Evaluation of a novel university-based testing platform to increase access to SARS-CoV-2 testing during the COVID-19 pandemic in a cohort study.

OBJECTIVE: We aimed to evaluate the feasibility and utility of an unsupervised testing mechanism, in which participants pick up a swab kit, self-test (unsupervised) and return the kit to an on-campus drop box, as compared with supervised self-testing at staffed locations. DESIGN: University SARS-CoV-2 testing cohort. SETTING: Husky Coronavirus Testing provided voluntary SARS-CoV-2 testing at a university in Seattle, USA. OUTCOME MEASURES: We computed descriptive statistics to describe the characteristics of the study sample. Adjusted logistic regression implemented via generalised estimating equations was used to estimate the odds of a self-swab being conducted through unsupervised versus supervised testing mechanisms by participant characteristics, including year of study enrolment, pre-Omicron versus post-Omicron time period, age, sex, race, ethnicity, affiliation and symptom status. RESULTS: From September 2021 to July 2022, we received 92 499 supervised and 26 800 unsupervised self-swabs. Among swabs received by the laboratory, the overall error rate for supervised versus unsupervised swabs was 0.3% vs 4%, although this declined to 2% for unsupervised swabs by the spring of the academic year. Results were returned for 92 407 supervised (5% positive) and 25 836 unsupervised (4%) swabs from 26 359 participants. The majority were students (79%), 61% were female and most identified as white (49%) or Asian (34%). The use of unsupervised testing increased during the Omicron wave when testing demand was high and stayed constant in spring 2022 even when testing demand fell. We estimated the odds of using unsupervised versus supervised testing to be significantly greater among those <25 years of age (p<0.001), for Hispanic versus non-Hispanic individuals (OR 1.2, 95% CI 1.0 to 1.3, p=0.01) and lower among individuals symptomatic versus asymptomatic or presymptomatic (0.9, 95% CI 0.8 to 0.9, p<0.001). CONCLUSIONS: Unsupervised swab collection permitted increased testing when demand was high, allowed for access to a broader proportion of the university community and was not associated with a substantial increase in testing errors.

A comparative framework for understanding and addressing interpersonal gun violence.

Gun violence, often characterized as a singular issue, is not one cohesive problem. Instead, it takes many forms resulting from the complex interplay of multiple factors. Outcomes of gun violence also vary significantly. They may be (a) physically non-injurious (a gun is brandished), (b) injurious but non-lethal, or (c) lethal. To understand and address gun violence effectively, it is essential to consider various risk factors for both non-lethal and lethal gun violence victimization, using a comprehensive, comparative framework. We present a novel comparative framework for better understanding gun violence, and for developing policy responses to this violence. We disaggregate gun violence into its various forms and propose a conceptualization of risk factors in discrete categories, each with important implications for policy intervention. While we emphasize the value of this framework for understanding and combatting interpersonal gun violence in America, the research and policy approaches discussed here should be equally applicable to other international contexts with gun violence as a serious public health issue as well.

Causes and outcomes of non-chemotherapy induced neutropenic fever in hospitalized adults: An observational study.

Neutropenic fever in adults undergoing chemotherapy for cancer treatment is a medical emergency and has been the focus of numerous studies. However, there is a paucity of data about non-chemotherapy induced neutropenic fever (non-CINF). We retrospectively reviewed 383 adults with neutropenic fever hospitalized at one academic medical center between October 2015 and September 2020 to characterize the frequency, causes, and outcomes of non-CINF. Twenty-six percent of cases of neutropenic fever were non-chemotherapy induced. Among these, the major causes of neutropenia were hematologic malignancy, infection, and rheumatologic disease, and the major causes of fever were infections. Patients with non-CINF had a higher 30-day mortality than those with chemotherapy induced neutropenic fever (25% vs 13%, P = .01). Non-CINF constituted > 25% of neutropenic fever events in hospitalized adults and was associated with a high mortality rate.

Metal-assisted chemical etching beyond Si: applications to III-V compounds and wide-bandgap semiconductors.

