Introduction
COVID‐19 pandemic and associated lockdown measures have deeply modified the natural course of seasonal viral infections, such as respiratory syncytial virus (RSV).
Methods
We analyzed ...French national data from three networks: emergency departments (ED) of French hospitals, general practitioners (GP), and hospital laboratories. We compared the number of ED or GP visits for bronchiolitis in children <2 years of age, and the percentage of RSV positive tests in the 2020 to 2021 season with those of the two previous seasons (2018–2019 and 2019–2020). We used time series of the previous 5 years to calculate epidemic thresholds.
Results
During the 2020–2021 season, the epidemic begun in February (Week 05) in the Ile de France (Paris and suburbs) region, 12 weeks later compared with the previous seasons and progressively spread across all the French metropolitan regions. The highest number of bronchiolitis cases in 2021 (Week 12) occurred 10–12 weeks after the previous seasonal peaks of previous seasons, but the number of cases remained lower than in the previous seasonal peaks.
Conclusion
We identified a delayed RSV epidemic in the period that usually corresponds at the end of the epidemic season, raising concerns for the burden of RSV in the already strained healthcare systems during the COVID‐19 pandemic.
The risk of stroke in children with sickle cell disease (SCD) is detected by abnormal intracranial arterial time-averaged mean of maximum velocities (TAMVs ≥200 cm/s). Recently, extracranial internal ...carotid artery (eICA) arteriopathy has been reported, and a cross-sectional study showed that eICA-TAMVs ≥160 cm/s are significantly associated with eICA kinkings and stenosis. The cumulative incidence of and predictive risk factors for intracranial arteriopathy are well described in sickle cell anemia (SCA=SS/Sβ0) but are lacking for SC/Sβ+ children, as is the cumulative incidence of eICA arteriopathy. We report a prospective longitudinal cohort study including 493 children with SCD (398 SCA, 95 SC/Sβ+), all assessed by transcranial and cervical color Doppler ultrasound. Cerebral MRI/MRA data were available in 375 children with SCD and neck MRA in 365 children. eICA kinkings were defined as eICA tortuosities on neck MRA, with an internal acute angle between the two adjacent segments <90°. The median follow-up was 10.6 years. The cumulative incidence of kinkings was significantly lower in SC/Sβ+ children than in children with SCA, and no SC/Sβ+ child developed intra- or extracranial stenotic arteriopathy. The 10-year KM estimate of cumulative incidence (95% CI) for eICA-TAMVs ≥160 cm/s revealed its development in the 2nd year of life in children with SCA, reaching a plateau of 17.4% (13.2–21.6%) by about 10 years of age, while the plateau for eICA stenosis was 12.3% (8.3–16.3%). eICA assessment identified 13.5% (9.3–17.7%) patients at risk of stroke who were not detected by transcranial color Doppler ultrasound. We also show, for the first time, that in addition to a congenital origin, eICA kinkings sin patients with SCD can develop progressively with aging as a function of eICA-TAMVs, themselves related to anemia severity. Ongoing hydroxyurea treatment was significantly associated with a lower risk of abnormal intracranial arteriopathy and eICA kinkings. After adjustment with hydroxyurea, baseline low hemoglobin, high reticulocyte, and WBC counts remained independent risk factors for intracranial arteriopathy, while low hemoglobin and SEN β-haplotype number were independent risk factors for extracranial arteriopathy. The association between extracranial arteriopathy and SEN β-haplotype number suggested a genetic link between the ethnic origin and incidence of eICA kinkings. This prospective cohort study shows the importance of systematically assessing the eICA and of recording biological parameters during the 2nd year of life before any intensive therapy to predict the risk of cerebral arteriopathy and treat patients with severe baseline anemia.
The early initiation of antiretroviral therapy (ART) in HIV-1-infected infants reduces mortality and prevents early CD4 T-cell loss. However, the impact of early ART on the immune system has not been ...thoroughly investigated in children over five years of age or adolescents. Here, we describe the levels of naive CD4 and CD8 T lymphocytes (CD4/CD8T
), reflecting the quality of immune reconstitution, as a function of the timing of ART initiation (early (<6 months) versus late (≥24 months of age)).
The ANRS-EP59-CLEAC study enrolled 27 children (5-12 years of age) and nine adolescents (13-17 years of age) in the early-treatment group, and 19 children (L-Ch) and 21 adolescents (L-Ado) in the late-treatment group. T lymphocytes were analyzed by flow cytometry and plasma markers were analyzed by ELISA. Linear regression analysis was performed with univariate and multivariate models.
