Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10.

Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical roles in mitochondrial function and morphology. On the other hand, all four ORFs altered mitochondrial dynamics and function, but only ORF3a and ORF9c induced a marked alteration in mitochondrial cristae structure. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features both shared across all accessory proteins and specific for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention.

Recurrent bacteremia and endocarditis due to Staphylococcus capitis in a patient with Bowen's disease: a case report.

This case report details the management of a 79-year-old male with recurrent methicillin-resistant Staphylococcus capitis bacteremia and endocarditis. The patient's clinical journey encompassed multiple hospital admissions, with challenges in managing endocarditis, pacemaker replacements, and potential cutaneous sources of infection. The treatment regimen included intravenous antibiotic therapy during hospitalization and suppressive antibiotic treatment upon discharge, alongside a decolonization strategy for his scalp lesions.

Position statement on infection screening, prophylaxis, and vaccination of pediatric patients with rheumatic diseases and immunosuppressive therapies, part 3: precautions in situations of surgery, fever, and opportunistic infections.

The objective of this study is to provide practical recommendations on the management of pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapies. The recommendations specifically address the cases of surgery, fever, and opportunistic infections (varicella, herpes-zoster, tuberculosis, invasive fungal disease). A qualitative approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using MeSH terms and free text to identify publications on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapies. The results were presented and discussed in a nominal group meeting, comprising a committee of 12 pediatric rheumatologists from the Infection Prevention and Treatment Working Group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process; this was extended to members of the Spanish Society of Pediatric Rheumatology and Spanish Society of Pediatric Infectious Disease of the Spanish Association of Pediatrics. Participants produced a score ranging from 0 (totally disagree) to 10 (totally agree). Agreement was defined as a vote ≥ 7 by at least 70% of participants. The literature review included more than 400 articles. Overall, 63 recommendations (19 on surgery, fever, and opportunistic infections) were generated and voted by 59 pediatric rheumatologists and other pediatric specialists. Agreement was reached for all 63 recommendations. The recommendations on special situations cover management in cases of surgery, fever, and opportunistic infections (varicella, herpes-zoster, tuberculosis, and invasive fungal disease).  Conclusions: Hereby, we provided consensus and updated of recommendations about the management of special situations such as surgery, fever, and opportunistic in children with immune-mediated rheumatic diseases receiving immunosuppressive therapies. Several of the recommendations depend largely on clinical judgement and specific balance between risk and benefit for each individual and situation. To assess this risk, the clinician should have knowledge of the drugs, the patient's previous situation as well as the current infectious disease, in addition to experience. What is Known: • Infectious diseases and related complications are a major cause of morbidity and mortality in patients with immune-mediated rheumatic diseases. • Information on how to manage the treatment in situations of fever, opportunistic infections, and surgery in children is limited, and guidelines for action are often extrapolated from adults. What is New: • In the absence of strong evidence, a literature review and a Delphi survey were conducted to establish a series of expert recommendations that could support the clinical practice, providing a practical and simple day-to-day approach to be used by pediatric rheumatologists.

NUM-score: A clinical-analytical model for personalised imaging after urinary tract infections.

AIM: To identify predictive variables and construct a predictive model along with a decision algorithm to identify nephrourological malformations (NUM) in children with febrile urinary tract infections (fUTI), enhancing the efficiency of imaging diagnostics. METHODS: We performed a retrospective study of patients aged <16 years with fUTI at the Emergency Department with subsequent microbiological confirmation between 2014 and 2020. The follow-up period was at least 2 years. Patients were categorised into two groups: 'NUM' with previously known nephrourological anomalies or those diagnosed during the follow-up and 'Non-NUM' group. RESULTS: Out of 836 eligible patients, 26.8% had underlying NUMs. The study identified six key risk factors: recurrent UTIs, non-Escherichia coli infection, moderate acute kidney injury, procalcitonin levels >2 µg/L, age <3 months at the first UTI and fUTIs beyond 24 months. These risk factors were used to develop a predictive model with an 80.7% accuracy rate and elaborate a NUM-score classifying patients into low, moderate and high-risk groups, with a 10%, 35% and 93% prevalence of NUM. We propose an algorithm for approaching imaging tests following a fUTI. CONCLUSION: Our predictive score may help physicians decide about imaging tests. However, prospective validation of the model will be necessary before its application in daily clinical practice.

