Characterizing Long COVID in Children and Adolescents

ImportanceMost research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.ObjectiveTo identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.Design, setting, and participantsMulticenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.ExposureSARS-CoV-2 infection.Main outcomes and measuresPASC and 89 prolonged symptoms across 9 symptom domains.ResultsA total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.Conclusions and relevanceThis study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges

Manual physical therapy and exercise versus electrophysical agents and exercise in the management of plantar heel pain: A multicenter randomized clinical trial

STUDY DESIGN: Randomized clinical trial. OBJECTIVE: To compare the effectiveness of 2 different conservative management approaches in the treatment of plantar heel pain. BACKGROUND: There is insufficient evidence to establish the optimal physical therapy management strategies for patients with heel pain, and little evidence of long-term effects. METHODS: Patients with a primary report of plantar heel pain underwent a standard evaluation and completed a number of patient self-report questionnaires, including the Lower Extremity Functional Scale (LEFS), the Foot and Ankle Ability Measure (FAAM), and the Numeric Pain Rating Scale (NPRS). Patients were randomly assigned to be treated with either an electrophysical agents and exercise (EPAX) or a manual physical therapy and exercise (MTEX) approach. Outcomes of interest were captured at baseline and at 4-week and 6-month follow-ups. The primary aim (effects of treatment on pain and disability) was examined with a mixed-model analysis of variance (ANOVA). The hypothesis of interest was the 2-way interaction (group by time). RESULTS: Sixty subjects (mean [SD] age, 48.4 [8.7] years) satisfied the eligibility criteria, agreed to participate, and were randomized into the EPAX (n = 30) or MTEX group (n = 30). The overall group-by-time interaction for the ANOVA was statistically significant for the LEFS (P = .002), FAAM (P = .005), and pain (P = .043). Between-group differences favored the MTEX group at both 4-week (difference in LEFS, 13.5; 95% Cl: 6.3,20.8) and 6-month (9.9; 95% Cl: 1.2,18.6) follow-ups. CONCLUSION: The results of this study provide evidence that MTEX is a superior management approach over an EPAX approach in the management of individuals with plantar heel pain at both the short- and long-term follow-ups. Future studies should examine the contribution of the different components of the exercise and manual physical therapy programs

Cryo-EM structure of the extracellular domain of murine Thrombopoietin Receptor in complex with Thrombopoietin

Abstract Thrombopoietin (Tpo) is the primary regulator of megakaryocyte and platelet numbers and is required for haematopoetic stem cell maintenance. Tpo functions by binding its receptor (TpoR, a homodimeric Class I cytokine receptor) and initiating cell proliferation or differentiation. Here we characterise the murine Tpo:TpoR signalling complex biochemically and structurally, using cryo-electron microscopy. Tpo uses opposing surfaces to recruit two copies of receptor, forming a 1:2 complex. Although it binds to the same, membrane-distal site on both receptor chains, it does so with significantly different affinities and its highly glycosylated C-terminal domain is not required. In one receptor chain, a large insertion, unique to TpoR, forms a partially structured loop that contacts cytokine. Tpo binding induces the juxtaposition of the two receptor chains adjacent to the cell membrane. The therapeutic agent romiplostim also targets the cytokine-binding site and the characterisation presented here supports the future development of improved TpoR agonists