Gastroenteritis Is Less Severe But Is More Often Associated With Systemic Inflammation in SARS-CoV-2-positive Than in SARS-CoV-2-negative Children.

This study aims to characterize the clinical and metabolic features of acute gastroenteritis in children with and without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A multicenter case-control study was conducted in 2022 including 200 children. Clinical data and laboratory tests were analyzed. Children with SARS-CoV-2 presented less frequently hyponatremia and metabolic acidosis, but more often systemic inflammation as compared with children without SARS-CoV-2.

Case report: Post-COVID new-onset neurocognitive decline with bilateral mesial-temporal hypometabolism in two previously healthy sisters.

Background: Long coronavirus disease (COVID) is increasingly recognized in adults and children; however, it is still poorly characterized from a clinical and diagnostic perspective, particularly in the younger populations. Case presentation: We described the story of two sisters-with high social and academic performance before their severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-who reported severe neurocognitive problems, initially classified as psychologic pandemic distress and eventually found to have significant brain hypometabolism. Conclusions: We provided a detailed clinical presentation of neurocognitive symptoms in two sisters with long COVID associated with brain hypometabolism documented in both sisters. We believe that the evidence of objective findings in these children further supports the hypothesis that organic events cause persisting symptoms in a cohort of children after SARS-CoV-2 infection. Such findings highlight the importance of discovering diagnostics and therapeutics.

Role of Lung Ultrasound in the Follow-Up of Children with Previous SARS-CoV-2 Infection: A Case-Control Assessment of Children with Long COVID or Fully Recovered.

Lung ultrasound (LUS) can detect lower respiratory tract involvement in children with acute SARS-CoV-2 infection. However, its role in follow-up assessments is still unclear. To describe LUS findings in children after SARS-CoV-2 infection, we conducted a prospective study in a population of pediatric patients referred to the post-COVID unit in a tertiary center during the study period from February 2021 to May 2022. Children were classified as recovered from acute infection or with persisting symptoms. LUS was performed in all children and a LUS score (ranging from 0 to 36 points) was calculated according to the Italian Academy of Thoracic Ultrasound. Six hundred forty-seven children (304 females, 47%) were enrolled. The median follow-up evaluation was two months. The median age was 7.9 (IQR: 6) years. At the follow-up evaluation, 251 patients (38.8%) had persistent symptoms, of whom 104 (16.1%) had at least one respiratory symptom. The median LUS level was 2 (IQR: 4). LUS findings and LUS scores did not differ in children with Long COVID compared to the group of children fully recovered from the initial infection. In conclusion, after SARS-CoV-2 infection, LUS was mostly normal or showed minimal artifacts in all groups of children.

Risk factors for post-COVID-19 condition (Long Covid) in children: a prospective cohort study.

Background: Adults and children can develop post-Covid-19 condition (PCC) (also referred to as Long Covid). However, existing evidence is scarce, partly due to a lack of a standardised case definition, short follow up duration, and heterogenous study designs, resulting in wide variation of reported outcomes. The primary aim of this study was to characterise risk factors for PCC and longitudinal rates of recovery in a cohort of children and young people using a standardised protocol. Methods: We performed a prospective "disease-based" cohort study between 01/02/2020 to 31/10/2022 including children aged 0-18 years old, with a previous diagnosis of Covid-19. Children with microbiologically confirmed SARS-CoV-2 infection, were invited for an in-clinic follow-up assessment at a paediatric post-covid clinic in Rome, Italy, at serial intervals (3-, 6-, 12- and 18-months post-onset). PCC was defined as persistence of otherwise unexplained symptoms for at least three months after initial infection. The statistical association between categorical variables was obtained by Chi-squared tests or Fisher's exact tests. Multivariable logistic regressions are presented using odds ratios (OR) and 95% confidence interval (CI). Survival analysis was conducted using the Kaplan-Meier method. Findings: 1243 children were included, median age: 7.5 (4-10.3) years old; 575 (46.3%) were females. Of these, 23% (294/1243) were diagnosed with PCC at three months post-onset. Among the study population, 143 patients remained symptomatic at six months, 38 at 12 months, and 15 at 18 months follow up evaluation. The following risk factors were associated with PCC: >10 years of age (OR 1.23; 95% CI 1.18-1.28), comorbidities (OR 1.68; 95% CI 1.14-2.50), and hospitalisation during the acute phase (OR 4.80; 95%CI 1.91-12.1). Using multivariable logistic regression, compared to the Omicron variant, all other variants were significantly associated with PCC at 3 and 6 months. At least one dose of vaccine was associated with a reduced, but not statistically significant risk of developing PCC. Interpretation: In our study, acute-phase hospitalisation, pre-existing comorbidity, being infected with pre-Omicron variants and older age were associated with a higher risk of developing PCC. Most children recovered over time, but one-in-twenty of those with PCC at three months reported persistent symptoms 18 months post-Sars-CoV-2 infection. Omicron infection was associated with shorter recovery times. We did not find a strong protective effect of vaccination on PCC development. Although our cohort cannot be translated to all Italian children with PCC as more nationwide studies are needed, our findings highlight the need of new strategies to prevent and treat pediatric PCC are needed. Funding: This study has been funded by Pfizer non-competitive grant, granted to DB (# 65925795).

