Abstract Background There are contradictory reports regarding the association of COVID-19 with sudden cardiac deaths. It is unclear whether these deaths are the result of known cardiac disease and risk factors or are unexpected based on prevalent risk factors. Our aim was to determine the association between COVID-19 infection and UCD among individuals who died of a cardiac cause in Qatar. Study Flowsheet Methods All deaths in Qatar in adults >18 years old with any cardiac cause listed as the primary or immediate cause of death were individually reviewed to determine whether the death was unexpected based on the individual’s clinical risk profile. For each case of validated UCD, up to 5 controls with a non-cardiac primary cause of death were identified, matched on age groups, sex, nationality, number of coexisting conditions, and vaccine doses to individuals who died of non-cardiac causes in the same calendar month. Adjusted odds ratios (aOR) comparing odds of prior COVID-19 infection in cases relative to controls were estimated using conditional logistic regression. Association between prior COVID-19 infection and incidence of Unexpected Cardiac Deaths (UCD) in the matched cohorts. Results Among a total of 10,541 deaths, we matched 326 UCD cases to 604 controls with a non-cardiac cause of death. The median age was 48 years for cases and 49 years for controls, 87% were male, and 18% of cases and 20% of controls were Qatari nationals. Approximately three-quarters in each group had no documented comorbidities, and approximately two-thirds were unvaccinated. Prior COVID-19 infection was not associated with a higher risk of UCD (aOR 0.74, 95% CI 0.48, 1.13). No association was observed between prior COVID-19 and UCD in subgroup analyses by age groups, or vaccination status. Qatari nationals, females, and those with > 4 comorbidities were less likely to experience UCD associated with prior COVID-19. Conclusion COVID-19 is not associated with an increased risk of UCD. The observed cardiac deaths are more likely due to the underlying risk profile of the decedents. Disclosures Adeel A. Butt, MD, MS, Gilead Sciences: Grant/Research Support

Concerns about waning immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the emergence of new variants underscore the need for booster doses. Using a matched cohort design, this study evaluated the relative effectiveness and durability of a fourth dose of ancestral-strain mRNA vaccines (BNT162b2 or mRNA-1273) in preventing SARS-CoV-2 infection, compared to three doses, between February 10, 2021 and May 13, 2024 in Qatar. The fourth dose conferred modest additional protection against infection, with an adjusted hazard ratio for infection of 0.91 (95% CI: 0.81-1.02), corresponding to a relative vaccine effectiveness of 9.2% (95% CI: - 1.7 to 18.9%). Protection peaked within the first three months of vaccination at 35.0% (95% CI: 20.6-46.8%) but waned rapidly thereafter, becoming negligible beyond that period. These findings highlight the modest and short-term protection of ancestral-strain vaccines against omicron subvariants and support the need for next-generation vaccines offering more durable immunity.

BACKGROUND:Childhood diarrhoea is a major contributor to morbidity and mortality among children under five years of age. This study provides an analysis of global childhood diarrhoea prevalence, drawing on standardised, nationally representative survey data collected from 1985 to 2024. METHODS:A systematic review of Demographic and Health Surveys and Multiple Indicator Cluster Surveys conducted up to October 30, 2024, was undertaken, with findings reported in accordance with PRISMA guidelines. Random-effects meta-analyses and meta-regression analyses were conducted. Factor analysis was employed to construct a Socioeconomic and Child Nutrition Index, integrating socioeconomic, water, sanitation, hygiene, and nutrition indicators. FINDINGS:The analysis identified 593 relevant studies, estimating a global pooled mean childhood diarrhoea prevalence of 14.4% (95% CI: 13.8-15.0%) across all regions and time periods. Prevalence declined at a rate of 1% per year, falling from 22.3% in 1985-1989 to 10.9% in 2020-2024, with consistent declines observed in all regions except the Eastern Mediterranean Region. Prevalence was highest in the African Region and lowest in the European Region. Higher prevalence was observed in countries with larger household sizes, longer water collection times, and higher rates of underweight, stunting, and wasting. In contrast, lower prevalence was associated with higher levels of urbanisation, maternal education, population density, Human Development Index, income per capita, and access to improved water sources and sanitation facilities. A higher Socioeconomic and Child Nutrition Index was strongly and consistently associated with lower diarrhoea prevalence, demonstrating a dose-response relationship. INTERPRETATION:Childhood diarrhoea prevalence has declined over recent decades, apparently reflecting the synergistic effects of targeted public health interventions and broader socioeconomic progress in addressing upstream determinants of child health. FUNDING:This work was supported by the Biostatistics, Epidemiology, and Biomathematics Research Core at Weill Cornell Medicine-Qatar. The statements made herein are solely the responsibility of the authors.

