Annals of Internal Medicine

Background Six years after its emergence, SARS-CoV-2 continues to have a substantial burden. The impact of vaccination and the optimal timing of its rollout remain uncertain given existing population immunity and variability in outbreak timing between summer and winter. Methods The US Scenario Modeling Hub convened its 19th round of ensemble projections for COVID-19 hospitalizations and deaths in the United States, where eight teams projected trajectories in each US state and nationally from April 2025 to April 2026 under five scenarios regarding vaccine recommendations and timing. Recommendations had two eligibility scenarios (high-risk individuals only and all-eligible) and two timing scenarios (classic start: mid-August, earlier start: late June). These were crossed to create four scenarios and were compared against a counterfactual scenario with no vaccination. Findings Compared to no vaccination, our ensemble projections estimated 90,000 (95% PI 53,000-126,000) hospitalizations averted in the high-risk and classic timing scenario across the US. Expanding to all-eligible age-groups averted an additional 26,000 (95% PI 14,000-39,000) hospitalizations, which when coupled with the early vaccination timing, was projected to further reduce national hospitalizations by 15,000 (95% PI -3,000-33,000). The majority of teams projected both summer and winter waves. Implications We project COVID-19 will cause significant hospitalizations and deaths in the US in the 2025-26 season and estimate significant benefits from a broad all-eligible vaccination recommendation. The results also suggest an additional benefit is likely to be gained from an earlier vaccination campaign. Funding Centers for Disease Control and Prevention; National Institute of Health (US), National Science Foundation (US)

BackgroundIn clinical contexts where disease burden differs across demographic groups, enforcing demographic parity -- equal prediction rates regardless of group -- may reduce screening for the populations that need it most. We demonstrate this using HIV testing prediction as a case study. MethodsUsing the Behavioral Risk Factor Surveillance System (BRFSS) 2024 dataset (N=386,775), we trained four classifiers to predict HIV testing uptake and evaluated disparities using demographic parity difference (DPD), equalized odds difference (EOD), and calibration across eight racial/ethnic groups. We applied threshold optimization and exponentiated gradient mitigation and quantified their impact on high-burden populations, including intersectional effects across race and sex. ResultsBaseline selection rates ranged from 12.1% (Asian) to 66.0% (Black), mirroring differential HIV burden (DPD 0.519-0.634). Race-blind models retained 70% of baseline disparity through correlated social determinants. Enforcing demographic parity reduced Black true positive rates from 78.2% to 30.0% (61.6% relative decrease), causing 1,610 additional missed individuals. Race-only optimization worsened sex-based disparity by 71%; multi-objective optimization reduced intersectional DPD from 0.609 to 0.076 but at the same cost to high-burden groups. Exponentiated gradient AUC fell from 0.671 to 0.592 (11.8% relative decrease). Survey-weighted sensitivity analysis confirmed unweighted estimates underestimated disparities. ConclusionsDemographic parity is an inappropriate fairness criterion in differential-burden clinical contexts because it reduces screening access for high-risk populations. Fairness audits in healthcare should use need-appropriate metrics (equalized odds, calibration) rather than defaulting to demographic parity, and metric selection should involve clinician and community stakeholder deliberation.

Tuberculosis screening is not mandatory for prospective tissue donors. In 2021 and 2023, two different bone allograft products caused nationwide tuberculosis outbreaks. We assessed the morbidity and mortality of the second outbreak and reviewed donor and tissue screening to identify deficiencies. Thirty-six people residing in nine states received the product during spinal and dental procedures. Twenty-seven recipients had tuberculosis infection, 11 had microbiologic or imaging evidence of tuberculosis disease, and two died from tuberculosis within 12 months of outbreak detection. Another recipient died from tuberculosis nearly 3 years after product implantation. The bone donor died of pneumonia and septic shock. Polymerase chain reaction testing of the product before and after distribution did not detect Mycobacterium tuberculosis. Mycobacterial culture was not performed until after outbreak detection, when M. tuberculosis was isolated from 2 of 6 unused product units. This outbreak demonstrates persistent gaps in tissue transplant safety. Appropriate selection of donors and mycobacterial culture of donated tissues could reduce but not eliminate the risk of M. tuberculosis transmission. Therefore, it is important that clinicians monitor tissue recipients and promptly report adverse events to tissue establishments and health authorities.