Metal-assisted chemical etching (MacEtch) has emerged as a versatile technique for fabricating a variety of semiconductor nanostructures. Since early investigations in 2000, research in this field has provided a deeper understanding of the underlying mechanisms of catalytic etching processes and enabled high control over etching conditions for diverse applications. In this Review, we present an overview of recent developments in the application of MacEtch to nanomanufacturing and processing of III-V based semiconductor materials and other materials beyond Si. We highlight the key findings and developments in MacEtch as applied to GaAs, GaN, InP, GaP, InGaAs, AlGaAs, InGaN, InGaP, SiC, ß-Ga2O3, and Ge material systems. We further review a series of active and passive devices enabled by MacEtch, including light-emitting diodes (LEDs), field-effect transistors (FETs), optical gratings, sensors, capacitors, photodiodes, and solar cells. By reviewing demonstrated control of morphology, optimization of etch conditions, and catalyst-material combinations, we aim to distill the current understanding of beyond-Si MacEtch mechanisms and to provide a bank of reference recipes to stimulate progress in the field.

Pathologic Outcomes of Short-Course and Long-Course Radiotherapy for Locally Advanced Rectal Cancers Treated With Total Neoadjuvant Therapy.

INTRODUCTION: Total neoadjuvant therapy (TNT) for patients with locally advanced rectal cancer (LARC) is now the standard of care. Randomized trials suggest the use of short-course radiotherapy (SCRT) and long-course radiotherapy (LCRT) are oncologically equivalent. OBJECTIVE: To describe pathologic outcomes after surgical resections of patients receiving SCRT versus LCRT as part of TNT for LARC. PARTICIPANTS: All patients with LARC treated at a single tertiary hospital who underwent proctectomy after completing TNT were included. Patients were excluded if adequate details of TNT were not available in the electronic medical record. RESULTS: A total of 53 patients with LARC were included. Thirty-nine patients (73.5%) received LCRT and 14 (26.4%) received SCRT. Forty-nine patients (92.5%) were clinical stage III (cN1-2) prior to treatment. The average lymph node yield after proctectomy was 20.9 for SCRT and 17.0 for LCRT (P = .075). Of the 49 patients with clinically positive nodes before treatment, 76.9% of those who received SCRT and 72.2% of those who received LCRT achieved pN0 disease after TNT. Additionally, there were no significant differences in rates of pathologic complete response between patients who received SCRT and LCRT, 7.1% and 12.8%, respectively (P = .565). CONCLUSION: Pathologic outcomes of patients with LARC treated with SCRT or LCRT, as part of TNT, may be similar. Further prospective trials are needed to assess long-term clinical outcomes and to determine best treatment protocols.

Chasing and surfing seasonal waves: Avian migration through the US tracks land surface phenology in fall, but not spring.

Climate change is altering the timing of seasonal events for many taxa. There is limited understanding of how northward/southward songbird migration follows or is limited by the latitudinal progression of seasonal transitions. Consistent environmental conditions that migrating birds encounter across latitudes likely represent or correlate with important resources or limiting factors for migration. We tested whether migratory passage-observed via radar-consistently tracked land surface variables and phenophases across latitudes in the US Central Flyway in both spring and fall. The daily temperatures, precipitation and vegetation greenness occurring on 10%, 50% and 90% cumulative passage dates changed substantially with latitude, indicating that most migrants experienced rapidly changing conditions as they headed north or south. Temperature did not limit the progression of migration in either season. Peak spring migration in the southern US occurred nearly 40 days after the spring green wave, the northward progression of vegetation growth, but nearly caught up to green-up at 48° N. Spring migration phenology may have evolved to prioritize earlier arrival for breeding. Across all latitudes, peak fall migration coincided with the same land surface phenophase, an interval of 26 days prior to dormancy onset. Migrants may rely on phenological events in vegetation during fall stopovers. Considering that (a) migratory passage tracked fall land surface phenology across latitudes at a continental scale, (b) previous studies at local scales have demonstrated the importance of fruit during fall migratory stopover and (c) fruiting phenology in North America is occurring later over time while fall migration is advancing, the potential for mismatch between fall fruiting and bird migration phenology urgently needs further investigation.

Psychological effects of anti-Arab politics on American and Arab peoples' views of each other.

Disparaging rhetoric about Arab people was prevalent during Donald Trump's political rise in the United States. Although this rhetoric was intended to energize conservative Americans, it also echoed throughout many liberal parts of the United States and around the world. In this research, we experimentally examined the effects of such rhetoric on American and Arab people's attitudes and visual representations of each other before and after Trump was elected. Although people overwhelmingly reported not liking the negative rhetoric, the rhetoric alone did not influence explicit and implicit intergroup biases in either location, as measured by feeling thermometers and Implicit Association Tests. However, the election outcome moderated the way rhetoric influenced how American and Arab people visually represented each other. Our research sheds light on nuanced effects of global politics on various information processing stages within intergroup perception.