Lung perfusion assessment in children with long-COVID: A pilot study.

BACKGROUND: There is increasing evidence that chronic endotheliopathy can play a role in patients with Post-Covid Condition (PCC, or Long Covid) by affecting peripheral vascularization. This pilot study aimed at assessing lung perfusion in children with Long-COVID with 99m Tc-MAA SPECT/CT. MATERIALS AND METHODS: lung 99m Tc-MAA SPECT/CT was performed in children with Long-COVID and a pathological cardiopulmonary exercise testing (CPET). Intravenous injections were performed on patients in the supine position immediately before the planar scan according to the EANM guidelines for lung scintigraphy in children, followed by lung SPECT/CT acquisition. Reconstructed studies were visually analyzed. RESULTS: Clinical and biochemical data were collected during acute infection and follow-up in 14 children (6 females, mean age: 12.6 years) fulfilling Long-COVID diagnostic criteria and complaining of chronic fatigue and postexertional malaise after mild efforts, documented by CPET. Imaging results were compared with clinical scenarios during acute infection and follow-up. Six out of 14 (42.8%) children showed perfusion defects on 99m Tc-MAA SPECT/CT scan, without morphological alterations on coregistered CT. CONCLUSIONS: This pilot investigation confirmed previous data suggesting that a small subgroup of children can develop lung perfusion defects after severe acute respiratory syndrome coronavirus 2 infection. Larger cohort studies are needed to confirm these preliminary results, providing also a better understanding of which children may deserve this test and how to manage those with lung perfusion defects.

Risk Factors for Persistent Anosmia and Dysgeusia in Children with SARS-CoV-2 Infection: A Retrospective Study.

BACKGROUND: Olfactory and gustative dysfunctions are two of the most common post-acute sequelae of SARS-CoV-2 infection in children, which can have a negative impact on the routines of children and families. As several children have had COVID-19 since the Omicron variant, it is important to investigate if this increase in infections is reflected in higher olfactory/taste disfunctions. The primary aim of this study was to characterize the presence of olfactory/gustative problems in a cohort of children, its evolution, and its association with risk factors such as COVID-19 variant, hospitalization, presence of olfactory/gustative dysfunction during the acute phase, and vaccination. METHODS: This was a retrospective analysis of children with microbiologically confirmed SARS-CoV-2 infection evaluated in person at a referral pediatric post-COVID-19 clinic in Rome, Italy. We included children younger than 19 years old, evaluated from the beginning of the pandemic up to October 2022. At specific timepoints, we investigated the presence of olfactory/taste disfunctions and evaluated them according to the SARS-CoV-2 variants circulating at the time of infection. RESULTS: A total of 1250 children (650 females; 52.0%) with a mean age of 6.77 (±4.12) years were included in the study. At 3, 6, 12, and 18 months, 12 (9.6%), 7 (5.6%), 2 (1.6%), and 1 (0.8%) of the children reported anosmia and dysgeusia post-COVID-19 infection, respectively. The presence of anosmia and dysgeusia during the acute phase of infection and being infected with a pre-Omicron variant were found to be significant risk factors for persistent olfactory and gustatory dysfunction during all follow-up periods. CONCLUSIONS: anosmia and dysgeusia symptoms tended to decrease gradually over time, but not all children recovered quickly.

Diagnosis and management of post-COVID (Long COVID) in children: a moving target.

