Characteristics and Risk Factors Associated with SARS-CoV-2 Pneumonias in Hospitalized Pediatric Patients: A Pilot Study.

SARS-CoV-2 pneumonia in children has a lower incidence and severity compared to adults. Risk factors are adolescence and comorbidities. Our aims were to describe the characteristics of children admitted with SARS-CoV-2 pneumonia, identify risk factors associated with severity and compare the cases according to the variant of SARS-CoV-2. This was a descriptive and retrospective study, including patients aged 0-18 years hospitalized in a tertiary-care hospital between 1 March 2020 and 1 March 2022. Epidemiological, clinical, diagnostic and therapeutic data were analyzed. Forty-four patients were admitted; twenty-six (59%) were male and twenty-seven (61%) were older than 12 years. Thirty-six (82%) had comorbidities, the most frequent of which were obesity and asthma. Seven (15.9%) patients required high-flow oxygen, eleven (25%) non-invasive ventilation and four (9.1%) conventional mechanical ventilation. In critically ill patients, higher levels of anemia, lymphopenia, procalcitonin, lactate dehydrogenase (LDH) and hypoalbuminemia and lower levels of HDL-cholesterol were detected (all p < 0.05). Prematurity (p = 0.022) was associated with intensive care unit admission. Patients were younger during the Omicron wave (p < 0.01); no variant was associated with greater severity. In conclusion, pediatric patients with a history of prematurity or with anemia, lymphopenia, elevated procalcitonin, elevated LDH levels, hypoalbuminemia and low HDL-cholesterol levels may require admission and present more severe forms. Apart from age, no notable differences between SARS-CoV-2 variant periods were found.

Multisystem inflammatory syndrome in children (MIS-C) and sepsis differentiation by a clinical and analytical score: MISSEP score.

Differential diagnosis between Multisystem Inflammatory Syndrome in Children (MIS-C) and other causes of systemic inflammatory response such as sepsis is complex. The aims were to evaluate the differences between pediatric patients with MIS-C and sepsis and to develop a score to distinguish both entities. This was a retrospective study that compared demographic, clinical, diagnostic, and therapeutic data of pediatric patients with MIS-C (cohort 2020-2022) and sepsis (cohorts 2010-2014 and 2017-2018) admitted to a Pediatric Intensive Care Unit (PICU) of a tertiary care hospital. A diagnostic score was developed with variables that differentiated the two conditions. Twenty-nine patients with MIS-C were identified, who were matched 1:3 with patients with sepsis (n = 87). Patients with MIS-C were older (10 vs. 4 years old), and the majority were male (69%). Clinical characteristics that demonstrated differences were prolonged fever and signs and symptoms affecting skin-mucosa and gastrointestinal system. Leukocytes, PCT, and ferritin were higher in sepsis, while thrombocytopenia, lymphopenia, and elevated fibrinogen and adrenomedullin (biomarker with a role for the detection of invasive infections) were more frequent in MIS-C. MIS-C patients presented greater myocardial dysfunction (p < 0.001). Five criteria were selected and included in the MISSEP score after fitting them into a multivariate logistic regression model: fever > 48 hours (20 points), thrombocytopenia < 150 × 103/µL (6 points), abdominal pain (15 points), conjunctival erythema (11 points), and Vasoactive Inotropic Score (VIS) > 10 (7 points). The cutoff > 25 points allowed to discriminate MIS-C from sepsis with a sensitivity of 0.89 and specificity of 0.95.     Conclusion: MIS-C phenotype overlaps with sepsis. MISSEP score could be useful to distinguish between both entities and direct specific treatment. What is Known: • Differential diagnosis between Multisystem Inflammatory Syndrome in Children (MIS-C) and other causes of systemic inflammatory response such as sepsis is complex. • It is essential to establish an accurate initial diagnosis and early specific treatment in both cases of MIS-C and sepsis to improve the prognosis of these patients. What is New: • Patients with MIS-C are older and have characteristic symptoms of prolonged fever, gastrointestinal symptoms, skin-mucosal involvement, and greater myocardial dysfunction, compared to patients with sepsis. • The use of diagnostic scores, such as the MISSEP score, can be very useful to distinguish between the two entities and help direct specific treatment.