Management of Anticoagulation and Antifibrinolytics in Catastrophic Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disorder that presents with hypercoagulability and results in a lab artifact of prolonged PTT. The most severe form is catastrophic antiphospholipid antibody syndrome (CAPS), which manifests as rapidly progressing thromboses in multiple organ systems leading to multi-organ ischemia. The mainstay management CAPS is anticoagulation and systemic corticosteroids. Antifibrinolytic agents have previously been thought to be relatively contraindicated in CAPS due to the pro-thrombotic nature of the disease; the complex coagulation profile of CAPS can make it difficult to assess the risks and benefits of antifibrinolytic therapy. Also, should a patient with CAPS require cardiopulmonary bypass (CPB) for surgery, it poses a unique challenge in providing appropriate anticoagulation in the setting of prolonged ACT. We present a case of a 32-year-old postpartum female with CAPS requiring heart transplant who safely received intraoperative antifibrinolytic therapy and was successfully anticoagulated during CPB after perioperative plasmapheresis.

Rectal Cancer Survival for Residual Carcinoma In Situ Versus Pathologic Complete Response After Neoadjuvant Therapy.

BACKGROUND: Pathologic complete response after neoadjuvant chemoradiotherapy for rectal cancer is associated with improved survival. It is unclear whether residual carcinoma in situ portends a similar outcome. OBJECTIVE: To compare the survival of patients with locally advanced rectal cancer who received neoadjuvant therapy and achieved pathologic carcinoma in situ versus pathologic complete response. DESIGN: Retrospective cohort study. SETTING: National public database. PATIENTS: A total of 4594 patients in the National Cancer Database from 2006 to 2016 with locally advanced rectal cancer who received neoadjuvant therapy, underwent surgery, and had node-negative ypTis or ypT0 on final pathology were included. Of these, 4321 patients (94.1%) had ypT0 and 273 (5.9%) had ypTis on final pathology. MAIN OUTCOME MEASURE: Overall survival. RESULTS: The median age was 60 years, and 1822 patients (39.7%) were women. On initial staging, 54.5% (n = 2503) had stage II disease and 45.5% (n = 2091) had stage III disease. The ypTis group had decreased overall survival compared to the ypT0 group (HR 1.42; 95% CI, 1.04-1.95; p = 0.028). Other factors associated with decreased overall survival were older age at diagnosis, increasing Charlson-Deyo score, and poorly differentiated tumor grade. Variables associated with improved survival were female sex, private insurance, and receipt of both neoadjuvant and adjuvant chemotherapy. For the total cohort, there was no difference in survival between clinical stage II and stage III. LIMITATIONS: Standard therapy versus total neoadjuvant therapy could not be abstracted. Overall survival was defined as the time from surgery to death from any cause or last contact, allowing for some erroneously misclassified deaths. CONCLUSIONS: ypTis is associated with worse overall survival than ypT0 for patients with locally advanced rectal cancer who receive neoadjuvant chemoradiotherapy followed by surgery. For this cohort, clinical stage was not a significant predictor of survival. Prospective trials comparing survival for these pathologic outcomes are needed. See Video Abstract . SUPERVIVENCIA DEL CNCER DE RECTO PARA EL CARCINOMA RESIDUAL IN SITU VS RESPUESTA PATOLGICA COMPLETA DESPUS DE LA TERAPIA NEOADYUVANTE: ANTECEDENTESLa respuesta patológica completa después de la quimiorradioterapia neoadyuvante para el cáncer de recto se asocia con una mayor supervivencia. No está claro si el carcinoma residual in situ presagia un resultado similar.OBJETIVOComparar la supervivencia de pacientes con cáncer de recto localmente avanzado que recibieron terapia neoadyuvante y lograron un carcinoma patológico in situ versus una respuesta patológica completa.DISEÑOEstudio de cohorte retrospectivo.ESCENARIOBase de datos pública nacional.PACIENTESSe incluyeron 4,594 pacientes de la Base de Datos Nacional de Cáncer de 2006 a 2016 con cáncer de recto localmente avanzado que recibieron terapia neoadyuvante, fueron sometidos a cirugía y tuvieron ganglios negativos, ypTis o ypT0 en el reporte patológico final. 4.321 (94,1%) tuvieron ypT0 y 273 (5,9%) tuvieron ypTis en el reporte final.PRINCIPALES MEDIDAS DE RESULTADOSupervivencia general.RESULTADOSLa mediana de edad fue de 60 años. 1.822 pacientes (39,7%) fueron mujeres. El 54,5% (n = 2.503) tuvo la enfermedad en estadio II y el 45,5% (n = 2.091) tuvo la enfermedad en estadio III según la estadificación inicial. El grupo ypTis tuvo una supervivencia general reducida en comparación con el grupo ypT0 (HR 1,42, IC 95 % 1,04-1,95, p = 0,028). Otros factores asociados con una menor supervivencia general fueron una edad más avanzada al momento del diagnóstico, un aumento de la puntuación de Charlson-Deyo y un grado tumoral poco diferenciado. Las variables asociadas con una mejor supervivencia fueron el sexo femenino, el seguro privado y la recepción de quimioterapia neoadyuvante y adyuvante. Para la cohorte total, no hubo diferencias en la supervivencia entre el estadio clínico 2 y el estadio 3.LIMITACIONESNo se pudo resumir el tratamiento estándar versus el tratamiento neoadyuvante total. La supervivencia general se definió como el tiempo transcurrido desde la cirugía hasta la muerte por cualquier causa o último contacto, lo que permite algunas muertes erróneamente clasificadas.CONCLUSIONESypTis se asocia con una peor supervivencia general que ypT0 en pacientes con cáncer de recto localmente avanzado que reciben quimiorradioterapia neoadyuvante seguida de cirugía. Para esta cohorte, el estadio clínico no fue un predictor significativo de supervivencia. Se necesitan ensayos prospectivos que comparen la supervivencia de estos resultados patológicos. ( Traducción-Dr Osvaldo Gauto ).

