Vaccine Effectiveness Against Influenza A-Associated Hospitalization, Organ Failure, and Death: United States, 2022-2023.

BACKGROUND: Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain. METHODS: To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative control-patients. RESULTS: A total of 3707 patients, including 714 influenza cases (33% vaccinated) and 2993 influenza- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls (49% vaccinated) were analyzed. VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%-46%) and varied by age (18-64 years: 47% [30%-60%]; ≥65 years: 28% [10%-43%]), and virus (A[H3N2]: 29% [6%-46%], A[H1N1]: 47% [23%-64%]). VE against more severe influenza-associated outcomes included: 41% (29%-50%) against influenza with hypoxemia treated with supplemental oxygen; 65% (56%-72%) against influenza with respiratory, cardiovascular, or renal failure treated with organ support; and 66% (40%-81%) against influenza with respiratory failure treated with invasive mechanical ventilation. CONCLUSIONS: During an early 2022-2023 influenza season with a well-matched influenza vaccine, vaccination was associated with reduced risk of influenza-associated hospitalization and organ failure.

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity-IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

BACKGROUND: Assessing variant-specific COVID-19 vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages. METHODS: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. RESULTS: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. CONCLUSIONS: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB.

Superficial CD34 fibroblastic tumors and PRDM10-rearranged soft tissue neoplasm: An evolving diagnosis.

Superficial CD34 fibroblastic tumors (SCD34FT) and PRDM10-rearranged tumors (PRTs) are mesenchymal tumors that have recently received increased scientific attention due to their irrefutable similarities yet debatable relationship. A 74-year-old male presented to the dermatology clinic with a violaceous, well-defined nodule on the left medial knee of 2-year duration. Shave biopsy demonstrated spindle cells arranged in a vaguely storiform pattern forming fascicles. Immunohistochemical stains were positive for vimentin, CD68, CD10, and CD34 diffusely. ERG, S-100, HMB45, and SOX-10 were negative. Molecular studies identified a mediator complex subunit 12 (MED12)-PR/SET Domain 10 (PRDM10) gene fusion thus favoring confirming the diagnosis of a PRT. Our patient underwent wide local excision with negative margins and had no complications. This case aims to provide context for considering SCD34FT and PRT as intersecting entities and to discuss a diagnostic approach when encountering these tumors.

Toxic epidermal necrolysis-like cutaneous toxicity following chimeric antigen receptor T-cell therapy in recurrent large B-cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable success in treating various B-cell malignancies, redirecting T-cell cytotoxicity toward cancer cells. Despite its efficacy, CAR-T therapy is associated with potential risks, including cytokine release syndrome (CRS) and cytopenia. We present a case of a 69-year-old man with diffuse large B-cell lymphoma treated with axicabtagene-ciloleucel CAR-T therapy, who developed a rare and severe cutaneous toxicity resembling toxic epidermal necrolysis (TEN). The patient exhibited persistent fevers, CRS, and subsequent development of a widespread erythematous macular eruption, progressing to vesiculation with bullae. Notably, allopurinol-induced TEN was considered with the patient's recent exposure to allopurinol, although the onset and minimal mucosal involvement did not align with typical presentations of allopurinol-induced cases. The cutaneous reaction, distinct from typical SJS/TEN, showed minimal mucosal involvement and coincided with the cytokine release storm, differing from allopurinol-induced TEN. Despite the absence of guidelines, the patient was managed with systemic steroids, achieving significant improvement. This case expands the spectrum of CAR-T therapy-related cutaneous toxicities, highlighting the need for early recognition of histopathology and tailored management by dermatologists. Further understanding of these reactions is crucial for optimizing the safety profile of this groundbreaking immunotherapy.

Red crusty plaques in a young man.

