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Objectives: Scant data are available on syphilis infection within migrant populations worldwide and in the population of the Middle East and North Africa region. This study investigated the prevalence of both lifetime and recent syphilis infections among migrant craft and manual workers (MCMWs) in Qatar, a diverse demographic representing 60% of the country's population., Methods: Sera specimens collected during a nationwide cross-sectional survey of SARS-CoV-2 seroprevalence among the MCMW population, conducted between 26 July and 9 September 2020, were analysed. Treponema pallidum antibodies were detected using the Mindray CL-900i Chemiluminescence Immunoassay Analyzer. To differentiate recent infections, rapid plasma reagin (RPR) testing was performed, with an RPR titre of ≥1:8 considered indicative of recent infection. Logistic regression analyses were employed to identify factors associated with lifetime syphilis infection. Sampling weights were incorporated into all statistical analyses to obtain population-level estimates., Results: T. pallidum antibodies were identified in 38 of the 2528 tested sera specimens. Prevalence of lifetime infection was estimated at 1.3% (95% CI 0.9% to 1.8%). Among the 38 treponemal-positive specimens, 15 were reactive by RPR, with three having titres ≥1:8, indicating recent infection. Prevalence of recent infection was estimated at 0.09% (95% CI 0.01 to 0.3%). Among treponemal-positive MCMWs, the estimated proportion with recent infection was 8.1% (95% CI: 1.7 to 21.4%). The adjusted OR for lifetime infection increased with age, reaching 8.68 (95% CI 2.58 to 29.23) among those aged ≥60 years compared with those ≤29 years of age. Differences in prevalence were observed by nationality and occupation, but no differences were found by educational attainment or geographic location., Conclusions: Syphilis prevalence among MCMWs in Qatar is consistent with global levels, highlighting a disease burden with implications for health and social well-being. These findings underscore the need for programmes addressing both sexually transmitted infections and the broader sexual health needs of this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study provides a head-to-head comparison of the protection provided by the BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2 infection and against severe COVID-19, covering primary series and third dose/booster vaccinations over up to 3 years of follow-up, both before and after the emergence of the omicron variant., Methods: Two national, matched, retrospective cohort studies were conducted on Qatar's vaccinated population from December 16, 2020, to February 18, 2024. Subgroup analyses by pre-vaccination SARS-CoV-2 infection history, as well as sensitivity analyses, were also conducted., Results: The adjusted hazard ratio (AHR) comparing infection incidence in those vaccinated with BNT162b2 versus mRNA-1273 was 1.03 (95% CI: 1.02-1.05) after the primary series and 1.11 (95% CI: 1.09-1.13) after the third (booster) dose. The corresponding AHRs for any severe, critical, or fatal COVID-19 were 1.31 (95% CI: 0.81-2.11) and 1.00 (95% CI: 0.20-4.94), respectively. Subgroup analyses by prior infection status hinted at a dose-dependent immune imprinting effect, where a combination of two types of immunity, pre-omicron and omicron, offered greater protection against infection than one type alone, with this effect being amplified by the higher antigen dose of mRNA-1273 compared to BNT162b2. Sensitivity analyses confirmed the study findings., Conclusions: BNT162b2 provided slightly less protection against infection than mRNA-1273 following both primary series and booster vaccinations while offering comparable protection against severe COVID-19 outcomes. The findings suggested that the vaccine antigen dose in interaction with infection history may determine the extent of immune protection against infection., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Inula viscosa is a widely used plant in traditional Mediterranean and Middle Eastern medicine for various illnesses. I. viscosa has been shown to have anticancer effects against various cancers, but its effects against lung cancer have been under limited investigation. At the same time, I. viscosa is rich in terpenoids whose anti-lung cancer effects have been poorly investigated. This study aimed to examine the potential anticancer properties of methanolic and aqueous extracts of stems and leaves of I. viscosa and its terpenoid-rich fraction against human lung cancer A549 cells. Results showed that the methanolic extracts of I. viscosa had significantly higher polyphenol and flavonoid content and radical scavenging capacity than the aqueous extracts. In addition, leaves methanolic extracts (IVLM) caused the highest reduction in viability of A549 cells among all the extracts. IVLM also reduced the viability of human ovarian SK-OV-3, breast MCF-7, liver HepG2, and colorectal HCT116 cancer cells. A terpenoid-rich I. viscosa fraction (IVL DCM), prepared by liquid-liquid separation of IVLM in dichloromethane (DCM), displayed a substantial reduction in the viability of A549 cells (IC 50 = 27.8 ± 1.5 µg/mL at 48 h) and the panel of tested cancerous cell lines but was not cytotoxic to normal human embryonic fibroblasts (HDFn). The assessment of IVL DCM phytochemical constituents using GC-MS analysis revealed 21 metabolites, highlighting an enrichment in terpenoids, such as lupeol and its derivatives, caryophyllene oxide, betulin, and isopulegol, known to exhibit proapoptotic and antimetastatic functions. IVL DCM also showed robust antioxidant capacity and decent polyphenol and flavonoid contents. Furthermore, Western blotting analysis indicated that IVL DCM reduced proliferation (reduction of proliferation marker Ki67 and induction of proliferation inhibitor proteins P21 and P27), contaminant with P38 MAP kinase activation, and induced the intrinsic apoptotic pathway (P53/BCL2/BAX/Caspase3/PARP) in A549 cells. IVL DCM also reduced the migration of A549 cells, potentially by reducing FAK activation. Future identification of anticancer metabolites of IVL DCM, especially terpenoids, is recommended. These data place I. viscosa as a new resource of herbal anticancer agents.

Background: Vaccines were developed and deployed to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to characterize patterns in the protection provided by the BNT162b2 and mRNA-1273 mRNA vaccines against a spectrum of SARS-CoV-2 infection symptoms and severities., Methods: A national, matched, test-negative, case-control study was conducted in Qatar between January 1 and December 18, 2021, utilizing a sample of 238,896 PCR-positive tests and 6,533,739 PCR-negative tests. Vaccine effectiveness was estimated against asymptomatic, symptomatic, severe coronavirus disease 2019 (COVID-19), critical COVID-19, and fatal COVID-19 infections. Data sources included Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalization, and death., Results: Effectiveness of two-dose BNT162b2 vaccination was 75.6% (95% CI: 73.6-77.5) against asymptomatic infection and 76.5% (95% CI: 75.1-77.9) against symptomatic infection. Effectiveness against each of severe, critical, and fatal COVID-19 infections surpassed 90%. Immediately after the second dose, all categories-namely, asymptomatic, symptomatic, severe, critical, and fatal COVID-19-exhibited similarly high effectiveness. However, from 181 to 270 days post-second dose, effectiveness against asymptomatic and symptomatic infections declined to below 40%, while effectiveness against each of severe, critical, and fatal COVID-19 infections remained consistently high. However, estimates against fatal COVID-19 often had wide 95% confidence intervals. Analogous patterns were observed in three-dose BNT162b2 vaccination and two- and three-dose mRNA-1273 vaccination. Sensitivity analyses confirmed the results., Conclusion: A gradient in vaccine effectiveness exists and is linked to the symptoms and severity of infection, providing higher protection against more symptomatic and severe cases. This gradient intensifies over time as vaccine immunity wanes after the last vaccine dose. These patterns appear consistent irrespective of the vaccine type or whether the vaccination involves the primary series or a booster., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). 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).)