SARS-CoV-2 transmission in teenagers and young adults in Fútbol Club Barcelona's Multidisciplinary Sports Training Academy.

Most studies, aimed at determining the incidence and transmission of SARS-CoV-2 in children and teenagers, have been developed in school settings. Our study conducted surveillance and inferred attack rates focusing on the practice of sports. Prospective and observational study of those attending the sports facilities of Fútbol Club Barcelona (FCB), in Barcelona, Spain, throughout the 2020-2021 season. Participants were young players (from five different sports) and adult workers, who belonged to stable teams (shared routines and were involved in same quarantine rules). Biweekly health questionnaires and SARS-CoV-2 screening were conducted. From the 234 participants included, 70 (30%) both lived and trained in the FCB facilities (Recruitment Pathway 1;RP1) and 164 (70%) lived at their own household and just came to the facilities to train (RP2). During the study, 38 positive cases were identified; none had severe symptoms or needed hospitalization. The overall weekly incidence in the cohorts did not differ compared to the one expected in the community, except for 2 weeks when an outbreak occurred. The attack rate (AR) was three times higher for the participants from RP1, in comparison to those from RP2 (p < 0.01). A Basketball team showed a significant higher AR.  Conclusion: Physical activities in stable teams are not related to an increased risk of transmission of SARS-CoV-2, since there were the same observed cases than expected in the community. The risk is higher in indoor sports (Basketball vs. Football), and in closed cohort living settings (RP1 vs. RP2). The fulfilment of preventive measures is essential. What is Known: • Despite the low numerical impact caused in paediatric hospitalizations during COVID-19 pandemic, the social impact has been maximum. • The transmission potential in children and teenagers is limited, and it had been widely demonstrated in school settings. What is New: • Group physical activities in children and teenagers are not also related to an increased risk of transmission of SARS-CoV-2, when preventive measures, such as washing hands, and screening protocols are applied. • Routine and semi-professional sports activities seem safe environments to promote during this pandemic.

Quantification of a qualitative sepsis code: laying the foundations for the automation revolution.

To quantify a qualitative screening tool for the early recognition of sepsis in children with fever either visiting the emergency department or already admitted to hospital. Prospective observational study including febrile patients under 18 years of age. Sepsis diagnosis was the main outcome. A multivariable analysis was performed with 4 clinical variables (heart rate, respiratory rate, disability, and poor skin perfusion). The cut-off points, odds ratio, and coefficients of these variables were identified. The quantified tool was then obtained from the coefficients. The area under the curve (AUC) was obtained and internal validation was performed using k-fold cross-validation. Two hundred sixty-six patients were included. The multivariable regression confirmed the independent association of the 4 variables with the outcome. The quantified screening tool yielded an excellent AUC, 0.825 (95%CI 0.772-0.878, p < 0.001), for sepsis prediction.  Conclusion: We successfully quantified a sepsis screening tool, and the resulting model has an excellent discriminatory power. What is Known: • Screening tests have to be based only on clinical variables that needs minimum technological support. • The current Sepsis Code is a qualitative screening tool. What is New: • The current screening tool was quantified using four clinical variables, weighted according to the deviation from normality and differentiated according to the age of the patient. • The resulting model has an excellent discriminatory power in identifying septic patients among febrile pediatric patients.

Ventilator-associated pneumonia is linked to a worse prognosis than community-acquired pneumonia in children.