Introduction. Pre-existing immunity to human coronaviruses (HCoVs) may shape the immune response in COVID-19 patients. Increasing evidence suggests that immune cross-reactivity between SARS-CoV-2 and other coronaviruses may determine clinical prognosis.Hypothesis. SARS-CoV-2 disease severity is influenced by pre-existing immunity to HCoVs, with distinct antibody profiles and cross-reactivity patterns.Aim. To investigate the antibody response of ICU and non-ICU SARS-CoV-2 patients against different HCoV proteins and assess the potential impact of pre-existing immunity on SARS-CoV-2 disease outcomes.Methodology. This study used a comprehensive HCoVs antigen bead array to measure antibody response to pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, SARS-CoV-2 and the four seasonal HCoVs in 70 ICU and 63 non-ICU COVID-19 patients.Results. Our analysis demonstrates an overall higher antibody response in ICU than in non-ICU COVID-19 patients. Interestingly, the anti-S1 IgG and IgA were significantly higher among ICU than in non-ICU patients. Similarly, the anti-S1 IgG against NL63 showed a lower response among ICU compared to non-ICU. Cross-reactivity was evident between SARS-CoV-2 and SARS-CoV antibodies but not with MERS-CoV and seasonal HCoVs. The subclass analysis of antibodies recognizing SARS-CoV-2 revealed that anti-S1 IgG1, IgG3, IgA1 and IgA2 were significantly higher in ICU compared to non-ICU. The predominant IgA subtype among SARS-CoV-2 patients was IgA1. We applied machine learning algorithms to subclass serological responses to build classifiers that could distinguish between ICU patients and patients with milder COVID-19. Out of 90 variables used in two different types of models, the variable of highest influence in determining the ICU status was IgG3 against SARS-CoV-2 S, and the top 8 variables of influence included the presence of IgG3 against S-trimer as well as IgA against SARS-CoV-2 S.Conclusion. Understanding the complexities of humoral immunity in various patients is critical for early medical intervention, disease management, selective vaccination and passive immunotherapy.

Objectives: The chemiluminescence immunoassay automated Abbott ARCHITECT hepatitis B surface antigen (HBsAg) screening assay is globally recognized for its superior sensitivity but notably low specificity. This mandates positive results confirmation by another confirmatory assay, such as the widely used Abbott ARCHITECT HBsAg neutralizing assay. This study aimed to evaluate the performance of the new chemiluminescence immunoassay, Mindray CL-900i HBsAg screening assay in comparison to the ARCHITECT neutralizing/confirmatory assay. Methods: A total of 200 archived HBsAg-positive and-negative samples by ARCHITECT screening were selected for this study. These samples were classified as follows: true positive (n = 39): positive by ARCHITECT screening and confirmatory assays, true negative (n = 144): negative by ARCHITECT screening and confirmatory assays, and false positive (n = 17): positive by ARCHITECT screening but negative by confirmatory assay. All samples were retested using the Mindray CL-900i HBsAg screening assay. Results: Compared with ARCHITECT confirmatory assay, the Mindray HBsAg CL-900i demonstrated perfect agreement with the confirmatory assay, as indicated by a Cohen kappa value of 0.98 (0.95-1.02). Mindray CL-900i exhibited a sensitivity of 97%, positive predictive value of 100%, and negative predictive value of 99%. The specificity was 100% because none of the true-negative and false-positive results were identified as positive. Conclusions: Mindray CL-900i could offer a cost-effective alternative for HBsAg screening, boasting perfect specificity and overcoming the limitations of current automated assays.