Coronavirus Disease 2019 (COVID-19) manifestations range from mild to severe life-threatening symptoms, including death. COVID-19 susceptibility has been associated with various factors, but studies in Qatar are limited. The objective of this study was to investigate the correlation between COVID-19 susceptibility and various sociodemographic and lifestyle factors, including age, gender, body mass index, smoking status, education level, dietary patterns, supplement usage, physical activity, a history of bariatric surgery, diabetes, and hypertension. We utilized logistic regression to analyze these associations, using the data of 10,000 adult participants, aged from 18 to 79, from Qatar Biobank. In total, 10.5% ( n = 1045) of the participants had COVID-19. Compared to non-smokers, current and ex-smokers had lower odds of having COVID-19 (odds ratio [OR] = 0.55; 95% CI: 0.44-0.68 and OR = 0.70; 95% CI: 0.57-0.86, respectively). Vitamin D supplement use was associated with an 18% reduction in the likelihood of contracting COVID-19 (OR = 0.82; 95% CI: 0.69-0.97). Obesity (BMI ≥ 30 kg/m 2 ), a history of bariatric surgery, and higher adherence to the modern dietary pattern-characterized by the consumption of foods high in saturated fat and refined carbohydrates-were positively associated with COVID-19. Our findings indicate that adopting a healthy lifestyle may be helpful in the prevention of COVID-19 infection.

Introduction: Reinfections are increasingly becoming a feature in the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, accurately defining reinfection poses methodological challenges. Conventionally, reinfection is defined as a positive test occurring at least 90 days after a previous infection diagnosis. Yet, this extended time window may lead to an underestimation of reinfection occurrences. This study investigated the prospect of adopting an alternative, shorter time window for defining reinfection., Methods: A longitudinal study was conducted to assess the incidence of reinfections in the total population of Qatar, from February 28, 2020 to November 20, 2023. The assessment considered a range of time windows for defining reinfection, spanning from 1 day to 180 days. Subgroup analyses comparing first versus repeat reinfections and a sensitivity analysis, focusing exclusively on individuals who underwent frequent testing, were performed., Results: The relationship between the number of reinfections in the population and the duration of the time window used to define reinfection revealed two distinct dynamical domains. Within the initial 15 days post-infection diagnosis, almost all positive tests for SARS-CoV-2 were attributed to the original infection. However, surpassing the 30-day post-infection threshold, nearly all positive tests were attributed to reinfections. A 40-day time window emerged as a sufficiently conservative definition for reinfection. By setting the time window at 40 days, the estimated number of reinfections in the population increased from 84,565 to 88,384, compared to the 90-day time window. The maximum observed reinfections were 6 and 4 for the 40-day and 90-day time windows, respectively. The 40-day time window was appropriate for defining reinfection, irrespective of whether it was the first, second, third, or fourth occurrence. The sensitivity analysis, confined to high testers exclusively, replicated similar patterns and results., Discussion: A 40-day time window is optimal for defining reinfection, providing an informed alternative to the conventional 90-day time window. Reinfections are prevalent, with some individuals experiencing multiple instances since the onset of the pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chemaitelly, Ayoub, Tang, Yassine, Al Thani, Hasan, Coyle, Al-Kanaani, Al-Kuwari, Jeremijenko, Kaleeckal, Latif, Shaik, Abdul-Rahim, Nasrallah, Al-Kuwari, Butt, Al-Romaihi, Al-Thani, Al-Khal, Bertollini and Abu-Raddad.)

Traumatic brain injury (TBI) is a leading cause of mortality and long-term impairment globally. TBI has a dynamic pathology, encompassing a variety of metabolic and molecular events that occur in two phases: primary and secondary. A forceful external blow to the brain initiates the primary phase, followed by a secondary phase that involves the release of calcium ions (Ca 2+ ) and the initiation of a cascade of inflammatory processes, including mitochondrial dysfunction, a rise in oxidative stress, activation of glial cells, and damage to the blood-brain barrier (BBB), resulting in paracellular leakage. Currently, there are no FDA-approved drugs for TBI, but existing approaches rely on delivering micro- and macromolecular treatments, which are constrained by the BBB, poor retention, off-target toxicity, and the complex pathology of TBI. Therefore, there is a demand for innovative and alternative therapeutics with effective delivery tactics for the diagnosis and treatment of TBI. Tissue engineering, which includes the use of biomaterials, is one such alternative approach. Biomaterials, such as hydrogels, including self-assembling peptides and electrospun nanofibers, can be used alone or in combination with neuronal stem cells to induce neurite outgrowth, the differentiation of human neural stem cells, and nerve gap bridging in TBI. This review examines the inclusion of biomaterials as potential treatments for TBI, including their types, synthesis, and mechanisms of action. This review also discusses the challenges faced by the use of biomaterials in TBI, including the development of biodegradable, biocompatible, and mechanically flexible biomaterials and, if combined with stem cells, the survival rate of the transplanted stem cells. A better understanding of the mechanisms and drawbacks of these novel therapeutic approaches will help to guide the design of future TBI therapies.

Background: We investigated the contribution of age, coexisting medical conditions, sex, and vaccination to incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe, critical, or fatal COVID-19 in older adults since pandemic onset., Methods: A national retrospective cohort study was conducted in the population of Qatar aged ≥50 years between February 5, 2020 and June 15, 2023. Adjusted hazard ratios (AHRs) for infection and for severe coronavirus disease 2019 (COVID-19) outcomes were estimated through Cox regression models., Results: Cumulative incidence was 25.01% (95% confidence interval [CI]: 24.86-25.15%) for infection and 1.59% (95% CI: 1.55-1.64%) for severe, critical, or fatal COVID-19 after a follow-up duration of 40.9 months. Risk of infection varied minimally by age and sex but increased significantly with coexisting conditions. Risk of infection was reduced with primary-series vaccination (AHR: 0.91, 95% CI: 0.90-0.93) and further with first booster vaccination (AHR: 0.75, 95% CI: 0.74-0.77). Risk of severe, critical, or fatal COVID-19 increased exponentially with age and linearly with coexisting conditions. AHRs for severe, critical, or fatal COVID-19 were 0.86 (95% CI: 0.7-0.97) for one dose, 0.15 (95% CI: 0.13-0.17) for primary-series vaccination, and 0.11 (95% CI: 0.08-0.14) for first booster vaccination. Sensitivity analysis restricted to only Qataris yielded similar results., Conclusion: Incidence of severe COVID-19 in older adults followed a dynamic pattern shaped by infection incidence, variant severity, and population immunity. Age, sex, and coexisting conditions were strong determinants of infection severity. Vaccine protection against severe outcomes showed a dose-response relationship, highlighting the importance of booster vaccination for older adults., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Objectives: We assessed short-, medium-, and long-term all-cause mortality risks after a primary SARS-CoV-2 infection., Methods: A national, matched, retrospective cohort study was conducted in Qatar to assess risk of all-cause mortality in the national SARS-CoV-2 primary infection cohort compared with the national infection-naïve cohort. Associations were estimated using Cox proportional-hazards regression models. Analyses were stratified by vaccination status and clinical vulnerability status., Results: Among unvaccinated persons, within 90 days after primary infection, the adjusted hazard ratio (aHR) comparing mortality incidence in the primary-infection cohort with the infection-naïve cohort was 1.19 (95% confidence interval 1.02-1.39). aHR was 1.34 (1.11-1.63) in persons more clinically vulnerable to severe COVID-19 and 0.94 (0.72-1.24) in those less clinically vulnerable. Beyond 90 days after primary infection, aHR was 0.50 (0.37-0.68); aHR was 0.41 (0.28-0.58) at 3-7 months and 0.76 (0.46-1.26) at ≥8 months. The aHR was 0.37 (0.25-0.54) in more clinically vulnerable persons and 0.77 (0.48-1.24) in less clinically vulnerable persons. Among vaccinated persons, mortality incidence was comparable in the primary-infection versus infection-naïve cohorts, regardless of clinical vulnerability status., Conclusions: COVID-19 mortality was primarily driven by an accelerated onset of death among individuals who were already vulnerable to all-cause mortality, but vaccination prevented these accelerated deaths., Competing Interests: Declaration of competing interests Dr. Butt has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. The remaining authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Laboratory evidence suggests a possibility of immune imprinting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the differences in the incidence of SARS-CoV-2 reinfection in a cohort of persons who had a primary Omicron infection, but different vaccination histories using matched, national, retrospective, cohort studies. Adjusted hazard ratio for reinfection incidence, factoring adjustment for differences in testing rate, was 0.43 [95% confidence interval (CI): 0.39 to 0.49] comparing history of two-dose vaccination to no vaccination, 1.47 (95% CI: 1.23 to 1.76) comparing history of three-dose vaccination to two-dose vaccination, and 0.57 (95% CI: 0.48 to 0.68) comparing history of three-dose vaccination to no vaccination. Divergence in cumulative incidence curves increased markedly when the incidence was dominated by BA.4/BA.5 and BA.2.75* Omicron subvariants. The history of primary-series vaccination enhanced immune protection against Omicron reinfection, but history of booster vaccination compromised protection against Omicron reinfection. These findings do not undermine the public health utility of booster vaccination.