BACKGROUND: Around 12-20% of patients with community-acquired pneumonia (CAP) require critical care. Ventilator-associated pneumonia (VAP) is the second cause of nosocomial infection in Paediatric Intensive Care Units (PICU). As far as we know, there are no studies comparing both types of pneumonia in children, thus it remains unclear if there are differences between them in terms of severity and outcomes. OBJECTIVE: The aim was to compare clinical and microbiological characteristics and outcomes of patients with severe CAP and VAP. METHODS: A retrospective descriptive study, including patients diagnosed of VAP and CAP, with a positive respiratory culture and under mechanical ventilation, admitted to the PICU from 2015 to 2019. RESULTS: 238 patients were included; 163 (68.4%) with CAP, and 75 (31.5%) with VAP. Patients with VAP needed longer mechanical ventilation (14 vs. 7 days, p<0.001) and more inotropic support (49.3 vs. 30.7%, p = 0.006). Patients with VAP had higher mortality (12 vs. 2.5%, p = 0.005). Enterobacterales were more involved with VAP than with CAP (48 vs. 9%, p<0.001). Taking into account only the non-drug sensitive microorganisms, patients with VAP tended to have more multidrug-resistant bacteria (30 vs. 10.8%, p = 0.141) than patients with CAP. CONCLUSION: Patients with VAP had worse prognosis than patients with CAP, needing longer mechanical ventilation, more inotropic support and had higher mortality. Patients with VAP were mainly infected by Enterobacterales and had more multidrug resistant microorganisms than patients with CAP.

Antimicrobial Stewardship Improvement in Pediatric Intensive Care Units in Spain-What Have We Learned?

Antibiotic misuse in pediatric intensive care units (PICUs) can lead to increased antimicrobial resistance, antibiotic-triggered side effects, hospital costs, and mortality. We performed a multicenter, prospective study, analyzing critically ill pediatric patients (≥1 month to ≤18 years) admitted to 26 Spanish PICUs over a 3-month period each year (1 April−30 June) from 2014−2019. To make comparisons and evaluate the influence of AMS programs on antibiotic use in PICUs, the analysis was divided into two periods: 2014−2016 and 2017−2019 (once 84% of the units had incorporated an AMS program). A total of 11,260 pediatric patients were included. Total antibiotic prescriptions numbered 15,448 and, overall, 8354 patients (74.2%) received at least one antibiotic. Comparing the two periods, an increase was detected in the number of days without antibiotics in patients who received them divided by the number of days in PICUs, for community-acquired infections (p < 0.001) and healthcare-associated infections (HAIs) acquired in PICUs (p < 0.001). Antibiotics were empirical in 7720 infections (85.6%), with an increase in appropriate antibiotic indications during the second period (p < 0.001). The main indication for antibiotic adjustment was de-escalation, increasing in the second period (p = 0.045). Despite the high rate of antibiotic use in PICUs, our results showed a significant increase in appropriate antibiotic use and adjustment following the implementation of AMS programs.

RISK score for developing ventilator-associated pneumonia in children: The RISVAP study.

OBJECTIVES: Ventilator-associated pneumonia (VAP) is the second most common healthcare-associated infection in children. The aim of this study was to determine the risk factors for VAP in children and to create a risk score for developing VAP (RISVAP score). STUDY DESIGN: It was a prospective observational study, including children who required mechanical ventilation (MV), registered in the multicentre ENVIN-HELICS database from 2014 to 2019. The regression coefficients of each independent risk factor for VAP were used to create the RISVAP score. Each factor scored 0 if it was absent, or, if it was present, an assigned value from 1 to 7, according to the regression coefficient. RESULTS: A total of 3798 patients were included, 97(2.5%) developing VAP. The independent risk factors for VAP were: female (odds ratio [OR]: 1.642, p = 0.024), MV > 4 days (OR: 26.79, p < 0.001), length in pediatric intensive care unit > 7 days (OR: 11.74, p < 0.001), and previous colonisation (OR: 4.18, p < 0.001). The RISVAP was calculated for each patient as the sum of all the independent risk factors. Three risk groups were obtained: low (0-5 points), intermediate (6-12 points), and high risk for VAP (13-16 points). The area under the curve for the final score was 0.905 (95%confidence interval: 0.888-0.923, p < 0.001). CONCLUSIONS: The RISVAP is the first risk score for VAP in pediatric populations. Using this predictive score, might be helpful to detect vulnerable patients and therefore implement preventative strategies.

Risk factors and incidence of invasive bacterial infection in severe bronchiolitis: the RICOIB prospective study.

