IMPORTANCE: School and daycare closures were enforced as measures to confine the novel coronavirus disease 2019 (COVID-19) pandemic, based on the assumption that young children may play a key role in ...severe acute respiratory coronavirus 2 (SARS-CoV-2) spread. Given the grave consequences of contact restrictions for children, a better understanding of their contribution to the COVID-19 pandemic is of great importance. OBJECTIVE: To describe the rate of SARS-CoV-2 infections and the seroprevalence of SARS-CoV-2 antibodies in children aged 1 to 10 years, compared with a corresponding parent of each child, in a population-based sample. DESIGN, SETTING, AND PARTICIPANTS: This large-scale, multicenter, cross-sectional investigation (the COVID-19 BaWü study) enrolled children aged 1 to 10 years and a corresponding parent between April 22 and May 15, 2020, in southwest Germany. EXPOSURES: Potential exposure to SARS-CoV-2. MAIN OUTCOMES AND MEASURES: The main outcomes were infection and seroprevalence of SARS-CoV-2. Participants were tested for SARS-CoV-2 RNA from nasopharyngeal swabs by reverse transcription–polymerase chain reaction and SARS-CoV-2 specific IgG antibodies in serum by enzyme-linked immunosorbent assays and immunofluorescence tests. Discordant results were clarified by electrochemiluminescence immunoassays, a second enzyme-linked immunosorbent assay, or an in-house Luminex-based assay. RESULTS: This study included 4964 participants: 2482 children (median age, 6 range, 1-10 years; 1265 boys 51.0%) and 2482 parents (median age, 40 range, 23-66 years; 615 men 24.8%). Two participants (0.04%) tested positive for SARS-CoV-2 RNA. The estimated SARS-CoV-2 seroprevalence was low in parents (1.8% 95% CI, 1.2–2.4%) and 3-fold lower in children (0.6% 95% CI, 0.3-1.0%). Among 56 families with at least 1 child or parent with seropositivity, the combination of a parent with seropositivity and a corresponding child with seronegativity was 4.3 (95% CI, 1.19-15.52) times higher than the combination of a parent who was seronegative and a corresponding child with seropositivity. We observed virus-neutralizing activity for 66 of 70 IgG-positive serum samples (94.3%). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, the spread of SARS-CoV-2 infection during a period of lockdown in southwest Germany was particularly low in children aged 1 to 10 years. Accordingly, it is unlikely that children have boosted the pandemic. This SARS-CoV-2 prevalence study, which appears to be the largest focusing on children, is instructive for how ad hoc mass testing provides the basis for rational political decision-making in a pandemic.
Background
Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disorder affecting children and adolescents. Previously classified as a rare disease, recent studies suggest a higher ...incidence of the disease. CNO may develop into the clinical presentation of chronic recurrent osteomyelitis (CRMO) with high relapse rate and multifocality.
Main body
Diagnosis of CNO/CRMO is often delayed, with implications for disease severity and relapse rate. This can be significantly improved by knowledge of the disease entity and its characteristics. Imaging plays a key role in diagnosis, differential diagnosis and therapy monitoring. Magnetic resonance imaging (MRI) has several advantages compared to other imaging methods and is increasingly applied in clinical studies. Recent studies show that a whole-body (WB) coverage (WB-MRI) without contrast agent administration is a rational approach. This educational review is based on a systematic analysis of international peer-reviewed articles and presents our own clinical experiences. It provides an overview of disease entity, incidence and clinical diagnosis. The role of imaging, especially of whole-body MRI, is discussed in detail. Finally, practical advice for imaging, including flowcharts explaining when and how to apply imaging, is provided.
Conclusion
Knowing the specifics of CNO/CRMO and the importance of MRI/whole-body MRI allows rapid and efficient diagnosis as well as therapy support and helps to avoid irreversible secondary damage.