Autoimmune diseases (ADs) are common conditions in which an individual's immune system reacts against its healthy cells. This condition is a common cause of morbidity and mortality, with an estimated prevalence ranging from 5 per 100,000 to more than 500 per 100,000. According to the National Stem Cell Foundation (NSCF), ADs are prevalent in about 4% of the world's population, which creates a burden on society due to the high treatment cost. ADs show a clear gender bias with a higher prevalence among women, occurring at a rate of 2:1 female-to-male ratio. The etiology of ADs includes genetic and environmental factors. ADs are more likely to develop in genetically susceptible individuals. The higher concordance ratio between monozygotic twins compared to dizygotic twins or other siblings validates the role of genetic factors in the pathogenesis of many ADs. ADs diagnosis includes conventional immunoassay such as indirect immunofluorescence, complement fixation, passive agglutination, autoantibodies detection, and most recent advances, including multiplex platforms such as microspots, line-blot, addressable microbeads and barcoded nanoparticles that allow multiplex parallel testing of autoantibodies. ADs treatment includes biological and synthetic drugs that block many pathways and components of the immune system, including Janus kinase (JAK) inhibitors, non-receptor tyrosine-protein kinase (TYK2), and other cytokines. Generally, recent immune-modulatory drugs used in ADs treatment are non-disease specific with broad action and are associated with many side effects like infection and malignant diseases. Furthermore, gene therapy seeks to control the levels of proinflammatory cytokine molecules and lymphocyte infiltration through the delivery and expression of therapeutic genes. Recent genomic-wide association studies (GWAS) have allowed the identification of various genetic loci associated with disease susceptibility and have revealed candidate genes that can be used in targeted therapeutics. This review summarizes recent literature on the genetic factors associated with susceptibility to the 11 most common ADs, namely: Type 1 diabetes mellitus (T1DM), Multiple sclerosis (MS), Grave's disease, Sjögren's syndrome (SS), Celiac disease, Hashimoto's thyroiditis (HT), Anti-phospholipid syndrome (APS), Autoimmune hemolytic anemia, Rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE), and Scleroderma (systemic sclerosis).

Background: Protection against SARS-CoV-2 symptomatic infection and severe COVID-19 of previous infection, mRNA two-dose vaccination, mRNA three-dose vaccination, and hybrid immunity of previous infection and vaccination were investigated in Qatar for the Alpha, Beta, and Delta variants., Methods: Six national, matched, test-negative, case-control studies were conducted between January 18 and December 18, 2021 on a sample of 239,120 PCR-positive tests and 6,103,365 PCR-negative tests., Findings: Effectiveness of previous infection against Alpha, Beta, and Delta reinfection was 89.5% (95% CI: 85.5-92.3%), 87.9% (95% CI: 85.4-89.9%), and 90.0% (95% CI: 86.7-92.5%), respectively. Effectiveness of two-dose BNT162b2 vaccination against Alpha, Beta, and Delta infection was 90.5% (95% CI, 83.9-94.4%), 80.5% (95% CI: 79.0-82.0%), and 58.1% (95% CI: 54.6-61.3%), respectively. Effectiveness of three-dose BNT162b2 vaccination against Delta infection was 91.7% (95% CI: 87.1-94.7%). Effectiveness of hybrid immunity of previous infection and two-dose BNT162b2 vaccination was 97.4% (95% CI: 95.4-98.5%) against Beta infection and 94.5% (95% CI: 92.8-95.8%) against Delta infection. Effectiveness of previous infection and three-dose BNT162b2 vaccination was 98.1% (95% CI: 85.7-99.7%) against Delta infection. All five forms of immunity had >90% protection against severe, critical, or fatal COVID-19 regardless of variant. Similar effectiveness estimates were observed for mRNA-1273. A mathematical model accurately predicted hybrid immunity protection by assuming that the individual effects of previous infection and vaccination acted independently., Interpretation: Hybrid immunity, offering the strongest protection, was mathematically predicted by assuming that the immunities obtained from previous infection and vaccination act independently, without synergy or redundancy., Funding: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114., Competing Interests: Declaration of interests Dr. Butt has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. Otherwise, we declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. 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.)

Metabolomics is an analytical approach that involves profiling and comparing the metabolites present in biological samples. This scoping review article offers an overview of current metabolomics approaches and their utilization in evaluating metabolic changes in biological fluids that occur in response to viral infections. Here, we provide an overview of metabolomics methods including high-throughput analytical chemistry and multivariate data analysis to identify the specific metabolites associated with viral infections. This review also focuses on data interpretation and applications designed to improve our understanding of the pathogenesis of these viral diseases.

Metformin constitutes the foundation therapy in type 2 diabetes (T2D). Despite its multiple beneficial effects and widespread use, there is considerable inter-individual variability in response to metformin. Our objective is to identify metabolic signatures associated with poor and good responses to metformin, which may improve our ability to predict outcomes for metformin treatment. In this cross-sectional study, clinical and metabolic data for 119 patients with type 2 diabetes taking metformin were collected from the Qatar Biobank. Patients were empirically dichotomized according to their HbA 1C levels into good and poor responders. Differences in the level of metabolites between these two groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. Good responders showed increased levels of sphingomyelins, acylcholines, and glutathione metabolites. On the other hand, poor responders showed increased levels of metabolites resulting from glucose metabolism and gut microbiota metabolites. The results of this study have the potential to increase our knowledge of patient response variability to metformin and carry significant implications for enabling personalized medicine.

Background: We characterized and identified the genetic and antigenic variations of circulating rotavirus strains in comparison to used rotavirus vaccines., Methods: Rotavirus-positive samples (n = 231) were collected and analyzed. The VP7 and VP4 genes were sequenced and analyzed against the rotavirus vaccine strains. Antigenic variations were illustrated on the three-dimensional models of surface proteins., Results: In all, 59.7% of the hospitalized children were vaccinated, of which only 57.2% received two doses. There were no significant differences between the vaccinated and non-vaccinated groups in terms of clinical outcome. The G3 was the dominant genotype (40%) regardless of vaccination status. Several amino acid changes were identified in the VP7 and VP4 antigenic epitopes compared to the licensed vaccines. The highest variability was seen in the G3 (6 substitutions) and P[4] (11 substitutions) genotypes in comparison to RotaTeq®. In comparison to Rotarix®, G1 strains possessed three amino acid changes in 7-1a and 7-2 epitopes while P[8] strains possessed five amino acid changes in 8-1 and 8-3 epitopes., Conclusions: The current use of Rotarix® vaccine might not be effective in preventing the infection due to the higher numbers of G3-associated cases. The wide range of mutations in the antigenic epitopes compared to vaccine strains may compromise the vaccine's effectiveness., Impact: The reduced rotavirus vaccine effectiveness necessitate regular evaluation of the vaccine content to ensure optimal protection. We characterized and identified the genetic and antigenic variations of circulating rotavirus strains in comparison to the Rotarix vaccine strain that is used in Qatar. The study highlight the importance for regular monitoring of emerging rotavirus variants and their impact on vaccine effectiveness in young children., (© 2023. The Author(s).)

