Point-of-care lung ultrasound score for predicting escalated care in children with respiratory distress.

PURPOSE: Respiratory distress due to lower respiratory illnesses is a leading cause of death in children. Early recognition of high-risk populations is critical for the allocation of adequate resources. Our goal was to assess whether the lung ultrasound (US) score obtained at admission in children with respiratory distress predicts the need for escalated care. METHODS: This prospective study included 0-18-year-old patients with respiratory distress admitted to three emergency departments in the state of Sao Paulo, Brazil, between July 2019 and September 2021. The enrolled patients underwent lung US performed by a pediatric emergency physician within two hours of arrival. Lung ultrasound scores ranging from 0 to 36 were computed. The primary outcome was the need for high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), or mechanical ventilation within 24 h. RESULTS: A total of 103 patients were included. The diagnoses included wheezing (33%), bronchiolitis (27%), pneumonia (16%), asthma (9%), and miscellaneous (16%). Thirty-five patients (34%) required escalated care and had a higher lung ultrasound score: median 13 (0-34) vs 2 (0-21), p < 0.0001; area under the curve (AUC): 0.81 (95% confidence interval [CI]: 0.71-0.90). The best cut-off score derived from Youden's index was seven (sensitivity: 71.4%; specificity: 79.4%; odds ratio (OR): 9.6 [95% CI: 3.8-24.7]). A lung US score above 12 was highly specific and had a positive likelihood ratio of 8.74 (95% CI:3.21-23.86). CONCLUSION: An elevated lung US score measured in the first assessment of children with any type of respiratory distress was predictive of severity as defined by the need for escalated care with HFNC, NIV, or mechanical ventilation.

The importance of viral load in the severity of acute bronchiolitis in hospitalized infants.

OBJECTIVE: The relationship between viral load and the clinical evolution of bronchiolitis is controversial. Therefore, we aimed to analyze viral loads in infants hospitalized for bronchiolitis. METHODS: We tested for the presence of human respiratory syncytial virus (HRSV) or human rhinovirus (HRV) using quantitative molecular tests of nasopharyngeal secretions and recorded severity outcomes. RESULTS: We included 70 infants [49 (70%) HRSV, 9 (13%) HRV and 12 (17%) HRSV+HRV]. There were no differences among the groups according to the outcomes analyzed individually. Clinical scores showed greater severity in the isolated HRSV infection group. A higher isolated HRSV viral load was associated with more prolonged ventilatory support, oxygen therapy, and hospitalization days, even after adjustment for the age and period of nasopharyngeal secretion collection. In the co-infection groups, there was a longer duration of oxygen therapy when the HRSV viral load was predominant. Isolated HRV infection and co-infection with a predominance of HRV were not associated with severity. CONCLUSION: Higher HRSV viral load in isolated infections and the predominance of HRSV in co-infections, independent of viral load, were associated with greater severity. These results contribute to the development of therapeutic and prophylactic approaches and a greater understanding of the pathophysiology of bronchiolitis.

In Nasal Mucosal Secretions, Distinct IFN and IgA Responses Are Found in Severe and Mild SARS-CoV-2 Infection.

Likely as in other viral respiratory diseases, SARS-CoV-2 elicit a local immune response, which includes production and releasing of both cytokines and secretory immunoglobulin (SIgA). Therefore, in this study, we investigated the levels of specific-SIgA for SARS-CoV-2 and cytokines in the airways mucosa 37 patients who were suspected of COVID-19. According to the RT-PCR results, the patients were separated into three groups: negative for COVID-19 and other viruses (NEGS, n = 5); negative for COVID-19 but positive for the presence of other viruses (OTHERS, n = 5); and the positive for COVID-19 (COVID-19, n = 27). Higher specific-SIgA for SARS-CoV-2, IFN-ß, and IFN-γ were found in the COVID-19 group than in the other groups. Increased IL-12p70 levels were observed in OTHERS group as compared to COVID-19 group. When the COVID-19 group was sub stratified according to the illness severity, significant differences and correlations were found for the same parameters described above comparing severe COVID-19 to the mild COVID-19 group and other non-COVID-19 groups. For the first time, significant differences are shown in the airway's mucosa immune responses in different groups of patients with or without respiratory SARS-CoV-2 infection.

