In addition, VIDAS ® 3 demonstrated the best correlation (r = 0.75) with the sVNT. The present study provides insights on the performance of three fully automated assays, which could help diagnostic laboratories in the choice of a particular assay according to the intended use.

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., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The recent outbreak of the coronavirus disease 2019 (COVID-19) has quickly spread globally since its discovery in Wuhan, China, in December 2019. A comprehensive strategy - including surveillance, diagnostics, research, and clinical treatment - is urgently needed to win the battle against COVID-19. Recently, numerous studies have reported the incidence of SARS-CoV-2 in asymptomatic patients. Yet, the incidence and viral transmission from the asymptomatic cases are not yet apparent., Aim: To estimate the incidence of COVID-19 among asymptomatic cases and describe its epidemiological and clinical significance this review systematically examined the published literature on SARS-CoV-2 in asymptomatic patients., Methods: The literature was searched through four scientific databases: PubMed, Web of Science, Scopus, and Science Direct., Results: Sixty-three studies satisfied the inclusion criteria. The majority of the reported studies were from China. However, there was a lack of SARS-CoV-2 epidemiological studies, from several countries worldwide, tracing the actual incidence of COVID-19, especially in asymptomatic patients. Studies with a large sample size (>1000) estimated that the percentage of people contracting SARS-CoV-2 and likely to be asymptomatic ranged from 1.2-12.9%. However, other studies with a smaller sample size reported a much higher incidence and indicated that up to 87.9% of COVID-19 infected individuals could be asymptomatic. Most of these studies indicated that asymptopatics are a potential source of infection to the community., Conclusion: This review highlighted the need for more robust and well-designed studies to better estimate COVID-19 incidence among asymptomatic patients worldwide. Early identification of asymptomatic cases, as well as monitoring and tracing close contacts, could help in mitigating the spread of COVID-19., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The recent outbreak of the Coronavirus disease 2019 (COVID-19) has quickly spread worldwide since its discovery in Wuhan city, China in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, clinical treatment, and development of vaccines, is urgently needed to win the battle against COVID-19. The past three unprecedented outbreaks of emerging human coronavirus infections at the beginning of the 21st century have highlighted the importance of readily available, accurate, and rapid diagnostic technologies to contain emerging and re-emerging pandemics. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) based assays performed on respiratory specimens remain the gold standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging with high sensitivity and specificity as well. Even though excellent techniques are available for the diagnosis of symptomatic patients with COVID-19 in well-equipped laboratories; critical gaps still remain in screening asymptomatic people who are in the incubation phase of the virus, as well as in the accurate determination of live viral shedding during convalescence to inform decisions for ending isolation. This review article aims to discuss the currently available laboratory methods and surveillance technologies available for the detection of COVID-19, their performance characteristics and highlight the gaps in current diagnostic capacity, and finally, propose potential solutions. We also summarize the specifications of the majority of the available commercial kits (PCR, EIA, and POC) for laboratory diagnosis of COVID-19., Competing Interests: The authors declare no conflict of interest.

Homocystinuria is an inborn error of metabolism due to the deficiency in cystathionine beta-synthase (CBS) enzyme activity. It leads to the elevation of both homocysteine and methionine levels in the blood and urine. Consequently, this build-up could lead to several complications such as nearsightedness, dislocated eye lenses, a variety of psychiatric and behavioral disorders, as well as vascular system complications. The prevalence of homocystinuria is around 1/200,000 births worldwide. However, its prevalence in the Gulf region, notably Qatar, is exceptionally high and reached 1:1800. To date, more than 191 pathogenic CBS mutations have been documented. The majority of these mutations were identified in Caucasians of European ancestry, whereas only a few mutations from African-Americans or Asians were reported. Approximately 87% of all CBS mutations are missense and do not target the CBS catalytic site, but rather result in unstable misfolded proteins lacking the normal biological function, designating them for degradation. The early detection of homocystinuria along with low protein and methionine-restricted diet is the best treatment approach for all types of homocystinuria patients. Yet, less than 50% of affected individuals show a significant reduction in plasma homocysteine levels after treatment. Patients who fail to lower the elevated homocysteine levels, through high protein-restricted diet or by B6 and folic acid supplements, are at higher risk for cardiovascular diseases, neurodegenerative diseases, neural tube defects, and other severe clinical complications. This review aims to examine the mutations spectrum of the CBS gene, the disease management, as well as the current and potential treatment approaches with a greater emphasis on studies reported in the Middle East and North Africa (MENA) region.

Human cytomegalovirus (CMV) is a highly prevalent herpesvirus worldwide. According to the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO), CMV infects people of all ages, and by the age of five, approximately one-third of children in the United States are infected. Although the infection is generally asymptomatic, it can cause severe disease in immunocompromised patients, transplant and transfusion recipients, as well as newborn neonates. The objective of this study is to systematically review published literature on CMV in the MENA region to estimate its incidence in the region and describe its epidemiological and clinical significance. The literature was searched through four scientific databases: PubMed, Scopus, Science Direct, and Web of Science. A total of 72 studies from 11 countries satisfied the inclusion criteria, covering a period from 1988-2019. The CMV IgG seroprevalence ranged from 8.7%-99.2% (SD = 38.95%). CMV incidence in these countries ranged between 1.22% and 77% in transplant and transfusion recipients, with an increase in incidence with advanced age. However, the incidence rate was unclear for congenital CMV due to the variability of the reporting. This review highlights the need for more robust and well-designed studies to better estimate CMV incidence in the MENA region, standardize diagnostic criteria, and consider prophylactic and pre-emptive treatments to limit the morbidity and mortality of the disease., Competing Interests: The authors declare no conflict of interest.

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.