Background: Waning of natural infection protection and vaccine protection highlight the need to evaluate changes in population immunity over time. Population immunity of previous SARS-CoV-2 infection or of COVID-19 vaccination are defined, respectively, as the overall protection against reinfection or against breakthrough infection at a given point in time in a given population., Methods: We estimated these population immunities in Qatar's population between July 1, 2020 and November 30, 2022, to discern generic features of the epidemiology of SARS-CoV-2. Effectiveness of previous infection, mRNA primary-series vaccination, and mRNA booster (third-dose) vaccination in preventing infection were estimated, month by month, using matched, test-negative, case-control studies., Findings: Previous-infection effectiveness against reinfection was strong before emergence of Omicron, but declined with time after a wave and rebounded after a new wave. Effectiveness dropped after Omicron emergence from 88.3% (95% CI: 84.8-91.0%) in November 2021 to 51.0% (95% CI: 48.3-53.6%) in December 2021. Primary-series effectiveness against infection was 84.0% (95% CI: 83.0-85.0%) in April 2021, soon after introduction of vaccination, before waning gradually to 52.7% (95% CI: 46.5-58.2%) by November 2021. Effectiveness declined linearly by ∼1 percentage point every 5 days. After Omicron emergence, effectiveness dropped from 52.7% (95% CI: 46.5-58.2%) in November 2021 to negligible levels in December 2021. Booster effectiveness dropped after Omicron emergence from 83.0% (95% CI: 65.6-91.6%) in November 2021 to 32.9% (95% CI: 26.7-38.5%) in December 2021, and continued to decline thereafter. Effectiveness of previous infection and vaccination against severe, critical, or fatal COVID-19 were generally >80% throughout the study duration., Interpretation: High population immunity against infection may not be sustained beyond a year, but population immunity against severe COVID-19 is durable with slow waning even after Omicron emergence., Funding: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114., Competing Interests: We declare no competing interests., (© 2023 The Author(s).)

Background: Long-term effectiveness of COVID-19 mRNA boosters in populations with different previous infection histories and clinical vulnerability profiles is inadequately understood. We aimed to investigate the effectiveness of a booster (third dose) vaccination against SARS-CoV-2 infection and against severe, critical, or fatal COVID-19, relative to that of primary-series (two-dose) vaccination over a follow-up duration of 1 year., Methods: This observational, matched, retrospective, cohort study was done on the population of Qatar in people with different immune histories and different clinical vulnerability to infection. The source of data are Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalisation, and death. Associations were estimated using inverse-probability-weighted Cox proportional-hazards regression models. The primary outcome of the study is the effectiveness of COVID-19 mRNA boosters against infection and against severe COVID-19., Findings: Data were obtained for 2 228 686 people who had received at least two vaccine doses starting from Jan 5, 2021, of whom 658 947 (29·6%) went on to receive a third dose before data cutoff on Oct 12, 2022. There were 20 528 incident infections in the three-dose cohort and 30 771 infections in the two-dose cohort. Booster effectiveness relative to primary series was 26·2% (95% CI 23·6-28·6) against infection and 75·1% (40·2-89·6) against severe, critical, or fatal COVID-19, during 1-year follow-up after the booster. Among people clinically vulnerable to severe COVID-19, effectiveness was 34·2% (27·0-40·6) against infection and 76·6% (34·5-91·7) against severe, critical, or fatal COVID-19. Effectiveness against infection was highest at 61·4% (60·2-62·6) in the first month after the booster but waned thereafter and was modest at only 15·5% (8·3-22·2) by the sixth month. In the seventh month and thereafter, coincident with BA.4/BA.5 and BA.2·75* subvariant incidence, effectiveness was progressively negative albeit with wide CIs. Similar patterns of protection were observed irrespective of previous infection status, clinical vulnerability, or type of vaccine (BNT162b2 vs mRNA-1273)., Interpretation: Protection against omicron infection waned after the booster, and eventually suggested a possibility for negative immune imprinting. However, boosters substantially reduced infection and severe COVID-19, particularly among individuals who were clinically vulnerable, affirming the public health value of booster vaccination., Funding: The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core (both at Weill Cornell Medicine-Qatar), Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, and Qatar University Biomedical Research Center., Competing Interests: Declaration of interests AAB has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

RT-qPCR is considered the gold standard for diagnosis of COVID-19; however, it is laborious, time-consuming, and expensive. RADTs have evolved recently as relatively inexpensive methods to address these shortcomings, but their performance for detecting different SARS-COV-2 variants remains limited. RADT test performance could be enhanced using different antibody labeling and signal detection techniques. Here, we aimed to evaluate the performance of two antigen RADTs for detecting different SARS-CoV-2 variants: (i) the conventional colorimetric RADT (Ab-conjugated with gold beads); and (ii) the new Finecare™ RADT (Ab-coated fluorescent beads). Finecare™ is a meter used for the detection of a fluorescent signal. 187 frozen nasopharyngeal swabs collected in Universal transport (UTM) that are RT-qPCR positive for different SARS-CoV-2 variants were selected, including Alpha (n = 60), Delta (n = 59), and Omicron variants (n = 108). Sixty flu and 60 RSV-positive samples were included as negative controls (total sample number = 347). The conventional RADT showed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 62.4% (95%CI: 54-70), 100% (95%CI: 97-100), 100% (95%CI: 100-100), and 58% (95%CI: 49-67), respectively. These measurements were enhanced using the Finecare™ RADT: sensitivity, specificity, PPV, and NPV were 92.6% (95%CI: 89.08-92.3), 96% (95%CI: 96-99.61), 98% (95%CI: 89-92.3), and 85% (95%CI: 96-99.6) respectively. The sensitivity of both RADTs could be greatly underestimated because nasopharyngeal swab samples collected UTM and stored at -80 °C were used. Despite that, our results indicate that the Finecare™ RADT is appropriate for clinical laboratory and community-based surveillance due to its high sensitivity and specificity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors.)

Exercise has many benefits for physical and mental well-being. Metabolomics research has allowed scientists to study the impact of exercise on the body by analyzing metabolites released by tissues such as skeletal muscle, bone, and the liver. Endurance training increases mitochondrial content and oxidative enzymes, while resistance training increases muscle fiber and glycolytic enzymes. Acute endurance exercise affects amino acid metabolism, fat metabolism, cellular energy metabolism, and cofactor and vitamin metabolism. Subacute endurance exercise alters amino acid metabolism, lipid metabolism, and nucleotide metabolism. Chronic endurance exercise improves lipid metabolism and changes amino acid metabolism. Acute resistance exercise changes several metabolic pathways, including anaerobic processes and muscular strength. Chronic resistance exercise affects metabolic pathways, resulting in skeletal muscle adaptations. Combined endurance-resistance exercise alters lipid metabolism, carbohydrate metabolism, and amino acid metabolism, increasing anaerobic metabolic capacity and fatigue resistance. Studying exercise-induced metabolites is a growing field, and further research can uncover the underlying metabolic mechanisms and help tailor exercise programs for optimal health and performance.

