Factors Affecting Presentation and Treatment of Pediatric/Adolescent Cancer Patients Diagnosed With SARS-CoV-2.

BACKGROUND: It is thought that the clinical course of actively treated pediatric/adolescent cancer patients diagnosed with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is more severe than experienced by the general pediatric population. We describe the clinical course, risk factors affecting presentation, and management of coronavirus disease 2019 (COVID-19) infection for these patients. METHODS: Patients at a single institution receiving cancer therapy while diagnosed with SARS-CoV-2 between January 2020 and June 2021 were retrospectively reviewed. Data collected included age at SARS-CoV-2 diagnosis, sex, ethno-race, adjusted body mass index, and active therapies. RESULTS: Twenty-nine patients met inclusion criteria, with 16 (55.2%) experiencing symptoms. Twenty-three (79.3%) patients required no institutional support; 10 (34.4%) required hospitalization, of which 80.0% required oxygen, 30.0% required intensive care, and 10.0% required intubation. Three (10.3%) patients developed MIS-C. Obesity increased odds of hospitalization (odds ratio=25.5; P =0.002) and oxygenation (odds ratio=14.88; P =0.012). CONCLUSIONS: Hospitalization and MIS-C rates were significantly higher than, whereas mortality rates and symptom presentations were consistent with, rates in the general pediatric population. Obesity was the only risk factor predictive of clinical severity. Cancer treatment modifications and pre-emptive administration of COVID-19 treatment did not modify clinical course.

Inhibition of SARS-CoV-2 infection in cellular systems using engineered trimeric receptor-binding domain of spike protein.

Here, we provide a protocol for the design, expression, purification, and functional studies of an engineered trimeric version of the receptor-binding domain (tRBD) of SARS-CoV-2 spike protein. We describe the use of tRBD to block SARS-CoV-2 spike pseudovirus and true virus binding to cellular angiotensin converting enzyme-2 (ACE2), thereby blocking viral infection. This protocol is applicable to generate a trimeric version of any protein of interest. For complete details on the use and execution of this protocol, please refer to Basavarajappa et al. (2022).1.

Trimeric receptor-binding domain of SARS-CoV-2 acts as a potent inhibitor of ACE2 receptor-mediated viral entry.

The COVID-19 pandemic has caused over four million deaths and effective methods to control CoV-2 infection, in addition to vaccines, are needed. The CoV-2 binds to the ACE2 on human cells through the receptor-binding domain (RBD) of the trimeric spike protein. Our modeling studies show that a modified trimeric RBD (tRBD) can interact with three ACE2 receptors, unlike the native spike protein, which binds to only one ACE2. We found that tRBD binds to the ACE2 with 58-fold higher affinity than monomeric RBD (mRBD) and blocks spike-dependent pseudoviral infection over 4-fold more effectively compared to the mRBD. Although mRBD failed to block CoV-2 USA-WA1/2020 infection, tRBD efficiently blocked the true virus infection in plaque assays. We show that tRBD is a potent inhibitor of CoV-2 through both competitive binding to the ACE2 and steric hindrance, and has the potential to emerge as a first-line therapeutic method to control COVID-19.

Healthcare spending in U.S. emergency departments by health condition, 2006-2016.

