IgG antispike persistence and immunophenotype in children infected by SARS-CoV-2.

AIM: The immune status of children recovering from SARS-CoV-2 infection is not completely understood. We describe IgG antispike persistence in children infected during the first two pandemic waves. In addition, we compared with healthy controls their leukocyte populations and CD64 expression. METHODS: Cross-sectional study. Carried out from October 2021 to February 2022 in nonreinfected and nonvaccinated children with SARS-CoV-2 in 2020. The presence of antispike IgG was studied using chemiluminescent immunoassay. Leukocyte populations were analysed using flow cytometry and marked for CD45, CD4, CD8 and CD64. Statistical minor than 0.05 was considered significant. RESULTS: One hundred and eighty-three control and 77 patients were included. IgG antispike determinations were performed after a median of 501 days (262-464); 52 of 77 children were positive. Cases showed significantly higher percentages of monocytes, lymphocytes, CD8+ and CD4+ . In addition, CD64 expression was higher in monocytes and neutrophils. The presence of IgG antispike was accompanied by a higher percentage of CD64+ neutrophils. CONCLUSION: In our series, the SARS-CoV-2 IgG antispike protein was usually positive beyond 1 year after infection. Furthermore, leukocyte populations from cases differ from controls, with higher CD64 expression on neutrophils and monocytes. Prospective clinical observations are required to confirm the implications of these findings.

Palliative home-based care to pediatric cancer patients: characteristics and healthcare delivered.

OBJECTIVES: Cancer patients constitute an important group in pediatric palliative care. Though the patients' home is the preferred place of care, little is known about the characteristics of patients attended by units that provide home assistance. Our objective is to describe the characteristics of cancer patients and healthcare delivered by a pediatric palliative care unit with a home hospitalization program. METHODS: Retrospective study based on clinical records of deceased patients attended by the pediatric palliative care unit of Madrid over 10 years. Data collected included general characteristics, type of cancer, whether they received home assistance, place of death, healthcare delivered (hospitalizations, devices, oncological treatments…), and symptom prevalence. RESULTS: After excluding 47 patients, the clinical records of 144 patients were analyzed. The median age at referral was 9.4 years (IQR: 5.6-14.1), 61.2% were males; 44.2% had solid non-CNS tumors, 35.4% CNS tumors, and 20.4% hematological malignancies; 137 received home care with 89 not requiring further hospital admissions and 70.1% dying at home. The median follow-up time was 1.6 months (IQR: 0.5-2.9). The most used devices were venous ports (71.4%) and oxygen (49.4%); 53.5% of the patients received oncological support therapies. The most common symptoms were pain (91.8%) dyspnea (49.0%) and fatigue (46.9%). CONCLUSIONS: Home assistance was provided in a high number of patients, with a large proportion needing one or no hospital admissions and 70.1% of them dying at home. Further studies characterizing these patients and the factors which promote early access to palliative care are needed.

Shock and Myocardial Injury in Children With Multisystem Inflammatory Syndrome Associated With SARS-CoV-2 Infection: What We Know. Case Series and Review of the Literature.