Human Metapneumovirus Infections during COVID-19 Pandemic, Spain.

We describe an unusual outbreak of respiratory infections caused by human metapneumovirus in children during the sixth wave of COVID-19 in Spain, associated with the Omicron variant. Patients in this outbreak were older than usual and showed more hypoxia and pneumonia, longer length of stay, and greater need for intensive care.

Nasal TSLP and periostin in infants with severe bronchiolitis and risk of asthma at 4 years of age.

BACKGROUND: Severe bronchiolitis is often associated with subsequent respiratory morbidity, mainly recurrent wheezing and asthma. However, the underlying immune mechanisms remain unclear. The main goal of this study was to investigate the association of nasal detection of periostin and thymic stromal lymphopoietin (TSLP) during severe bronchiolitis with the development of asthma at 4 years of age. METHODS: Observational, longitudinal, post-bronchiolitis, hospital-based, follow-up study. Children hospitalized for bronchiolitis between October/2013 and July/2017, currently aged 4 years, included in a previous study to investigate the nasal airway secretion of TSLP and periostin during bronchiolitis, were included. Parents were contacted by telephone, and were invited to a clinical interview based on a structured questionnaire to obtain information on the respiratory evolution. The ISAAC questionnaire for asthma symptoms for 6-7-year-old children, was also employed. RESULTS: A total of 248 children were included (median age 4.4 years). The mean age at admission for bronchiolitis was 3.1 (IQR: 1.5-6.5) months. Overall, 21% had ever been diagnosed with asthma and 37% had wheezed in the last 12 months. Measurable nasal TSLP was detected at admission in 27(11%) cases and periostin in 157(63%). The detection of nasal TSLP was associated with the subsequent prescription of maintenance asthma treatment (p = 0.04), montelukast (p = 0.01), and the combination montelukast/inhaled glucocorticosteroids (p = 0.03). Admissions for asthma tended to be more frequent in children with TSLP detection (p = 0.07). In the multivariate analysis, adjusting for potential confounders, the detection of TSLP remained independently associated with chronic asthma treatment prescription (aOR:2.724; CI 1.051-7.063, p:0.04) and with current asthma (aOR:3.41; CI 1.20-9.66, p:0.02). Nasal detection of periostin was associated with lower frequency of ever use of short-acting beta2-agonists (SABA) (p = 0.04), lower prevalence of current asthma (p = 0.02), less prescription of maintenance asthma treatment in the past 12 months (p = 0.02, respectively). In the multivariate analysis, periostin was associated with lower risk of asthma at 4 years, independently of the atopic status (aOR:0.511 CI 95% 0.284-0.918, p:0.025). CONCLUSIONS: Our results show a positive correlation between nasal TSLP detection in severe bronchiolitis and the presence of current asthma, prescription of asthma maintenance treatment and respiratory admissions up to the age of 4 years. By contrast, we found a protective association between nasal periostin detection and current asthma at 4 years, ever diagnosis of asthma, maintenance asthma treatment prescription, and respiratory admissions.

Usefulness of daptomycin lock therapy in children with catheter-related bacteremia after failed vancomycin lock therapy.