At the time of evaluation, all patients were on ART and had a good immunovirological status: 83% had HIV RNA loads below 50 copies/mL and the median CD4 T-cell count was 856 cells/µL (interquartile range: 685-1236 cells/µL). In children, early ART was associated with higher CD8T
percentages (medians: 48.7% vs. 31.0%,
= 0.001), and a marginally higher CD4T
(61.2% vs. 53.1%,
= 0.33). In adolescents, early ART was associated with low CD4T
percentages and less differentiated memory CD8 T cells. CD4T
and CD8T
levels were inversely related to cellular activation and gut permeability.
In children and adolescents, the benefits of early ART for CD8T
were clear after long-term ART. The impact of early ART on CD4T
appears to be modest, because pediatric patients treated late respond to HIV-driven CD4 T-lymphocyte loss by the
production of T
cells in the thymus. Our data also suggest that current immune activation and/or gut permeability has a negative impact on T
levels.
ClinicalTrials.gov, identifier NCT02674867.
Naso-pharyngeal RT-PCR is the gold standard for the diagnosis of COVID-19, but there is a need for rapid and reliable tests. Some validation studies have used frozen aliquots mainly from adults. The ...aim of this real-life study was to test the performance of a SARS-CoV-2 rapid antigen test (SC2-RAT) in children. Symptomatic patients aged 0 to 17 years were recruited in the emergency department of the University Hospital of Creteil and in primary care pediatric practices from October 10, 2020 for 7 weeks. Each enrolled child had a SARS-CoV-2 RT-PCR test and a SC2-RAT from two distinct nasopharyngeal swabs. Among the 308 patients (mean SD age 4.9 5.3 years), fever was the main symptom (73.4%), with no difference between COVID-19–negative and –positive groups. The prevalence of COVID-19 was 10.7% (95% CI 7.5–14.7). On the whole cohort, the sensitivity and specificity of the SC2-RAT compared to RT-PCR was 87.9% (95% CI 71.8–96.6) and 98.5% (95% CI 96.3–99.6). Considering samples with cycle threshold >25, the sensibility was lower: 63.6% (95% CI 30.8–89.1) and the specificity 99.6% (95% CI 98.0–100.0). The mean delay to obtain an SC2-RAT result was <15 min but was 3.2 h (SD 5.5) for an RT-PCR result. Contact with a COVID-19–positive person was more frequent for COVID-19–positive than –negative patients (
n
= 21, 61.6%, vs.
n
= 64, 24.6%;
p
< 0.01). In real life, SC2-RAT seems reliable for symptomatic children, allowing to detect contagious children.
Patients with type 1 Gaucher disease (GD1) present thrombocytopenia, anemia, organomegaly, and bone complications. Most experts consider that the less aggressive forms do not require specific ...treatment. However, little is known about the disease course of these forms. The objective of this cross-sectional retrospective study was to compare the clinical, radiological, and laboratory characteristics of patients with less severe GD1 at diagnosis and at the last evaluation to identify features that might lead to potential complications. Non-splenectomized and never-treated patients (19 women and 17 men) were identified in the French Gaucher Disease Registry (FGDR). Their median age was 36.6 years (2.4–75.1), and their median follow-up was 7.8 years (0.4–32.4). Moreover, 38.7% were heterozygous for the GBA1 N370S variant, and 22.6% for the GBA1 L444P variant. From diagnosis to the last evaluation, GD1 did not worsen in 75% of these patients. Some parameters improved (fatigue and hemoglobin concentration), whereas platelet count and chitotriosidase level remained stable. In one patient (2.7%), Lewy body dementia was diagnosed at 46 years of age. Bone lesion onset was late and usually a single event in most patients. This analysis highlights the genotypic heterogeneity of this subgroup, in which disease could remain stable and even improve spontaneously. It also draws attention to the possible risk of Lewy body disease and late onset of bone complications, even if isolated, to be confirmed in larger series and with longer follow-up.