Pemphigus foliaceus is a superficial blistering disorder characterized by erosions and scaling in a seborrheic distribution. The condition typically occurs in healthy individuals but issues arise from delayed diagnosis. Many cases remain undiagnosed or misdiagnosed due to the lack of awareness of the condition. With use of common diagnostic tools, pemphigus foliaceus can be easily identified and monitored. Histological analysis exhibits "chicken wire" patterning along keratinocytes in the upper epidermis, whereas immunofluorescence study displays subcorneal acantholysis. Pemphigus foliaceus is confirmed via ELISA studies revealing the presence of autoantibodies against desmoglein 1. Once correctly diagnosed, typically the condition is responsive to corticosteroid therapy. However in recalcitrant cases such as in ours, adjunctive immunosuppressive therapy with dapsone or rituximab may be indicated.

Examining the roles of emotion dysregulation and impulsivity in the relationship between psychological trauma and substance abuse among women with bulimic-spectrum pathology.

Individuals with bulimia nervosa report elevated rates of childhood maltreatment, which appears to increase risk for co-occurring substance use problems and negatively impact clinical course. The current study sought to examine the mechanistic pathways by which specific forms of childhood maltreatment may give rise to substance use problems among individuals with bulimic-spectrum pathology. Women with bulimic-spectrum disorders (N = 204) completed measures of childhood trauma, emotion dysregulation, impulsivity, and substance use. Path analysis was used to examine emotion dysregulation and impulsivity as mediators of the relationship between distinct forms of childhood trauma (physical abuse, physical neglect, emotional abuse, emotional neglect, and sexual abuse) and the presence of problematic alcohol/drug use. In the full path model, significant pathways from childhood emotional abuse to emotion dysregulation, childhood emotional neglect to impulsivity, and emotion dysregulation to problematic substance use emerged. Further, emotion dysregulation significantly mediated the relationship between emotional abuse and substance use. Results indicate that emotion dysregulation may be an important mechanism linking a history of childhood emotional maltreatment to later eating and substance use problems, and therefore may be an important treatment target among individuals with co-occurring eating and substance use concerns.Childhood emotional abuse was related to greater emotion dysregulation.Childhood emotional neglect was related to greater impulsivity.Emotion dysregulation was related to greater problematic substance use.Emotional abuse may impact substance use through emotion dysregulation.Creating emotion dysregulation may improve substance and eating disorder symptoms.

Sclerosing perineurioma: a rare benign tumor in a pediatric patient.

A 15-year-old boy presented to outpatient dermatology clinic for evaluation of a lesion on the hand. Originally small and asymptomatic, the lesion had rapidly enlarged in the six months prior to evaluation. A shave biopsy was performed and histopathologic evaluation demonstrated a well-circumscribed nodular proliferation of dense, bland, epithelioid to spindle cells on a fibrillary background. Tumor cells were diffusely epithelial membrane antigen (EMA) positive; S100 and Melan-A were negative. These findings are consistent with a diagnosis of sclerosing perineurioma. This case illustrates the presentation of sclerosing perineurioma in a pediatric patient and we review the pertinent pathologic and immunohistochemical findings necessary for diagnosis. It is imperative to distinguish this entity from other soft tissue tumors on the hand, both benign and malignant, to avoid overly aggressive surgical intervention.

Dietary phosphate restriction attenuates polycystic kidney disease in mice.

Studies in rodents with reduced nephron mass have suggested a strong positive correlation between dietary phosphate consumption and CKD progression. Prior work by our group demonstrated that dietary phosphate restriction can prevent tubular injury and microcyst formation in rodents with glomerulonephritis. Tubular injury and cystic dilation of tubules are key contributors to kidney function decline in polycystic kidney disease (PKD). Here, we determined whether dietary phosphate restriction slows renal cyst growth and fibrosis in a mouse model of PKD. Pcy/pcy mice received a normal phosphate (0.54%) or a phosphate-restricted (0.02%) diet (n = 10/group) from 7 to 20 wk of age. All of the other major dietary constituents, including protein source and content, were comparable between the two diets. At 20 wk, body weight, kidney weight-to-body weight ratio (KW/BW), cystic area, cyst number, and kidney fibrosis were quantified. Pcy/pcy mice fed a phosphate-restricted diet had lower serum phosphate, fibroblast growth factor 23, and parathyroid hormone levels, along with elevated serum calcium levels and increased kidney Klotho gene expression compared with mice that consumed the control diet. Dietary phosphate restriction resulted in a 25% lower KW/BW ratio and reduced the cyst number, cystic index, and gene expression for the tubular injury markers neutrophil gelatinase-associated lipocalin and interleukin-18. Mice fed the phosphate-restricted diet exhibited lower kidney expression for pathways involved in collagen deposition and myofibroblast activation (collagen type I-α1, phosphorylated SMAD3, and α-smooth muscle actin); however, histological differences in kidney fibrosis were not appreciated. Dietary phosphate restriction slows cystogenesis and inhibits the activation of key pathways in the generation of kidney fibrosis in PKD mice.