PURPOSE: Catheter-related bacteremia (CRB) is a significant cause of morbidity, resource expenditure and prolonged hospital stays in patients with long-term catheters, whose numbers have increased considerably in recent years. Antibiotic lock therapy reaches high concentrations in the catheter, allowing good penetration into the biofilm, being vancomycin the most commonly used one in gram-positive infections. Several authors have recently reported the superior in vitro efficacy of daptomycin compared with vancomycin, especially for eradicating biofilms. Although there is some data on the use of daptomycin for antibiotic lock in animal models and adults, there are no data on its use in children. METHODS: A descriptive study was conducted in a tertiary hospital, including patients younger than 16 years in whom daptomycin lock therapy was employed between 2018 and 2022. RESULTS: We report three pediatric patients in whom CRB was confirmed on admission by paired blood cultures positive for CoNS sensitive to vancomycin, daptomycin and linezolid. All patients started vancomycin lock therapy and systemic antibiotic therapy with proven sensitivity for the isolated bacteria, without achieving negative blood cultures. Due to the persistence of positive cultures, vancomycin lock therapy was replaced by daptomycin, and blood cultures turned negative, with no relapses or need for catheter removal. CONCLUSION: The use of daptomycin lock therapy could be considered in children with CoNS catheter infection, especially when other antibiotic lock therapy had failed.

Hyponatremia and other potential markers of ultrasound abnormalities after a first febrile urinary tract infection in children.

Urinary tract infections are the initial manifestation in 30% of urinary tract malformations. Identifying these patients, who could benefit from a specific treatment, is still challenging. Hyponatremia during urinary tract infection has been proposed as a urinary tract malformation marker. We evaluate the prevalence of hyponatremia during febrile urinary tract infections and its association with subjacent urinary tract malformations. We performed a retrospective study of healthy patients under 16 years, diagnosed with a first episode of febrile urinary tract infection, who had undergone blood testing in the acute episode and at least one renal ultrasound during follow-up (January 2014-November 2020). Hyponatremia was defined as (serum sodium ≤ 130 mEq/L). According to imaging findings, we classified patients into three groups: normal kidney ultrasound, mild pelviectasis, and significant urinary tract malformation. We performed logistic regression models to identify independent risk factors for urinary tract malformation and mild pelviectasis. We included 492 patients and 2.8% presented hyponatremia. We identified normal ultrasound in 77%, mild pelviectasis in 10.8%, and urinary tract malformation in 12% of patients. We found an association between mild pelviectasis and hyponatremia [OR 6.6 (CI95% 1.6-26.6)]. However, we found no association between hyponatremia and urinary tract malformation. The parameters that were associated with malformations were presenting a non-E. coli infection, C-reactive-protein levels over 80 mg/L, and bacteremia. CONCLUSION: Hyponatremia during the first episode of febrile urinary tract infection is present in 2.8% of patients and is associated with mild pelviectasis in imaging. However, hyponatremia does not indicate a greater need for complementary tests to screen for urinary tract malformations. WHAT IS KNOWN: • Urinary tract infection is the first manifestation in 30% of children with urinary tract malformation. • Hyponatremia could be a marker to identify these children and guide the imaging approach. WHAT IS NEW: • Around 12% of children with a first episode of febrile urinary tract infection have a urinary tract malformation. • Non-E. coli infection, C-reactive protein levels over 80 mg/L, and bacteremia are markers for malformations to guide diagnostic imaging tests, but hyponatremia (Na ≤ 130 mEq/l) is not a reliable marker.

Position statement on infection screening, prophylaxis, and vaccination in pediatric patients with rheumatic diseases and immunosuppressive therapies, part 2: infection prophylaxis.