The importance of viral load in the severity of acute bronchiolitis in hospitalized infants

OBJECTIVE: The relationship between viral load and the clinical evolution of bronchiolitis is controversial. Therefore, we aimed to analyze viral loads in infants hospitalized for bronchiolitis. METHODS: We tested for the presence of human respiratory syncytial virus (HRSV) or human rhinovirus (HRV) using quantitative molecular tests of nasopharyngeal secretions and recorded severity outcomes. RESULTS: We included 70 infants [49 (70%) HRSV, 9 (13%) HRV and 12 (17%) HRSV+HRV]. There were no differences among the groups according to the outcomes analyzed individually. Clinical scores showed greater severity in the isolated HRSV infection group. A higher isolated HRSV viral load was associated with more prolonged ventilatory support, oxygen therapy, and hospitalization days, even after adjustment for the age and period of nasopharyngeal secretion collection. In the co-infection groups, there was a longer duration of oxygen therapy when the HRSV viral load was predominant. Isolated HRV infection and co-infection with a predominance of HRV were not associated with severity. CONCLUSION: Higher HRSV viral load in isolated infections and the predominance of HRSV in co-infections, independent of viral load, were associated with greater severity. These results contribute to the development of therapeutic and prophylactic approaches and a greater understanding of the pathophysiology of bronchiolitis.

Point-of-care lung ultrasound imaging in pediatric COVID-19.

BACKGROUND: There has been limited data regarding the usefulness of lung ultrasound (US) in children with COVID-19. OBJECTIVE: To describe lung US imaging findings and aeration score of 34 children with COVID-19. METHODS: This study included 0-16-year-old patients with confirmed COVID-19, who were admitted between April 19 and June 18, 2020 in two hospitals in the city of Sao Paulo, Brazil. Lung US was performed as part of the routine evaluation by a skilled Pediatric Emergency physician. Clinical and laboratory data were collected and severity classifications were done according to an available clinical definition. The lung US findings were described for each lung field and a validated ultrasound lung aeration score was calculated. Data obtained was correlated with clinical information and other imaging modalities available for each case. RESULTS: Thirty-four confirmed COVID-19 patients had a lung US performed during this period. Eighteen (18/34) had abnormalities on the lung US, but eight of them (8/18) had a normal chest radiograph. Ultrasound lung aeration score medians for severe/critical, moderate, and mild disease were 17.5 (2-30), 4 (range 0-14), 0 (range 0-15), respectively (p = 0.001). Twelve patients (12/34) also had a chest computed tomography (CT) performed; both the findings and topography of lung compromise on the CT were consistent with the information obtained by lung US. CONCLUSION: Point-of-care lung US may have a key role in assessing lung injury in children with COVID-19.

Multisystem Inflammatory Syndrome Associated With COVID-19 With Neurologic Manifestations in a Child: A Brief Report.

Although first considered a benign infection, recent studies have disclosed severe and potentially lethal inflammatory manifestations of COVID-19 in children. We report the case of a 4-year-old child with a post-infectious multisystem inflammatory syndrome associated with COVID-19, with a Kawasaki-like shock and prominent neurologic features, for whom a cytokine storm and reduced brain-derived neurotrophic factor were well documented.

Lower cost alternatives for molecular diagnosis of COVID-19: conventional RT-PCR and SYBR Green-based RT-qPCR.