Healthy non-obese insulin resistant (IR) individuals are at higher risk of metabolic syndrome. The metabolic signature of the increased risk was previously determined. Physical activity can lower the risk of insulin resistance, but the underlying metabolic pathways remain to be determined. In this study, the common and unique metabolic signatures of insulin sensitive (IS) and IR individuals in active and sedentary individuals were determined. Data from 305 young, aged 20-30, non-obese participants from Qatar biobank, were analyzed. The homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires were utilized to classify participants into four groups: Active Insulin Sensitive (ISA, n = 30), Active Insulin Resistant (IRA, n = 20), Sedentary Insulin Sensitive (ISS, n = 21) and Sedentary Insulin Resistant (SIR, n = 23). Differences in the levels of 1000 metabolites between insulin sensitive and insulin resistant individuals in both active and sedentary groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. The study indicated significant differences in fatty acids between individuals with insulin sensitivity and insulin resistance who engaged in physical activity, including monohydroxy, dicarboxylate, medium and long chain, mono and polyunsaturated fatty acids. On the other hand, the sedentary group showed changes in carbohydrates, specifically glucose and pyruvate. Both groups exhibited alterations in 1-carboxyethylphenylalanine. The study revealed different metabolic signature in insulin resistant individuals depending on their physical activity status. Specifically, the active group showed changes in lipid metabolism, while the sedentary group showed alterations in glucose metabolism. These metabolic discrepancies demonstrate the beneficial impact of moderate physical activity on high risk insulin resistant healthy non-obese individuals by flipping their metabolic pathways from glucose based to fat based, ultimately leading to improved health outcomes. The results of this study carry significant implications for the prevention and treatment of metabolic syndrome in non-obese individuals.

Background: The cross-protective nature of Bacillus Calmette-Guerin (BCG) vaccine against SARS-CoV-2 virus was previously suggested, however its effect in COVID-19 patients with type 2 diabetes (T2D) and the underlying metabolic pathways has not been addressed. This study aims to investigate the difference in the metabolomic patterns of type 2 diabetic patients with BCG vaccination showing different severity levels of COVID-19 infection., Methods: Sixty-seven COVID-19 patients were categorized into diabetic and non-diabetic individuals who had been previously vaccinated or not with BCG vaccination. Targeted metabolomics were performed from serum samples from all patients using tandem mass spectrometry. Statistical analysis included multivariate and univariate models., Results: Data suggested that while BCG vaccination may provide protection for individuals who do not have diabetes, it appears to be linked to more severe COVID-19 symptoms in T2D patients (p = 0.02). Comparing the metabolic signature of BCG vaccinated T2D individuals to non-vaccinated counterparts revealed that amino acid (sarcosine), cholesterol esters (CE 20:0, 20:1, 22:2), carboxylic acid (Aconitic acid) were enriched in BCG vaccinated T2D patients, whereas spermidine, glycosylceramides (Hex3Cer(d18:1_22:0), Hex2Cer(d18:1/22:0), HexCer(d18:1/26:1), Hex2Cer(d18:1/24:0), HexCer(d18:1/22:0) were higher in BCG vaccinated non- T2D patients. Furthermore, data indicated a decrease in sarcosine synthesis from glycine and choline and increase in spermidine synthesis in the BCG vaccinated cohort in T2D and non-T2D groups, respectively., Conclusion: This pilot study suggests increased severity of COVID-19 in BCG vaccinated T2D patients, which was marked by decreased sarcosine synthesis, perhaps via lower sarcosine-mediated removal of viral antigens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Anwardeen, Cyprian, Yassine, Al-Thani, Abdallah, Emara and Elrayess.)

One Health is increasingly recognized as an optimal approach to address the global risk of health threats originating at the human, animal, and ecosystem interface, and their impact. Qatar has successfully practiced One Health approach for investigation and surveillance of zoonotic diseases such as MERS-CoV, and other health threats. However, the current gaps at institution and policy level hinder the sustainment of One Health. In this paper, we have assessed the potential for implementation of One Health Framework to reinforce and sustain One Health capacities in Qatar for 2022-2027. To implement One Health Framework in the country, Qatar Joint External Evaluation (JEE) report, lessons learnt during One Health experiences on zoonotic, vector-borne, and food borne diseases were used to present an outline for multisectoral coordination. In addition, technical capacities of One Health and factors that are required to operationalize it in the country were also assessed in series of meetings and workshops held at Ministry of Public Health on March 2022. Present health care infrastructure and resources were found to be conducive for effective management and response to shared health threats as evident during MERS-CoV, despite being more event based. Regardless, the need for more sustainable capacity development was unanimously emphasized. The consensus between all relevant stakeholders and partners was that there is a need for better communication channels, policies and protocols for data sharing, and the need to invest more resources for better sustainability. The proposed framework is expected to strengthen and facilitate multilateral coordination, enhanced laboratory capacity and network, improve active surveillance and response, risk communication, community engagement, maximize applied research, and build One Health technical work force. This would enable advancement and sustainment of One Health activities to prevent and control health threats shared between humans-animals-ecosystem interface., Competing Interests: The authors declare there is no conflict of interest., (© 2023 Published by Elsevier B.V.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly evolving RNA virus that mutates within hosts and exists as viral quasispecies. Here, we evaluated the within-host diversity among vaccinated and unvaccinated individuals (n = 379) infected with different SARS-CoV-2 Variants of Concern. The majority of samples harbored less than 14 intra-host single-nucleotide variants (iSNVs). A deep analysis revealed a significantly higher intra-host diversity in Omicron samples than in other variants (p value < 0.05). Vaccination status and type had a limited impact on intra-host diversity except for Beta-B.1.315 and Delta-B.1.617.2 vaccinees, who exhibited higher diversity than unvaccinated individuals (p values: <0.0001 and <0.0021, respectively). Three immune-escape mutations were identified: S255F in Delta and R346K and T376A in Omicron-B.1.1.529. The latter 2 mutations were fixed in BA.1 and BA.2 genomes, respectively. Overall, the relatively higher intra-host diversity among vaccinated individuals and the detection of immune-escape mutations, despite being rare, suggest a potential vaccine-induced immune pressure in vaccinated individuals., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Acute gastroenteritis is the cause of considerable mortality and morbidity worldwide, particularly among children under five years in underdeveloped countries. Most acute gastroenteritis (AGE) cases are attributed to viral etiologies, including rotavirus, norovirus, adenovirus, astrovirus, and sapovirus. This paper aimed to determine the prevalence rate of different viral etiologies of AGE in the Middle East and North Africa (MENA) region. Moreover, this paper explored rotavirus phylogenetic relatedness, compared VP7 and VP4 antigenic regions of rotavirus with vaccine strains, and explored the availability of vaccines in the MENA region. The literature search identified 160 studies from 18 countries from 1980 to 2019. The overall prevalence of rotavirus, norovirus, adenovirus, astrovirus, and sapovirus were 29.8 %, 13.9 %, 6.3 %, 3.5 %, and 3.2 % of tested samples, respectively. The most common rotavirus genotype combinations in the MENA region were G1P[8], G9P[9], and G2P[4], whereas GII.4 was the predominant norovirus genotype all of which were reported in almost all the studies with genotyping data. The comparison of VP7 and VP4 between circulating rotavirus in the MENA region and vaccine strains has revealed discrete divergent regions, including the neutralizing epitopes. Rotavirus vaccine was introduced to most of the countries of the MENA region; however, only a few studies have assessed the effectiveness of vaccine introduction. This paper provides a comprehensive update on the prevalence of the different viral agents of AGE in the MENA region., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