This study aims to provide practical recommendations on prophylaxis for infection in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to receive immunosuppressive therapy. A qualitative approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using MeSH terms and free text to identify articles that analyzed data on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapy. The results were presented and discussed in a nominal group meeting comprising a committee of 12 pediatric rheumatologists from the Prevention and Treatment of Infections Working Group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process that was extended to members of the Spanish Society of Pediatric Rheumatology and the Vaccine Advisory Committee of the Spanish Association of Pediatrics. Participants produced a score ranging from 0 (completely disagree) to 10 (completely agree). Agreement was considered to have been reached if at least 70% of participants voted ≥ 7. The literature review included more than 400 articles. Overall, 63 recommendations were generated (23 on infection prophylaxis) and voted by 59 pediatric rheumatologists and other pediatric specialists, all of whom achieved the pre-established level of agreement. The recommendations on prophylaxis of infection cover vaccination and prophylaxis against varicella zoster virus, tuberculosis, Pneumocystis jiroveccii, and invasive fungal infections in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to receive immunosuppressive therapy.  Conclusion: Based on current evidence and a Delphi process, we provided consensus and updated recommendations on prophylaxis and treatment of infections to guide those caring for pediatric rheumatology patients. What is Known: •Data largely derived from adults find that infectious diseases and related complications are a major cause of morbidity and mortality in patients with immune-mediated rheumatic diseases. •It is crucial to be aware of the preventive measures that should be implemented to prevent these infections in children, although most guidelines are often extrapolated from adult cases. What is New: •In the absence of evidence, a literature review and a Delphi survey were conducted to establish a series of expert recommendations that could prove useful in clinical practice, providing a practical and simple day-to-day approach to be used by pediatric rheumatologists. •The recommendations focus on tuberculosis, herpes zoster virus, fungal infections, and Pneumocystis jirovecii.

Treatments for multi-system inflammatory syndrome in children - discharge, fever, and second-line therapies.

Scarce evidence exists about the best treatment for multi-system inflammatory syndrome (MIS-C). We analyzed the effects of steroids, intravenous immunoglobulin (IVIG), and their combination on the probability of discharge over time, the probability of switching to second-line treatment over time, and the persistence of fever 2 days after treatment. We did a retrospective study to investigate the effect of different treatments on children with MIS-C from 1 March 2020 to 1 June 2021. We estimated the time-to-event probability using a Cox model weighted by propensity score to balance the baseline characteristics. Thirty of 132 (22.7%) patients were initially treated with steroids alone, 29/132 (21.9%) with IVIG alone, and 73/132 (55%) with IVIG plus steroids. The probability of early discharge was higher with IVIG than with IVIG plus steroids (hazard ratio [HR] 1.65, 95% CI 1.11-2.45, p = 0.013), but with a higher probability of needing second-line therapy compared to IVIG plus steroids (HR 3.05, 95% CI 1.12-8.25, p = 0.028). Patients on IVIG had a higher likelihood of persistent fever than patients on steroids (odds ratio [OR] 4.23, 95% CI 1.43-13.5, p = 0.011) or on IVIG plus steroids (OR 4.4, 95% CI 2.05-9.82, p < 0.001). No differences were found for this endpoint between steroids or steroids plus IVIG.    Conclusions: The benefits of each approach may vary depending on the outcome assessed. IVIG seemed to increase the probability of earlier discharge over time but also of needing second-line treatment over time. Steroids seemed to reduce persistent fever, and combination therapy reduced the need for escalating treatment. What is Known: • Steroids plus intravenous immunoglobulin, compared with intravenous immunoglobulin alone for multi-system inflammatory syndrome (MIS-C) might reduce the need for hemodynamic support and the duration of fever, but the certainty of the evidence is low. What is New: • Intravenous immunoglobulin, steroids, and their combination for MIS-C may have different outcomes. • In this study, intravenous immunoglobulin increased the probability of discharge over time, steroids reduced persistent fever, while combination therapy reduced the need for second-line treatments.

Epidemiology and clinical features of Streptococcus pyogenes bloodstream infections in children in Madrid, Spain.