Decreased Kidney Function Is Associated with Enhanced Hepatic Flavin Monooxygenase Activity and Increased Circulating Trimethylamine N-Oxide Concentrations in Mice.

Circulating trimethylamine N-oxide (TMAO) predicts poor cardiovascular outcomes in patients with chronic kidney disease (CKD). Accumulation of serum TMAO has been observed in CKD patients; however, the mechanisms contributing to this finding have been inadequately explored. The purpose of this study was to investigate the mechanisms responsible for TMAO accumulation in the setting of decreased kidney function using a CKD mouse model. Mice were fed a diet supplemented with 0.2% adenine to induce CKD, which resulted in increased serum TMAO concentrations (females: CKD 29.4 ± 32.1 µM vs. non-CKD 6.9 ± 6.1 µM, P < 0.05; males: CKD 18.5 ± 13.1 µM vs. non-CKD 1.0 ± 0.5 µM, P < 0.001). As anticipated, accumulation of circulating TMAO was accompanied by a decrease in renal clearance (females: CKD 5.2 ± 3.8 µl/min vs. non-CKD 90.4 ± 78.1 µl/min, P < 0.01; males: CKD 10.4 ± 8.1 µl/min vs. non-CKD 260.4 ± 134.5 µl/min; P < 0.001) and fractional excretion of TMAO. Additionally, CKD animals exhibited an increase in hepatic flavin monooxygenase (FMO)-mediated formation of TMAO (females: CKD 125920 ± 2181 pmol/mg per 60 minutes vs. non-CKD 110299 ± 4196 pmol/mg per 60 minutes, P < 0.001; males: CKD 131286 ± 2776 pmol/mg per 60 minutes vs. non-CKD 74269 ± 1558 pmol/mg per 60 minutes, P < 0.001), which likely resulted from increased FMO3 expression in CKD mice. The current study provides evidence that both decreased renal clearance and increased hepatic production of TMAO may contribute to increments in serum TMAO in the setting of CKD. Hepatic FMO activity may represent a novel therapeutic target for lowering circulating TMAO in CKD patients.

Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden.

Trimethlyamine-N-oxide (TMAO) was recently identified as a promoter of atherosclerosis. Patients with CKD exhibit accelerated development of atherosclerosis; however, no studies have explored the relationship between TMAO and atherosclerosis formation in this group. This study measured serum concentrations and urinary excretion of TMAO in a CKD cohort (n=104), identified the effect of renal transplant on serum TMAO concentration in a subset of these patients (n=6), and explored the cross-sectional relationship between serum TMAO and coronary atherosclerosis burden in a separate CKD cohort (n=220) undergoing coronary angiography. Additional exploratory analyses examined the relationship between baseline serum TMAO and long-term survival after coronary angiography. Serum TMAO concentrations demonstrated a strong inverse association with eGFR (r(2)=0.31, P<0.001). TMAO concentrations were markedly higher in patients receiving dialysis (median [interquartile range], 94.4 µM [54.8-133.0 µM] for dialysis-dependent patients versus 3.3 µM [3.1-6.0 µM] for healthy controls; P<0.001); whereas renal transplantation resulted in substantial reductions in TMAO concentrations (median [min-max] 71.2 µM [29.2-189.7 µM] pretransplant versus 11.4 µM [8.9-20.2 µM] post-transplant; P=0.03). TMAO concentration was an independent predictor for coronary atherosclerosis burden (P=0.02) and predicted long-term mortality independent of traditional cardiac risk factors (hazard ratio, 1.26 per 10 µM increment in TMAO concentration; 95% confidence interval, 1.13 to 1.40; P<0.001). In conclusion, serum TMAO concentrations substantially increase with decrements in kidney function, and this effect is reversed by renal transplantation. Increased TMAO concentrations correlate with coronary atherosclerosis burden and may associate with long-term mortality in patients with CKD undergoing coronary angiography.