BACKGROUND:Supply constraints during the coronavirus disease 2019 (COVID-19) pandemic led to vaccination strategies that prioritized first-dose coverage. To evaluate the merit of this approach, this study compared the development of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 following a single dose versus two doses across three widely used vaccine platforms. METHODS:National, matched, test-negative case-control analyses were conducted in Qatar between December 1, 2020, and December 18, 2021, to evaluate vaccine effectiveness. The one-dose analysis included 227,309 cases and 4,170,786 controls; the two-dose analysis included 234,314 cases and 6,445,858 controls. RESULTS:For BNT162b2, single-dose effectiveness against infection increased steadily from 9.9 % (95 % CI: 6.7-13.0 %) in the first two weeks post-vaccination to 71.5 % (95 % CI: 45.5-85.1 %) by month 3, closely approaching the 74.5 % (95 % CI: 72.9-76.0 %) effectiveness observed after the two-dose primary series. Similar trends were observed for mRNA-1273 and ChAdOx1 nCoV-19, with mRNA-1273 reaching two-dose levels of effectiveness as early as month 2. In contrast to the gradual buildup of protection against infection, single-dose effectiveness against severe, critical, or fatal COVID-19 increased rapidly for all three vaccines, exceeding 85 % by day 21 and closely matching the protection achieved after two doses. CONCLUSION:A single COVID-19 vaccine dose provides rapid, strong protection against severe outcomes, supporting first-dose prioritization during supply constraints. The slower development of protection against infection highlights the second dose's role in accelerating the immune response. Antigen dose appears to influence the speed of protection buildup.

Qatar implemented a mass primary-series vaccination campaign to mitigate the impact of the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to retrospectively evaluate the cost-effectiveness of this program both before and after onset of the omicron wave. An economic evaluation was conducted from the public healthcare system perspective between January 5, 2021, and September 18, 2023. Cost-effectiveness was determined using an epidemiological retrospective cohort study and health economic modeling that compared the cohort of individuals who received two vaccine doses with the unvaccinated cohort with respect to incidence of infection, incidence of severe COVID-19 forms, quality-adjusted life years (QALYs), and medical costs. During the pre-omicron phase, primary-series vaccination incurred an additional cost of $104,422,358, led to a gain of 724.7 QALYs, and savings of $54,790,858 in direct medical costs. The incremental cost-effectiveness ratio (ICER) was $68,485 per QALY gained. The number needed to vaccinate was 35.4 individuals (95% CI: 24.4-49.9) to prevent one infection and 718.0 individuals (95% CI: 469.4-984.0) to prevent one severe COVID-19 outcome. The cost per infection averted was $3,180 (95% CI: $2,189-$4,484) and per severe COVID-19 outcome averted was $64,468 (95% CI: $42,146-$88,354). Vaccination of individuals ≥50 years of age, those more clinically vulnerable to severe COVID-19, and those with multiple coexisting conditions was substantially more cost-effective. Cost-effectiveness of primary-series vaccination was substantially reduced during the omicron phase, but vaccination remained cost-effective. Sensitivity analyses confirmed the findings. Primary-series vaccination was cost-effective with an ICER below the 1 GDP per capita threshold during the pre-omicron phase and within the 1-3 GDP per capita thresholds during the omicron phase. Targeted vaccination strategies for those most vulnerable to COVID-19 were the most cost-effective and remained essential, even in situations of moderate vaccine effectiveness or reduced infection severity.

Background SARS-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.Methods A 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.Results Effectiveness 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.Conclusions A 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.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved over short timescales, leading to the emergence of more transmissible variants such as Alpha and Delta1-3. The arrival of the Omicron variant marked a major shift, introducing numerous extra mutations in the spike gene compared with earlier variants1,2. These evolutionary changes have raised concerns regarding their potential impact on immune evasion, disease severity and the effectiveness of vaccines and treatments1,3. In this epidemiological study, we identified two distinct patterns in the protective effect of natural infection against reinfection in the Omicron versus pre-Omicron eras. Before Omicron, natural infection provided strong and durable protection against reinfection, with minimal waning over time. However, during the Omicron era, protection was robust only for those recently infected, declining rapidly over time and diminishing within a year. These results demonstrate that SARS-CoV-2 immune protection is shaped by a dynamic interaction between host immunity and viral evolution, leading to contrasting reinfection patterns before and after Omicron's first wave. This shift in patterns suggests a change in evolutionary pressures, with intrinsic transmissibility driving adaptation pre-Omicron and immune escape becoming dominant post-Omicron, underscoring the need for periodic vaccine updates to sustain immunity.