In March 2020, WHO declared a pandemic state due to SARS-CoV-2 having spread. TaqMan-based real-time RT-qPCR is currently the gold standard for COVID-19 diagnosis. However, it is a high-cost assay, inaccessible for the majority of laboratories around the world, making it difficult to diagnose on a large scale. The objective of this study was to standardize lower cost molecular methods for SARS-CoV-2 identification. E gene primers previously determined for TaqMan assays by Colman et al. (2020) were adapted in SYBR Green assay and RT-PCR conventional. The cross-reactivity test was performed with 17 positive samples for other respiratory viruses, and the sensibility test was performed with 8 dilutions (10 based) of SARS-CoV-2 isolated and 63 SARS-CoV-2-positive samples. The SYBR Green assays and conventional RT-PCR have not shown amplification of the 17 respiratory samples positives for other viruses. The SYBR Green-based assay was able to detect all 8 dilutions of the isolate. The conventional PCR detected until 107 dilution, both assays detected the majority of the 63 samples, 98.42% of positivity in SYBR Green, and 93% in conventional PCR. The average Ct variation between SYBR Green and TaqMan was 1.92 and the highest Ct detected by conventional PCR was 35.98. Both of the proposed assays are less sensitive than the current gold standard; however, our data shows a low sensibility variation, suggesting that these methods could be used by laboratories as a lower cost molecular method for SARS-CoV-2 diagnosis.

Distinct transcriptional modules in the peripheral blood mononuclear cells response to human respiratory syncytial virus or to human rhinovirus in hospitalized infants with bronchiolitis.

Human respiratory syncytial virus (HRSV) is the main cause of bronchiolitis during the first year of life, when infections by other viruses, such as rhinovirus, also occur and are clinically indistinguishable from those caused by HRSV. In hospitalized infants with bronchiolitis, the analysis of gene expression profiles from peripheral blood mononuclear cells (PBMC) may be useful for the rapid identification of etiological factors, as well as for developing diagnostic tests, and elucidating pathogenic mechanisms triggered by different viral agents. In this study we conducted a comparative global gene expression analysis of PBMC obtained from two groups of infants with acute viral bronchiolitis who were infected by HRSV (HRSV group) or by HRV (HRV group). We employed a weighted gene co-expression network analysis (WGCNA) which allows the identification of transcriptional modules and their correlations with HRSV or HRV groups. This approach permitted the identification of distinct transcription modules for the HRSV and HRV groups. According to these data, the immune response to HRSV infection-comparatively to HRV infection-was more associated to the activation of the interferon gamma signaling pathways and less related to neutrophil activation mechanisms. Moreover, we also identified host-response molecular markers that could be used for etiopathogenic diagnosis. These results may contribute to the development of new tests for respiratory virus identification. The finding that distinct transcriptional profiles are associated to specific host responses to HRSV or to HRV may also contribute to the elucidation of the pathogenic mechanisms triggered by different respiratory viruses, paving the way for new therapeutic strategies.

Infections Caused by HRSV A ON1 Are Predominant among Hospitalized Infants with Bronchiolitis in São Paulo City.

Human respiratory syncytial virus is the main cause of respiratory infections in infants. Several HRSV genotypes have been described. Goals. To describe the main genotypes that caused infections in São Paulo (2013-2015) and to analyze their clinical/epidemiological features. Methods. 94 infants (0-6 months) with bronchiolitis were studied. Clinical/epidemiological information was collected; a search for 16 viruses in nasopharyngeal secretion (PCR-real-time and conventional, sequencing, and phylogenetic analyses) was performed. Results. The mean age was 2.4 m; 48% were male. The mean length of hospital stay was 4.4 d (14% in the Intensive Care Unit). The positive rate of respiratory virus was 98.9%; 73 cases (77.6%) were HRSV (76,7% HRSVA). HRSVA formed three clusters: ON1 (n = 34), NA1 (n = 1), and NA2 (n = 4). All HRSVB were found to cluster in the BA genotype (BA9-n = 10; BA10-n = 3). Clinical analyses showed no significant differences between the genotype AON1 and other genotypes. Conclusion. This study showed a high rate of HRSV detection in bronchiolitis. HRSVA ON1, which has recently been described in other countries and has not been identified in previous studies in the southeast region of Brazil, was predominant. The clinical characteristics of the infants that were infected with AON1 were similar to infants with infections by other genotypes.