BACKGROUND: Healthcare spending in the emergency department (ED) setting has received intense focus from policymakers in the United States (U.S.). Relatively few studies have systematically evaluated ED spending over time or disaggregated ED spending by policy-relevant groups, including health condition, age, sex, and payer to inform these discussions. This study's objective is to estimate ED spending trends in the U.S. from 2006 to 2016, by age, sex, payer, and across 154 health conditions and assess ED spending per visit over time. METHODS AND FINDINGS: This observational study utilized the National Emergency Department Sample, a nationally representative sample of hospital-based ED visits in the U.S. to measure healthcare spending for ED care. All spending estimates were adjusted for inflation and presented in 2016 U.S. Dollars. Overall ED spending was $79.2 billion (CI, $79.2 billion-$79.2 billion) in 2006 and grew to $136.6 billion (CI, $136.6 billion-$136.6 billion) in 2016, representing a population-adjusted annualized rate of change of 4.4% (CI, 4.4%-4.5%) as compared to total healthcare spending (1.4% [CI, 1.4%-1.4%]) during that same ten-year period. The percentage of U.S. health spending attributable to the ED has increased from 3.9% (CI, 3.9%-3.9%) in 2006 to 5.0% (CI, 5.0%-5.0%) in 2016. Nearly equal parts of ED spending in 2016 was paid by private payers (49.3% [CI, 49.3%-49.3%]) and public payers (46.9% [CI, 46.9%-46.9%]), with the remainder attributable to out-of-pocket spending (3.9% [CI, 3.9%-3.9%]). In terms of key groups, the majority of ED spending was allocated among females (versus males) and treat-and-release patients (versus those hospitalized); those between age 20-44 accounted for a plurality of ED spending. Road injuries, falls, and urinary diseases witnessed the highest levels of ED spending, accounting for 14.1% (CI, 13.1%-15.1%) of total ED spending in 2016. ED spending per visit also increased over time from $660.0 (CI, $655.1-$665.2) in 2006 to $943.2 (CI, $934.3-$951.6) in 2016, or at an annualized rate of 3.4% (CI, 3.3%-3.4%). CONCLUSIONS: Though ED spending accounts for a relatively small portion of total health system spending in the U.S., ED spending is sizable and growing. Understanding which diseases are driving this spending is helpful for informing value-based reforms that can impact overall health care costs.

US Health Care Spending by Race and Ethnicity, 2002-2016.

Importance: Measuring health care spending by race and ethnicity is important for understanding patterns in utilization and treatment. Objective: To estimate, identify, and account for differences in health care spending by race and ethnicity from 2002 through 2016 in the US. Design, Setting, and Participants: This exploratory study included data from 7.3 million health system visits, admissions, or prescriptions captured in the Medical Expenditure Panel Survey (2002-2016) and the Medicare Current Beneficiary Survey (2002-2012), which were combined with the insured population and notified case estimates from the National Health Interview Survey (2002; 2016) and health care spending estimates from the Disease Expenditure project (1996-2016). Exposure: Six mutually exclusive self-reported race and ethnicity groups. Main Outcomes and Measures: Total and age-standardized health care spending per person by race and ethnicity for each year from 2002 through 2016 by type of care. Health care spending per notified case by race and ethnicity for key diseases in 2016. Differences in health care spending across race and ethnicity groups were decomposed into differences in utilization rate vs differences in price and intensity of care. Results: In 2016, an estimated $2.4 trillion (95% uncertainty interval [UI], $2.4 trillion-$2.4 trillion) was spent on health care across the 6 types of care included in this study. The estimated age-standardized total health care spending per person in 2016 was $7649 (95% UI, $6129-$8814) for American Indian and Alaska Native (non-Hispanic) individuals; $4692 (95% UI, $4068-$5202) for Asian, Native Hawaiian, and Pacific Islander (non-Hispanic) individuals; $7361 (95% UI, $6917-$7797) for Black (non-Hispanic) individuals; $6025 (95% UI, $5703-$6373) for Hispanic individuals; $9276 (95% UI, $8066-$10 601) for individuals categorized as multiple races (non-Hispanic); and $8141 (95% UI, $8038-$8258) for White (non-Hispanic) individuals, who accounted for an estimated 72% (95% UI, 71%-73%) of health care spending. After adjusting for population size and age, White individuals received an estimated 15% (95% UI, 13%-17%; P < .001) more spending on ambulatory care than the all-population mean. Black (non-Hispanic) individuals received an estimated 26% (95% UI, 19%-32%; P < .001) less spending than the all-population mean on ambulatory care but received 19% (95% UI, 3%-32%; P = .02) more on inpatient and 12% (95% UI, 4%-24%; P = .04) more on emergency department care. Hispanic individuals received an estimated 33% (95% UI, 26%-37%; P < .001) less spending per person on ambulatory care than the all-population mean. Asian, Native Hawaiian, and Pacific Islander (non-Hispanic) individuals received less spending than the all-population mean on all types of care except dental (all P < .001), while American Indian and Alaska Native (non-Hispanic) individuals had more spending on emergency department care than the all-population mean (estimated 90% more; 95% UI, 11%-165%; P = .04), and multiple-race (non-Hispanic) individuals had more spending on emergency department care than the all-population mean (estimated 40% more; 95% UI, 19%-63%; P = .006). All 18 of the statistically significant race and ethnicity spending differences by type of care corresponded with differences in utilization. These differences persisted when controlling for underlying disease burden. Conclusions and Relevance: In the US from 2002 through 2016, health care spending varied by race and ethnicity across different types of care even after adjusting for age and health conditions. Further research is needed to determine current health care spending by race and ethnicity, including spending related to the COVID-19 pandemic.