Cross-reactivity between different human coronaviruses (HCoVs) might contribute to COVID-19 outcomes. Here, we aimed to predict conserved peptides among different HCoVs that could elicit cross-reacting B cell and T cell responses. Three hundred fifty-one full-genome sequences of HCoVs, including SARS-CoV-2 (51), SARS-CoV-1 (50), MERS-CoV (50), and common cold species OC43 (50), NL63 (50), 229E (50), and HKU1 (50) were downloaded aligned using Geneious Prime 20.20. Identification of epitopes in the conserved regions of HCoVs was carried out using the Immune Epitope Database (IEDB) to predict B- and T-cell epitopes. Further, we identified sequences that bind multiple common MHC and modeled the three-dimensional structures of the protein regions. The search yielded 73 linear and 35 discontinuous epitopes. A total of 16 B-cell and 19 T-cell epitopes were predicted through a comprehensive bioinformatic screening of conserved regions derived from HCoVs. The 16 potentially cross-reactive B-cell epitopes included 12 human proteins and four viral proteins among the linear epitopes. Likewise, we identified 19 potentially cross-reactive T-cell epitopes covering viral proteins. Interestingly, two conserved regions: LSFVSLAICFVIEQF (NSP2) and VVHSVNSLVSSMEVQSL (spike), contained several matches that were described epitopes for SARS-CoV. Most of the predicted B cells were buried within the SARS-CoV-2 protein regions' functional domains, whereas T-cell stretched close to the functional domains. Additionally, most SARS-CoV-2 predicted peptides (80%) bound to different HLA types associated with autoimmune diseases. We identified a set of potential B cell and T cell epitopes derived from the HCoVs that could contribute to different diseases manifestation, including autoimmune disorders., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Recent progress in genomics and bioinformatics technologies have allowed for the emergence of immunogenomics field. This intersection of immunology and genetics has broadened our understanding of how the immune system responds to infection and vaccination. While the immunogenetic basis of the huge clinical variability in response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently being extensively studied, the host genetic determinants of SARS-CoV-2 vaccines remain largely unknown. Previous reports evidenced that vaccines may not protect all populations or individuals equally, due to multiple host- and vaccine-specific factors. Several studies on vaccine response to measles, rubella, hepatitis B, smallpox, and influenza highlighted the contribution of genetic mutations or polymorphisms in modulating the innate and adaptive immunity following vaccination. Specifically, genetic variants in genes encoding virus receptors, antigen presentation, cytokine production, or related to immune cells activation and differentiation could influence how an individual responds to vaccination. Although such knowledge could be utilized to generate personalized vaccine strategies to optimize the vaccine response, studies in this filed are still scarce. Here, we briefly summarize the scientific literature related to the immunogenetic determinants of vaccine-induced immunity, highlighting the possible role of host genetics in response to SARS-CoV-2 vaccines as well., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Smatti, Alkhatib, Al Thani and Yassine.)

COVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention. Here, we profile 893 plasma proteins from 50 severe and 50 mild-moderate COVID-19 patients, and 50 healthy controls, and show that 375 proteins are differentially expressed in the plasma of severe COVID-19 patients. These differentially expressed plasma proteins are implicated in the pathogenesis of COVID-19 and present targets for candidate drugs to prevent or treat severe complications. Based on the plasma proteomics and clinical lab tests, we also report a 12-plasma protein signature and a model of seven routine clinical tests that validate in an independent cohort as early risk predictors of COVID-19 severity and patient survival. The risk predictors and candidate drugs described in our study can be used and developed for personalized management of SARS-CoV-2 infected patients., (© 2022. The Author(s).)

Objectives: Over the last decades, there has been a significant increase in antimicrobial prescribing and consumption associated with the development of patients' adverse events and antimicrobial resistance (AMR) to the point of becoming a global priority. This study aims at evaluating antibiotic prescribing during COVID-19 pandemic from November 2019 to December 2020. Materials and Methods: A systematic review was conducted primarily through the NCBI database, using PRISMA guidelines to identify relevant literature for the period between November 1, 2019 and December 19, 2020, using the keywords: COVID-19 OR SARS-Cov-2 AND antibiotics restricted to the English language excluding nonclinical articles. Five hundred twenty-seven titles were identified; all articles fulfilling the study criteria were included, 133 through the NCBI, and 8 through Google Scholar with a combined total of 141 studies. The patient's spectrum included all ages from neonates to elderly with all associated comorbidities, including immune suppression. Results: Of 28,093 patients included in the combined studies, 58.7% received antibiotics (16,490/28,093), ranging from 1.3% to 100% coverage. Antibiotics coverage was less in children (57%) than in adults with comorbidities (75%). Broad-spectrum antibiotics were prescribed presumptively without pathogen identifications, which might contribute to adverse outcomes. Conclusions: During the COVID-19 pandemic, there has been a significant and wide range of antibiotic prescribing in patients affected by the disease, particularly in adults with underlying comorbidities, despite the paucity of evidence of associated bacterial infections. The current practice might increase patients' immediate and long-term risks of adverse events, susceptibility to secondary infections as well as aggravating AMR.

The COVID-19 pandemic is still posing a devastating threat to social life and economics. Despite the modest decrease in the number of cases during September-November 2020, the number of active cases is on the rise again. This increase was associated with the emergence and spread of the new SARS-CoV-2 variants of concern (VOCs), such as the U.K. (B1.1.7), South Africa (B1.351), Brazil (P1), and Indian (B1.617.2) strains. The rapid spread of these new variants has raised concerns about the multiple waves of infections and the effectiveness of available vaccines. In this review, we discuss SARS-CoV-2 reinfection rates in previously infected and vaccinated individuals in relation to humoral responses. Overall, a limited number of reinfection cases have been reported worldwide, suggesting long protective immunity. Most reinfected patients were asymptomatic during the second episode of infection. Reinfection was attributed to several viral and/or host factors, including (i) underlying immunological comorbidities; (ii) low antibody titers due to the primary infection or vaccination; (iii) rapid decline in antibody response after infection or vaccination; and (iv) reinfection with a different SARS-CoV-2 variant/lineage. Infections after vaccination were also reported on several occasions, but mostly associated with mild or no symptoms. Overall, findings suggest that infection- and vaccine-induced immunity would protect from severe illness, with the vaccine being effective against most VOCs.

Human influenza viruses are occasionally detected in the stools of influenza patients., Objectives: Here, we investigated the molecular and biological characteristics of intestinal influenza viruses and their potential role in virus transmission., Methods: Fecal samples were first screened for the presence of influenza viral RNA using RT-qPCR. Positive fecal samples were subjected to cell culture. Isolated viruses were then sequenced using MiSeq platform. Replication kinetics and receptor binding affinity were also evaluated., Results: Influenza RNA was detected in stool samples of 41% (36/87) of influenza A positive patients. Among the 36 stool samples subjected to viral isolation, 5 showed virus growth. Sequence analysis of isolated viruses revealed two distinct mutation patterns in fecal viruses. Set I viruses was able to replicate to higher titers in cell culture despite the limited number of mutations (6 mutations) compared to set II viruses (>10 mutations). Functional analysis of both sets revealed the ability to replicate efficiently in differentiated human bronchial cells. Receptor binding testing has also demonstrated their ability to bind α 2,3 and α 2,6 sialic acid receptors., Conclusion: The ability of fecal influenza viruses to replicate in intestinal cells and human 3D bronchial cells might suggest their possible contribution in virus transmission., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Taleb, Yassine, Benslimane, Smatti, Schuchardt, Albagha, Al-Thani, Ait Hssain, Diboun and Elrayess.)