Studies have shown increased invasive Group A Streptococcus (GAS) disease, including bloodstream infections (GAS-BSI). However, the epidemiological data of GAS-BSI are limited in children. We aimed to describe GAS-BSI in children in Madrid, over 13 years (2005-2017). Multicenter retrospective cohort study from 16 hospitals from Madrid, Spain. Epidemiology, symptomatology, laboratory, treatment, and outcome of GAS-BSI in children ≤ 16 years were analyzed. 109 cases of GAS-BSI were included, with incidence rate of 4.3 episodes/100,000 children attended at the emergency department/year. We compared incidence between two periods (P1: 2005-June 2011 vs P2: July 2011-2017) and observed a non-significant increase along the study period (annual percentage change: + 6.0% [95%CI: -2.7, + 15.4]; p = 0.163). Median age was 24.1 months (IQR: 14.0-53.7), peaking during the first four years of life (89/109 cases; 81.6%). Primary BSI (46.8%), skin and soft tissue (21.1%), and osteoarticular infections (18.3%) were the most common syndromes. We compared children with primary BSI with those with a known source and observed that the former had shorter hospital stay (7 vs. 13 days; p = 0.003) and received intravenous antibiotics less frequently (72.5% vs. 94.8%; p = 0.001) and for shorter duration of total antibiotic therapy (10 vs. 21 days; p = 0.001). 22% of cases required PICU admission. Factors associated with severity were respiratory distress, pneumonia, thrombocytopenia, and surgery, but in multivariate analysis, only respiratory distress remained significant (adjusted OR:9.23 [95%CI: 2.16-29.41]). Two children (1.8%) died.   Conclusion: We observed an increasing, although non-significant, trend of GAS-BSI incidence within the study. Younger children were more frequently involved, and primary BSI was the most common and less severe syndrome. PICU admission was frequent, being respiratory distress the main risk factor. What is known: • In recent decades, several reports have shown a worldwide increase in the incidence of invasive Group A streptococcal disease (GAS), including bloodstream infection (BSI). Recently, there have been a few reports showing an increase in severity as well. • There needs to be more information on the epidemiology in children since most studies predominantly include adults. What is new: • This study, carried out in children with GAS-BSI in Madrid, shows that GAS-BSI affects mostly younger children, with a broad spectrum of manifestations, needing PICU admission frequently. Respiratory distress was the leading risk factor for severity, whereas primary BSI seemed to be less severe. • We observed an increasing, although non-significant, trend of GAS-BSI incidence in recent years (2005-2017).

Blood analysis for screening of electrolyte and kidney function alterations in patients with febrile urinary tract infection.

AIM: To describe the prevalence, severity, risk factors, and clinical relevance of electrolyte disturbances and acute kidney injury (AKI) during febrile urinary tract infection (fUTI). METHODS: Retrospective observational study of well/fair-appearing patients between 2 months and 16 years, with no previous relevant medical history, diagnosed with fUTI in the paediatric emergency department (PED) with subsequent microbiological confirmation. Analytical alteration (AA) data were considered: AKI (creatinine elevation × 1.5 the median for age), plasma sodium alteration (≤130 or ≥150 mEq/L), and potassium alteration (≤3 or ≥6 mEq/L). RESULTS: We included 590 patients, 17.8% presented AA (13 hyponatremia, 7 hyperkalaemia, and 87 AKI). No patient presented severe analytic alterations or a higher frequency of symptoms potentially attributable to these alterations (seizures, irritability, or lethargy). Risk factors associated with these AA were clinical dehydration (OR = 3.5 95% CI: 1.04-11.7; p = 0.044) and presenting a temperature >39°C (OR = 1.9 95% CI: 1.14-3.1; p = 0.013). CONCLUSIONS: Electrolyte and renal function disturbances are infrequent in the previously healthy paediatric population with a fUTI. If present, they are asymptomatic and not severe. Based on our results, performing systematic blood analysis to rule out AA appears no longer justified, especially in the absence of risk factors.

Genomic characterisation of respiratory syncytial virus: a novel system for whole genome sequencing and full-length G and F gene sequences.