PURPOSE OF REVIEW: This review describes recent findings about post-COVID condition (PCC, or Long COVID) in children, including current knowledge about its epidemiology, clinical presentation, pathogenesis and care. RECENT FINDINGS: There is no internationally agreed definition of PCC, although now most researchers agree that it is a complex clinical symptomatology persisting for at least 3 months after COVID-19, without an alternative diagnosis. There are several uncertainties about paediatric PCC. So far, available literature suggest that 1-3% of recognized children with Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV-2) infection may develop PCC. Its pathogenesis is unknown, although there is increasing evidence about possible abnormalities in the immune responses, cellular metabolism and intestinal microbiota, along with chronic endothelitis. SUMMARY: Management of PCC in children is complex and require a multidisciplinary approach, with the goal of offering the best care possible to support diagnostics, research, mental health and access to research projects.

The Prevalence, Characteristics and Risk Factors of Persistent Symptoms in Non-Hospitalized and Hospitalized Children with SARS-CoV-2 Infection Followed-Up for up to 12 Months: A Prospective, Cohort Study in Rome, Italy.

Previous studies assessing the prevalence of COVID-19 sequelae in children have included either a small number of children or a short follow-up period, or have only focused on hospitalized children. We investigated the prevalence of persistent symptoms amongst children and assessed the risk factors, including the impact of variants. A prospective cohort study included children (≤18 years old) with PCR-confirmed SARS-CoV-2 infection. The participants were assessed via telephone and face-to-face visits at 1-5, 6-9 and 12 or more months post-SARS-CoV-2 diagnosis using the ISARIC COVID-19 follow-up survey. Of the 679 children enrolled, 51% were female; 488 were infected during the wild virus wave, and 29 were infected with the Alpha, 42 with the Delta and 120 with the Omicron variants. Fatigue (19%), headache (12%), insomnia (7.5%), muscle pain (6.9%) and confusion with concentration issues (6.8%) were the most common persistent symptoms. Families reported an overall improvement over time, with 0.7% of parents interviewed at 12 months or more of the follow-up period reporting a poor recovery. Patients that had not recovered by 6-9 months had a lower probability of recovering during the next follow-up period. Children infected with a variant or the wild virus had an overall similar rate of persistent symptoms (although the pattern of reported symptoms differed significantly) and recovery rates. Conclusions: Recovery rates after SARS-CoV-2 infection improved as time passed from the initial infection, ranging from 4% of children having poor recovery at 1-5 months' follow-up to 1.3% at 6-9 months and 0.7% at 12 months. The patterns of persistence changed according to the variants involved at the time of infection. This study reinforces that a subgroup of children develop long-lasting persistent symptoms and highlights the need for further studies investigating the reasons behind the development of PCC.

Extended coagulation profile of children with Long Covid: a prospective study.

Emerging data suggests that endotheliopathy changes can be associated with post covid condition (PCC) in adults. Research on the matter in children is lacking. We analyzed an extended coagulation profile including biomarkers of endothelial damage in children with PCC and compared it with a control group of children that fully recovered post- SARS-CoV-2 infection. A case-control study enrolling children below 18 years of age with previous microbiologically confirmed SARS-CoV-2 infection in a pediatric post-covid unit in Italy ≥ 8 weeks after the initial infection. Samples were taken at 8 and 12 weeks after the SARS-CoV-2 diagnosis and analyzed for coagulation profiling (fibrinogen, prothrombin time, international normalized ratio, activated partial thromboplastin time, d-dimers, factor VIII coagulant activity, plasma von Willebrand factor (VWF) antigen and VWF ristocetin cofactor (RC)). We compared coagulation profiles in samples from children identified with PCC (at least one, or three or more symptoms, which could not be explained by an alternative diagnosis, at the 8- and 12-week follow-up assessment using the pediatric Long Covid International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) survey. Seventy-five children were enrolled, 49.3% were females, the median age was 10.2 (IQR 4.9) years. Forty-six (61%) of the children had at least one persisting symptom at the eight weeks post-onset, (PCC8); 39/75 (52%) had persistent symptoms for more than 12 weeks (PCC12) and 15/75(32%) had at least three persisting symptoms (PCC ≥ 3) at 12 weeks. Children with PCC presented more frequently with abnormal D-Dimer levels above the reference range compared to children that had fully recovered at the 8-12 weeks (39.1% vs. 17.2%, p = 0.04), and 12 week follow up or more (41% vs. 17.2%, p = 0.05), and in children with three or more symptoms at 12 weeks follow up compared to those that had recovered (64.3% vs. 22.2%, p = 0.002). For the other coagulation profiles, there were abnormal values detected for VWF, FVIII, RC and Fibrinogen but no significant differences between children with PCC compared to controls. Although the majority of children in our cohort showed coagulation profile within or close to normal ranges, we found that a higher proportion of children with PCC, and specifically those with a more severe spectrum characterized with three or more persisting symptoms, had abnormal D-dimer levels compared to other children that fully recovered from an acute SARS-CoV-2 infection.