BACKGROUND: Bacterial infection (BI), both community-acquired (CA-BI) and hospital-acquired (HAI), might present as a severe complication in patients with bronchiolitis. This study aimed to describe BI in children with severe bronchiolitis, and to define risk factors for BI. METHODS: This was a prospective, descriptive study that included infants admitted to the pediatric intensive care unit (PICU) due to bronchiolitis between 2011 and 2017. The BROSJOD score was calculated to rate the severity of bronchiolitis. RESULTS: Inclusion of 675 patients, with a median age of 47 days (IQR 25-99). 175 (25.9%) patients developed BI, considered HAI in 36 (20.6%). Patients with BI had higher BROSJOD score, PRISM III, and required invasive mechanical ventilation and inotropic support more frequently (p < 0.001). BI was independently associated with BROSJOD higher than 12 (OR 2.092, 95%CI 1.168-3.748) CA-BI was associated to BROSJOD > 12 (OR 2.435, 95%CI 1.379-4.297) and bacterial co-infection (OR 2.294 95%CI 1.051-5.008). Concerning HAI, an independent association was shown with mechanical ventilation longer than 7 days (OR 5.139 95%CI 1.802-14.652). Infants with BI had longer PICU and hospital stay (p < 0.001), Mortality was higher in patients with HAI. CONCLUSIONS: A quarter of infants with severe bronchiolitis developed BI. A BROSJOD > 12 may alert the presence of CA-BI, especially pneumonia. Patients with BI have higher morbidity and mortality.

New multivariable prediction model PEdiatric SEpsis recognition and stratification (PESERS score) shows excellent discriminatory capacity.

AIM: To develop a quantitative predictive scoring model for the early recognition and assessment of paediatric sepsis. METHODS: Prospective observational study including emergency department and in-hospital febrile patients under 18 years. Sepsis diagnose (Goldstein 2005 definitions) was the main outcome. Variables associated with the outcome were included in a multivariable analysis. Cut-off points, odds ratio and coefficients for the variables kept after the multivariable analysis were identified. The score was obtained from the coefficients, The AUC was obtained from ROC-analysis, and internal validation was performed using k-fold cross-validation. RESULTS: The analysis included 210 patients. 45 variables were evaluated and the bivariate analysis identified 24 variables associated with the outcome. After the multivariable regression, 11 variables were kept and the score was obtained. The model yielded an excellent AUC of 0.886 (95% CI 0.845-0.927), p < 0.001 for sepsis recognition. With a cut-off value of 5 for the score, we obtained a sensitivity of 98%, specificity of 76.7%, positive predictive value of 87.9% and negative predictive value of 93.3%. CONCLUSION: The proposed scoring model for paediatric sepsis showed adequate discriminatory capacity and sufficient accuracy, which is of great clinical significance in detecting sepsis early and predicting its severity. Nevertheless external validation is needed before clinical use.

Multiplex Antibody Analysis of IgM, IgA and IgG to SARS-CoV-2 in Saliva and Serum From Infected Children and Their Close Contacts.

COVID-19 affects children to a lesser extent than adults but they can still get infected and transmit SARS-CoV-2 to their contacts. Field deployable non-invasive sensitive diagnostic techniques are needed to evaluate the infectivity dynamics of SARS-CoV-2 in pediatric populations and guide public health interventions, particularly if this population is not fully vaccinated. We evaluated the utility of high-throughput Luminex assays to quantify saliva IgM, IgA and IgG antibodies against five SARS-CoV-2 spike (S) and nucleocapsid (N) antigens in a contacts and infectivity longitudinal study in 122 individuals (52 children and 70 adults). We compared saliva versus serum/plasma samples in infected children and adults diagnosed by weekly RT-PCR over 35 days (n=62), and those who consistently tested negative over the same follow up period (n=60), in the Summer of 2020 in Barcelona, Spain. Saliva antibody levels in SARS-CoV-2 RT-PCR positive individuals were significantly higher than in negative individuals and correlated with those measured in sera/plasmas. Asymptomatic infected individuals had higher levels of anti-S IgG than symptomatic individuals, suggesting a protective anti-disease role for antibodies. Higher anti-S IgG and IgM levels in serum/plasma and saliva, respectively, in infected children compared to infected adults could also be related to stronger clinical immunity in them. Among infected children, males had higher levels of saliva IgG to N and RBD than females. Despite overall correlation, individual clustering analysis suggested that responses that may not be detected in blood could be patent in saliva, and vice versa. In conclusion, measurement of SARS-CoV-2-specific saliva antibodies should be considered as a complementary non-invasive assay to serum/plasma to determine COVID-19 prevalence and transmission in pediatric populations before and after vaccination campaigns.

