The kinetics and durability of antibody and T-cell responses to SARS-CoV-2 in children.

BACKGROUND: The kinetics and durability of T-cell responses to SARS-CoV-2 in children are not well-characterized. We studied a cohort of children aged 6 months to 20 years with COVID-19 in whom peripheral blood mononuclear cells (PBMC) and sera were archived at approximately 1, 6, and 12 months post-symptom onset. METHODS: We compared antibody (N = 85) and T-cell responses (N = 26) to nucleocapsid (N) and spike (S) glycoprotein over time across four age strata: 6 months to 5 years, 5-9, 10-14, and 15-20 years. RESULTS: N-specific antibody responses declined over time, becoming undetectable in 26/32 (81%) children by approximately one year post-infection. Functional breadth of anti-N CD4+ T-cell responses also declined over time and were positively correlated with N-antibody responses (Pearson's r = 0.31, p = 0.008). CD4+ T-cell responses to S displayed greater functional breadth than N in unvaccinated children, and, along with neutralization titers, were stable over time and similar across age strata. Functional profiles of CD4+ T-cell responses against S were not significantly modulated by vaccination. CONCLUSIONS: Our data reveal durable, age-independent T-cell immunity to SARS-CoV-2 structural proteins in children over time following COVID-19 infection as well as S-Ab responses overall, in comparison to declining antibody responses to N.

Family Hardship Following Youth Concussion: Beyond the Medical Bills.

PURPOSE: The costs facing families after pediatric concussion are not limited to medical expenses for treatment and rehabilitation care. The objective of this research was to examine the economic hardship facing families following concussion. DESIGN AND METHODS: Eighteen youth (10-18 years old) with a diagnosed concussion injury and sixteen parents (13 parent/youth dyads) answered open-ended questions regarding experiences associated with concussion care and recovery, specifically as they related to cost. Participants were recruited from a concussion clinic, social media, and via snowball sampling. Interviews were audio recorded, transcribed verbatim, and coded using deductive qualitative content analysis. RESULTS: In addition to direct health care expenses (e.g. copays and deductibles), families of youth with concussion faced indirect costs associated with tutoring and transportation to medical appointments, in some cases over long distances. Financial cost-sharing for concussion care varied widely across participants. CONCLUSIONS: Lost productivity included parents missing work to care for their child and for travel to appointments. Research that describes costs of care using claims or survey data lack the experiential perspective of the economic burden on families following concussion. PRACTICE IMPLICATIONS: To fully understand the impact of concussion on patients and families, healthcare providers must consider non-monetary costs, such as opportunity costs, transportation required to obtain healthcare, or the productivity cost associated with missed work and school.

A National Survey Examining Manuscript Dissertation Formats Among Nursing PhD Programs in the United States.

PURPOSE: Among research-focused nursing doctoral (PhD) programs in the United States, the traditional dissertation format has recently given way to a series of publication-ready manuscripts, often bookended by introduction and conclusion chapters. To help programs make decisions about the use of these formats, this study undertook a national survey of programs offering PhDs in nursing. The purpose of this study was to explore the advantages and disadvantages of the traditional format versus manuscript option for dissertations among nursing PhD programs in the United States. DESIGN: Cross-sectional census survey of U.S. nursing PhD programs. METHODS: A web-based survey was administered to all U.S. nursing PhD programs. Respondents indicated formats offered, factors contributing to decisions of which formats to offer, and lessons learned. Descriptive statistics and inductive content analyses were used for analysis. FINDINGS: Of 121 eligible institutions, 79 provided eligible responses (66.7%). The majority (59%) offered both formats; 11% offered the manuscript option only, and 24% offered the traditional format only. Faculty support (or lack thereof) contributed to adoption (or not) of the manuscript option. Respondents' approaches to the manuscript option (e.g., number of papers) and advice are summarized. CONCLUSIONS: Manuscript option dissertations are commonly offered and provide benefits to students and faculty; however, thoughtful implementation is critical. Programs need to agree upon clear expectations and have graduate school support (e.g., formatting). Faculty need mentorship in advising manuscript option students who choose to use this format, and the time and support. Finally, students need additional writing skills that could be provided through coursework or via individual work with mentors. CLINICAL RELEVANCE: As nursing education continues to expand further into doctoral research, programs must examine dissertation formats in order to both prepare future nurse scholars and disseminate nursing research that is critical to improving nursing education, patient care, and clinical practice.

Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children's sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.

Transcription factor NF-κB in a basal metazoan, the sponge, has conserved and unique sequences, activities, and regulation.

Herein, we characterize transcription factor NF-κB from the demosponge Amphimedon queenslandica (Aq). Aq-NF-κB is most similar to NF-κB p100/p105 among vertebrate proteins, with an N-terminal DNA-binding domain, a C-terminal Ankyrin (ANK) repeat domain, and a DNA binding-site profile akin to human NF-κB proteins. Like mammalian NF-κB p100, C-terminal truncation allows nuclear translocation of Aq-NF-κB and increases its transcriptional activation activity. Expression of IκB kinases (IKKs) induces proteasome-dependent C-terminal processing of Aq-NF-κB in human cells, and processing requires C-terminal serines in Aq-NF-κB. Unlike NF-κB p100, C-terminal sequences of Aq-NF-κB do not inhibit its DNA-binding activity. Tissue of a black encrusting demosponge contains NF-κB site DNA-binding activity, as well as nuclear and processed NF-κB. Treatment of sponge tissue with LPS increases both DNA-binding activity and processing of NF-κB. A. queenslandica transcriptomes contain homologs to upstream NF-κB pathway components. This is first functional characterization of NF-κB in sponge, the most basal multicellular animal.