Retail Food Store Access in Rural Appalachia: A Mixed Methods Study.

OBJECTIVE: To describe how characteristics of food retail stores (potential access) and other factors influence self-reported food shopping behavior (realized food access) among low-income, rural Central Appalachian women. DESIGN AND SAMPLE: Cross-sectional descriptive. Potential access was assessed through store mapping and in-store food audits. Factors influencing consumers' realized access were assessed through in-depth interviews. Results were merged using a convergent parallel mixed methods approach. Food stores (n = 50) and adult women (n = 9) in a rural Central Appalachian county. RESULTS: Potential and realized food access were described across five dimensions: availability, accessibility, affordability, acceptability, and accommodation. Supermarkets had better availability of healthful foods, followed by grocery stores, dollar stores, and convenience stores. On average, participants lived within 10 miles of 3.9 supermarkets or grocery stores, and traveled 7.5 miles for major food shopping. Participants generally shopped at the closest store that met their expectations for food availability, price, service, and atmosphere. Participants' perceptions of stores diverged from each other and from in-store audit findings. CONCLUSIONS: Findings from this study can help public health nurses engage with communities to make affordable, healthy foods more accessible. Recommendations are made for educating low-income consumers and partnering with food stores.

Still Separate, Still Unequal: Social Determinants of Playground Safety and Proximity Disparities in St. Louis.

Physical activity among youth is shaped by the natural and built environment within which they live; however, few studies have focused on assessing playground safety and proximity in detail as part of the built environment for youth physical activity. We analyzed data on 100 publicly accessible playgrounds from Play Across St. Louis, a community-partnered study of the built environment for youth physical activity. Outcomes included overall playground safety, maintenance, and construction scores; distance to nearest playground; and distance to nearest top playground. Independent variables included neighborhood % youth, % black residents, % owner-occupied units, and % vacant units. Playgrounds in the city have varying degrees of safety and proximity. Mean overall playground safety score was 67.0 % (CI = 63.5, 70.4). Neighborhood % youth and % black residents were inversely associated with overall playground safety (p = 0.03 and p < 0.01) and maintenance (p < 0.01 and p < 0.0001). Mean distance to nearest playground was 638.1 and 1488.3 m to nearest top playground. Clusters of low safety scores were found in the northern and central areas while all high safety score clusters were found in the southern part of St. Louis. Public playground safety and proximity vary across St. Louis neighborhoods, especially by neighborhood demographics. Disparities in playground safety and proximity reveal an opportunity to develop community-wide interventions focused on playgrounds for youth activity. Further work is needed to examine the association between playground safety, proximity, and use and youth physical activity and weight.

Racial and Ethnic Heterogeneity in Self-Reported Diabetes Prevalence Trends Across Hispanic Subgroups, National Health Interview Survey, 1997-2012.

INTRODUCTION: We examined racial/ethnic heterogeneity in self-reported diabetes prevalence over 15 years. METHODS: We used National Health Interview Survey data for 1997 through 2012 on 452,845 adults aged 18 years or older. Annual self-reported diabetes prevalence was estimated by race/ethnicity and education. We tested for trends over time by education and race/ethnicity. We also analyzed racial/ethnic and education trends in average annual prevalence. RESULTS: During the 15 years studied, diabetes prevalence differed significantly by race/ethnicity (P < .001) and by Hispanic subgroup (P < .001). Among participants with less than a high school education, the 5-year trend in diabetes prevalence was highest among Cubans and Cuban Americans (ß(5YR) = 4.8, P = .002), Puerto Ricans (ß(5YR) = 2.2, P = .06), non-Hispanic blacks (ß(5YR) = 2.2, P < .001), and non-Hispanic whites (ß(5YR) = 2.1, P < .001). Among participants with more than a high school education, non-Hispanic blacks had the highest average annual prevalence (5.5%) and Puerto Ricans had the highest 5-year trend in annual diabetes prevalence (ß(5YR) = 2.6, P = .001). CONCLUSIONS: In this representative sample of US adults, results show ethnic variations in diabetes prevalence. The prevalence of diabetes is higher among Hispanics than among non-Hispanic whites, unevenly distributed across Hispanic subgroups, and more pronounced over time and by education. Findings support disaggregation of data for racial/ethnic populations in the United States to monitor trends in diabetes disparities and the use of targeted, culturally appropriate interventions to prevent diabetes.