Low levels of CIITA and high levels of SOCS1 predict COVID-19 disease severity in children and adults.

It is unclear why COVID-19 ranges from asymptomatic to severe. When SARS-CoV-2 is detected, interferon (IFN) response is activated. When it is insufficient or delayed, it might lead to overproduction of cytokines and severe COVID-19. The aim was to compare cytokine and IFN patterns in children and adults with differing severity with SARS-CoV-2.It was a prospective, observational study, including 84 patients. Patients with moderate/severe disease had higher cytokines' values than patients with mild disease (p< 0.001).Two IFN genes were selected to build a decision tree for severity classification: SOCS1 (representative of the rest of the IFN genes) and CIITA (inverse correlation). Low values of CIITA and high values of SOCS1 indicated severe disease. This method correctly classified 33/38(86.8%) of children and 27/34 (79.4%) of adults. To conclude, patients with severe disease had an elevated cytokine pattern, which correlated with the IFN response, with low CIITA and high SOCS1 values.

Mid-regional pro-adrenomedullin for diagnosing evolution after cardiac surgery in newborns: the PRONEW study.

Newborns are the most vulnerable patients after cardiac surgery. Although mortality risk scores before surgery may help predict the risk of poor outcome, new tools are required, and biomarkers could add objective data to these tools. The aim of this study was to assess the ability of mid-regional pro-adrenomedullin (pro-ADM) and pro-atrial natriuretic peptide (pro-ANP) to predict poor outcome after cardiac surgery. This is a pilot diagnostic accuracy study that includes newborns and infants under 2 months admitted to an intensive care unit after cardiac surgery. Pro-ADM and pro-ANP were determined immediately upon admission. Poor outcome was defined as mortality, cardiac arrest, requiring extracorporeal support, requiring renal replacement therapy, or neurological injury. Forty-four patients were included. Twenty-six (59%) had a STAT category of ≥ 4. Ten patients (22.7%) presented a poor outcome, four of whom (9.1%) died. Pro-ADM was higher in patients with poor outcome (p = 0.024) and death (p = 0.012). Pro-ADM showed the best area under curve (AUC) for predicting poor outcome (0.735) and mortality alone (0.869). A pro-ADM of 2 nmol/L had a Sn of 75% and a Sp of 85% for predicting mortality. Pro-ADM > 2 nmol/L was independently associated with poor outcome (OR 5.8) and mortality (OR 14.1). Although higher pro-ANP values were associated with poor outcomes, no cut-off point were found. The combination of STAT ≥ 4 and the biomarkers did not enhance predictive power for poor outcome or mortality.Conclusion: Pro-ADM and pro-ANP determined immediately after surgery could be helpful for stratifying risk of poor outcome and mortality in newborns. What is Known: • Some congenital heart diseases must be corrected/palliated during the first days of life. A useful tool to predict the risk of severe complications has not been proposed. • Most unstable newborns would have higher values of biomarkers such as pro-ADM and pro-ANP related to shock and compensatory actions. What is New: • Pro-ADM and pro-ANP seem to be good biomarkers to predict poor outcome after cardiac surgery. A pro-ADM < 2 nmol/L would imply a low likelihood of a poor outcome. • Deepening the analysis of biomarkers can help in making decisions to prevent/treat complications.

Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Children in Summer Schools Applying Stringent Control Measures in Barcelona, Spain.