BACKGROUND:This study assessed the real-world effectiveness of the ChAdOx1 nCoV-19 vaccine in adults against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, symptomatic infection, and severe coronavirus disease 2019 (COVID-19) during periods of Beta and Delta variant dominance in Qatar. METHODS:A national, matched, test-negative case-control study was conducted using 186,130 PCR-positive tests (cases) and 667,289 PCR-negative tests (controls) collected between January 1 and December 18, 2021. Subgroup analyses were performed to evaluate vaccine effectiveness across key strata. RESULTS:The median time between the first and second doses was 61 days (interquartile range, 56-64 days). Two-dose primary-series effectiveness was 66.0% (95% CI, 55.1-74.3%) against any SARS-CoV-2 infection and 73.0% (95% CI, 44.1-87.0%) against symptomatic infection. Effectiveness was estimated at 100% (95% CI, 64.0-100%) against any Beta variant infection and 65.3% (95% CI, 54.2-73.8%) against any Delta infection. Protection against any infection of any variant peaked at 78.4% (95% CI, 50.7-90.5%) within the first month after the second dose, gradually declining to 45.6% (95% CI, 5.5-68.7%) after 150 days. Effectiveness against severe, critical, or fatal COVID-19, irrespective of variant, was 100% (95% CI, 49.3-100%), with no vaccinated individuals progressing to severe, critical, or fatal disease after infection. Effectiveness of a single dose was 59.9% (95% CI, 51.0-67.3%) against any infection-65.0% (95% CI, 49.7-75.6%) against Beta and 55.9% (95% CI, 43.8-65.5%) against Delta-78.4% (95% CI, 60.9-88.0%) against symptomatic infection, and 100% (95% CI, 88.9-100%) against severe, critical, or fatal COVID-19. CONCLUSION:The ChAdOx1 nCoV-19 vaccine provided substantial protection against infection and strong protection against severe outcomes during periods dominated by the Beta and Delta variants, although protection against infection waned within the first few months following the primary series.

Chlamydia trachomatis (CT) is among the most common sexually transmitted infections and is associated with substantial health and economic burdens. Vaccination may offer a promising strategy for its global control. A deterministic, age-structured mathematical model was applied to assess the global impact of a hypothetical CT vaccine. The analysis explored a range of assumptions for vaccine efficacy against infection acquisition ( VE_S ), duration of protection, and coverage, across both adult catch-up and adolescent-targeted vaccination strategies. Vaccinating individuals aged 15–49 years beginning in 2030 with a vaccine of VE_S=50% and 20-year protection, scaled to 80 VE_S , longer protection duration, and inclusion of breakthrough effects on infectiousness and infection duration. While adolescent vaccination achieved substantial impact, its benefits accrued more slowly than those of adult-targeted strategies. Vaccination against CT can substantially reduce global infection burden, even with moderate efficacy. Impact is enhanced by targeted strategies, with adolescent vaccination aiding long-term control and catch-up programs ensuring immediate benefit. These findings highlight the urgency of vaccine development and integration into public health efforts.

Background:Accurately assessing SARS-CoV-2 infection severity is essential for understanding the health impact of the infection and evaluating the effectiveness of interventions. This study investigated whether SARS-CoV-2-associated hospitalizations can reliably measure true COVID-19 severity. Methods:The diagnostic accuracy of SARS-CoV-2-associated acute care and ICU hospitalizations as indicators of infection severity was assessed in Qatar from 6 September 2021 to 13 May 2024. WHO criteria for severe, critical, and fatal COVID-19 served as the reference standard. Two indicators were assessed: (1) any SARS-CoV-2-associated hospitalization in acute care or ICU beds and (2) ICU-only hospitalizations. Results:A total of 644 176 SARS-CoV-2 infections were analyzed. The percent agreement between any SARS-CoV-2-associated hospitalization (acute care or ICU) and WHO criteria was 98.7% (95% confidence interval (CI), 98.6-98.7); however, Cohen's kappa was only 0.17 (95% CI, 0.16-0.18), indicating poor agreement. Sensitivity, specificity, PPV, and negative predictive value were 100% (95% CI, 99.6-100), 98.7% (95% CI, 98.6-98.7), 9.7% (95% CI, 9.1-10.3), and 100% (95% CI, 100-100), respectively. For SARS-CoV-2-associated ICU-only hospitalizations, the percent agreement was 99.8% (95% CI, 99.8-99.9), with a kappa of 0.47 (95% CI, 0.44-0.50), indicating fair-to-good agreement. Sensitivity, specificity, PPV, and negative predictive value were 46.6% (95% CI, 43.4-49.9), 99.9% (95% CI, 99.9-99.9), 47.9% (95% CI, 44.6-51.2), and 99.9% (95% CI, 99.9-99.9), respectively. Conclusions:Generic hospital admissions are unreliable indicators of COVID-19 severity, whereas ICU admissions are somewhat more accurate. The findings demonstrate the importance of applying specific, robust criteria-such as WHO criteria-to reduce bias in epidemiological and vaccine effectiveness studies.