Background: Antibody-mediated rejection (AMR) after heart transplant (HT) is associated with increased risk of mortality and graft loss. Contemporary studies delineating AMR presentation, management, and response to treatment are lacking, especially for patients who do not have typical immunohistological evidence of rejection (biopsy-negative, BN-AMR). In this study, we sought to describe the prevalence and clinical course of BN-AMR compared to biopsy-positive (BP-AMR) patients in a multicenter HT population. Methods: We conducted a retrospective analysis of all adult HT recipients at 2 academic medical centers. AMR was further divided into BP-AMR and BN-AMR, depending on their endomyocardial biopsy findings. The primary outcome was death and secondary outcome was a composite of death, retransplant, and new International Society of Heart and Lung Transplant grade 2 or 3 coronary artery vasculopathy. Results: A total of 742 patients were included in this study. We found that AMR occurred in 10% of HT recipients and was associated with worse overall survival compared to those with only cellular rejection or no rejection. BN-AMR accounted for 33% of AMR cases. Compared to BP-AMR, BN-AMR was diagnosed later, less aggressively treated, and associated with high morbidity and mortality. The long-term outcomes between BP-AMR and BN-AMR were similarly poor, with 5-year mortality approaching 50% after diagnosis. Conclusions: AMR after HT is associated with poor clinical outcomes and BN-AMR is common. Future studies should focus on incorporating novel tools for earlier detection of AMR and investigating AMR sub-phenotypes and optimal modes of treatment.

Background and Aims SARS-CoV-2 infection is associated with an increased risk of cardiovascular, cerebrovascular and venous thromboembolism events. We aimed to assess the impact of COVID-19 vaccination prior to SARS-CoV-2 infection on the risk of these events post-infection. Methods Embase and MEDLINE were searched from January 2021 to 11 September 2025, supplemented by citation searching. Observational studies were included if they reported risks of cardiovascular, cerebrovascular, or venous thromboembolic events after SARS-CoV-2 infection between different vaccination groups (e.g. unvaccinated, vaccinated, or booster vaccinated), or reported risk of events after SARS-CoV-2 infection compared with no infection, stratified by vaccination status. Random-effects meta-analyses were conducted to estimate pooled hazard ratios (HRs) comparing vaccinated and unvaccinated individuals across prespecified outcomes. Results Twenty-three studies were included in the systematic review; most reported an association between vaccination and a reduced risk of post-infection vascular events. Ten studies were included across meta-analyses comparing vaccinated and unvaccinated individuals. Pre-infection vaccination was associated with significantly reduced risks of composite cardiovascular/cerebrovascular events (HR 0.60, 95% confidence intervals [CI] 0.51-0.69), stroke (HR 0.75, 95% CI 0.64-0.88), acute coronary syndrome (HR 0.70, 95% CI 0.52-0.95), arrhythmias (HR 0.82, 95% CI 0.69-0.98), and venous thromboembolism (HR 0.51, 95% CI 0.36-0.73). No statistically significant reduction was observed for heart failure (HR 0.72 [95% CI 0.47-1.10]). Conclusions Pre-infection COVID-19 vaccination is associated with lower risks of cardiovascular, cerebrovascular and venous thromboembolism events following SARS-CoV-2 infection in the pre- and post-Omicron eras, supporting its role within broader prevention strategies