GATA-2 deficiency was recently described as common cause of overlapping syndromes of immunodeficiency, lymphedema, familiar myelodysplastic syndrome or acute myeloid leukemia. The aim of our study ...was to analyze bone marrow and peripheral blood samples of children with myelodysplastic syndrome or aplastic anemia to define prevalence of the GATA2 mutation and to assess whether mutations in GATA-2 transcription factor exhibit specific immunophenotypic features. The prevalence of a GATA2 mutation in a consecutively diagnosed cohort of children was 14% in advanced forms of myelodysplastic syndrome (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and myelodysplasia-related acute myeloid leukemia), 17% in refractory cytopenia of childhood, and 0% in aplastic anemia. In GATA-2-deficient cases, we found the most profound B-cell lymphopenia, including its progenitors in blood and bone marrow, which correlated with significantly diminished intronRSS-Kde recombination excision circles in comparison to other myelodysplastic syndrome/aplastic anemia cases. The other typical features of GATA-2 deficiency (monocytopenia and natural killer cell lymphopenia) were less discriminative. In conclusion, we suggest screening for GATA2 mutations in pediatric myelodysplastic syndrome, preferentially in patients with impaired B-cell homeostasis in bone marrow and peripheral blood (low number of progenitors, intronRSS-Kde recombination excision circles and naïve cells).
To identify the most efficient methods of immunological protection against SARS-CoV-2, including the currently most widespread variants of concern (VOCs)—B.1.1.7, B.1.351 and P.1—a simultaneous ...side-by-side-comparison of available vaccination regimes is required. In this observational cohort study, we compared immunological responses in 144 individuals vaccinated with the mRNA vaccines BNT162b2 or mRNA-1273 and the vector vaccine ChAdOx1-nCoV-19, either alone, in combination, or in the context of COVID-19-convalescence. Unvaccinated COVID-19-convalescent subjects served as a reference. We found that cellular and serological immune responses, including neutralizing capacity against VOCs, were significantly stronger with mRNA vaccines as compared with COVID-19-convalescent individuals or vaccinated individuals receiving the vector vaccine ChAdOx1-nCoV-19. Booster immunizations with mRNA vaccines triggered strong and broadly neutralizing antibody and IFN-γ responses in 100% of vaccinated individuals investigated. This effect was particularly strong in COVID-19-convalescent and ChAdOx1-nCoV-19-primed individuals, who were characterized by comparably moderate cellular and neutralizing antibody responses before mRNA vaccine booster. Heterologous vaccination regimes and convalescent booster regimes using mRNA vaccines may allow enhanced protection against SARS-CoV-2, including current VOCs. Furthermore, such regimes may facilitate rapid (re-)qualification of convalescent plasma donors with high titers of broadly neutralizing antibodies.
Resolving the role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in households with members from different generations is crucial for containing the current pandemic. ...We conducted a large-scale, multicenter, cross-sectional seroepidemiologic household transmission study in southwest Germany during May 11-August 1, 2020. We included 1,625 study participants from 405 households that each had ≥1 child and 1 reverse transcription PCR-confirmed SARS-CoV-2-infected index case-patient. The overall secondary attack rate was 31.6% and was significantly higher in exposed adults (37.5%) than in children (24.6%-29.2%; p = <0.015); the rate was also significantly higher when the index case-patient was >60 years of age (72.9%; p = 0.039). Other risk factors for infectiousness of the index case-patient were SARS-CoV-2-seropositivity (odds ratio OR 27.8, 95% CI 8.26-93.5), fever (OR 1.93, 95% CI 1.14-3.31), and cough (OR 2.07, 95% CI 1.21-3.53). Secondary infections in household contacts generate a substantial disease burden.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
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).
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.
Ministry of Science, Research and the Arts, Baden-Württemberg, Germany.
The risk of developing severe COVID‐19 rises dramatically with age. Schoolchildren are significantly less likely than older people to die from SARS‐CoV‐2 infection, but the molecular mechanisms ...underlying this age‐dependence are unknown. In primary infections, innate immunity is critical due to the lack of immune memory. Children, in particular, have a significantly stronger interferon response due to a primed state of their airway epithelium. In single‐cell transcriptomes of nasal turbinates, we find increased frequencies of immune cells and stronger cytokine‐mediated interactions with epithelial cells, resulting in increased epithelial expression of viral sensors (RIG‐I, MDA5) via IRF1. In vitro, adolescent peripheral blood mononuclear cells produce more cytokines, priming A549 cells for stronger interferon responses to SARS‐CoV‐2. Taken together, our findings suggest that increased numbers of immune cells in the airways of children and enhanced cytokine‐based interactions with epithelial cells tune the setpoint of the epithelial antiviral system. Our findings shed light on the molecular basis of children's remarkable resistance to COVID‐19 and may suggest a novel concept for immunoprophylactic treatments.