In-Person and Telehealth Ambulatory Contacts and Costs in a Large US Insured Cohort Before and During the COVID-19 Pandemic.

Importance: This study assesses the role of telehealth in the delivery of care at the start of the COVID-19 pandemic. Objectives: To document patterns and costs of ambulatory care in the US before and during the initial stage of the pandemic and to assess how patient, practitioner, community, and COVID-19-related factors are associated with telehealth adoption. Design, Setting, and Participants: This is a cohort study of working-age persons continuously enrolled in private health plans from March 2019 through June 2020. The comparison periods were March to June in 2019 and 2020. Claims data files were provided by Blue Health Intelligence, an independent licensee of the Blue Cross and Blue Shield Association. Data analysis was performed from June to October 2020. Main Outcomes and Measures: Ambulatory encounters (in-person and telehealth) and allowed charges, stratified by characteristics derived from enrollment files, practitioner claims, and community characteristics linked to the enrollee's zip code. Results: A total of 36 568 010 individuals (mean [SD] age, 35.71 [18.77] years; 18 466 557 female individuals [50.5%]) were included in the analysis. In-person contacts decreased by 37% (from 1.63 to 1.02 contacts per enrollee) from 2019 to 2020. During 2020, telehealth visits (0.32 visit per person) accounted for 23.6% of all interactions compared with 0.3% of contacts in 2019. When these virtual contacts were added, the overall COVID-19 era patient and practitioner visit rate was 18% lower than that in 2019 (1.34 vs 1.64 visits per person). Behavioral health encounters were far more likely than medical contacts to take place virtually (46.1% vs 22.1%). COVID-19 prevalence in an area was associated with higher use of telehealth; patients from areas within the top quintile of COVID-19 prevalence during the week of their encounter were 1.34 times more likely to have a telehealth visit compared with those in the lowest quintile (the reference category). Persons living in areas with limited social resources were less likely to use telehealth (most vs least socially advantaged neighborhoods, 27.4% vs 19.9% usage rates). Per enrollee medical care costs decreased by 15% between 2019 and 2020 (from $358.32 to $306.04 per person per month). During 2020, those with 1 or more COVID-19-related service (1 470 721 members) had more than 3 times the medical costs ($1701 vs $544 per member per month) than those without COVID-19-related services. Persons with 1 or more telehealth visits in 2020 had considerably higher costs than persons having only in-person ambulatory contacts ($2214.10 vs $1337.78 for the COVID-19-related subgroup and $735.87 vs $456.41 for the non-COVID-19 subgroup). Conclusions and Relevance: This study of a large cohort of patients enrolled in US health plans documented patterns of care at the onset of COVID-19. The findings are relevant to policy makers, payers, and practitioners as they manage the use of telehealth during the pandemic and afterward.