Physiological Factors Associated with Unsatisfied Inspiration at Peak Exercise in Healthy Adults.

INTRODUCTION: Contrary to common belief, a growing body of evidence suggests that unsatisfied inspiration (UI), an inherently uncomfortable quality of dyspnea, is experienced by ostensibly healthy adults during high-intensity exercise. Based on our understanding of the mechanisms of UI among people with chronic respiratory conditions, this analysis tested the hypothesis that the experience of UI at peak exercise in young, healthy adults reflects the combination of high ventilatory demand and critical inspiratory constraints. METHODS: In a retrospective analysis design, data included 321 healthy individuals (129 females) aged 25 ± 5 yrs. Data were collected during one visit to the laboratory, which included anthropometrics, spirometry, and an incremental cardiopulmonary cycling test to exhaustion. Metabolic and cardiorespiratory variables were measured at peak exercise, and qualitative descriptors of dyspnea at peak exercise were assessed using a list of 15 descriptor phrases. RESULTS: 34% of participants (n = 109) reported sensations of UI at peak exercise. Compared to the Non-UI group, the UI group achieved a significantly higher peak work rate (243 ± 77 vs. 235 ± 69 W, P = 0.016, d = 0.10), rate of O2 consumption (3.32 ± 1.02 vs. 3.27 ± 0.96 L·min-1, P = 0.018, d = 0.05), minute ventilation (120 ± 38 vs. 116 ± 35 L·min-1, P = 0.047, d = 0.11), and breathing frequency (50 ± 9 vs. 47 ± 9 breaths·min-1, P = 0.014, d = 0.33), while having a lower exercise-induced change (peak-baseline) in inspiratory capacity (0.07 ± 0.41 vs. 0.20 ± 0.49 L, P = 0.023, d = 0.29). The inspiratory reserve volume to minute ventilation ratio at peak exercise was also lower in the UI vs. Non-UI group. Dyspnea intensity and unpleasantness ratings were significantly higher in the UI vs. Non-UI group at peak exercise (both P < 0.001). CONCLUSIONS: Healthy individuals reporting UI at peak exercise have relatively greater inspiratory constraints compared to those who do not select UI.

From alkaline earth to coinage metal carboranyls.