BACKGROUND: Multisystem inflammatory syndrome associated with SARS-CoV-2 infection can lead to myocardial injury and shock in children, likely the result of a severe inflammatory state, and can mimic Kawasaki disease. OBJECTIVE: To describe the characteristics of shock and myocardial injury in children with confirmed or suspeted COVID-19 during the SARS-CoV-2 pandemic in Spain, including clinical presentation, laboratory and imaging findings, treatment, disease course, and outcome. An extensive literature review is provided. METHODS: Retrospective case series including all children (age 1 month-18 years) admitted to a pediatric intensive care unit in Madrid, Spain, between March 15 and April 30, 2020 with suspected or confirmed SARS-CoV-2 infection and shock. RESULTS: Twelve previously healthy patients with shock, age 5 to 14 years, were included. All required volume resuscitation and 75% required vasoactive/inotropic support. Distributive shock was present on admission in 67% (n = 8), and 4 patients (33%) showed features of cardiogenic shock. Myocardial injury was diagnosed in 67% (n = 8) and ventricular dysfunction in 33% (n = 4). The most common symptoms on presentation were fever (100%), anorexia (100%), diarrhea (75%), and vomiting (75%). Five patients showed signs of Kawasaki disease but none met the criteria for the classic form. Laboratory findings revealed lymphopenia (83%), thrombocytopenia (83%), and increased inflammatory markers (100%). Respiratory status was not significantly impacted. Chest X-ray showed bilateral alveolar infiltrates in 7 (58%) and bilateral pneumonia in 3 (25%). COVID-19 was confirmed in 11 cases (92%). All received empirical therapy against COVID-19, thromboprophylaxis and immunomodulation. Median stay in the PICU and inpatient ward was 4.5 and 10 days, respectively. No patients died. CONCLUSION: Multisystem inflammatory syndrome in children with COVID-19 can mimic Kawasaki disease and lead to a combination of distributive and cardiogenic shock, probably secondary to a hyperinflammatory state that remains to be precisely defined. Treatment strategies include hemodynamic support, empirical therapies against COVID-19, thromboprophylaxis, and immunomodulation.

Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain.

BACKGROUND: Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia. METHODS: A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared. RESULTS: Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5-11.8) vs 3.4 years (IQR 0.4-9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5-8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group. CONCLUSIONS: MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients.

Children in Critical Care Due to Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Experience in a Spanish Hospital.

OBJECTIVES: Spain has been one of the countries most severely affected by the coronavirus disease 2019. This study aims to describe a series of children admitted to a PICU due to coronavirus disease 2019 infection. DESIGN: Prospective observational study. SETTING: Tertiary hospital in Madrid, Spain. PATIENTS: Children admitted to the PICU with severe acute respiratory syndrome coronavirus 2 (severe acute respiratory syndrome coronavirus 2) infection, from March 1, 2020, to April 15, 2020. INTERVENTIONS: Observational study. MEASUREMENTS AND MAIN RESULTS: Epidemiologic data, previous clinical characteristics, support therapy needed, imaging tests, laboratory observations on admission, and pharmacologic therapy. Eleven children were admitted to the PICU, with suspected coronavirus disease 2019; the polymerase chain reaction test was positive in seven. The median age was 100.7 months (range, 0.5-162). Five were admitted from the emergency department and two from the ward. The Pediatric Sequential Organ Failure Assessment score was 3 (range, 0-9), and Pediatric Risk of Mortality II score was 4 (range, 0-16). All children were previously healthy except one (allogeneic hematopoietic stem cell transplantation). Respiratory symptoms and fever were prevalent. A chest radiograph led to a pneumonia diagnosis. Not all patients presented with lymphopenia on admission. D-Dimer and ferritin were elevated. All patients needed oxygen therapy through a nasal cannula; five patients received high-flow nasal cannula therapy, which was later substituted with noninvasive ventilation in four. Mechanical ventilation was necessary in two patients on the first day of PICU admission. Two children required mechanical ventilation and inotropic support. Tocilizumab was applied in two intubated children. Also, four children received heparin. No patients died. CONCLUSIONS: On the whole, the children were previously healthy and are more than 1 year old. Respiratory symptoms were the leading cause of PICU admission, making respiratory support the principal therapy. Patients requiring mechanical ventilation showed deterioration on the first day of admission. These children seemed to require close monitoring, and multicenter studies are necessary.

Normal fecal calprotectin levels in healthy children are higher than in adults and decrease with age.

