Faculty Bibliography

OBJECTIVE:To evaluate whether the risk of long COVID among individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy differs from that of individuals who were not pregnant at time of virus acquisition. METHODS:We conducted a multicenter observational cohort study at 79 NIH RECOVER (Researching COVID to Enhance Recovery) sites. Individuals assigned female at birth aged 18-45 years with an index (first) SARS-CoV-2 infection on or after December 1, 2021, were included. The exposure was pregnancy (any gestational age) at the time of index SARS-CoV-2 infection. The primary outcome was long COVID 6 months after index infection , defined as RECOVER-Adult Long COVID Research Index score 11 or higher based on a detailed symptom survey. To account for confounding and differential selection between participants who were pregnant and not pregnant at infection, propensity score-matching methods were used to balance the groups on variables potentially associated with both pregnancy status and long COVID. RESULTS:Overall 2,423 participants were included; 580 (23.9%) were pregnant at index SARS-CoV-2 infection. The median age at infection was 33 years (interquartile range 28-38 years), and 2,131 of participants (90.0%) with known vaccination status were vaccinated. After propensity score matching, the adjusted long COVID prevalence estimates 6 months after index infection were 10.2% (95% CI, 6.2-14.3%) among those pregnant at infection and 10.6% (95% CI, 8.8-12.4%) among those not pregnant at infection. Pregnancy was not associated with a difference in adjusted risk of long COVID (adjusted risk ratio 0.96, 95% CI, 0.63-1.48). CONCLUSION/CONCLUSIONS:Acquisition of SARS-CoV-2 during pregnancy was not associated with a differential risk of long COVID at 6 months compared with similar-aged individuals who acquired SARS-CoV-2 outside of pregnancy.

BACKGROUND:Prior authorizations could hinder the filling of life-saving heart failure (HF) medications, such as angiotensin receptor neprilysin inhibitors (ARNIs) and sodium glucose cotransporter 2 inhibitors (SGLT2is). OBJECTIVES/OBJECTIVE:The aim of the study was to determine whether prior authorizations were associated with delayed or decreased filling for ARNI and SGLT2i. METHODS:This was a retrospective cohort study using electronic health record, pharmacy fill, and neighborhood-level data from a large, academic health system. We included patients with HF and a new prescription for ARNI or SGLT2i between April 1, 2021, and April 30, 2023, and assessed for presence of prior authorization requirement. Outcomes included days to first fill and never filling the prescription. Analyses were conducted using inverse probability weighting methods. RESULTS:Among 2,183 patients, 12.2% (152/1,243) and 14.3% (165/1,150) had a prior authorization requirement for ARNI or SGLT2i, respectively. Patients requiring prior authorization tended to be younger, identify as non-Hispanic Black or Hispanic, have non-Medicare insurance, and have fewer comorbidities. In weighted models, patients requiring prior authorization took 3.03 (95% CI: 2.16-4.25) times longer to fill ARNI, 6.75 (95% CI: 4.44-10.3) times longer to fill SGLT2i, and were 2.23 (95% CI: 1.37-3.65) times more likely to never fill SGLT2i prescriptions (all P < 0.001). CONCLUSIONS:Prior authorization requirements were more common for patients identifying as Black or Hispanic and were associated with decreased and delayed filling of ARNI and SGLT2i. Our findings highlight an important barrier to mortality-reducing, guideline-recommended medications for HF.

OBJECTIVE:To assess associations between exposure to intrauterine SARS-CoV-2 and subsequent child neurodevelopment in a large, diverse cohort with confirmation of maternal SARS-CoV-2 status. STUDY DESIGN/METHODS:edition (ASQ-3) and at 18 months with the ASQ Social-Emotional (ASQ-SE) and the Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R). We compared exposed and unexposed infants' ASQ-3 total and subdomain scores, ASQ-SE and M-CHAT-R scores, and proportions meeting published referral thresholds, using multivariable linear and logistic regression. RESULTS:Among 1179 participants enrolled, 1008 (85.5%) had exposure, with 806 (80.0%) exposed during Omicron predominance. Of those with known timing, 349 (41.4%) and 295 (35.0%) were exposed in the second and third trimesters of pregnancy respectively. Exposure was not associated with differences in ASQ-3 (adjusted difference: -0.61, 95% CI: -10.03, 8.81) or ASQ-3 subdomains at 12 months, ASQ-SE at 18 months (adjusted difference: 0.19, 95% CI: -4.02, 4.41), or M-CHAT-R scores. Findings were similar for proportions meeting referral thresholds, and when stratified by variant or by trimester. CONCLUSIONS:In this multicenter cohort largely exposed since Omicron and in second or third trimester, intrauterine SARS-CoV-2 exposure was not associated with neurodevelopmental screening outcomes through 18 months of age. Further assessments of the impact of intrauterine SARS-CoV-2 on neurodevelopment beyond 18 months of age are needed.