BackgroundWe aimed to identify data-driven FEV1 trajectory phenotypes post-chronic lung allograft dysfunction (CLAD), relate these phenotypes to patient factors and future graft loss, and develop a classification approach for prospective patients. MethodsWe studied adult first lung recipients with probable CLAD from two prospective multicenter cohorts: CTOT-20 (n=206) and LTOG (n=1418). FEV1 trajectories over the first nine months post-CLAD were characterized using joint latent class mixed models, jointly modelling time-to-graft loss to account for informative censoring. Models were fit independently in both cohorts and also only among LTOG bilateral recipients. A classification and regression tree (CART) model was derived in LTOG bilateral recipients and applied to CTOT-20 bilateral recipients. FindingsFour distinct early FEV1 trajectory classes were identified in CTOT-20, with large differences in nine-month graft loss (72{middle dot}3%, 31{middle dot}1%, 2{middle dot}2%, 0%). In LTOG, similar trajectory patterns were reproduced, with an additional class demonstrating early post-CLAD FEV1 improvement. Among bilateral recipients, trajectory classes showed a clear risk gradient, including a high-risk class with 100% graft loss and a low-risk class with no early graft loss. A CART model incorporating clinical and spirometric variables demonstrated good discrimination in LTOG bilateral recipients (multiclass AUC 0{middle dot}85) and consistent class assignment and trajectory patterns when applied to CTOT-20. InterpretationWe identified reproducible, clinically meaningful early post-CLAD FEV1 trajectory phenotypes with differential graft loss risk. These phenotypes and a pragmatic classification tool may support risk stratification, trial enrichment, and improved prognostication for patients and clinicians. FundingNational Institutes of Health, Cystic Fibrosis Foundation

Heart transplantation (HT) is the durable therapy for end-stage heart failure (HF). Despite advances in immunosuppression, cardiac allograft vasculopathy (CAV) remains a leading cause of late graft failure and mortality in the modern era. Prior studies have established donor age and immunological phenomena, such as acute cellular rejection (ACR), antibody-mediated rejection (AMR), and development of donor-specific antibodies (DSAs) as risk factors for CAV. However, it remains unclear whether acute rejection (AR) that occurs early post-HT, when individuals experience the highest degree of immunosuppression, reflects higher baseline immune activity and confers a higher risk of future CAV compared to later AR, when immunosuppression is minimized. We therefore examined whether AR occurring during pre-specified early and intermediate intervals compared to those who did not experience AR in the first post-HT year was associated with future CAV among recipients without CAV at 1 year.

BackgroundComputed tomography (CT) is a cornerstone of timely diagnosis for stroke, trauma, and oncologic conditions, and delays in access are associated with worsened outcomes. Although Houston, Texas, is home to one of the worlds largest medical complexes, the geographic distribution of CT imaging infrastructure has not been systematically examined against neighborhood-level measures of socioeconomic vulnerability. MethodsWe conducted a cross-sectional geospatial analysis of CT imaging facilities across the Greater Houston metropolitan area. Facility locations -- including hospital-based scanners, independent imaging centers, and freestanding emergency facilities -- were compiled from publicly available imaging directories, Texas Department of State Health Services (DSHS) facility listings, Centers for Medicare & Medicaid Services (CMS) provider data, and CT location data contributed by MD Anderson Cancer Center. Census tract-level indicators (median household income, percent uninsured, poverty rate) were obtained from the U.S. Census Bureau American Community Survey. Facility locations were geocoded and overlaid on census-tract choropleths in ArcGIS Online and ArcGIS StoryMaps to identify tracts with elevated socioeconomic vulnerability and limited proximity to CT infrastructure. ResultsCT imaging facilities were markedly clustered in the central urban core and in higher-income corridors, with hospital-based and independent scanners concentrated in census tracts with lower poverty rates, higher median household income (>$119,300), and higher insurance coverage. Conversely, peripheral and southeastern tracts with elevated poverty (>24%), median household income below $37,800, and uninsured rates exceeding 16% contained comparatively sparse CT infrastructure, generating spatial "gaps" in advanced diagnostic capacity. The pattern persisted across facility type: freestanding emergency and independent imaging centers did not meaningfully compensate for the undersupply of hospital-based scanners in vulnerable communities. ConclusionsIn Houston, the spatial distribution of CT imaging resources mirrors rather than offsets underlying socioeconomic inequality. Neighborhoods with higher poverty and uninsured rates face compounded barriers of distance and coverage. Citywide spatial analysis renders these inequities visible in ways individual clinical encounters cannot, and supports equity-informed health-system planning, targeted investment in underserved catchments, and policies linking imaging-capacity expansion to measurable community need.