BACKGROUND: Understanding the role of children in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is critical to guide decision-making for schools in the pandemic. We aimed to describe the transmission of SARS-CoV-2 among children and adult staff in summer schools. METHODS: During July 2020, we prospectively recruited children and adult staff attending summer schools in Barcelona who had SARS-CoV-2 infection. Primary SARS-CoV-2 infections were identified through (1) a surveillance program in 22 summer schools of 1905 participants, involving weekly saliva sampling for SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) during 2-5 weeks; and (2) cases identified through the Catalonian Health Surveillance System of children diagnosed with SARS-CoV-2 infection by nasopharyngeal RT-PCR. All centers followed prevention protocols: bubble groups, handwashing, face masks, and conducting activities mostly outdoors. Contacts of a primary case within the same bubble were evaluated by nasopharyngeal RT-PCR. Secondary attack rates and the effective reproduction number in summer schools (Re*) were calculated. RESULTS: Among the >2000 repeatedly screened participants, 30 children and 9 adults were identified as primary cases. A total of 253 close contacts of these primary cases were studied (median, 9 [interquartile range, 5-10] for each primary case), among which 12 new cases (4.7%) were positive for SARS-CoV-2. The Re* was 0.3, whereas the contemporary rate in the general population from the same areas in Barcelona was 1.9. CONCLUSIONS: The transmission rate of SARS-CoV-2 infection among children attending school-like facilities under strict prevention measures was lower than that reported for the general population. This suggests that under preventive measures schools are unlikely amplifiers of SARS-CoV-2 transmission, supporting current recommendations for school opening.

Antibody conversion rates to SARS-CoV-2 in saliva from children attending summer schools in Barcelona, Spain.

BACKGROUND: Surveillance tools to estimate viral transmission dynamics in young populations are essential to guide recommendations for school opening and management during viral epidemics. Ideally, sensitive techniques are required to detect low viral load exposures among asymptomatic children. We aimed to estimate SARS-CoV-2 infection rates in children and adult populations in a school-like environment during the initial COVID-19 pandemic waves using an antibody-based field-deployable and non-invasive approach. METHODS: Saliva antibody conversion defined as ≥ 4-fold increase in IgM, IgA, and/or IgG levels to five SARS-CoV-2 antigens including spike and nucleocapsid constructs was evaluated in 1509 children and 396 adults by high-throughput Luminex assays in samples collected weekly in 22 summer schools and 2 pre-schools in 27 venues in Barcelona, Spain, from June 29th to July 31st, 2020. RESULTS: Saliva antibody conversion between two visits over a 5-week period was 3.22% (49/1518) or 2.36% if accounting for potentially cross-reactive antibodies, six times higher than the cumulative infection rate (0.53%) assessed by weekly saliva RT-PCR screening. IgG conversion was higher in adults (2.94%, 11/374) than children (1.31%, 15/1144) (p=0.035), IgG and IgA levels moderately increased with age, and antibodies were higher in females. Most antibody converters increased both IgG and IgA antibodies but some augmented either IgG or IgA, with a faster decay over time for IgA than IgG. Nucleocapsid rather than spike was the main antigen target. Anti-spike antibodies were significantly higher in individuals not reporting symptoms than symptomatic individuals, suggesting a protective role against COVID-19. CONCLUSION: Saliva antibody profiling including three isotypes and multiplexing antigens is a useful and user-friendlier tool for screening pediatric populations to detect low viral load exposures among children, particularly while they are not vaccinated and vulnerable to highly contagious variants, and to recommend public health policies during pandemics.

Infection what else? The usefulness of procalcitonin in children after cardiac surgery.