AIMS/OBJECTIVE:To describe management of life with a left ventricular assist device (LVAD) by patients and caregivers and to determine the fit of self- and family management as a guiding concept in LVAD research. METHODS AND RESULTS/RESULTS:We applied dimensional analysis techniques to this concept analysis, beginning with a literature search (2010-25) of PubMed, CINAHL, Embase, PsycINFO, and Web of Science. Two reviewers screened and analysed 28 articles capturing perspectives on daily LVAD management among patients, caregivers, and healthcare professionals. Fourteen studies were qualitative, 12 were quantitative, and 2 were mixed methods. We identified five dimensions of patient and family management of LVAD therapy: patient facilitators and barriers; caregiver facilitators and barriers; processes of self- and family management; clinician facilitators and barriers/processes; and outcomes. These dimensions align with the concept of self- and family management and with core components of the Middle Range Theory of Self- and Family Management of Chronic Illness. CONCLUSION/CONCLUSIONS:This dimensional concept analysis advances understanding of managing life with an LVAD by clarifying the collaborative roles of patients, caregivers, LVAD coordinators, and other healthcare professionals. Our analysis supports the use of self- and family management as a guiding concept and the application of the Middle Range Theory of Self- and Family Management of Chronic Illness in LVAD research. A new conceptual definition of LVAD self- and family management reflects this theoretical grounding. Our work offers direction for future research, clinical practice, and education aimed at improving outcomes for patients and caregivers managing life with an LVAD.

IMPORTANCE/UNASSIGNED:Millions of children worldwide are experiencing prolonged symptoms after SARS-CoV-2 infection, yet social risk factors for developing long COVID are largely unknown. As child health is influenced by the environment in which they live and interact, adverse social determinants of health (SDOH) may contribute to the development of pediatric long COVID. OBJECTIVE/UNASSIGNED:To identify whether adverse SDOH are associated with increased odds of long COVID in school-aged children and adolescents in the US. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cross-sectional analysis of a multicenter, longitudinal, meta-cohort study encompassed 52 sites (health care and community settings) across the US. School-aged children (6-11 years; n = 903) and adolescents (12-17 years; n = 3681) with SARS-CoV-2 infection history were included. Those with an unknown date of first infection, history of multisystem inflammatory syndrome in children, or symptom surveys with less than 50% of questions completed were excluded. Participants were recruited via health care systems, long COVID clinics, fliers, websites, social media campaigns, radio, health fairs, community-based organizations, community health workers, and existing research cohorts from March 2022 to August 2024, and surveys were completed by caregivers between March 2022 and August 2024. EXPOSURE/UNASSIGNED:Twenty-four individual social determinant of health factors were grouped into 5 Healthy People 2030 domains: economic stability, social and community context, caregiver education access and quality, neighborhood and built environment, and health care access and quality. Latent classes were created within each domain and used in regression models. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Presence of long COVID using caregiver-reported, symptom-based, age-specific research indices. RESULTS/UNASSIGNED:The mean (SD) age among 4584 individuals included in this study was 14 (3) years, and 2330 (51%) of participants were male. The number of latent classes varied by domain; the reference group was the class with the least adversity. In unadjusted analyses, most classes in each domain were associated with higher odds of long COVID. After adjusting for many factors, including age group, sex, timing of infection, referral source, and other social determinant of health domains, economic instability characterized by difficulty covering expenses, poverty, receipt of government assistance, and food insecurity were associated with an increased risk of having long COVID (class 2 adjusted odds ratio [aOR], 1.57; 95% CI, 1.18-2.09; class 4 aOR, 2.39; 95% CI, 1.73-3.30); economic instability without food insecurity (class 3) was not (aOR, 0.93; 95% CI, 0.70-1.23). Poorer social and community context (eg, high levels of discrimination and low social support) was also associated with long COVID (aOR, 2.17; 95% CI, 1.77-2.66). Sensitivity analyses stratified by age group and adjusted for race and ethnicity did not alter or attenuate these results. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this study, economic instability that included food insecurity and poor social and community context were associated with greater odds of pediatric long COVID. Those with food security, despite experiencing other economic challenges, did not have greater odds of long COVID. Further study is needed to determine if addressing SDOH factors can decrease the rate of pediatric long COVID.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with an increased risk of vascular dysfunction and cardiovascular disease. We validate our previously developed Systemic Lupus Erythematosus Activity Platelet-Gene Expression Signature (SLAP-GES) score and investigate its relationship with platelet activity and vascular health. SLAP-GES was associated with the SLE Disease Activity Index (Padj < 0.001) and consistent over time (r = 0.76; P = 9 × 10^-5). Moreover, SLAP-GES was associated increased platelet aggregation in response to submaximal epinephrine (P = 0.084), leukocyte platelet aggregates (P = 0.014), and neutrophil platelet aggregates (P = 0.043). SLAP-GES was also associated with impaired glycocalyx (P = 0.011) and brachial artery flow-mediated dilation (P = 0.045). Altogether, SLAP-GES is associated with SLE disease activity, platelet activity, and impaired vascular health.

