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Acute gastroenteritis remains a major cause of morbidity and mortality among young children worldwide. It accounts for approximately 1.34 million deaths annually in children younger than five years. Infection can be caused by viral, bacterial and/or parasitic microorganisms. Dysbiosis due to such infections could dramatically affect disease prognosis as well as development of chronic illness. The aim of this study was to analyze gut microbiome and clinical outcomes in young children suffering from viral or mixed viral-bacterial infection. We evaluated gut microbiota composition in children suffering from viral or mixed viral-bacterial infection with two major viruses rotavirus (RV) and norovirus (NoV) and two pathogenic bacteria [ Enteroaggregative E . coli (EAEC), and Enteropathogenic E . coli (EPEC)]. We sequenced 16S ribosomal RNA (V4 region) genes using Illumina MiSeq in 70 hospitalized children suffering from gastroenteric infections plus nine healthy controls. The study summarized Operational Taxonomic Unit (OTU) abundances with the Bray-Curtis index and performed a non-metric multidimensional scaling analysis to visualize microbiome similarities. We used a permutational multivariate analyses of variance to test the significance of group differences. We also analyzed the correlation between microbiome changes and clinical outcomes. Our data demonstrated a significant increase in the severity score in children with viral-bacterial mixed infections compared to those with virus infections alone. Statistical analysis by overall relative abundance denoted lesser proportions of Bacteroides in the infected children, whereas Bifidobacteriaceae richness was more prominent in the bacterial-viral mixed infections. Pairwise differences of gut microbiota were significantly higher in RV + EAEC (P = 0.009) and NoV + EAEC (P = 0.009) co-infections, compared to EPEC mixed infection with both, RV (P = 0.045) and NoV (P = 0.188). Shannon diversity index showed considerable more variation in microbiome diversity in children infected with RV cohort compared to NoV cohort. Our results highlight that richness of Bifidobacteriaceae , which acts as probiotics, increased with the severity of the viral-bacterial mixed infections. As expected, significant reduction of relative numbers of Bacteroides was characterized in both RV and NoV infections, with more reduction observed in co-infection pathogenic E . coli . Although mixed infection with EAEC resulted in significant microbiota differences compared to viral infection only or mixed infection with EPEC, the clinical condition of the children were worsened with both pathogenic E . coli co-infections. Further, in comparison with RV cohort, augmented number of differential abundant pathogenic OTUs were peculiarly noticed only with NoV mixed infection.

Before new vaccines are made widely available, their efficacy and safety are tested in laboratories and clinical trials. Once approved, researchers can continue to monitor how these vaccines perform in the ‘real world’ by analysing healthcare data. This can provide further insights over a longer timeframe and across a broader range of people. However, these real-world analyses can be skewed by a range of factors. For example, if healthier people are more likely to receive the vaccine, researchers may overestimate its effectiveness due to fewer deaths or severe illnesses amongst that group. This ‘healthy vaccinee effect’ has been observed in influenza vaccines among older people, for example. To determine whether the healthy vaccinee effect influenced COVID-19 vaccine studies, Chemaitelly et al. analysed national health records in Qatar. Groups of vaccinated and unvaccinated people were selected to have matching demographics, such as age, sex and number of preexisting conditions. Overall, the study confirmed strong protection from vaccination against severe forms of COVID-19. However, the results showed that, compared to their unvaccinated peers with similar characteristics, vaccinated people were 65 per cent less likely to die due to reasons unrelated to COVID-19 in the next six months after having received the vaccination. This effect was even stronger among individuals aged 50 years or older, as well as those with clinical vulnerabilities. Chemaitelly et al. suggest that this likely reflects lower vaccine uptake among seriously ill, end-of-life individuals and less mobile older populations with short life expectancy. Future work may be needed to understand if this can be generalised to countries that differ from Qatar, whose population mainly consists of healthy adult migrant workers.