Non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 were implemented in March 2020. These measures were followed by a major impact on viral and non-viral diseases. We aimed to ...assess the impact of NPI implementation in France on hospitalized community-acquired pneumonia (hCAP) frequency and the clinical and biological characteristics of the remaining cases in children. We performed a quasi-experimental interrupted time-series analysis. Between June 2014 and December 2020, eight pediatric emergency departments throughout France reported prospectively all cases of hCAP in children from age 1 month to 15 years. We estimated the impact on the monthly number of hCAP using segmented linear regression with autoregressive error model. We included 2,972 hCAP cases; 115 occurred during the NPI implementation period. We observed a sharp decrease in the monthly number of hCAP after NPI implementation -63.0% (95 confidence interval, -86.8 to -39.2%);
< 0.001. Children with hCAP were significantly older during than before the NPI period (median age, 3.9 vs. 2.3 years;
< 0.0001), and we observed a higher proportion of low inflammatory marker status (43.5 vs. 33.1%;
= 0.02). Furthermore, we observed a trend with a decrease in the proportion of cases with pleural effusion (5.3% during the NPI period vs. 10.9% before the NPI;
= 0.06). NPI implementation during the COVID-19 (coronavirus disease 2019) pandemic led not only to a strong decrease in the number of hCAP cases but also a modification in the clinical profile of children affected, which may reflect a change in pathogens involved.
Over the past 3 decades, the pediatric department of the university Intercommunal Créteil hospital, a referral center for sickle cell disease (SCD), has prospectively evaluated immunoglobulin (Ig) ...levels in a cohort of 888 children with SCD, including 731 with severe sickle genotypes (HbSS and HbSβ0 thalassemia) and 157 with milder genotypes (HbSC and HbSβ+ thalassemia). We found consistent sickle genotype differences in levels of IgG and IgA, with increased levels of IgA and IgG in the severe versus milder genotype, from early childhood to late adolescence. Additionally, our results revealed a low serum IgM level, irrespective of sickle genotype. Finally, we found that IgA and IgG levels were significantly increased after therapeutic intensification with hydroxyurea but were stabilized in children receiving a transfusion program. The mechanisms contributing to these changes in Ig levels are unclear as is their clinical significance. We believe they should be further investigated.
This prospective observational study sought to ascertain clinical and laboratory parameters associated with the development of acute chest syndrome (ACS) during vaso-occlusive episodes (VOE) in ...children with sickle cell disease (SCD). It was performed at the pediatric department of the university Intercommunal Créteil hospital. All children with SCD (all sickle genotypes) consecutively admitted from November 2013 to December 2016 for painful VOEs and no evidence of ACS were included. Clinical and laboratory parameters collected at admission and within 48 h after admission were compared for children in whom ACS developed or not. Variables that were statistically significant on univariate analysis or considered to be clinically relevant were included in a multivariable model to ascertain the risk factors associated with the development of ACS during a VOE. The variables retained in the multivariate model were used to construct a predictive score for ACS. For each included child and during the study period, only data from the first VOE and/or the first ACS were analyzed. Among 191 hospitalizations for painful VOEs, for 176 children with SCD, ACS developed in 35 during hospitalization. Mean hospital stay was longer for children with ACS versus VOEs alone (7.6 (±2.3) vs. 3.3 (±1.8) days,
< 0.0001), and all children with ACS versus 28/156 (17.9%) with VOEs alone received red blood cell transfusion (
< 0.0001). The multivariate model retained pain score (≥9/10), pain localization (abdominal or spinal pain or involving more than two limbs), and high reticulocyte (≥260 × 10
/L) and neutrophil (>10 × 10
/L) counts, at admission, as independently associated with ACS development. The area under the receiver operating characteristic curve for the ACS predictive score was 0.82 (95% CI: 0.74-0.89), and the negative predictive value was 97.7%. The evolution profiles during the first 48 h differed between children with ACS and VOEs alone, with a more rapid decline of pain score and leucocytosis in children with VOEs. Clinical and laboratory measurements at admission may be simple parameters to identify children with increased risk of ACS development during VOEs and to facilitate early diagnosis of this respiratory complication. Also, the persistent elevation of leukocyte count on day 2 may be considered a sign of evolving ACS.
Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but ...the optimal therapeutic strategy remains unknown.
To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C.
Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021.
IVIG and methylprednisolone vs IVIG alone.
The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1.
Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females 52%; median age, 8.6 years interquartile range, 4.7 to 12.1). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 95% CI, -0.48 to -0.08; odds ratio OR, 0.25 95% CI, 0.09 to 0.70; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 95% CI, -0.40 to -0.04; OR, 0.19 95% CI, 0.06 to 0.61; P = .004), hemodynamic support (absolute risk difference, -0.17 95% CI, -0.34 to -0.004; OR, 0.21 95% CI, 0.06 to 0.76), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 95% CI, -0.35 to -0.01; OR, 0.20 95% CI, 0.06 to 0.66), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 95% CI, -4.0 to -0.7).
Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.
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