BACKGROUND/OBJECTIVES: The paediatric reference range of fecal calprotectin (FC) has not been decisively established and previous studies show a wide within-age variability, suggesting that other factors like anthropometric data or type of feeding can influence FC. Our aims were to establish the normal levels of FC in healthy children grouped by age and analyze whether sex, gestational age, birth weight, type of delivery, type of feeding, or anthropometric data influence FC values. METHODS: This multicentre, cross-sectional, and observational study enrolled healthy donors under 18 years of age who attended their Primary Health Care Centre for their routine Healthy Child Program visits. The exclusion criteria were: (i) immunodeficiency, (ii) autoimmune or (iii) gastrointestinal disease; (iv) medication usage; (v) gastrointestinal symptoms; or (vi) positive finding in the microbiological study. RESULTS: We enrolled 395 subjects, mean age was 4.2 years (range 3 days to 16.9 years), and 204 were male. The median FC was 77.0 mcg/g (interquartile range 246). A negative correlation between age and FC was observed (Spearman's rho = -0.603, P<0.01), and none of the other factors analyzed were found to influence FC levels. CONCLUSIONS: Normal FC values in healthy children (particularly in infants) are higher than those considered to be altered in adults and show a negative correlation with age. It is necessary to reconsider the upper limits of FC levels for paediatric patients according to age, with further studies required to determine other factors that influence FC during infancy.

Accuracy of CD64 expression on neutrophils and monocytes in bacterial infection diagnosis at pediatric intensive care admission.

The CD64 receptor has been described as an interesting bacterial infection biomarker. Its expression has not been studied in previously healthy children admitted to pediatric critical care unit (PICU). Our objective was firstly to describe the CD64 expression and secondly study its diagnostic accuracy to discriminate bacterial versus viral infection in this children. We made a prospective double-blind observational study (March 2016-February 2018). A flow cytometry (FC) was done from peripheral blood at PICU admission. We studied the percentage of CD64+ neutrophils and the CD64 mean fluorescence intensity (MFI) on neutrophils (nCD64) and monocytes (mCD64). Statistical analyses were performed with non-parametric tests (p < 0.05). Twenty children in the bacterial infection group (BIG) and 25 in the viral infection group (VIG). Children in BIG showed higher values of CD64+ neutrophils (p = 0.000), nCD64 (p = 0.001), and mCD64 (p = 0.003). In addition, CD64+ neutrophils and nCD64 expression have positive correlation with procalcitonin and C reactive protein. The nCD64 area under the curve (AUC) was 0.83 (p = 0.000). The %CD64+ neutrophils showed an AUC of 0.828 (p = 0.000). The mCD64 AUC was 0.83 (p = 0.003). The nCD64 and %CD64+ neutrophils also showed higher combined values of sensitivity (74%) and specificity (90%) than all classical biomarkers.In our series CD64 expression allows to discriminate between bacterial and viral infection at PICU admission. Future studies should confirm this and be focused in the study of CD64 correlation with clinical data and its utility as an evolution biomarker in critical care children.

Pediatric Disseminated Lemierre Syndrome in 2 Infants: Not Too Young for an Ancient Disease.

The Lemierre syndrome is characterized by an oropharyngeal infection, thrombosis of the internal jugular vein, and multiple septic metastases. Fusobacterium necrophorum is a common cause of it. The incidence is 0.6 to 2.3 cases per million with a mortality rate of 4% to 18%. Its fast evolution and the possibility of severe complications require a high index of suspicion for its diagnosis. We present 2 infants with Lemierre syndrome. The younger case, a 6-month-old infant, was fully recovered. In the other side, and despite an aggressive therapy, an 18-month-old infant developed cerebral palsy. We also provide a short literature review with a focus on clinical presentation and differential diagnosis in order to initiate an early and adequate therapy.

Respiratory Failure in Children With Hemato-oncological Diseases Admitted to the PICU: A Single-center Experience.

Respiratory failure (RF) is a main cause of pediatric intensive care unit (PICU) admission in children with hemato-oncological diseases. We present a retrospective chart review of children admitted to our PICU because of RF (January 2006 to December 2010). The aims of this study are the following: (1) to describe the demographical and clinical characteristics and respiratory management of these children; and (2) to identify the factors associated with mechanical ventilation (MV) and mortality. A total of 69 patients, encompassing 88 episodes, were included (55/88 cases were hypoxemic RF). The first respiratory support at PICU admission was, in decreasing order of frequency, high-flow oxygen nasal cannula (HFNC; 50/88), noninvasive ventilation (NIV; 13/88), and oxygen nasal cannula (16/88). MV was necessary in 47/88 episodes, 38/47 after another respiratory support. In 18/28 children with initial NIV, MV was required later. MV was associated with O-PRISM score, NIV requirement, suspected respiratory infection, and days of PICU treatment. Patients without MV showed an increased survival rate (P=0.001). In summary, the hypoxemic RF was the main cause of PICU admission, and HFNC or NIV was almost always the first respiratory support. The use of MV was associated with a higher mortality rate. The utility of precocious HFNC or NIV should be investigated in larger clinical studies.