To advance our understanding of respiratory syncytial virus (RSV) impact through genomic surveillance, we describe two PCR-based sequencing systems, (i) RSVAB-WGS for generic whole-genome sequencing and (ii) RSVAB-GF, which targets major viral antigens, G and F, and is used as a complement for challenging cases with low viral load. These methods monitor RSV genetic diversity to inform molecular epidemiology, vaccine effectiveness and treatment strategies, contributing also to the standardisation of surveillance in a new era of vaccines.

Respiratory syncytial virus outbreak during the COVID-19 pandemic. How has it changed?

Introduction: The epidemiology of respiratory syncytial virus (RSV) infection has changed during the COVID-19 pandemic. Our objectives were to describe the RSV epidemic in 2021 and compare it with the previous years to the pandemic. Methods: Retrospective study performed in Madrid (Spain) in a large pediatric hospital comparing the epidemiology and clinical data of RSV admissions during 2021 and the two previous seasons. Results: 899 children were admitted for RSV infection during the study period. During 2021, the outbreak peaked in June and the last cases were identified in July. Previous seasons were detected in autumn-winter. The number of admissions in 2021 was significantly lower than in previous seasons. There were no differences between seasons regarding age, sex or disease severity. Conclusion: RSV hospitalizations during 2021 in Spain moved to summer with no cases in autumn and winter 2020-2021. Unlike other countries, clinical data were similar between epidemics.

Introducción: La epidemiología de la infección por virus respiratorio sincitial (VRS) ha cambiado durante la pandemia de COVID-19. Nuestros objetivos fueron describir la epidemia de VRS en 2021 y compararla con las de los años previos a la pandemia. Métodos: Estudio retrospectivo realizado en Madrid (España), en un hospital pediátrico terciario, que compara los datos epidemiológicos y clínicos de los ingresos por VRS durante 2021 y las 2 temporadas anteriores. Resultados: Ingresaron 899 niños por infección por VRS en el período de estudio. Durante 2021, el brote alcanzó su punto máximo en junio y los últimos casos se identificaron en julio. En las temporadas anteriores se detectaron en otoño-invierno. El número de hospitalizaciones en 2021 fue significativamente menor que en temporadas anteriores. No hubo diferencias entre temporadas en cuanto a edad, sexo o gravedad de la enfermedad. Conclusión: Las hospitalizaciones por VRS durante 2021 en España se trasladaron a verano, sin casos en otoño e invierno 2020-2021. A diferencia de otros países, los datos clínicos fueron similares entre epidemias.

Mycobacterium mageritense Lymphadenitis in Child.

Although human infections caused by Mycobacterium mageritense are rare, there are some case reports involving sinusitis, pneumonia, and hospital-acquired infections in adults. We report a case of lymphadenitis caused by M. mageritense in a child in Spain.

Dynamics of Reverse Transcription-Polymerase Chain Reaction and Serologic Test Results in Children with SARS-CoV-2 Infection.

OBJECTIVES: To determine the time to reverse transcription-polymerase chain reaction (RT-PCR) negativity after the first positive RT-PCR test, factors associated with longer time to RT-PCR negativity, proportion of children seroconverting after proven severe acute respiratory syndrome coronavirus 2 infection, and factors associated with the lack of seroconversion. STUDY DESIGN: The Epidemiological Study of Coronavirus in Children of the Spanish Society of Pediatrics is a multicenter study conducted in Spanish children to assess the characteristics of coronavirus disease 2019. In a subset of patients, 3 serial RT-PCR tests on nasopharyngeal swab specimens were performed after the first RT-PCR test, and immunoglobulin G serology for severe acute respiratory syndrome coronavirus 2 antibodies was performed in the acute and follow-up (<14 and ≥14 days after diagnosis) phase. RESULTS: In total, 324 patients were included in the study. The median time to RT-PCR negativity was 17 days (IQR, 8-29 days), and 35% of patients remained positive more than 4 weeks after the first RT-PCR test. The probability of RT-PCR negativity did not differ across groups defined by sex, disease severity, immunosuppressive drugs, or clinical phenotype. Globally, 24% of children failed to seroconvert after infection. Seroconversion was associated with hospitalization, persistence of RT-PCR positivity, and days of fever. CONCLUSIONS: Time to RT-PCR negativity was long, regardless of the severity of symptoms or other patient features. This finding should be considered when interpreting RT-PCR results in a child with symptoms, especially those with mild symptoms. Seroprevalence and postimmunization studies should consider that 11 in 4 infected children fail to seroconvert.