ObjectiveLeukemic and hematopoietic cell transplant patients have one of the highest incidences of C. difficile infection (CDI). While CDI patients are considered the primary source of transmission, asymptomatic colonized patients (AC) can progress to CDI or contribute to in-unit transmission. We aim to quantify the roles of CDI and AC patients in C. difficile importation and transmission within oncological units. DesignProspective cohort study SettingTwo leukemia and HCT transplant units in a large tertiary care hospital in the US MethodsWe developed a stochastic, individual-based network model to simulate C. difficile acquisition and transmission. Data from cultures and nucleic acid amplification testing (NAAT) obtained at admission and weekly, and toxin enzyme immunoassay (EIA) tests used for CDI diagnosis were used to calibrate the model. Healthcare worker room assignments informed the network structure. Key parameters were estimated via particle filtering. ResultsThe model reproduced observed weekly test counts and transmission pairs. AC patients were the primary source of new colonizations: 51% were due to importation (of those, 88% were admitted as AC), and 49% were due to transmission (AC was the source in 92% of transmissions). Sensitivity analysis showed that these findings were most influenced by the colonization rate and rates of environmental contamination and cleaning. ConclusionsThese findings reinforce the role of AC, particularly via admission importation, in sustaining C. difficile transmission in high-risk hospital settings. Infection control focused on CDI effectively reduced onward transmission, as indicated by CDIs low contribution to new colonizations.

In January 2026, the United States Department of Health and Human Services downgraded the recommendation for infant immunization with rotavirus vaccine to one of shared clinical decision-making. We use a validated model for the transmission dynamics of rotavirus to predict the magnitude and timing of increases in the number of rotavirus hospitalizations in the US and in representative states given possible decreases in vaccine coverage. Rotavirus hospitalizations are likely to increase within two to three years following a drop in vaccine coverage, resulting in over 200,000 hospitalizations between July 2026-June 2031 if coverage were to drop to 20%. The burden is likely to fall disproportionately on southern states that currently experience higher rates of rotavirus hospitalization.

Background: COVID vaccination with periodically updated compositions remains important as SARS-CoV-2 continues to circulate, cause disease, and evolve. Available COVID-19 vaccines in the 2024-2025 season differed by platform, including mRNA-1273, an mRNA-based vaccine, and NVX-CoV2705, a recombinant protein-based vaccine and antigen composition (KP.2-targeted and JN.1-targeted, respectively). There is limited head-to-head real-world evidence comparing the effectiveness of these different approaches to prevention of severe outcomes with COVID-19. We compared mRNA-1273 with protein-based NVX-CoV2705 in insured US adults vaccinated during the 2024-2025 season. Methods: We conducted a retrospective matched cohort study in a large US claims database. Adults aged 18 years or older who received mRNA-1273 or NVX-CoV2705 between Aug 31, 2024 and Feb 28, 2025 were eligible. Recipients were exactly matched 2:1 on key demographic and clinical factors and then weighted with stabilized inverse probability of treatment weights. Outcomes were medically-attended COVID-19 and hospitalization with COVID-19 from day 7 after vaccination through up to 180 days of follow-up. We calculated comparative vaccine effectiveness (cVE) as 100 x (1-- hazard ratio). Results: Of 858,138 eligible mRNA-1273 recipients and 34,667 eligible NVX-CoV2705 recipients, 69,140 and 34,570, respectively, entered the matched cohort. Median (Q1, Q3) follow-up was 180 (163, 180) days for mRNA-1273 and 180 (162,180) for NVX-CoV2705. Medically attended COVID-19 occurred in 706 (1.02%) mRNA-1273 recipients and 512 (1.48%) NVX-CoV2705 recipients; adjusted cVE (95% CI) was 31.7% (23.4%, 39.1%). Hospitalization with COVID-19 occurred in 61 (0.09%) and 49 (0.14%) recipients, respectively; adjusted cVE (95% CI) was 40.7% (13.5%, 59.4%). In the 47,754 mRNA-1273 recipients matched to 23,877 NVX-CoV2705 recipients aged [≥]65, adjusted cVE (95% CI) was 25.7% (15.4%, 34.8%) against medically-attended COVID-19 and 41.7% (14.3%, 60.4%) against hospitalization with COVID-19. Conclusions: In this insured US adult population, mRNA-1273 demonstrated greater effectiveness against medically attended COVID-19 and hospitalization with COVID-19 than the protein-based NVX-CoV2705. These findings highlight the potential public-health importance of considering vaccine platform and variant selection when planning for upcoming seasons.