OBJECTIVES: Procalcitonin is a useful biomarker for predicting bacterial infection after cardiac surgery. However, sometimes procalcitonin rises following cardiac surgery without a confirmation of bacterial infection. The aim was to analyse procalcitonin levels in children without a bacterial infection after cardiac surgery. STUDY DESIGN: This is a prospective, observational study of children <18 years old admitted to the pediatric intensive care unit after cardiac surgery. RESULTS: 1,042 children were included, 996 (95.6%) without a bacterial infection. From them, severe complications occurred in 132 patients (13.3%). Procalcitonin increased differentially depending on the type of complication. Patients who presented a poor outcome (n = 26, 2.6%) had higher procalcitonin values in the postoperative period than the rest of patients (<24 hours: 5.8 ng/mL vs. 0.6 ng/mL; 24-48 hours, 5.1 ng/mL vs. 0.8 ng/mL, and 48-72 hours, 5.3 ng/mL vs. 1.2 ng/mL), but these values remained stable over time (p = 0.732; p = 0.110). The AUC for procalcitonin for predicting poor outcome was 0.876 in the first 24 hours. The cut-off point to predict poor outcome was 2 ng/mL in the first 24 hours (sensitivity 86.9%, specificity 77.3%). Patients with bacterial infection (n = 46) presented higher values of procalcitonin initially, but they decreased in the 48-72 hours period (<24 hours: 4.9 ng/mL; 24-48 hours, 5.8 ng/mL, and 48-72 hours, 4.5 ng/mL). CONCLUSIONS: A procalcitonin value<2 ng/mL may indicate the absence of infection and poor outcome after cardiac surgery. The evolution of the values of this biomarker might help to discern between infection (where procalcitonin will decrease) and poor outcome (where procalcitonin will not decrease).

Weaning from neonatal and pediatric ECMO with stand-by cannula.

The precise moment for weaning a patient off extracorporeal membrane oxygenation (ECMO) is not always easy to establish. Also, mechanical causes may obligate to disconnect the patient from the circuit before the optimal weaning off. In these selected cases, the patient can be disconnected from the circuit and the cannula can be left in place (stand-by cannula) until the patient's stability without ECMO is assured. The aim was to describe our experience with the stand-by cannula. Single-institution, long-term retrospective study in a pediatric tertiary care hospital. Neonatal and pediatric patients who were under ECMO and needed stand-by cannula before definitive de-cannulation were included. During 18 years, 166 children required ECMO. In 31 patients (18.7%), stand-by cannula was performed before the weaning off. Twenty patients (64.5%) were newborn. The main reason for requiring ECMO in these newborn was persistent pulmonary hypertension. Eleven patients were pediatric and their main cause for requiring ECMO was cardiogenic shock (six patients, 54.4%). The reasons for requiring stand-by cannula were the uncertainty of a successful weaning off in 17 patients (54.8%), to undergo surgery in 10 patients (32.3%) and to replace the circuit in four cases (12.9%). The median duration of stand-by cannula was 12 h (IQR 6-24). Heparinized saline serum was the main maintenance perfusion (28 patients, 90.3%). Three patients needed to restart support with ECMO. Only one mechanical complication was detected. Stand-by cannula is a safe technique, which allows performing a quick re-entrance on ECMO if the weaning off fails.

Similarities and differences between the immunopathogenesis of COVID-19-related pediatric multisystem inflammatory syndrome and Kawasaki disease.

Multisystem inflammatory syndrome associated with the SARS-CoV-2 pandemic has recently been described in children (MIS-C), partially overlapping with Kawasaki disease (KD). We hypothesized that (a) MIS-C and prepandemic KD cytokine profiles may be unique and justify the clinical differences observed, and (b) SARS-CoV-2-specific immune complexes (ICs) may explain the immunopathology of MIS-C. Seventy-four children were included: 14 with MIS-C, 9 patients positive for SARS-CoV-2 by PCR without MIS-C (COVID), 14 with prepandemic KD, and 37 healthy controls (HCs). Thirty-four circulating cytokines were quantified in pretreatment serum or plasma samples and the presence of circulating SARS-CoV-2 ICs was evaluated in MIS-C patients. Compared with HCs, the MIS-C and KD groups showed most cytokines to be significantly elevated, with IFN-γ-induced response markers (including IFN-γ, IL-18, and IP-10) and inflammatory monocyte activation markers (including MCP-1, IL-1α, and IL-1RA) being the main triggers of inflammation. In linear discriminant analysis, MIS-C and KD profiles overlapped; however, a subgroup of MIS-C patients (MIS-Cplus) differentiated from the remaining MIS-C patients in IFN-γ, IL-18, GM-CSF, RANTES, IP-10, IL-1α, and SDF-1 and incipient signs of macrophage activation syndrome. Circulating SARS-CoV-2 ICs were not detected in MIS-C patients. Our findings suggest a major role for IFN-γ in the pathogenesis of MIS-C, which may be relevant for therapeutic management.