Serum sRAGE as a potential biomarker for pediatric bronchiolitis: a pilot study.

PURPOSE: Traditional inflammatory biomarkers are insufficient for the evaluation of bronchiolitis severity. Recent investigations have shown that the receptor for advanced glycation end product (RAGE) and its soluble isoforms (sRAGE) play a critical role in the pathogenesis of lung injury. Main objective was to assess the serum levels of sRAGE of children with severe bronchiolitis admitted to the pediatric intensive care unit (PICU). Secondary objective was to study sRAGE correlation with the evolution and traditional biomarkers. METHODS: Prospective, observational and descriptive study, 43 healthy controls and 37 patients (December 2011-February 2012) were enrolled. sRAGE levels were assessed and compared. In patients, the relation between sRAGE levels and clinical evolution, respiratory assistance, white blood cell count, absolute neutrophils count, serum C-reactive protein, and serum procalcitonin was analyzed. RESULTS: A statistical difference was found in the mean value of sRAGE at PICU admission between patients and controls (1,215.7 ± 535 vs 849 ± 579 pg/ml). Also a significant inverse correlation was found between sRAGE and the Wood-Downes Score at admission (p = 0.02). CONCLUSIONS: Serum sRAGE could be elevated in children with bronchiolitis. Larger clinical studies are necessary to elucidate its role as a bronchiolitis inflammatory and/or lung injury biomarker.

Palliative care in children with spinal muscular atrophy type I: What do they need?

OBJECTIVE: Our aim was to describe the clinical evolution and needs of children with spinal muscular atrophy type I treated in a domiciliary palliative care program. METHOD: We undertook a retrospective chart review of nine consecutive patients. Descriptions of the clinical and demographic profile of children with spinal muscular atrophy (SMA) type I were referred to a pediatric palliative care team (PPCT). RESULTS: Six males and three females were admitted to the PPCT, all before six months of age, except for one afflicted with SMA type I with respiratory distress. The median time of attention was 57 days (range 1-150). The domiciliary attention mainly consisted of respiratory care. The patient with SMA type I with respiratory distress required domiciliary mechanical ventilation by tracheotomy. In all cases, a nasogastric tube (NT) was indicated. As end-of-life care, eight required morphine to manage the dyspnea, four received it only by enteral (oral or NT) administration, and four received it first by enteral administration with continuous subcutaneous infusion (CSI) later. Three of the four patients with CSI also received benzodiazepines. While they were attended by the PPCT, none required hospital admission. All the patients died at home except for the one attended to for just one day. SIGNIFICANCE OF RESULTS: Domiciliary care for these patients is possible. The respiratory morbidity and its management are the main issues. Application of an NT is useful to maintain nutritional balance. Morphine administration is necessary to manage the dyspnea. Palliative sedation is not always necessary.

High-flow nasal cannula in Spanish Pediatric Intensive Care Services: A national web survey about its use and indications.

OBJECTIVE: To describe the high-flow nasal cannula (HFNC) indications in the Spanish pediatric critical care units (PICUs). DESIGN: Descriptive cross-sectional observational study. SETTING: Electronic survey among members of the Spanish Society of Pediatric Intensive Care (SECIP). It was sent weekly from April 10, 2023, to May 21, 2023. PARTICIPANTS: All SECIP members. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: The questions focused on workplace, years of experience, use or non-use of HFNC, justification and expectations regarding its application, starting point within each center, clinical criteria for indication, existence of clinical guidelines, evaluation during its use, and criteria and mode of withdrawal. RESULTS: Two hundred and two participants, 176 were from Spain. Of these, 87/176 had over ten years of experience. One hundred sixty two use HFNC and 66/162 have HFNC clinical guidelines. Acute bronchiolitis (138/162) and respiratory assistance after extubation (106/56) are the two main indications. For 62/162 HFNC may reduce therapeutic escalation. Neuromuscular diseases (105/162) and anatomical airway diseases (135/162) are the two main contraindications. The reasons to do not use HFNC were the absence of evidence about it effectiveness (8/14) and its inadequate cost/effectiveness balance (8/14). CONCLUSIONS: A majority of Spanish pediatric intensivists use HFNC. Its application and withdrawal appears to be primarily based on clinical experience. Besides, those who use HFNC are aware of its limitations and the lack of evidence in some cases. It is necessary to develop single-center and multicenter studies to elucidate the effectiveness of this therapy in the context of critically ill children.

Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine.

Sepsis is characterised by a dysregulated host immune response to infection. Despite recognition of its significance, immune status monitoring is not implemented in clinical practice due in part to the current absence of direct therapeutic implications. Technological advances in immunological profiling could enhance our understanding of immune dysregulation and facilitate integration into clinical practice. In this Review, we provide an overview of the current state of immune profiling in sepsis, including its use, current challenges, and opportunities for progress. We highlight the important role of immunological biomarkers in facilitating predictive enrichment in current and future treatment scenarios. We propose that multiple immune and non-immune-related parameters, including clinical and microbiological data, be integrated into diagnostic and predictive combitypes, with the aid of machine learning and artificial intelligence techniques. These combitypes could form the basis of workable algorithms to guide clinical decisions that make precision medicine in sepsis a reality and improve patient outcomes.

Management of unstable pediatric hemato-oncology patient: results of a Web-based survey to pediatric oncologists in Spain.

UNLABELLED: The current management and monitoring of unstable pediatric hemato-oncology patient (UPHOP) in the oncology ward is not well defined. To evaluate this concept, an anonymous Web-based survey was sent to the 150 Spanish pediatric oncologists registered in the Spanish Society of Pediatric Hemato-Oncology. The response rate was 57 %, with the following main results: Pediatric intensive consulting was available for 97 %, and it was made in case of UPHOP by 37 % of oncologists, up to 65 % if hemodynamic instability. In case of inotropic support initiation, 32 % of respondents never consulted the intensivist. Dopamine is first chosen inotropic; 28 % of surveyed considered there is no limit in its dosage or it is superior to 20 µg/kg/min before an intensivist consulting. Pediatric intensive care admission was considered necessary in case of fever with hemodynamic instability by 15 % of respondents. Respiratory monitoring was mainly done by clinical signs (67 %). In case of respiratory insufficiency, the noninvasive respiratory support by high-flow ventilation with nasal cannula was applied by 57 % in the oncology ward. In case of acute kidney injury, diuretics were generally the initial therapy. The anticonvulsive drugs most frequently applied were valproic acid (93 %), diazepam (88 %), and phenytoin (81 %). CONCLUSION: A consensus should be achieved among oncologists and intensivists. The creation and training of rapid response teams could be useful to improve the UPHOP management.

Fatal Pulmonary Veno-Occlusive Disease and Systemic Juvenile Idiopathic Arthritis: Case Report and Literature Review.

Systemic juvenile idiopathic arthritis (sJIA) is a chronic childhood inflammatory disease. SJIA accounts for approximately 5-15 per cent of all cases of JIA and has a high morbidity and mortality rate. In this disease, pulmonary complications (PC) other than pleuritis are much less frequent and not easily recognised by clinicians. Pulmonary hypertension, the most severe PC, is associated with uncontrolled disease and use of biologic therapies. We present a case of a school-age female with sJIA who died of acute cardiopulmonary instability secondary to pulmonary venous-occlusive disease demonstrated by necropsy. We describe her clinical evolution. We also undertook a narrative review of the literature about PC in sJIA to discuss the current state of the art regarding this complication. High disease activity and the use of multiple therapies include disease-modifying anti-rheumatic drugs should be a red flag for clinicians when discounting PC and pulmonary hypertension. The combination of chest X-ray, electrocardiogram and echocardiogram appear to be the best tests to achieve an early diagnosis.