Background: Long COVID presents with one or multiple symptoms or diagnosable conditions after SARS-CoV-2 infection. To study whether use of the antiviral remdesivir in persons hospitalized with acute COVID-19 is associated with reduced Long COVID, we created a computational phenotype for Long COVID. Methods: In electronic health records (EHR) from a multistate healthcare system (US), hospital admissions from 5/1/20 - 9/30/22 were reviewed. The study group was hospitalized with acute COVID-19 and the control group was hospitalized for other reasons without prior SARS-CoV-2 infection. The populations were balanced with overlap weights based on a high-dimensional propensity score of pre-specified variables and the top 100 comorbidities differing between the groups. Hazard ratios (HR) were calculated for the combined primary outcome: U09.9 (Post-Covid Conditions) or any incident secondary outcome from 90 to 365 days after admission. Secondary outcomes included 27 individual incident diagnoses, corrected for multiplicity with Holm-Bonferroni. Results: Admissions included 45,540 with, and 409,186 without COVID-19 during the study period, evaluable for the primary outcome. After weighting, standardized difference was < 0.01 for all measured confounders including demographic and clinical features. In the COVID+ and non-COVID groups 38.0% and 29.3% met the combined primary outcome, respectively. Weighted HR (95%CI) for the primary outcome was 1.37 (1.35, 1.40), p < 0.0001. All secondary outcomes were associated with the COVID+ group, when adjusted for multiplicity. Incident diagnoses with strong associations (HR > 2) included thromboembolism, hair loss, diabetes mellitus, obesity, and hypoxia. Anosmia/dysgeusia was associated with COVID, but wide confidence intervals reflected few charted diagnoses. Conclusions: Manifestations of Long COVID at population scale are detectable as part of routine symptoms and clinical diagnoses in the EHR after admissions for COVID-19, compared with all other hospital admissions. This a prior computational phenotype for Long COVID will be used to assess whether remdesivir use is associated with decreased Long COVID.

Background: The observational literature on comparative effectiveness is expanding rapidly but remains difficult to synthesize. Discordant findings often stem from structural differences in cohort definitions, inclusion criteria, and follow up windows, leaving stakeholders without a cohesive evidence base. Furthermore, studies typically focus on a narrow subset of outcomes, neglecting the broader needs of diverse healthcare stakeholders 1,2,3,4. Methods We developed a high throughput evidence generation workflow using linked EHR and administrative claims data. The cornerstone is a prespecified measurement architecture applied uniformly across clinical scenarios: six post index windows (acute to two year follow.up); 28 Elixhauser comorbidities; 14 healthcare resource utilization (HCRU) categories; 29 laboratory measures with 52 binary thresholds; and 42 adverse event categories. We generated unadjusted treatment comparisons across ~1,038 outcomes per scenario, including effect-measure modification (EMM) assessments across 130 baseline features. Results Across 40 clinical domains, the workflow produced approximately 32,982,552 outcome evaluations. An evaluation included a treatment comparison outcome population effect estimate with uncertainty bounds and supporting diagnostics. Approximately 5,000 narrative summaries underwent structured clinical and statistical quality control before dissemination. Conclusions Standardized, high throughput workflows can shift evidence generation away from fragmented studies toward comprehensive evidence packages. This shared evidence base supports precision medicine by making treatment effect heterogeneity visible across clinically meaningful subpopulations, reducing the need for redundant, stakeholder-specific studies.