Impact of the rapid antigen detection test in diagnosis and treatment of acute pharyngotonsillitis in a pediatric emergency room.

OBJECTIVE: To evaluate the impact of the routine use of rapid antigen detection test in the diagnosis and treatment of acute pharyngotonsillitis in children. METHODS: This is a prospective and observational study, with a protocol compliance design established at the Emergency Unit of the University Hospital of Universidade de São Paulo for the care of children and adolescents diagnosed with acute pharyngitis. RESULTS: 650 children and adolescents were enrolled. Based on clinical findings, antibiotics would be prescribed for 389 patients (59.8%); using the rapid antigen detection test, they were prescribed for 286 patients (44.0%). Among the 261 children who would not have received antibiotics based on the clinical evaluation, 111 (42.5%) had positive rapid antigen detection test. The diagnosis based only on clinical evaluation showed 61.1% sensitivity, 47.7% specificity, 44.9% positive predictive value, and 57.5% negative predictive value. CONCLUSIONS: The clinical diagnosis of streptococcal pharyngotonsillitis had low sensitivity and specificity. The routine use of rapid antigen detection test led to the reduction of antibiotic use and the identification of a risk group for complications of streptococcal infection, since 42.5% positive rapid antigen detection test patients would not have received antibiotics based only on clinical diagnosis.

Severity of viral coinfection in hospitalized infants with respiratory syncytial virus infection.

OBJECTIVE: To compare the severity of single respiratory syncytial virus (RSV) infections with that of coinfections. METHODS: A historical cohort was studied, including hospitalized infants with acute RSV infection. Nasopharyngeal aspirate samples were collected from all patients to detect eight respiratory viruses using molecular biology techniques. The following outcomes were analyzed: duration of hospitalization and of oxygen therapy, intensive care unit admission and need of mechanical ventilation. Results were adjusted for confounding factors (prematurity, age and breastfeeding). RESULTS: A hundred and seventy six infants with bronchiolitis and/or pneumonia were included in the study. Their median age was 4.5 months. A hundred and twenty one had single RSV infection and 55 had coinfections (24 RSV + adenovirus, 16 RSV + human metapneumovirus and 15 other less frequent viral associations). The four severity outcomes under study were similar in the group with single RSV infection and in the coinfection groups, independently of what virus was associated with RSV. CONCLUSION: Virus coinfections do not seem to affect the prognosis of hospitalized infants with acute RSV infection.

Fever without source: evaluation of a guideline.

OBJECTIVE: To evaluate the applicability of a standardized guideline for children up to 36 months of age with fever without source (FWS). METHODS: Prospective cohort study involving children with FWS treated at the emergency department of Hospital Universitário, Universidade de São Paulo, São Paulo, Brazil, from June 2006 to May 2007. The guideline classifies the risk of serious bacterial infection (SBI) according to the presence or absence of toxemia, age, and temperature. Laboratory screening was based on risk assessment: complete blood count, blood culture, urinalysis, urine culture, and, if necessary, chest radiography, cerebrospinal fluid, and coproculture. RESULTS: We studied 251 children and, of these, 215 were followed up until the final diagnosis. Toxemia was found in 20 children, and 195 were well-appearing (30 up to 3 months old and 165 from 3 to 36 months old). Among those children from 3 to 36 months without toxemia, 95 had axillary temperature > 39 degrees C. In 107 (49.8%) children, there was spontaneous resolution of fever; in 88 (40.9%), benign self-limited disease was identified; and in 20 (9.3%), there was SBI. Among the cases of SBI, we identified 16 urinary tract infections, three cases of pneumonia and one occult bacteremia. Of the 215 children, 129 (60%) received no antibiotics, and 86 received antibiotics at some point (45 empirically). Empirical antibiotic treatment was maintained for an average of 72 hours. CONCLUSION: The guideline was shown to be appropriate to follow up these children using simple laboratory tests that can be carried out at most health facilities. The most frequent SBI in this sample was urinary tract infection.