Synopsis
SARS‐CoV‐2 infection is milder in children, but the underlying mechanisms are not fully understood. This study finds increased interactions between immune and epithelial cells in children's noses, priming the epithelium for stronger interferon responses upon infection.
The nasal mucosa of children exhibits stronger cytokine‐mediated interactions of immune cells with epithelial cells.
In vitro pretreatment of epithelial cells with cytokines increases virus sensor expression, enhancing SARS‐CoV‐2 recognition.
Decreasing epithelial expression of virus sensors with age associates with increasing risk of severe disease.
SARS‐CoV‐2 infection is milder in children, but the underlying mechanisms are not fully understood. This study finds increased interactions of immune and epithelial cells in children's noses, priming the epithelium for stronger interferon responses upon infection.
Data on cross‐neutralization of the SARS‐CoV‐2 omicron variant more than 1 year after SARS‐CoV‐2 infection are urgently needed, especially in children, to predict the likelihood of reinfection and to ...guide vaccination strategies. In a prospective observational cohort study, we evaluated live‐virus neutralization of the SARS‐CoV‐2 omicron (BA.1) variant in children compared with adults 14 months after mild or asymptomatic wild‐type SARS‐CoV‐2 infection. We also evaluated immunity to reinfection conferred by previous infection plus COVID‐19 mRNA vaccination. We studied 36 adults and 34 children 14 months after acute SARS‐CoV‐2 infection. While 94% of unvaccinated adults (16/17) and children (32/34) neutralized the delta (B.1.617.2) variant, only 1/17 (5.9%) unvaccinated adults, 0/16 (0%) adolescents and 5/18 (27.8%) children <12 years of age had neutralizing activity against omicron (BA.1). In convalescent adults, one or two doses of mRNA vaccine increased delta and omicron neutralization 32‐fold, similar to a third mRNA vaccination in uninfected adults. Neutralization of omicron was 8‐fold lower than that of delta in both groups. In conclusion, our data indicate that humoral immunity induced by previous SARS‐CoV‐2 wild‐type infection more than 1 year ago is insufficient to neutralize the current immune escape omicron variant.
ObjectiveInterim analysis of the RELIANCE registry, an on-going, non-interventional, open-label, multicentre, prospective study evaluating the long-term safety, dosing regimens and effectiveness of ...canakinumab in patients with cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), tumour-necrosis factor receptor-associated periodic syndrome (TRAPS) or mevalonate-kinase deficiency (MKD)/hyperimmunoglobulin-D syndrome (HIDS).MethodsFrom September 2017 for patients with CAPS, and June 2018 for patients with FMF, TRAPS or MKD/HIDS, the registry enrolled paediatric (aged ≥2 years) and adult patients (aged ≥18 years) receiving canakinumab as part of their routine medical care. Safety, canakinumab dose, disease activity and quality of life outcome measures were evaluated at baseline and every 6 months until end of study visit.ResultsAt the analysis cut-off date (December 2020), 168 patients (91 CAPS, 54 FMF, 16 TRAPS and 7 MKD/HIDS) were enrolled. 85 (50.9%) patients were female and 72 (43.1%) were children (<18 years). The median patient age was 20.0 years (range 2.0–79.0 years). In the CAPS cohort, serious infections and serious adverse drug-reactions were more common in patients receiving higher than the recommended starting dose (SD) of canakinumab. A trend to receive >SD of canakinumab was observed in the pooled population. The majority of patients were reported as having either absent or mild/moderate disease activity (physician’s global assessment) from baseline to Month 30, with a stable proportion of patients (~70%) in remission under canakinumab treatment. Patient-reported disease activity (Visual Analogue Scale (VAS), Autoinflammatory Disease Activity Index), fatigue (VAS); markers of inflammation (C-reactive protein, serum amyloid A and erythrocyte sedimentation rate) remained well-controlled throughout.ConclusionData from this analysis confirm the long-term safety and effectiveness of canakinumab for the treatment of CAPS, FMF, TRAPS and MKD/HIDS.
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