Introduction: COVID-19 transmission has not been evenly distributed across racial groups, with exposure being shaped by social and structural factors. The emergence of highly transmissible variants (i.e., Omicron) dramatically increased infection rates. However, it remains unclear whether racial disparities in transmission disappeared or persisted over the course of the pandemic. Objective: To understand how SARS-CoV-2 transmission differed by race in Canada and whether those disparities changed with the Omicron variant. Methods: We analyzed cross-sectional SARS-CoV-2 seroprevalence data from the Canadian Blood Services serosurveillance program (June 2020 to April 2023) using a previously described dynamic susceptible-infection model, while accounting for seroreversion. Race-specific force of infection was estimated for the pre-Omicron and Omicron periods (with the emergence of Omicron defined as beginning December 26, 2021). Results: Prior to Omicron, racialized individuals had a 74% higher force of infection (IRR = 2.205; 95% CI: 2.115-2.299). During the Omicron period, infection rates rose significantly within each racial group relative to the pre-Omicron period, with a 55.52-fold increase among White individuals and a 31.27-fold increase among racialized individuals. Despite this, racialized individuals remained disproportionately affected following the emergence of Omicron, with 24% higher infection rates than those of their White counterparts (IRR = 1.242; 95% CI: 1.231-1.253). Conclusion: Widespread transmission during Omicron did not result in epidemiologic equity, as racialized populations continued to experience higher infection risk despite crude seroprevalence depicting convergence.

Background. Infectious mononucleosis (IM) with hepatitis is associated with suppression of high-density lipoprotein cholesterol (HDL-C), but the magnitude, specificity, recovery kinetics, and long-term cardiovascular implications of this finding have not been systematically characterised. Methods. Using the TriNetX Global Collaborative Network (<190 million patients, 178 healthcare organisations), we conducted a retrospective real-world evidence study in 1,944 adults with IM and hepatitis. We compared HDL-C distributions at presentation across 14 propensity-score-matched (PSM) comparator cohorts spanning other infectious, metabolic, and immune-mediated conditions. Gaussian mixture modelling characterised the HDL distribution. Longitudinal HDL trajectory was assessed across six post-index time windows, with the number of patients contributing a measurement ranging from 318 (16-30 days) to 2,849 (1-3 years) per window. Long-term major adverse cardiovascular events (MACE) were analysed in PSM cohorts of IM patients with very low HDL ([&le;]20 mg/dL, n = 979 per arm after PSM) versus those without low HDL, over up to 20 years of follow-up, with COVID-19 (n = 83,888 per arm) and pharyngitis (n = 10,618 per arm) as comparators. Results. At presentation, mean HDL in IM hepatitis was 36.7 +/- 22.6 mg/dL (median 33 mg/dL), ~14-17 mg/dL lower compared to pre-illness values. Nearly one quarter (23.9%) had HDL [&le;]20 mg/dL and 43.9% had HDL [&le;]30 mg/dL. HDL suppression was equivalent to CMV hepatitis but substantially greater than pharyngitis and IM without hepatitis, supporting a hepatitis-driven mechanism. Gaussian mixture modelling identified a discrete suppressed subpopulation (mean 16 mg/dL, 41% of patients) absent in non-hepatitis controls. Recovery was rapid in most patients (mean HDL 50.0 mg/dL by 16-30 days) but prolonged among the severely suppressed ([&le;]20 mg/dL), who required 3-6 months to approach baseline. In PSM MACE analyses, IM patients with very low acute HDL had significantly higher long-term event rates for all outcomes (HR 1.92-2.47 versus IM without low HDL), a pattern mirrored in the COVID-19 cohort (HR 2.04-2.70) and, with attenuated effect size, in pharyngitis (HR 1.43-1.69). Conclusions. Very low HDL-C is a prevalent, hepatitis-driven finding in IM affecting approximately one quarter of patients. It identifies a subgroup at elevated long-term cardiovascular risk comparable to that observed after COVID-19. These findings warrant prospective evaluation of cardiovascular follow-up strategies for affected patients.