Food Insecurity Associated with Higher Stress, Depressive Symptoms, and Lower Diet Quality among Women Caregivers in North Carolina.

BACKGROUND: Research suggests a bidirectional relationship between food insecurity and stress, but few studies have examined associations of food insecurity with stress and other indicators of cardiometabolic health, including depression, diet quality, and body weight, among lower-income women in the U.S. METHODS: This cross-sectional study analyzed data from lower-income women caregivers living in North Carolina (n = 100): 42% Black/African American, 25% Hispanic/Latina, and 33% White women. Multivariable linear regression models were used to determine associations of food insecurity status with perceived stress, depressive symptoms, diet quality, and body mass index (BMI). Multivariable logistic regression models were used to determine associations of food insecurity with clinical depression and BMI ≥ 30 kg/m2. Associations were examined with and without adjustment for perceived stress. RESULTS: Forty-two percent of the sample were experiencing food insecurity. Compared to food secure caregivers, food-insecure caregivers had significantly higher perceived stress (ß: +7.51; 95%CI: 4.19, 10.84) and depressive symptoms (ß: +3.55; 95%CI: 0.54, 6.56) and lower diet quality (ß: -9.10; 95%CI: -15.81, -2.40). Associations with BMI outcomes were not statistically significant. CONCLUSION: Findings support removing stigma in nutrition assistance programs and clinical interactions, motivate future longitudinal studies, and inform the development of destigmatizing interventions for health promotion or disease prevention.

An Evaluation of ¡Haz Espacio Para Papi!, a Culturally Tailored Nutrition and Physical Activity Pilot Program for Mexican-Heritage Fathers.

Fathers are potential leaders of healthy behavior changes in their families. Culturally tailored programs are needed to support behavior changes within families, including Latino families; however, there have been few father-focused nutrition programs for Latino families. This study evaluated the immediate effects of ¡Haz Espacio Para Papi! (Make Room for Daddy!; HEPP), a six-week, father-focused, family-centered program focused on nutrition and physical activity near the Texas-Mexico border. A modified stepped-wedge study design included a treatment group for the HEPP pilot and a wait-listed control group. Pre/post-tests included instant skin carotenoid scores, the self-reported dietary intake of fruits and vegetables (FV), and healthy dietary behavior scores (HDBSs). A 2 × 2 mixed analysis of variance evaluated changes in outcomes across time and between groups for 42 fathers with pre/post-test measures. There were no statistically significant changes in fathers' VM scores and FV intake across time or between groups. Fathers' HDBSs increased across time (p ≤ 0.01, 95% CI [0.23, 1.38]). Age, educational attainment, and the number of children living in the household did not have a significant effect on the program outcomes (p > 0.05). The HEPP program may guide the design of future father-focused nutrition interventions aimed at dietary behavior changes.

Association of Hyperoxia During Cardiopulmonary Bypass and Postoperative Delirium in the Pediatric Cardiac ICU.