Introduction: Although hepatitis E virus (HEV) is mainly transmitted via the faecal-oral route, the rate of HEV transmission via blood donation is on the rise. However, the seroprevalence of HEV among blood donors is not well established and is thought to be affected by the type of diagnostic assay used. We aimed to evaluate performance and correlation among widely used commercial diagnostic assays for the seroprevalence assessment of HEV-IgM/IgG among blood donors., Methodology: A total of 1049 blood donor samples were tested for HEV IgG and IgM using different enzyme immunoassays (Wantai, Eruoimmune, MP diagnostics, Mikrogen immunoblot, HEV-IgM rapid test). The performance of each assay was evaluated according to our established silver standard value based on three or more IgG concordant assay results., Results: HEV seroprevalence varied considerably using these assays, ranging from 10.1 % (Euroimmune-ELISA) to 18.0 % (Wanti-ELISA) for HEV-IgG, and from 0.2 % (Wanti-ELISA) to 2.6 % (MP Rapid test) for HEV-IgM. A total of 155 of 216 (71.6%) samples tested positive for HEV-IgG by three or more concordant assays. On the other hand, IgM assays showed poor agreement as only 7.6 % (4/52) of the specimens were positive according to three or more concordant assay test results. All HEV-IgG assays revealed high sensitivity and specificity (ranging 96.5-100 %),and excellent Kappa concordance (0.88-0.95), except for Euroimmun ELISA (sensitivity=61.5 %, kappa=0.63). MP ELISA showed the highest levels of sensitivity (100 %) and specificity (98.5 %)., Conclusions: Due to discrepancies in the performance of various IgG and IgM assays, seroprevalence studies should be based on furher confirmatory testing for decisive conclusions to be reached.

The Epstein-Barr virus (EBV) is a DNA lymphotropic herpesvirus and the causative agent of infectious mononucleosis. EBV is highly prevalent since it affects more than 90% of individuals worldwide and has been linked to several malignancies including PTLDs, which are one of the most common malignancies following transplantation. Among all the EBV genes, most of the recent investigations focused on studying the LMP-1 oncogene because of its high degree of polymorphism and association with tumorigenic activity. There are two main EBV genotypes, Type 1 and 2, distinguished by the differences in the EBNA-2 gene. Further sub genotyping can be characterized by analyzing the LMP-1 gene variation. The virus primarily transmits through oral secretions and persists as a latent infection in human B-cells. However, it can be transmitted through organ transplantations and blood transfusions. In addition, symptoms of EBV infection are not distinguishable from other viral infections, and therefore, it remains questionable whether there is a need to screen for EBV prior to blood transfusion. Although the process of leukoreduction decreases the viral copies present in the leukocytes, it does not eliminate the risk of EBV transmission through blood products. Here, we provide a review of the EBV epidemiology and the genetic variability of the oncogene LMP-1. Then, we underscore the findings of recent EBV seroprevalence and viremia studies among blood donors as a highly prevalent transfusion transmissible oncovirus.

Hepatitis E virus (HEV) is an RNA virus that is an important cause of both acute and chronic hepatitis worldwide. To date, there are eight HEV genotypes that can infect mammals. HEV-1 and HEV-2 infect exclusively humans, while HEV-3 and HEV-4 infect humans and various animals, mainly pigs and deer. Additionally, two new genotypes (HEV-5 and HEV-6) infect mainly wild boar. Recently, newly discovered genotypes HEV-7 and HEV-8 were found to infect camels and possibly humans. Nevertheless, the epidemiological distribution of HEV-7 is not well established. HEV-8 is another newly discovered genotype that was identified in 2016 in Chinese Bactrian camels. Although faecal-oral transmission is the most common route of HEV transmission, HEV can be vertically transmitted from infected mothers to their fetuses. HEV may also spread by zoonotic transmission from infected animals to humans and through person-to-person contact. Nowadays, since the number of reported cases linked to blood donations is increasing annually, HEV is recognized as a transfusion-transmitted virus. Laboratory diagnostic techniques vary in their specificity and sensitivity for HEV detection. Direct techniques allow for detection of the viral proteins, antigens and viral nucleic acid, while HEV-specific IgG and IgM antibodies can help establish a diagnosis in acute and chronic infections. In this review, we will discuss recent technologies in the laboratory diagnosis of HEV, including serological and molecular methods to assess the specificity and sensitivity of currently available HEV commercial assays.

Hepatitis E virus (HEV) is an RNA virus with 4 main genotypes. HEV-1 and HEV-2 infect solely humans, while HEV-3 and HEV-4 infect humans and various animals such as pigs, deer, and rabbits. HEV-5 and HEV-6 infect mainly wild boar. Recently, new genotypes, known as HEV-7 and HEV-8, were found to infect camels and humans. HEV is globally distributed into different epidemiological patterns based on socioeconomic factors and ecology. Although HEV is mainly transmitted through the fecal-oral route, it was also recognized as a transfusion-transmitted virus. Transmission through blood donation was documented worldwide with rising annual observations, accounting for more than 2.5% of all transmissions. HEV infection is usually asymptomatic or subclinical in immunocompetent individuals, so it remains questionable whether there is an urgent need to screen for HEV prior to blood transfusion. Moreover, recent studies conducted in the Middle East and North Africa (MENA) region indicate that HEV is highly endemic. Here, we provide a review on HEV epidemiology, transmission, and laboratory diagnosis, giving special emphasis to the newly discovered genotypes, HEV-7 and HEV-8. Furthermore, we underscore the findings of recent HEV seroprevalence and viremia studies among blood donors worldwide. We also shed light on similar studies performed among blood donors in the MENA region., (Copyright © 2017 John Wiley & Sons, Ltd.)