The Association between Lifestyle Factors and COVID-19: Findings from Qatar Biobank.

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/m2), 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.

Protection of natural infection against reinfection with SARS-CoV-2 JN.1 variant.

Overall effectiveness of infection in preventing reinfection with SARS-CoV-2 JN.1 variant was estimated at 1.8% (95% CI: -9.3-12.6%), and demonstrated rapid decline over time since the previous infection, decreasing from 82.4% (95% CI: 40.9 to 94.7%) within 3 to less than 6 months, to a negligible level after one year.

Effectiveness of two and three doses of COVID-19 mRNA vaccines against infection, symptoms, and severity in the pre-omicron era: A time-dependent gradient.

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.

Addressing bias in the definition of SARS-CoV-2 reinfection: implications for underestimation.

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.

SARS-CoV-2 infection and effects of age, sex, comorbidity, and vaccination among older individuals: A national cohort study.

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.

History of primary-series and booster vaccination and protection against Omicron reinfection.

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.

Short- and longer-term all-cause mortality among SARS-CoV-2- infected individuals and the pull-forward phenomenon in Qatar: a national cohort study.

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.

Seroprevalence of herpes simplex virus type 1 and type 2 among the migrant workers in Qatar.

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.

Pharmacometabolomic Approach to Investigate the Response to Metformin in Patients with Type 2 Diabetes: A Cross-Sectional Study.

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 HbA1C 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.

Metabolomics Approaches for the Diagnosis, Treatment, and Better Disease Management of Viral Infections.

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.

Population immunity of natural infection, primary-series vaccination, and booster vaccination in Qatar during the COVID-19 pandemic: an observational study.

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.

Effects of previous infection, vaccination, and hybrid immunity against symptomatic Alpha, Beta, and Delta SARS-CoV-2 infections: an observational study.

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.

Exercise Metabolome: Insights for Health and Performance.

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.

Enhancing the sensitivity of rapid antigen detection test (RADT) of different SARS-CoV-2 variants and lineages using fluorescence-labeled antibodies and a fluorescent meter.

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.

The retrospective study of the metabolic patterns of BCG-vaccination in type-2 diabetic individuals in COVID-19 infection.

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.

The Metabolic Switch of Physical Activity in Non-Obese Insulin Resistant Individuals.

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.

Long-term COVID-19 booster effectiveness by infection history and clinical vulnerability and immune imprinting: a retrospective population-based cohort study.

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.

Vaccine evaluation and genotype characterization in children infected with rotavirus in Qatar.

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.