We aimed to understand to what extent knowledge of the prevalence of one sexually transmitted infection (STI) can predict the prevalence of another STI, with application for men who have sex with men (MSM). An individual-based simulation model was used to study the concurrent transmission of HIV, HSV-2, chlamydia, gonorrhea, and syphilis in MSM sexual networks. Using the model outputs, 15 multiple linear regression models were conducted for each STI prevalence, treating the prevalence of each as the dependent variable and the prevalences of up to four other STIs as independent variables in various combinations. For HIV, HSV-2, chlamydia, gonorrhea, and syphilis, the proportion of variation in prevalence explained by the 15 models ranged from 34.2% to 88.3%, 19.5%-70.5%, 43.7%-82.9%, 48.7%-86.3%, and 19.5%-67.2%, respectively. Including multiple STI prevalences as independent variables enhanced the models' predictive power. Gonorrhea prevalence was a strong predictor of HIV prevalence, while HSV-2 and syphilis prevalences were weak predictors of each other. Propagation of STIs in sexual networks reveals intricate dynamics, displaying varied epidemiological profiles while also demonstrating how the shared mode of transmission creates ecological associations that facilitate predictive relationships between STI prevalences. (c) 2024 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

BACKGROUND:Yemen, grappling with a protracted humanitarian crisis, armed conflict, forced displacements, and economic hardship, faces a burden of childhood diarrhea. This study aimed to assess diarrhea prevalence, trends, and underlying factors among children under five in this population. METHODS:Data were sourced from the population-based, nationally representative Yemen Demographic and Health Surveys (1991 and 2013) and Multiple Indicator Cluster Surveys (2006 and 2022). A three-level random-effects logistic regression model was used to identify risk factors, with clustering effects analyzed at both the neighborhood and household levels. RESULTS:The study included 6,451 children under five in 1991, 3,778 in 2006, 15,278 in 2013, and 19,501 in 2022. Diarrhea prevalence was 34.8% (95% CI: 32.6-37.1%) in 1991, 33.6% (95% CI: 31.6-35.6%) in 2006, 31.4% (95% CI: 30.1-32.7%) in 2013, and 37.4% (95% CI: 36.2-38.7%) in 2022. The adjusted odds ratios (aORs) for diarrhea were twice as high for children aged 12-23 months compared to those aged less than 12 months and decreased steadily with increasing age. Females had 15% lower odds of diarrhea than males. The aORs were higher for households in North Yemen, those without water on premises, or those with unimproved toilet facilities, but lower for households with more than five members and those in the highest wealth quintile. Between-cluster differences decreased between 1991 and 2006 but increased between 2013 and 2022. Disparities were much more pronounced between households than across neighborhoods. CONCLUSIONS:Using a three-level modeling approach and analyzing trends over a three-decade period, this study revealed a persistent and worsening burden of childhood diarrhea in Yemen, with prevalence more than twice the global average. Urgent action is needed to improve water and sanitation infrastructure and implement targeted programs to reduce diarrhea prevalence.