Kawasaki disease in children younger than 6 months of age: characteristics of a Spanish cohort.

A retrospective study that compared children younger than 6 months versus older children of a Spanish cohort of patients diagnosed with Kawasaki disease between 2011 and 2016 (Kawa-Race study). From the 598 patients recruited, 42 patients were younger than 6 months (7%) and presented more frequently with an incomplete diagnosis of Kawasaki disease (52.4 vs 27.9%, p = 0.001). Cardiac abnormalities detected by echocardiography were more common in younger patients (52.4 vs 30%, p = 0.002). These younger patients presented with a higher proportion of coronary aneurysms as well (19 vs 8.6%, p < 0.001). Shock at diagnosis (9.5 vs 1.9%, p = 0.016) and admission to intensive care units (17.7 vs 4.1%, p = 0.003) were more frequent in patients younger than 6 months. There were no statistically significant differences in relation to infections, non-response to IVIG, or mid- or long-term outcomes.Conclusion: Data of the Spanish cohort are consistent with other American and Asian studies, although Spanish children younger than 6 months had a lower rate of non-response to IVIG and better clinical outcomes. A high index of suspicion should be considered for this population due to a higher risk of coronary abnormalities, presentation of shock, and admission to the intensive care unit. What is Known: •Children below 6 months of age with Kawasaki disease (KD) have different features compared to older. •Younger patients usually have an incomplete form of KD and coronary artery abnormalities. What is New: •Younger than 6 months with KD presented with shock and required admission to PICU more frequently compared to older. •Infections play a similar role in KD despite the age of the patients.

Position statement of the Spanish Society of Pediatric Rheumatology on infection screening, prophylaxis, and vaccination of pediatric patients with rheumatic diseases and immunosuppressive therapies: Part 1 (screening).

This study provides practical recommendations on infection screening in pediatric patients with immune-mediated rheumatic diseases and immunosuppressive therapies. For this reason, a qualitative approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using Mesh and free texts to identify articles that analyzed data on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases and immunosuppressive therapies. The results were presented and discussed in a nominal group meeting, comprising a committee of 12 pediatric rheumatologists from the infections prevention and treatment working group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process that was extended to members of the Spanish Society of Pediatric Rheumatology and Vaccine Advisory Committee of the Spanish Association of Pediatrics. Participants to the process produced a score ranging from 0 = totally disagree to 10 = totally agree. Agreement was considered if at least 70% of participants voted ≥ 7. The literature review included more than 400 articles. Overall, 63 recommendations were generated (21 on infection screening) voted by 59 pediatric rheumatologists and other pediatric specialists, all of them achieving the pre-established agreement level. The recommendations on screening cover all the procedures (serology, assessment of risk factors, and other clinical activities) connected with the screening for infections including tuberculosis; hepatitis A, B, and C viruses; measles; mumps; rubella; diphtheria; and other infections. Conclusion: Screening for infections is an essential part of risk management in pediatric patients with immune-mediated rheumatic diseases and immunosuppressive therapies. What is Known: • Infectious diseases and related complications are a major cause of morbidity and mortality in patients with immune-mediated rheumatic diseases. • At present, practical information on infectious prophylaxis in children with rheumatic diseases is limited, and often extrapolated from children with cancer. What is New: • In the absence of evidence, a literature review and a Delphi survey were conducted to establish a series of expert recommendations that would be useful in clinical practice, providing a practical and simple day-to-day approach to be used by pediatric rheumatologists.

