Long COVID symptoms in exposed and infected children, adolescents and their parents one year after SARS-CoV-2 infection: A prospective observational cohort study.

BACKGROUND: Long COVID in children and adolescents remains poorly understood due to a lack of well-controlled studies with long-term follow-up. In particular, the impact of the family context on persistent symptoms following SARS-CoV-2 infection remains unknown. We examined long COVID symptoms in a cohort of infected children, adolescents, and adults and their exposed but non-infected household members approximately 1 year after infection and investigated clustering of persistent symptoms within households. METHODS: 1267 members of 341 households (404 children aged <14 years, 140 adolescents aged 14-18 years and 723 adults) were categorized as having had either a SARS-CoV-2 infection or household exposure to SARS-CoV-2 without infection, based on three serological assays and history of laboratory-confirmed infection. Participants completed questionnaires assessing the presence of long COVID symptoms 11-12 months after infection in the household using online questionnaires. FINDINGS: The prevalence of moderate or severe persistent symptoms was statistically significantly higher in infected than in exposed women (36.4% [95% CI: 30.7-42.4%] vs 14.2% [95% CI: 8.7-21.5%]), infected men (22.9% [95% CI: 17.9-28.5%] vs 10.3% [95% CI: 5.8-16.9%]) and infected adolescent girls (32.1% 95% CI: 17.2-50.5%] vs 8.9% [95%CI: 3.1-19.8%]). However, moderate or severe persistent symptoms were not statistically more common in infected adolescent boys aged 14-18 (9.7% [95% CI: 2.8-23.6%] or in infected children <14 years (girls: 4.3% [95% CI: 1.2-11.0%]; boys: 3.7% [95% CI: 1.1-9.6%]) than in their exposed counterparts (adolescent boys: 0.0% [95% CI: 0.0-6.7%]; girls < 14 years: 2.3% [95% CI: 0·7-6·1%]; boys < 14 years: 0.0% [95% CI: 0.0-2.0%]). The number of persistent symptoms reported by individuals was associated with the number of persistent symptoms reported by their household members (IRR=1·11, p=·005, 95% CI [1.03-1.20]). INTERPRETATION: In this controlled, multi-centre study, infected men, women and adolescent girls were at increased risk of negative outcomes 11-12 months after SARS-CoV-2 infection. Amongst non-infected adults, prevalence of negative outcomes was also high. Prolonged symptoms tended to cluster within families, suggesting family-level interventions for long COVID could prove useful. FUNDING: Ministry of Science, Research and the Arts, Baden-Württemberg, Germany.

Mathematical abilities in dyslexic children: a diffusion tensor imaging study.

Dyslexia is characterized by a deficit in language processing which mainly affects word decoding and spelling skills. In addition, children with dyslexia also show problems in mathematics. However, for the latter, the underlying structural correlates have not been investigated. Sixteen children with dyslexia (mean age 9.8 years [0.39]) and 24 typically developing children (mean age 9.9 years [0.29]) group matched for age, gender, IQ, and handedness underwent 3 T MR diffusion tensor imaging as well as cognitive testing. Tract-Based Spatial Statistics were performed to correlate behavioral data with diffusion data. Children with dyslexia performed worse than controls in standardized verbal number tasks, such as arithmetic efficiency tests (addition, subtraction, multiplication, division). In contrast, the two groups did not differ in the nonverbal number line task. Arithmetic efficiency, representing the total score of the four arithmetic tasks, multiplication, and division, correlated with diffusion measures in widespread areas of the white matter, including bilateral superior and inferior longitudinal fasciculi in children with dyslexia compared to controls. Children with dyslexia demonstrated lower performance in verbal number tasks but performed similarly to controls in a nonverbal number task. Further, an association between verbal arithmetic efficiency and diffusion measures was demonstrated in widespread areas of the white matter suggesting compensatory mechanisms in children with dyslexia compared to controls. Taken together, poor fact retrieval in children with dyslexia is likely a consequence of deficits in the language system, which not only affects literacy skills but also impacts on arithmetic skills.

A review of neuroimaging findings in repetitive brain trauma.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease confirmed at postmortem. Those at highest risk are professional athletes who participate in contact sports and military personnel who are exposed to repetitive blast events. All neuropathologically confirmed CTE cases, to date, have had a history of repetitive head impacts. This suggests that repetitive head impacts may be necessary for the initiation of the pathogenetic cascade that, in some cases, leads to CTE. Importantly, while all CTE appears to result from repetitive brain trauma, not all repetitive brain trauma results in CTE. Magnetic resonance imaging has great potential for understanding better the underlying mechanisms of repetitive brain trauma. In this review, we provide an overview of advanced imaging techniques currently used to investigate brain anomalies. We also provide an overview of neuroimaging findings in those exposed to repetitive head impacts in the acute/subacute and chronic phase of injury and in more neurodegenerative phases of injury, as well as in military personnel exposed to repetitive head impacts. Finally, we discuss future directions for research that will likely lead to a better understanding of the underlying mechanisms separating those who recover from repetitive brain trauma vs. those who go on to develop CTE.

Macrolide therapy targets a specific phenotype in respiratory medicine: from clinical experience to basic science and back.

For centuries a quest has been going on for the "holy grail" in respiratory medicine: a treatment for numerous devastating chronic lung disorders. Yet, it is only a decade ago that pharmacological interference with the activation of the innate immune system by a macrolide antibiotic silently moved into everyday clinical practice. Macrolides, with their unique molecular structure built around a lactone ring, are now known to target harmful exaggerated innate immune responses. However, not all chronic lung conditions benefit from macrolide therapy and interestingly, neither do all patients with an apparently identical chronic lung disease. A subgroup of 'responders' seems to display a single specific phenotype that can be recognized in the various lung conditions and that seems to be related to inflammatory responses with a predominant innate immune system component. Recently we have contributed to the introduction of macrolide therapy in lung transplantation medicine. Also we attempted to analyse this phenotype by describing its clinical, immunological, histological and radiological characteristics. The aim of this manuscript is to review the use of macrolides in the respiratory field and to apply the macrolide-responsive phenotype beyond the setting of lung transplantation and other conditions in which macrolides have been successful. The description of this "universal" macrolide-responsive phenotype can both help rationalize macrolide therapy in respiratory disorders, in which its benefit is already well-known, as well as promote the use of this treatment in respiratory conditions of unknown etiology but with a "macrolide responsive phenotype".