Accurate Vitamin B12 (Vit B12) quantification is essential for diagnosing deficiencies linked to neurological and hematological disorders. The Accre 8 Point-of-Care (POC) Chemiluminescent Immunoassay (CLIA) system offers a compact design, rapid single-step operation, and minimal calibration requirements. This study evaluates Accre 8’s performance against established CLIA immunoassays (Abbott and Roche) and LC-MS/MS, the gold standard for Vit B12 quantification. A total of 297 serum samples, spanning deficient to sufficient Vit B12 levels, were analyzed. Accre 8 demonstrated a strong correlation with LC-MS/MS (r = 0.94, p < 0.001), with median Vit B12 levels closely aligning with LC-MS/MS (256.0 pmol/L). Accre 8 exhibited high sensitivity (96.9%) and specificity (86.7%), with Cohen’s Kappa agreement (0.76). Bland-Altman analysis showed a mean bias of - 18.5%, while Passing-Bablok regression indicated proportional bias at higher concentrations (slope = 1.44). ROC analysis confirmed excellent diagnostic accuracy (AUC = 0.98). Accre 8’s strong diagnostic performance, minimal calibration needs, and low sample volume requirements position it as a practical alternative to conventional CLIA systems for Vit B12 assessment, particularly in clinical and resource-limited settings. These findings support its potential integration into routine diagnostic workflows for Vit B12 deficiency screening and monitoring.

BACKGROUND:Past immunological events can either enhance or compromise an individual's future immune protection. This study investigated how different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) natural infection histories before an omicron infection, with or without vaccination, influence protection against subsequent omicron reinfection. METHODS:Three national, matched, retrospective cohort studies were conducted in Qatar from February 28, 2020, to August 12, 2024 to compare incidence of omicron reinfection between individuals with two omicron infections (omicron double-infection cohort) and those with one (omicron single-infection cohort); the omicron double-infection cohort with individuals who had a pre-omicron infection followed by an omicron reinfection (pre-omicron-omicron double-infection cohort); and the pre-omicron-omicron double-infection cohort with the omicron single-infection cohort. RESULTS:Here we show that, in the first study, comparing the omicron double-infection cohort to the omicron single-infection cohort, the adjusted hazard ratio (aHR) is 1.27 (95% CI: 1.13-1.43); 0.93 (95% CI: 0.68-1.28) for the unvaccinated and 1.34 (95% CI: 1.18-1.52) for the vaccinated. In the second study, comparing the omicron double-infection cohort to the pre-omicron-omicron double-infection cohort, the aHR is 1.37 (95% CI: 1.13-1.65); 1.12 (95% CI: 0.63-1.97) for the unvaccinated and 1.42 (95% CI: 1.16-1.74) for the vaccinated. In the third study, comparing the pre-omicron-omicron double-infection cohort to the omicron single-infection cohort, the aHR is 0.97 (95% CI: 0.92-1.03); 0.75 (95% CI: 0.66-0.85) for the unvaccinated and 1.03 (95% CI: 0.97-1.09) for the vaccinated. CONCLUSIONS:Immune history shapes protection against omicron reinfection, with pre-omicron-omicron immunity enhancing protection, while repeated similar exposures reduce protection against new variants.

Hepatitis B virus (HBV) infection is a global health challenge, with the World Health Organization (WHO) targeting its elimination by 2030. Jordan lacks sufficient data on HBV epidemiology, including prevalence, incidence and clearance. This study addresses these gaps through a retrospective analysis of HBV testing data from 40,268 individuals collected at Biolab Diagnostic Laboratories (2010-2024). Using cross-sectional and cohort study designs, the study examined hepatitis B surface antigen (HBsAg) prevalence, temporal trends, incidence, clearance rates and associated risk factors. Statistical methods included regression analyses, Kaplan-Meier estimations and Poisson models. HBsAg prevalence was 3.8% (95% CI: 3.6%-4.0%), with a nationally weighted prevalence of 5.3% (95% CI: 4.4%-6.4%). Prevalence was around 1% in individuals under 20 years, increasing to 8.5% (95% CI: 7.7%-10.0%) in the 50-59 age group. Over the past 15 years, prevalence declined by 7% annually [adjusted odds ratio (aOR): 0.93; 95% CI: 0.92-0.94]. HBsAg positivity was significantly associated with age, male sex and governorate. Cumulative HBsAg incidence was 0.26% (95% CI: 0.11%-0.64%) after 5 years of follow-up, with an incidence rate of 0.63 per 1000 person-years (95% CI: 0.26-1.51). Cumulative HBsAg clearance was 7.45% (95% CI: 4.07%-13.43%) at the 6-month follow-up mark, with a clearance rate of 17.68 per 100 person-years (95% CI: 9.51-32.86). Among HBsAg-positive individuals with > 6 months of follow-up, cumulative HBsAg clearance reached 46.12% (95% CI: 24.50%-74.34%) after 13 years of follow-up, with a clearance rate of 5.27 per 100 person-years (95% CI: 3.32-8.36). HBV epidemiology in Jordan shows declining prevalence and incidence, likely driven by expanding HBV vaccination coverage. To meet the WHO's 2030 elimination targets, Jordan must prioritise scaling up birth-dose vaccination, improving case detection and ensuring timely treatment.