Clinical spectrum of COVID-19 and risk factors associated with severity in Spanish children.

We aimed to identify the spectrum of disease in children with COVID-19, and the risk factors for admission in paediatric intensive care units (PICUs). We conducted a multicentre, prospective study of children with SARS-CoV-2 infection in 76 Spanish hospitals. We included children with COVID-19 or multi-inflammatory syndrome (MIS-C) younger than 18 years old, attended during the first year of the pandemic. We enrolled 1200 children. A total of 666 (55.5%) were hospitalised, and 123 (18.4%) required admission to PICU. Most frequent major clinical syndromes in the cohort were mild syndrome (including upper respiratory tract infection and flu-like syndrome, skin or mucosae problems and asymptomatic), 44.8%; bronchopulmonary syndrome (including pneumonia, bronchitis and asthma flare), 18.5%; fever without a source, 16.2%; MIS-C, 10.6%; and gastrointestinal syndrome, 10%. In hospitalised children, the proportions were 28.5%, 25.7%, 16.5%, 19.1% and 10.2%, respectively. Risk factors associated with PICU admission were age in months (OR: 1.007; 95% CI 1.004 to 1.01), MIS-C (OR: 14.4, 95% CI 8.9 to 23.8), chronic cardiac disease (OR: 4.8, 95% CI 1.8 to 13), asthma or recurrent wheezing (OR: 2.5, 95% CI 1.2 to 5.2) and after excluding MIS-C patients, moderate/severe liver disease (OR: 8.6, 95% CI 1.6 to 47.6). However, asthmatic children were admitted into the PICU due to MIS-C or pneumonia, not due to asthma flare.Conclusion: Hospitalised children with COVID-19 usually present as one of five major clinical phenotypes of decreasing severity. Risk factors for PICU include MIS-C, elevation of inflammation biomarkers, asthma, moderate or severe liver disease and cardiac disease. What is Known: • All studies suggest that children are less susceptible to serious SARS-CoV-2 infection when compared to adults. Most studies describe symptoms at presentation. However, it remains unclear how these symptoms group together into clinically identifiable syndromes and the severity associated with them. What is New: • We have gathered the primary diagnoses into five major syndromes of decreasing severity: MIS-C, bronchopulmonary syndrome, gastrointestinal syndrome, fever without a source and mild syndrome. Classification of the children in one of the syndromes is unique and helps to assess the risk of critical illness and to define the spectrum of the disease instead of just describing symptoms and signs.

Comparative study shows that 1 in 7 Spanish children with COVID-19 symptoms were still experiencing issues after 12 weeks.

AIM: We investigated prolonged symptoms in children after COVID-19, including the clinical characteristics and risk factors. METHODS: This multicentre retrospective study focused on 451 children under 18 years old who were diagnosed with symptomatic COVID-19 between 14 March and 31 December 2020. Persistent symptoms were analysed with a telephone questionnaire by the attending physicians from 1 August to 30 September 2021. A control group of 98 with no history of COVID-19, who were treated for other reasons, was also included. RESULTS: Most (82.0%) of the cases had mild infections that required outpatient care and 5.1% were admitted to the paediatric intensive care unit (PICU). We found that 18.4% had symptoms that lasted 4-12 weeks. There were also 14.6% who were symptomatic for longer than 12 weeks and the odds risks were higher for children aged 5 years or more (OR 3.0), hospitalised (OR 3.9), admitted to the PICU (OR 4.3) and with relatives who were symptomatic for 12 weeks or more (OR 2.8). The controls had similar percentages of prolonged symptoms, despite having no history of COVID-19, especially those who were older than 5 years. CONCLUSION: This study confirmed that a worrying percentage of children had prolonged symptoms after COVID-19.