The ß-diketiminato calcium and magnesium complexes, [(BDI)MgnBu] and [(BDI)CaH]2 (BDI = HC{C(Me)NDipp}2; Dipp = 2,6-di-isopropylphenyl), react with ortho-carborane (o-C2B10H12) to provide the respective [(BDI)Ae(o-C2B10H11)] (Ae = Mg or Ca) complexes. While the lighter group 2 species is a monomer with magnesium in a distorted trigonal planar environment, the heavier analogue displays a puckered geometry at calcium in the solid state due to Ca⋯H-B intermolecular interactions. These secondary contacts are, however, readily disrupted upon addition of THF to provide the 4-coordinate monomer, [(BDI)Ca(THF)(o-C2B10H11)]. [(BDI)Mg(o-C2B10H11)] was reacted with [NHCIPrMCl] (NHCIPr = 1,3-bis(isopropyl)imidazol-2-ylidene; M = Cu, Ag, Au) to provide [NHCIPrM(o-C2B10H11)], rare C-bonded examples of coinage metal derivatives of unsubstituted (o-C2B10H11)- and confirming the alkaline earth compounds as viable reagents for the transmetalation of the carboranyl anion.

The Overlooked Association Between Nutrition and the Development of Acute Myeloid Leukaemia: A Scoping Review.

PURPOSE OF REVIEW: Acute Myeloid Leukaemia (AML) constitutes a mere 1% of global cancer cases. This scoping review aims to investigate the association between nutrition and the development of AML, providing a foundation for future research in this field. RECENT FINDINGS: A systematic search was conducted across PubMed, EBSCO, Taylor and Francis, Science Direct and Cochrane Library using specific keywords. Inclusion criteria comprised observational studies and clinical trials examining the association between nutrition and the development of AML. Articles selected for analysis were restricted to those published in English between 1990-2023, and available as full text articles. Among the twenty-five articles that were screened, only six met the criteria for data extraction. Four studies did not reveal statistically significant correlations between nutrition and the development of AML, while two studies provided evidence for significant associations. The findings indicated increased AML risk associated with (a) heightened caloric intake, consumption of white potatoes, and red meat (pork and beef) and (b) diminished consumption of vegetables, seafood, nuts, and seeds. The scarcity of comprehensive studies exploring the connection between nutrition and AML, highlights the urgent need for additional research, encompassing pre-clinical studies. This imperative is critical for enhancing our understanding of the molecular mechanisms that underlie the connection between diet and the aetiology of AML. Such knowledge is paramount in advancing effective strategies for both prevention and management of this significant disease.

High-titer manufacturing of SARS-CoV-2 Spike-pseudotyped VSV in stirred-tank bioreactors.

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic highlighted the importance of vaccine innovation in public health. Hundreds of vaccines built on numerous technology platforms have been rapidly developed against SARS-CoV-2 since 2020. Like all vaccine platforms, an important bottleneck to viral-vectored vaccine development is manufacturing. Here, we describe a scalable manufacturing protocol for replication-competent SARS-CoV-2 Spike-pseudotyped vesicular stomatitis virus (S-VSV)-vectored vaccines using Vero cells grown on microcarriers in a stirred-tank bioreactor. Using Cytodex 1 microcarriers over 6 days of fed-batch culture, Vero cells grew to a density of 3.95 ± 0.42 ×106 cells/mL in 1-L stirred-tank bioreactors. Ancestral strain S-VSV reached a peak titer of 2.05 ± 0.58 ×108 plaque-forming units (PFUs)/mL at 3 days postinfection. When compared to growth in plate-based cultures, this was a 29-fold increase in virus production, meaning a 1-L bioreactor produces the same amount of virus as 1,284 plates of 15 cm. In addition, the omicron BA.1 S-VSV reached a peak titer of 5.58 ± 0.35 × 106 PFU/mL. Quality control testing showed plate- and bioreactor-produced S-VSV had similar particle-to-PFU ratios and elicited comparable levels of neutralizing antibodies in immunized hamsters. This method should enhance preclinical and clinical development of pseudotyped VSV-vectored vaccines in future pandemics.

Utilizing a university testing program to estimate relative effectiveness of monovalent COVID-19 mRNA booster vaccine versus two-dose primary series against symptomatic SARS-CoV-2 infection.