Abstract Background SARS-CoV-2 infection protection against reinfection can be compromised by emergence of immune-evasive variants. Methods A national, matched, test-negative, case-control study was conducted on Qatar's population between February 5, 2020-February 12, 2024, to assess the level and durability of protection offered by omicron infection against omicron reinfection, compared to the protection provided by pre-omicron infection against pre-omicron reinfection. Subgroup and sensitivity analyses were performed. Results Effectiveness of pre-omicron infection against pre-omicron reinfection was 81.1% (95% CI: 80.4-81.8%). Effectiveness was 81.3% (95% CI: 80.6-82.1%) in the first year after the previous infection and 79.5% (95% CI: 77.1-81.5%) thereafter. In contrast, effectiveness of omicron infection against omicron reinfection was only 53.6% (95% CI: 52.1-55.0%) and demonstrated rapid waning. Effectiveness declined from 81.3% (95% CI: 79.6-82.9%) within the first 3-6 months post-infection to 59.8% (95% CI: 57.8-61.7%) in the subsequent 3 months, further dropping to 27.5% (95% CI: 22.7-32.0%) within the next 3 months, and reaching only 4.8% (95% CI: -2.7-11.8%) after one year. Effectiveness against symptomatic reinfection and for both unvaccinated and vaccinated individuals mirrored these patterns. Effectiveness of infection in preventing severe, critical, or fatal COVID-19 upon reinfection remained nearly 100% in both pre-omicron and omicron eras, showing no signs of waning over time. Conclusion SARS-CoV-2 natural immunity shows a dynamic interplay between host immunity and viral evolution, resulting in contrasting reinfection patterns before and after omicron emergence. These patterns suggest a shift in evolutionary pressures, with intrinsic transmissibility driving adaptation pre-omicron and immune escape becoming dominant post-omicron. Disclosures All Authors: No reported disclosures

Background: This study investigated the presence of the healthy vaccinee effect—the imbalance in health status between vaccinated and unvaccinated individuals—in two rigorously conducted COVID-19 vaccine effectiveness studies involving primary series and booster vaccinations. It also examined the temporal patterns and variability of this effect across different subpopulations by analyzing the association between COVID-19 vaccination and non-COVID-19 mortality in Qatar. Methods: Two matched, retrospective cohort studies assessed the incidence of non-COVID-19 death in national cohorts of individuals with a primary series vaccination versus no vaccination (two-dose analysis), and individuals with three-dose (booster) vaccination versus primary series vaccination (three-dose analysis), from January 5, 2021, to April 9, 2024. Results: The adjusted hazard ratio (aHR) for non-COVID-19 death was 0.76 (95% CI: 0.64–0.90) in the two-dose analysis and 0.85 (95% CI: 0.67–1.07) in the three-dose analysis. In the first 6 months of follow-up in the two-dose analysis, the aHR was 0.35 (95% CI: 0.27–0.46); however, the combined analysis of all subsequent periods showed an aHR of 1.52 (95% CI: 1.19–1.94). In the first 6 months of follow-up in the three-dose analysis, the aHR was 0.31 (95% CI: 0.20–0.50); however, the combined analysis of all subsequent periods showed an aHR of 1.37 (95% CI: 1.02–1.85). The overall effectiveness of the primary series and third-dose vaccinations against severe, critical, or fatal COVID-19 was 95.9% (95% CI: 94.0–97.1) and 34.1% (95% CI: –46.4–76.7), respectively. Subgroup analyses showed that the healthy vaccinee effect is pronounced among those aged 50 years and older and among those more clinically vulnerable to severe COVID-19. Conclusions: A pronounced healthy vaccinee effect was observed during the first 6 months following vaccination, despite meticulous cohort matching. This effect may have stemmed from a lower likelihood of vaccination among seriously ill, end-of-life individuals, and less mobile elderly populations. Funding: Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, and Junior Faculty Transition to Independence Program, all at Weill Cornell Medicine-Qatar, Qatar University, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and L’Oréal-UNESCO For Women In Science Middle East Regional Young Talents Program.