Background: Each year around 4,500 people in the UK receive an organ transplant. These surgeries can be life changing and life extending for patients but are also associated with significant costs for the health service. However, by reducing the need for other expensive interventions involved in non-transplant care for organ failure, such as dialysis, some of these costs may be recovered. Methods: We assessed the lifetime costs and benefits associated with transplantation focussing on deceased donor adult transplants for kidneys, livers, hearts, and lungs. We incorporated costs of organ retrieval, surgery, post-transplant secondary care, and medications, as well as impacts on quality and duration of life. These were compared to the cost of managing patients with end-stage organ failure for whom no transplant occurs. Results: Kidney transplants were found to be cost saving with lifetime costs approximately 220,000 GBP lower than alternative treatment. Heart transplants and liver transplants were found to be more cost-effective than thresholds used by NICE for new medicines at approximately 17,000 GBP to 18,000 GBP per quality adjusted life year gained. Lung transplants were the least cost-effective organ transplant with a cost per quality adjusted life year gained of over 50,000 GBP. Conclusions: Although transplants can be costly, not providing a transplant to a patient who needs one also brings significant costs. Kidney transplants can save the health system money by reducing the need for dialysis. Increasing the number of kidney's available for transplant could save the NHS money whilst saving and improving lives.

BackgroundTuberculosis (TB) incidence in the United States has remained elevated above pre-pandemic levels since 2021, with over 85% of cases resulting from reactivation of Mycobacterium tuberculosis (Mtb) infection. New vaccines that would prevent TB in adults are under development, but the potential health impact of a program prioritizing non-U.S.-born persons and persons with medical comorbidities, including persons living with HIV (PLWH), has not been evaluated. MethodsWe developed a deterministic compartmental transmission model that simulates Mtb infection, transmission, and progression to TB in the U.S., both in the general population and in key high-risk groups. We calibrated the model to 2024 U.S. TB surveillance data and estimated annual cases prevented, percent reduction in annual TB cases, and number needed to vaccinate (NNV, a measure of vaccine program efficiency) at equilibrium conditions for targeted vaccination strategies under optimistic and plausible scenarios, varying assumptions of vaccine efficacy, duration of protection, and achieved vaccination coverage in high-risk groups. FindingsUnder an optimistic scenario, vaccinating PLWH, non-U.S.-born persons, and persons with medical comorbidities (all high-risk groups) prevented 5,385 cases per year (51{middle dot}8% reduction, NNV = 366). Under a more conservative plausible scenario, the same strategy prevented 1,348 cases per year (13{middle dot}0% reduction, NNV = 510). The efficiency and impact of targeting strategies we considered were preserved across all sensitivity and uncertainty analyses. InterpretationTargeted vaccination of persons with Mtb infection in population subgroups recognized to be at high-risk for TB can reduce incidence substantially. Strategies that include non- U.S.-born persons and PLWH are most efficient and impactful. FundingAmerican Lung Association, U.S. National Institutes of Health, and the Ferguson Fellowship.

AI-assisted clinical care may compound, rather than correct, existing health inequities. We applied Omar and colleagues' validated four-domain emergency-medicine benchmark to OpenEvidence (OE), a literature-grounded clinical LLM used by tens of thousands of US physicians daily, across 100 emergency-department cases and 20 sociodemographic labels. OE was consistent on the codified clinical decisions, triage, workup, and treatment, but diverged sharply on mental-health screening, where it flagged many historically marginalized groups between three and ten times more often than demographically unmarked cases. Cases labeled as unhoused received recommendations in 78 to 87 percent of responses (versus a 9 percent no-identifier-control rate); cases labeled as transgender in 22 to 24 percent; and Black transgender women specifically in 47 percent. A pre- registered audit of 193 free-text rationales localized the differential to the inner layer of the response, in the structure and tone of the rationale rather than the recommendation itself. Literature grounding may redistribute sociodemographic disparity in clinical AI rather than remove it. As clinical LLMs move toward agentic deployment, equity audits should examine how evidence is applied to each patient, not only whether citations are present.