BACKGROUND:Patients with heart failure (HF) often have difficulty obtaining life-saving medications due to coverage barriers, such as prior authorizations and high out-of-pocket costs. To promote better coverage for high value therapies and inform policymakers about cost effectiveness, the American Heart Association/American College of Cardiology/Heart Failure Society of America added Value Statements to HF guidelines. We assessed whether these guidelines influenced Medicare drug coverage policies for 2 life-saving, costly HF medications: angiotensin receptor neprilysin inhibitors (ARNI-guideline "high value") and sodium glucose cotransporter-2 inhibitors (SGLT2i-guideline "intermediate value"). METHODS:We performed an observational study using Medicare prescription drug plan formulary files from April 2020 to April 2023 to separately assess for changes in coverage barriers to ARNI and SGLT2i after Value Statement publication (April 2022), and subsequent Medicare plan online update (October 2022). The primary outcome was the percentage of plans each month with any barrier to drug coverage (prior authorizations, tier ≥3 out-of-pocket cost-sharing, step therapy, or no coverage). Analyses used interrupted time series and difference-in-differences approaches. Difference-in-differences analyses used direct oral anticoagulants as a control due to their comparable cost and use as ARNI and SGLT2i, but without a Value Statement. RESULTS:Among 7396 Medicare drug plans, monthly rates of any coverage barrier ranged from 94.3% to 97.4% for ARNI and 93.2% to 96.6% for SGLT2i. Most barriers were due to tier ≥3 out-of-pocket cost-sharing requirements (ARNI: 94.3%-95.8%; SGLT2i: 93.2%-95.6%). Coverage barriers remained stable in April 2022 and declined slightly in October 2022. In difference-in-differences analyses, the presence of a Value Statement was associated with a ~1 percentage point decline in coverage barriers for both ARNI (difference-in-differences estimate, -1.07% [95% CI, -1.44% to -0.70%]) and SGLT2i (-1.32% [95% CI, -1.63% to -1.00%]). CONCLUSIONS:Coverage barriers to ARNI and SGLT2i were common and changed only slightly after publication of Value Statements in HF guidelines. There is a critical need for robust strategies to improve access to life-saving HF medications.

Ischemic heart disease is the leading cause of heart failure with reduced ejection fraction in the developed world. An evolution of background medical therapy over the past decade has spurred improvement in symptoms and a reduction in morbidity and mortality with ischemic cardiomyopathy. However, there is still ongoing debate about the role and impact of revascularization. Much of the societal guidance regarding revascularization with coronary artery bypass grafting in ischemic cardiomyopathy comes from the STICH trial (Surgical Treatment for Ischemic Heart Failure) which predates improvements in medical therapy. More recently, the REVIVED-BCIS2 trial (Revascularization for Ischemic Ventricular Dysfunction-British Cardiovascular Intervention Society) failed to show a benefit of percutaneous coronary intervention on heart failure hospitalization and mortality in ischemic cardiomyopathy over contemporary medical therapy alone. Yet, there are outstanding questions regarding the role and modality of revascularization required to improve outcomes. We review current data and future directions in the management of ischemic cardiomyopathy and the potential role of revascularization.

BACKGROUND:Inclusion of patients, caregivers, and community members in scientific research should be essential for patient-centered care. Patients’ lived experiences can propose new areas of focus that may not have previously been considered, ensure that potentially sensitive topics are addressed thoughtfully, contribute to the interpretation of findings, and identify future directions of research. Further, their inclusion in the drafting of manuscripts can ensure that research findings are translatable to real-world practice. To achieve this goal, the Researching COVID to Enhance Recovery (RECOVER) consortium developed a Representative Authorship system for development of scientific manuscripts that report RECOVER data. This paper describes a Quality Improvement (QI) project that was conducted to identify system strengths and improvement opportunities. METHODS:An online QI survey was distributed to RECOVER’s Representative Authors about a year into the implementation of the Representative Authorship System. The survey focused on several key aspects, including the clarity regarding the authorship process, training opportunities, the matching process, communication within writing groups, and the perceived impact of the representative engagement on the quality and applicability of research. The survey also explored participants’ satisfaction with compensation, support, and involvement in the system, as well as areas for improvement. RESULTS:The survey was sent to 49 representative authors with 17 respondents (35%). Most respondents reported positive experiences, highlighting the effective matching to manuscripts based on their expertise and the perceived positive impact of their involvement on research outcomes. Additionally, participants felt that including diverse voices enhanced the relevance of research for clinical practice. Several areas for improvement were identified, including communication challenges within writing groups, the utility of manuscript orientation calls, and the fairness of compensation. Respondents also indicated a need for more training opportunities and logistical support. CONCLUSIONS:RECOVER’s Representative Authorship system is effective in fostering collaboration and improving the inclusivity of scientific research. The survey findings indicate that there are logistical changes around communication, training, and compensation that could enhance the experience for all collaborators. Based on these findings, we plan to implement changes to improve awareness, understanding, and collaboration. Additional work is needed to solicit feedback from investigators and administrative staff to obtain a more holistic understanding of the system. SUPPLEMENTARY INFORMATION:The online version contains supplementary material available at 10.1186/s12913-025-12914-3.