For a long time, viruses have been shown to modify the clinical picture of several autoimmune diseases, including type 1 diabetes (T1D), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren’s syndrome (SS), herpetic stromal keratitis (HSK), celiac disease (CD), and multiple sclerosis (MS). Best examples of viral infections that have been proposed to modulate the induction and development of autoimmune diseases are the infections with enteric viruses such as Coxsackie B virus (CVB) and rotavirus, as well as influenza A viruses (IAV), and herpesviruses. Other viruses that have been studied in this context include, measles, mumps, and rubella. Epidemiological studies in humans and experimental studies in animal have shown that viral infections can induce or protect from autoimmunopathologies depending on several factors including genetic background, host-elicited immune responses, type of virus strain, viral load, and the onset time of infection. Still, data delineating the clear mechanistic interaction between the virus and the immune system to induce autoreactivity are scarce. Available data indicate that viral-induced autoimmunity can be activated through multiple mechanisms including molecular mimicry, epitope spreading, bystander activation, and immortalization of infected B cells. Contrarily, the protective effects can be achieved via regulatory immune responses which lead to the suppression of autoimmune phenomena. Therefore, a better understanding of the immune-related molecular processes in virus-induced autoimmunity is warranted. Here we provide an overview of the current understanding of viral-induced autoimmunity and the mechanisms that are associated with this phenomenon.

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. 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. 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). 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. 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.

Background/Objectives: Data on antimicrobial resistance (AMR) in goat-derived E. coli within the Gulf Cooperation Council (GCC) region remain limited, and are largely restricted to studies conducted in Saudi Arabia and the UAE, with no published reports from Qatar. This study provides the first baseline characterization of AMR and extended-spectrum β-lactamase (ESBL) profiles of E. coli isolated from goats in Qatar. Methods: A total of 280 fecal samples were collected from goats across nine locations in Qatar (140 healthy and 140 diseased goats; 12 samples did not yield E. coli cultures). A selective agar medium was used to isolate E. coli, and the isolates were subsequently confirmed using the VITEK® 2 Compact system. Antimicrobial susceptibility testing was performed to determine resistance profiles, and PCR assays were used to detect ESBL-associated genes. Results: 268 E. coli isolates were recovered from 280 samples. AMR analysis revealed a high prevalence of tetracycline resistance among E. coli isolates (53%), consistently observed across all nine sampling locations. Ampicillin resistance was also widespread. AMR was detected in isolates from both healthy and diseased goats; however, gentamicin resistance was found exclusively in the isolates from diseased animals. Overall, 44 isolates (16%) were classified as multidrug resistant (MDR), while nine isolates (3%) demonstrated ESBL production based on cefotaxime resistance. MDR and ESBL-producing E. coli were detected across all nine locations and in both healthy and diseased animals, with MDR strains occurring more frequently than ESBL producers. PCR analysis identified ESBL-associated genes, namely, blaCTX-M in nine isolates and blaTEM in three isolates. Conclusions: Goats in Qatar harbor multidrug-resistant and ESBL-producing E. coli, highlighting their role as AMR reservoirs within a One Health framework. The high resistance rates to commonly used antibiotics, particularly tetracycline and ampicillin, across health statuses and geographic locations suggest potential influences of local management practices and environmental factors. The detection of ESBL genes, notably blaCTX-M and blaTEM, underscores the need for prudent antimicrobial use and the implementation of integrated One Health surveillance programs to mitigate potential public health risks and to support national AMR surveillance and antimicrobial stewardship efforts across the region.

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.