OBJECTIVE: ICU delirium commonly complicates critical illness associated with factors such as cardiopulmonary bypass (CPB) time and the requirement of mechanical ventilation (MV). Recent reports associate hyperoxia with poorer outcomes in critically ill children. This study sought to determine whether hyperoxia on CPB in pediatric patients was associated with a higher prevalence of postoperative delirium. DESIGN: Secondary analysis of data obtained from a prospective cohort study. SETTING: Twenty-two-bed pediatric cardiac ICU in a tertiary children's hospital. PATIENTS: All patients (18 yr old or older) admitted post-CPB, with documented delirium assessment scores using the Preschool/Pediatric Confusion Assessment Method for the ICU and who were enrolled in the Precision Medicine in Pediatric Cardiology Cohort from February 2021 to November 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 148 patients, who underwent cardiac surgery, 35 had delirium within the first 72 hours (24%). There was no association between hyperoxia on CPB and postoperative delirium for all definitions of hyperoxia, including hyperoxic area under the curve above 5 predetermined Pao2 levels: 150 mm Hg (odds ratio [95% CI]: 1.176 [0.605-2.286], p = 0.633); 175 mm Hg (OR 1.177 [95% CI, 0.668-2.075], p = 0.572); 200 mm Hg (OR 1.235 [95% CI, 0.752-2.026], p = 0.405); 250 mm Hg (OR 1.204 [95% CI, 0.859-1.688], p = 0.281), 300 mm Hg (OR 1.178 [95% CI, 0.918-1.511], p = 0.199). In an additional exploratory analysis, comparing patients with delirium within 72 hours versus those without, only the z score for weight differed (mean [sd]: 0.09 [1.41] vs. -0.48 [1.82], p < 0.05). When comparing patients who developed delirium at any point during their ICU stay (n = 45, 30%), MV days, severity of illness (Pediatric Index of Mortality 3 Score) score, CPB time, and z score for weight were associated with delirium (p < 0.05). CONCLUSIONS: Postoperative delirium (72 hr from CPB) occurred in 24% of pediatric patients. Hyperoxia, defined in multiple ways, was not associated with delirium. On exploratory analysis, nutritional status (z score for weight) may be a significant factor in delirium risk. Further delineation of risk factors for postoperative delirium versus ICU delirium warrants additional study.

SARS-CoV-2 shedding and evolution in patients who were immunocompromised during the omicron period: a multicentre, prospective analysis.

BACKGROUND: Prolonged SARS-CoV-2 infections in people who are immunocompromised might predict or source the emergence of highly mutated variants. The types of immunosuppression placing patients at highest risk for prolonged infection have not been systematically investigated. We aimed to assess risk factors for prolonged SARS-CoV-2 infection and associated intrahost evolution. METHODS: In this multicentre, prospective analysis, participants were enrolled at five US medical centres. Eligible patients were aged 18 years or older, were SARS-CoV-2-positive in the previous 14 days, and had a moderately or severely immunocompromising condition or treatment. Nasal specimens were tested by real-time RT-PCR every 2-4 weeks until negative in consecutive specimens. Positive specimens underwent viral culture and whole genome sequencing. A Cox proportional hazards model was used to assess factors associated with duration of infection. FINDINGS: From April 11, 2022, to Oct 1, 2022, 156 patients began the enrolment process, of whom 150 were enrolled and included in the analyses. Participants had B-cell malignancy or anti-B-cell therapy (n=18), solid organ transplantation or haematopoietic stem-cell transplantation (HSCT; n=59), AIDS (n=5), non-B-cell malignancy (n=23), and autoimmune or autoinflammatory conditions (n=45). 38 (25%) participants were real-time RT-PCR-positive and 12 (8%) were culture-positive 21 days or longer after initial SARS-CoV-2 detection or illness onset. Compared with the group with autoimmune or autoinflammatory conditions, patients with B-cell dysfunction (adjusted hazard ratio 0·32 [95% CI 0·15-0·64]), solid organ transplantation or HSCT (0·60 [0·38-0·94]), and AIDS (0·28 [0·08-1·00]) had longer duration of infection, defined as time to last positive real-time RT-PCR test. There was no significant difference in the non-B-cell malignancy group (0·58 [0·31-1·09]). Consensus de novo spike mutations were identified in five individuals who were real-time RT-PCR-positive longer than 56 days; 14 (61%) of 23 were in the receptor-binding domain. Mutations shared by multiple individuals were rare (<5%) in global circulation. INTERPRETATION: In this cohort, prolonged replication-competent omicron SARS-CoV-2 infections were uncommon. Within-host evolutionary rates were similar across patients, but individuals with infections lasting longer than 56 days accumulated spike mutations, which were distinct from those seen globally. Populations at high risk should be targeted for repeated testing and treatment and monitored for the emergence of antiviral resistance. FUNDING: US Centers for Disease Control and Prevention.