Vaccine effectiveness (VE) studies utilizing the test-negative design are typically conducted in clinical settings, rather than community populations, leading to bias in VE estimates against mild disease and limited information on VE in healthy young adults. In a community-based university population, we utilized data from a large SARS-CoV-2 testing program to estimate relative VE of COVID-19 mRNA vaccine primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection from September 2021 to July 2022. We used the test-negative design and logistic regression implemented via generalized estimating equations adjusted for age, calendar time, prior SARS-CoV-2 infection, and testing frequency (proxy for test-seeking behavior) to estimate relative VE. Analyses included 2,218 test-positive cases (59 % received monovalent booster dose) and 9,615 test-negative controls (62 %) from 9,066 individuals, with median age of 21 years, mostly students (71 %), White (56 %) or Asian (28 %), and with few comorbidities (3 %). More cases (23 %) than controls (6 %) had COVID-19-like illness. Estimated adjusted relative VE of primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection was 40 % (95 % CI: 33-47 %) during the overall analysis period and 46 % (39-52 %) during the period of Omicron circulation. Relative VE was greater for those without versus those with prior SARS-CoV-2 infection (41 %, 34-48 % versus 33 %, 9 %-52 %, P < 0.001). Relative VE was also greater in the six months after receiving a booster dose (41 %, 33-47 %) compared to more than six months (27 %, 8-42 %), but this difference was not statistically significant (P = 0.06). In this relatively young and healthy adult population, an mRNA monovalent booster dose provided increased protection against symptomatic SARS-CoV-2 infection, overall and with the Omicron variant. University testing programs may be utilized for estimating VE in healthy young adults, a population that is not well-represented by routine VE studies.

Cesium Reduction of a Lithium Diamidochloroberyllate.

Room temperature reaction of elemental cesium with the dimeric lithium chloroberyllate [{SiNDipp}BeClLi]2 [{SiNDipp} = {CH2SiMe2N(Dipp)}2, where Dipp = 2,6-di-isopropylphenyl, in C6D6 results in activation of the arene solvent. Although, in contrast to earlier observations of lithium and sodium metal reduction, the generation of a mooted cesium phenylberyllate could not be confirmed, this process corroborates a previous hypothesis that such beryllium-centered solvent activation also necessitates the formation of hydridoberyllium species. These observations are further borne out by the study of an analogous reaction performed in toluene, in which case the proposed generation of formally low oxidation state beryllium radical anion intermediates induces activation of a toluene sp3 C-H bond and the isolation of the polymeric cesium benzylberyllate, [Cs({SiNDipp}BeCH2C6H5)]∞.

Status check: next-generation sequencing for infectious-disease diagnostics.

Next-generation sequencing (NGS) applications for the diagnostics of infectious diseases has demonstrated great potential with three distinct approaches: whole-genome sequencing (WGS), targeted NGS (tNGS), and metagenomic NGS (mNGS, also known as clinical metagenomics). These approaches provide several advantages over traditional microbiologic methods, though challenges still exist.

SARS-CoV-2 evolution during prolonged infection in immunocompromised patients.

Prolonged infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunocompromised patients provides an opportunity for viral evolution, potentially leading to the generation of new pathogenic variants. To investigate the pathways of viral evolution, we carried out a study on five patients experiencing prolonged SARS-CoV-2 infection (quantitative polymerase chain reaction-positive for 79-203 days) who were immunocompromised due to treatment for lymphoma or solid organ transplantation. For each timepoint analyzed, we generated at least two independent viral genome sequences to assess the heterogeneity and control for sequencing error. Four of the five patients likely had prolonged infection; the fifth apparently experienced a reinfection. The rates of accumulation of substitutions in the viral genome per day were higher in hospitalized patients with prolonged infection than those estimated for the community background. The spike coding region accumulated a significantly greater number of unique mutations than other viral coding regions, and the mutation density was higher. Two patients were treated with monoclonal antibodies (bebtelovimab and sotrovimab); by the next sampled timepoint, each virus population showed substitutions associated with monoclonal antibody resistance as the dominant forms (spike K444N and spike E340D). All patients received remdesivir, but remdesivir-resistant substitutions were not detected. These data thus help elucidate the trends of emergence, evolution, and selection of mutational variants within long-term infected immunocompromised individuals. IMPORTANCE: SARS-CoV-2 is responsible for a global pandemic, driven in part by the emergence of new viral variants. Where do these new variants come from? One model is that long-term viral persistence in infected individuals allows for viral evolution in response to host pressures, resulting in viruses more likely to replicate efficiently in humans. In this study, we characterize replication in several hospitalized and long-term infected individuals, documenting efficient pathways of viral evolution.