The different manifestations of COVID-19 in adults and children: a cohort study in an intensive care unit.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has collapsed health systems worldwide. In adults, the virus causes severe acute respiratory distress syndrome (ARDS), while in children the disease seems to be milder, although a severe multisystem inflammatory syndrome (MIS-C) has been described. The aim was to describe and compare the characteristics of the severe COVID-19 disease in adults and children. METHODS: This prospective observational cohort study included the young adults and children infected with SARS-CoV-2 between March-June 2020 and admitted to the paediatric intensive care unit. The two populations were analysed and compared focusing on their clinical and analytical characteristics and outcomes. RESULTS: Twenty patients were included. There were 16 adults (80%) and 4 children (20%). No mortality was recorded. All the adults were admitted due to ARDS. The median age was 32 years (IQR 23.3-41.5) and the most relevant previous pathology was obesity (n = 7, 43.7%). Thirteen (81.3%) needed mechanical ventilation, with a median PEEP of 13 (IQR 10.5-14.5). Six (37.5%) needed inotropic support due to the sedation. Eight (50%) developed a healthcare-associated infection, the most frequent of which was central line-associated bloodstream infection (n = 7, 71.4%). One patient developed a partial pulmonary thromboembolism, despite him being treated with heparin. All the children were admitted due to MIS-C. Two (50%) required mechanical ventilation. All needed inotropic support, with a median vasoactive-inotropic score of 27.5 (IQR 17.5-30). The difference in the inotropic requirements between the two populations was statistically significant (37.5% vs. 100%, p < 0.001). The biomarker values were higher in children than in adults: mid-regional pro-adrenomedullin 1.72 vs. 0.78 nmol/L (p = 0.017), procalcitonin 5.7 vs. 0.19 ng/mL (p = 0.023), and C-reactive protein 328.2 vs. 146.9 mg/L (p = 0.005). N-terminal pro-B-type natriuretic peptide and troponins were higher in children than in adults (p = 0.034 and p = 0.039, respectively). CONCLUSIONS: Adults and children had different clinical manifestations. Adults developed severe ARDS requiring increased respiratory support, whereas children presented MIS-C with greater inotropic requirements. Biomarkers could be helpful in identifying susceptible patients, since they might change depending on the clinical features.

Device-associated multidrug-resistant bacteria surveillance in critically ill children: 10 years of experience.

AIM: Multidrug-resistant bacterial infections are a public health problem worldwide. However, most of the information available refers to adults. The main objectives were to determine the incidence, risk factors, and outcomes for device-associated infections, especially those involving multidrug-resistant bacteria. METHODS: This is a prospective, observational study. Children aged ≥1 month and <18 years admitted to the paediatric intensive care unit from 2008 to 2017, with a device-associated infection microbiologically confirmed were included. Patients infected with resistant bacteria were compared with those who had a drug-susceptible infection. RESULTS: The study included 213 patients. Out of all the device-associated infections, 22% (48 patients) were caused by multidrug-resistant bacteria. The most frequent were extended-spectrum beta-lactamase (ESBL)-producing enterobacteria. Cardiovascular diseases, age under 1year, comorbidity, prolonged use of invasive device, and length of stay until infection were risk factors for resistant bacteria, but not specifically for ESBL-producing bacteria. Length of stay and mortality was increased in patients with multidrug-resistant bacteria. CONCLUSION: Being under 1-year-old and having a cardiovascular disease were the two major risk factors for resistant bacterial infection. ESBL-producing bacteria were the most frequent multidrug-resistant agents. However, patients with ESBL-producing bacteria did not have any additional risk factors, so they may have been colonised in the community.