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 (log 2 12.8) were present in infants at hospitalization, with an average log 2 EP titer of 10.2 directed to both F-protein conformations. Additionally, 61.4% of maternal NAbs (log 2 EC 50  = 9.4) were detected in infants (log 2 EC 50  = 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., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Acute gastroenteritis (AGE) remains a significant cause of diarrhea that affects children worldwide. It is usually caused by viral agents, including rotavirus (RV), norovirus (NoV), adenovirus (AdV), astrovirus (AstV), and sapovirus (SaV), and the disease severity varies accordingly. Here, we report the association of clinical severity among AGE-infected pediatrics caused by a single viral pathogen, coinfection (viral-viral), mixed infection (viral-bacterial), and AGE-negative samples., Methods: A total of 901 pediatric patients were admitted with AGE to the Pediatric Emergency Center of Hamad Medical Corporation in Qatar from June 2016 to June 2018. The age of the subjects ranged between 3 months and 14 years (median of 16 months). Virus antigens detection was performed by using Film Array Gastrointestinal (GI) Panel kit. AGE severity was assessed using the Vesikari Clinical Severity Scoring System. Multivariable multinomial logistic regression was used to model the five AGE viral agents' likelihood in relation to severity versus co-infection, mixed infection, and AGE-negative samples., Results: AGE was most common in pediatrics aged 1-3 years (median age = 1.25 years) and more frequent in males than females, with a ratio of 1:0.8. About 19.2% of the infections were caused by NoV, followed by RV (18.2%), AdV (6.5%), SaV (2.3%), and AstV (1.8%). The majority of viral agents were detected higher in mixed infection (32.1%) than coinfection (4.9%). Based on the Vesikari score system, severe clinical illness was recorded among pediatrics infected with RV (82.2%) and NoV (75.7%). Further on multivariable analysis, compared to testing negative, the odds of detecting RV was three times significantly higher in children with severe symptoms relative to those with moderate (adjusted-odds ratio [a-OR] = 3.10; 95% confidence interval [CI] = 1.82-5.28). Similar results were observed when considering RV relative to co-infection and mixed infection (a-OR = 2.59; 95% CI = 1.23-5.48 and a-OR = 2.06; 1.28-3.30, respectively). About one-third of the study sample were Qatari children with AGE (33%), whereas 35% and 32% were pediatrics from the Middle East and North Africa region, excluding Qatari and nonregions., Conclusion: This study underlines the association of disease severity among AGE-infected pediatrics in Qatar. The overall Vesikari median score was significantly high, followed by more frequent hospitalization among RV-infected pediatrics compared to others. There was no reduction in the disease severity among RV-infected regardless of the vaccine dose., (© 2021 Wiley Periodicals LLC.)

Little is known about the association between respiratory viral infections and their impact on intestinal microbiota. Here, we compared the effect of influenza types, A and B, and influenza shedding in patients' stools on the gut microbiota diversity and composition. Deep sequencing analysis was performed for the V4 region of the 16S rRNA gene. Fecal samples were collected from 38 adults with active respiratory influenza infection and 11 age-matched healthy controls. Influenza infection resulted in variations in intestinal bacterial community composition rather than in overall diversity. Overall, infected patients experienced an increased abundance of Bacteroidetes and a corresponding decrease in Firmicutes . Differential abundance testing illustrated that differences in gut microbiota composition were influenza type-dependent, identifying ten differentially abundant operational taxonomic units (OTUs) between influenza A- and influenza B-infected patients. Notably, virus shedding in fecal samples of some patients had significantly reduced gut bacterial diversity ( p = 0.023). Further taxonomic analysis revealed that the abundance of Bacteroides fragilis was significantly higher among shedders compared to non-shedders ( p = 0.037). These results provide fundamental evidence of the direct effect of influenza infection on gut microbiota diversity, as reported in patients shedding the virus.

Background: Little is known about the etiology of meningitis in the MENA region, including Qatar. Viral agents are considered the major cause for meningitis worldwide. Here, we present primary data about the etiology and clinical and demographic characteristics of viral meningitis (VM) in Qatar between 2015 and 2018. Methods: We retrospectively collected data from Hamad Medical Corporation (HMC), which provides about 80% of healthcare services in Qatar. Data were collected for the period between 2015 and 2018. During this time period, 6,705 specimens were collected from patients with suspected meningitis attending HMC and primary healthcare centers. These specimens were tested for a panel of viruses using the "FTD Viral meningitis" multiplex real-time PCR kit that detects Adenovirus (ADV), Human herpesvirus 1&2 (HSV1 and HSV2), Epstein-Barr virus (EBV), Enteroviruses (EV), Cytomegalovirus (CMV), Varicella zoster virus (VZV), and Parechovirus (PV). Results: Only 10.9% (732/6,705) of all suspected meningitis cases were caused by viral agents. 60.9% of the reported cases were males, compared to 39.1% in females. Most of the infections (73.9%) were reported in children younger than 10 years of age. EV were identified as the main causative agent (68.7%), followed by EBV (7.5%) and ADV (6.8%). Other viral agents including VZV, PV, HSV-1, and HSV-2 were also detected with a lower frequency. Confirmed VM were more prevalent among Qatari subjects compared to other nationalities. We observed no specific seasonality of viral agents, but a slight rise was recorded during the spring seasons (March to June). Fever (59.4%, 435/732) and acute central nervous system (CNS) infection (15.6%, 114/732) were initial symptoms of most cases. Conclusion: This is the first report about the molecular epidemiology of VM in Qatar. In line with the international records, our data showed that EV is responsible for 68.7% of Qatar's VM cases. Further studies are needed to genotype and serotype the identified viruses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mathew, Al Khatib, Al Ansari, Nader, Nasrallah, Younes, Coyle, Al Thani, Al Maslamani and Yassine.)

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.

Acute gastroenteritis (AGE) remains a major cause of diarrhea in developing and developed countries. Rotavirus (RV) is a leading cause of severe pediatric diarrhea worldwide. Here we report on the prevalence of circulating genotypes in association with demographics and clinical manifestations outcomes in Qatar. A total of 231 RV-positive fecal samples were collected from children suffering from AGE during 3 years study period between June 2016 and June 2019. The age of the subjects ranged between 2 months and 14 years (median of 16 months). The VP4 and VP7 were amplified and sequenced. Phylogenetic analyses were performed using MEGA7.0. Pearson's chi-squared test was used to determine significant differences for comparisons of general categorical variables. RV infections were most common in children between 1 and 3 years of age (49%), followed by those < 1 year and > 3 years of age (33% and 28%, respectively). RV infections were more frequent in males than females, with a ratio of 1.4:1. RV infections occurred throughout the year, with a noticeable increase in summer (42.8%) and a drop in winter (20.1%). RV genotypes G3P[8] (30.8%), G2P[8] (12.3%), G4P[8] (11.7%), and G1P[8] (10.4%) were the common genotypes during the study period. The G3P[8] strain detected in our study revealed similarities to the equine-like G3P[8] (10.3%; 24/231) (KT988229.1), Wa-like genomic constellation (9%; 21/231) (MF563894.1), and DS-1-like strains (6.4%; 15/231) (LC386081.1). Based on the Vesikari score system, severe clinical illness including diarrhea and vomiting (average frequency: 4 to 5 times/day) was recorded for G3P[8] group, followed by G9P[8], G4P[8], and G1P[8]. Higher incidence for G3P[8], G2P[8], G4P[8], and G1P[8] were reported in Qatari subjects compared to other nationalities. The multinational status of a small country explains the wide diversity of circulating RV genotypes in Qatar. The highest prevalence and severe illnesses were recorded to G3P[8], which is different from other surrounding countries/global levels.

Background: Rotavirus (RV) is a leading cause of pediatric diarrhea and mortality worldwide. The virus causes acute gastroenteritis characterized by moderate to severe vomiting, diarrhea, dehydration, and fever. Microbial dysbiosis caused by RV infection may significantly influence disease prognosis and the development of other chronic diseases. The gut microbiome plays a vital role in enteric immune response for rotavirus vaccine (RVV) that requires further elucidations. The current study evaluates the gut microbiome of RV positive children and compares gastroenteritis manifestation in children admitted to the Pediatric Emergency Centre, Hamad Medical Cooperation, Doha, Qatar. Stool samples were collected from thirty-nine RV positive and eight healthy control children. 16S rRNA sequence was performed using the Illumina MiSeq platform., Results: The data demonstrated a significant increase in microbiome diversity denoted by higher relative abundances of phylum Proteobacteria (p = 0.031), Fusobacteria (p = 0.044) and genus Streptococcus (p ≤ 0.001) in the infected group relative to the control. Similarly, district clustering pattern (PERMANOVA p = 0.01) and higher species richness (Shannon entropy p = 0.018) were observed in the children who received two RVV doses compared with the non-vaccinated or single-dose groups. These microbiome changes were represented by over-abundance of phylum Bacteroidetes (p = 0.003) and Verrucomicrobia (p ≤ 0.001), and lower expression of family Enterobacteriaceae in two RVV doses group. However, microbiome composition was not associated with diarrhea, vomiting, and other parameters of gastroenteritis., Conclusions: The observations assert significant microbial signatures of RVV, which is dose-dependent, and suggest manipulating these microbes as a novel approach for improving RVV efficacy. Further studies are warranted to investigate the immune status of these patients and mechanistic investigation to enhance RVV seroconversion.