In July 2021, the California Code of Regulations Title 17 required all laboratories performing SARS-CoV-2 whole genome sequencing (WGS) to report their sequencing results to the California Department of Public Health (CDPH). These viral genomic data and patient metadata were compiled into the Integrated Genomic Epidemiology Database (IGED). Linking anonymized viral sequences with patient-level information enabled monitoring of infectiousness, pathogenicity, transmission dynamics, evolution, and vaccine evasion among emerging SARS-CoV-2 lineages. Laboratories performing SARS-CoV-2 WGS transmitted sequencing results to CDPH through Electronic Laboratory Reporting (ELR) and non-ELR pathways. CDPH applied uniform reporting requirements but allowed flexibility in specific data formats to accommodate diverse data systems. To preserve data quality and interoperability across heterogeneous sources, CDPH implemented standardization, validation, and deduplication protocols. Snowflake, a cloud-based data storage and analytics platform, and Posit Connect, a cloud deployment and automation platform, supported the management, processing, and integration of data within the IGED. The IGED established links between SARS-CoV-2 WGS data and epidemiologic metadata for 801,418 sequences, representing 81.7% of all sequences reported in California. Lineages reported to the IGED showed strong concordance with lineage proportions in GISAID. Sequences reported to the IGED had average turnaround times longer than one month, and the majority of sequencing was performed in Southern California and Los Angeles. The IGED enhanced genomic surveillance through predictive modeling and monitoring concerning evolutionary trends such as recombination and saltations in persistent infections. Development of the IGED highlighted the need for standardized data requirements, sustained funding for sequencing, incentives for data submission, and interdisciplinary collaboration to build an effective genomic surveillance system. This framework for linking genomic and epidemiologic data has not only generated critical insights for SARS-CoV-2 but also provided the foundation for CDPH and other public health organizations to develop similar IGED-like systems for other priority pathogens as genomic surveillance expands.

Objectives In Quebec, Canada, vaccination against human papillomavirus (HPV) has been publicly-funded since January 2016 for gay, bisexual, and other men who have sex with men (GBM) aged [&le;]26 years. The study aimed to analyze data collected in Greater Montreal (Engage study) to evaluate the HPV vaccination program for GBM in Quebec. Study Design Engage is a cohort of sexually active GBM aged [&ge;]16 recruited via respondent-driven-sampling (RDS) in Canada. Participants completed a questionnaire and tested for sexually transmitted infections. Methods RDS-II weights were applied to adjust for recruitment. Subgroups were compared using standardized mean differences. Odds ratios of HPV vaccination and prevalence ratios of anal HPV infection adjusted for potential confounders were estimated using robust regression models. Results Of 1179 participants, 309 were eligible for free HPV vaccination. Vaccine coverage among eligible GBM was 42%. Among those who disclosed same-sex sexual activity and discussed HPV vaccination with their healthcare provider, coverage reached 82%. Anal HPV prevalence among eligible GBM was 26.5% for [&ge;]1 HPV-6/11/16/18 genotypes without significant difference between vaccinated and unvaccinated individuals. Among unvaccinated GBM aged [&le;]26 who were aware of the vaccine, 60% intended to get vaccinated within the next year. Conclusions One to two years after GBM aged [&le;]26 were included in the Quebec HPV vaccination program, 42% of eligible GBM in Greater Montreal had been vaccinated. Anal HPV prevalence was high among GBM. Vaccinees were more likely to self-report a prior STI diagnosis. Offering vaccination to all preadolescents in schools appears essential to maximize vaccination benefits.