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

BackgroundSARS-CoV-2 infection is associated with protection against reinfection. This study analysed this protection across different reinfection symptoms and severities, comparing the preomicron and omicron eras.MethodsA nationwide, matched, test-negative, case–control study was conducted in Qatar from 5 February 2020 to 12 March 2024. The preomicron analysis used a sample of 509 949 positive and 8 494 782 negative tests, while the omicron analysis included 682 257 positive and 6 904 044 negative tests. Data were sourced from Qatar’s national databases for COVID-19 laboratory testing, vaccination, hospitalisation and death.ResultsEffectiveness of preomicron infection against preomicron reinfection was estimated at 80.9% (95% CI: 79.1% to 82.6%) for asymptomatic reinfection, 87.5% (95% CI: 86.1% to 88.9%) for symptomatic reinfection, 97.8% (95% CI: 95.7% to 98.9%) for severe COVID-19 reinfection, 100.0% (95% CI: 97.5% to 100.0%) for critical COVID-19 reinfection and 88.1% (95% CI: 50.3% to 97.2%) for fatal COVID-19 reinfection. For omicron infection against omicron reinfection, the estimates were 46.4% (95% CI: 36.9% to 54.4%) for asymptomatic reinfection, 52.8% (95% CI: 44.4% to 60.0%) for symptomatic reinfection, 100.0% (95% CI: 55.4% to 100.0%) for severe COVID-19 reinfection, 100.0% (95% CI: 15.1% to 100.0%) for critical COVID-19 reinfection, and 75.2% (95% CI: −58.8% to 97.5%) for fatal COVID-19 reinfection. Effectiveness over time since previous infection showed no discernible decline in protection against all forms of reinfection in the preomicron era, but a rapid decline against asymptomatic and symptomatic reinfections in the omicron era.ConclusionsA gradient of protection against reinfection is evident, with the highest protection observed against severe forms of COVID-19. Over time, this gradient becomes more pronounced, as protection against asymptomatic and symptomatic reinfections decreases, while protection against severe outcomes remains strong.

Background The treatment of Enterobacteriaceae family including diarrheagenic E. coli (DEC) has been increasingly complicated due to the emergence of resistant strains. Here we report on the phenotypic resistance profiles and ESBL genotype and virulence profiles of Enteroaggregative E. coli (EAEC) and Enteropathogenic E. coli (EPEC) isolated from children hospitalized with acute gastroenteritis in Qatar (AGE). Results E. coli were isolated and characterized from 76 diarrheagenic stool positive samples, collected from hospitalized children less than 10 years old. Isolates were tested for antibiotic susceptibility against eighteen clinically relevant antibiotics using E-test method. Conventional PCR was performed to detect genes encoding ESBL and virulence factors. Chi-square test was performed to compare the individual antibiotic resistance between EPEC and EAEC. A significant percentage (73.7%) of isolates were resistant to at least one antibiotic. Overall, high resistance (70%) was reported to the first-line antibiotics such as ampicillin, tetracycline (46.4%), and sulfamethoxazole-trimethoprim (42.9%). Further, 39.5% of the isolates were multidrug resistant (MDR), with 22.4% being ESBL producers. On the other hand, all isolates were susceptible to carbapenem, fosfomycin, amikacin and colistin. The incidences of resistance to the 18 antibiotics between EPEC and EAEC were not significantly different by Pearson chi -square test ( P  > 0.05). Genetic analysis revealed that 88.23% of ESBL production was bla CTX-M-G1 ( bla CTX-M-15 , bla CTX-M-3 ) - encoded. Several different combinations of virulence markers were observed, however, there was no specific trend among the isolates apart from absence of the bundle-forming pilus (bfpA ) gene, which encodes the type IV fimbriae in EPEC adherence factor (EAF) plasmid (pEAF), among all EPEC (atypical). 15% of the EAEC strains were positive for a combination of astA , aap & capU , while 10% were positive for three different combinations. The aap , aatA , capU and aggR virulence genes showed the highest frequency of 65, 60, 55 and 55% respectively. Others genes, east , astA , and aai , showed frequencies of 35, 30 and 20% respectively. Conclusions Atypical EPEC and EAEC were the primary etiological agents of diarrhea in children among DEC pathotypes. Our results indicated high rate of antimicrobial resistance pattern of DEC strains, which necessities the development of regulatory programs and reporting systems of antimicrobial resistance in DEC and other AGE-associated bacteria to insure effective control of diarrheal diseases. Results from this study demand a further research on identifying the phenotypic and genotypic profiles of more DEC pathotypes in various clinical samples.

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 (Ca2+) 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.