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.

In December 2019, the latest member of the coronavirus family, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, leading to the outbreak of an unusual viral pneumonia known as coronavirus disease 2019 (COVID-19). COVID-19 was then declared as a pandemic in March 2020 by the World Health Organization (WHO). The initial mortality rate of COVID-19 declared by WHO was 2%; however, this rate has increased to 3.4% as of 3 March 2020. People of all ages can be infected with SARS-CoV-2, but those aged 60 or above and those with underlying medical conditions are more prone to develop severe symptoms that may lead to death. Patients with severe infection usually experience a hyper pro-inflammatory immune reaction (i.e., cytokine storm) causing acute respiratory distress syndrome (ARDS), which has been shown to be the leading cause of death in COVID-19 patients. However, the factors associated with COVID-19 susceptibility, resistance and severity remain poorly understood. In this review, we thoroughly explore the correlation between various host, viral and environmental markers, and SARS-CoV-2 in terms of susceptibility and severity.

Background: SARS-CoV-2 continues to claim hundreds of thousands of people's lives. It mostly affects the elderly and those with chronic illness but can also be fatal in younger age groups. This article is the first comprehensive analysis of the epidemiological and clinical outcomes of the travel-associated SARS-CoV-2 cases until April 19, 2020. Methods: Demographic and clinical data of travel-associated SARS-CoV-2 cases were collected for the period between January 16, 2020 and April 19, 2020. More than one hundred and eighty databases were searched, including the World Health Organization (WHO) database, countries' ministries websites, and official media sites. Demographic and clinical data were extracted and analyzed. Results: A total of 1,186 cases from 144 countries meeting the inclusion criteria were reported and included in the analysis. The mean age of the cases was 44 years, with a male to female ratio of 1.6:1. Travel-associated cases originated from more than 40 countries, with China, Italy, and Iran reporting the highest numbers at 208, 225, and 155, respectively. Clinical symptoms varied between patients, with some reporting symptoms during the flights (117 cases; 9.87%). A total of 312 (26.31%) cases were hospitalized, of which 50 cases (4.22%) were fatal. Conclusion: Major gaps exist in the epidemiology and clinical spectrum of the COVID-19 travel-associated cases due to a lack of reporting and sharing data of many counties. The identification and implementation of methodologies for measuring traveler's risk to coronavirus would help in minimizing the spread of the virus, especially in the next waves., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Marei, Emara, Elsaied, Nasrallah, Chivese, Al-Romaihi, Althani, Al Thani, Farag and Yassine.)

Autophagy is a homeostatic process that regulates and recycles intracellular structures and is a host defense mechanism that facilitates bacterial clearance. Uric acid in plasma is a major antioxidant but in certain conditions acts as an inflammatory danger signal. The aim of this study is to investigate the effect of soluble uric acid on autophagy and the inflammatory responses in macrophages during bacterial infection. Herein, we employed murine RAW264.7 macrophages that express uricase enzyme and human THP-1 cells that are uricase-deficient. Three different strains of Staphylococcus aureus and two different strains of Klebsiella pneumoniae were used to infect macrophages in presence and absence of soluble uric acid. We found that soluble uric acid enhanced autophagy flux in infected macrophages. We observed that IL-1β increased during bacterial infection but decreased when macrophages were co-stimulated with bacteria and uric acid. In contrast to IL-1β, soluble uric acid did not affect TNFα release and there were no dramatic differences when macrophages were infected with S. aureus or K. pneumoniae . In conclusion, uric acid enhances autophagy flux during bacterial infection, consequently reducing inflammasome activation in macrophages. Understanding the effect of uric acid on the interplay between autophagy and inflammation will facilitate therapeutic design.

Abstract: The spread of antibiotic resistance among bacterial strains has been associated with consumption of food contaminated with both pathogenic and nonpathogenic bacteria. The objective of this study was to determine the prevalence of antibiotic resistant Escherichia coli isolates in local and imported retail raw chicken meat in Qatar. A total of 270 locally produced (chilled) and imported (chilled or frozen) whole chicken carcasses were obtained from three Hypermarket stores in Qatar. The 216 E. coli isolates recovered from the chicken samples were subjected to antibiotic susceptibility testing with the disk diffusion method. Extended-spectrum β-lactamase (ESBL) production was evaluated with the double disk synergy test. Isolates harboring colistin resistance were identified with a multiplex PCR assay and DNA sequencing. Nearly 89% (192) of the 216 isolates were resistant to at least one of the 18 antibiotics tested. Isolates from local and imported chicken carcasses had relatively higher resistance to sulfamethoxazole (62% of isolates), tetracycline (59.7%), ampicillin and trimethoprim (52.3% each), ciprofloxacin (47.7%), cephalothin (45.4%), and colistin (31.9%). Less resistance was found to amoxicillin-clavulanic acid (6%), ceftriaxone (5.1%), nitrofurantoin (4.2%), piperacillin-tazobactam (4.2%), cefepime (2.3%), meropenem (1.4%), ertapenem (0.9%), and amikacin (0.9%). Nine isolates (4.2%) were ESBL producers, and 137 (63.4%) were multidrug resistant. The percentages of multidrug-resistant, ESBL-producing, and colistin resistant isolates were significantly higher among isolates from local chilled than from imported chilled and frozen chicken samples. Our findings indicate the high prevalence of antibiotic-resistant E. coli in chicken meat sold at retail in Qatar., (Copyright ©, International Association for Food Protection.)

Background: The ongoing pandemic of SARS-COV-2 has already infected more than eight million people worldwide. The majority of COVID-19 patients either are asymptomatic or have mild symptoms. Yet, about 15% of the cases experience severe complications and require intensive care. Factors determining disease severity are not yet fully characterized. Aim: Here, we investigated the within-host virus diversity in COVID-19 patients with different clinical manifestations. Methods: We compared SARS-COV-2 genetic diversity in 19 mild and 27 severe cases. Viral RNA was extracted from nasopharyngeal samples and sequenced using the Illumina MiSeq platform. This was followed by deep-sequencing analyses of SARS-CoV-2 genomes at both consensus and sub-consensus sequence levels. Results: Consensus sequences of all viruses were very similar, showing more than 99.8% sequence identity regardless of the disease severity. However, the sub-consensus analysis revealed significant differences in within-host diversity between mild and severe cases. Patients with severe symptoms exhibited a significantly ( p -value 0.001) higher number of variants in coding and non-coding regions compared to mild cases. Analysis also revealed higher prevalence of some variants among severe cases. Most importantly, severe cases exhibited significantly higher within-host diversity (mean = 13) compared to mild cases (mean = 6). Further, higher within-host diversity was observed in patients above the age of 60 compared to the younger age group. Conclusion: These observations provided evidence that within-host diversity might play a role in the development of severe disease outcomes in COVID-19 patients; however, further investigations are required to elucidate this association., (Copyright © 2020 Al Khatib, Benslimane, Elbashir, Coyle, Al Maslamani, Al-Khal, Al Thani and Yassine.)