Utility and Limits of Lung Ultrasound in Childhood Pulmonary Tuberculosis: Lessons from a Case Series and Literature Review.

Childhood pulmonary tuberculosis (PTB) diagnosis is often a challenge that requires a combination of history, clinical, radiological, immunological and microbiological findings. Radiological diagnosis is based today on the use of chest X-ray and chest CT that, in addition to being radio-invasive tools for children, are often not available in countries with low-resources. A non-invasive, easily usable and reproducible, low-cost diagnostic tool as LUS would therefore be useful to use to support the diagnosis of childhood PTB. Data on the use of LUS for the diagnosis and follow-up of childhood PTB are limited and in some respects contradictory. To help better define the potential role of LUS we have described the pros and cons of lung ultrasound method through a brief review of the studies in the literature and reporting some case series in which we describe clinical, laboratory, radiological results as well as detailed lung ultrasound findings of four children/adolescents with PTB.

Lactoferrin as Possible Treatment for Chronic Gastrointestinal Symptoms in Children with Long COVID: Case Series and Literature Review.

Long COVID is an emergent, heterogeneous, and multisystemic condition with an increasingly important impact also on the pediatric population. Among long COVID symptoms, patients can experience chronic gastrointestinal symptoms such as abdominal pain, constipation, diarrhea, vomiting, nausea, and dysphagia. Although there is no standard, agreed, and optimal diagnostic approach or treatment of long COVID in children, recently compounds containing multiple micronutrients and lactoferrin have been proposed as a possible treatment strategy, due to the long-standing experience gained from other gastrointestinal conditions. In particular, lactoferrin is a pleiotropic glycoprotein with antioxidant, anti-inflammatory, antithrombotic, and immunomodulatory activities. Moreover, it seems to have several physiological functions to protect the gastrointestinal tract. In this regard, we described the resolution of symptoms after the start of therapy with high doses of oral lactoferrin in two patients referred to our post-COVID pediatric unit due to chronic gastrointestinal symptoms after SARS-CoV-2 infection.

Are Lung Ultrasound Features More Severe in Children Diagnosed with Bronchiolitis after the COVID-19 Lockdown Period?

The non-pharmacological measures implemented during the SARS-CoV-2 pandemic disrupted the usual bronchiolitis seasonality. Some authors have speculated that, after the lock down period, there would be an increase in the number and severity of respiratory infections due to the re-introduction of respiratory viruses. We collected clinical, microbiological and lung ultrasound data using the classification of the Italian Society of Thoracic Ultrasound (ADET) in children with bronchiolitis during the pandemic compared to the pre-pandemic period, with the aim of assessing whether the epidemic of bronchiolitis during the pandemic was characterized by a more severe lung involvement documented by lung ultrasound. We enrolled 108 children with bronchiolitis (52 pre-pandemic and 56 COVID-19 period), with a median age of 1.74 months (interquartile range, IQR 1-3.68) and 39.8% were females. Rhinovirus detection and high-flow nasal cannula usage were both increased during the COVID-19 period, although overall need of hospitalization and pediatric intensive care unit admissions did not change during the two periods. Lung ultrasound scores were similar in the two cohorts evaluated. Conclusions: our study suggests that, despite changes in microbiology and treatments performed, lung ultrasound severity scores were similar, suggesting that that bronchiolitis during the pandemic period was no more severe than pre-pandemic period, despite children diagnosed during the pandemic had a higher, but it was not statistically significant, probably, due to small sample size, probability of being admitted.

Chronic Olfactory Dysfunction in Children with Long COVID: A Retrospective Study.

Olfactory dysfunction is one of the long-term consequences of acute SARS-CoV-2 infection in adults. This study aims to analyze the prevalence of chronic anosmia among COVID-19 children and to bring to light its impact on their families' quality of life and wellbeing. Children younger than 18 years old, who were detected as being COVID-19-positive by RT-PCR and were assessed in a pediatric post-COVID outpatient clinic at least 28 days after the onset of the acute infection, were included in the study. The patients suffering from persisting smell disorders were asked to answer a questionnaire about their symptoms and how they influence their daily life. Out of the 784 children evaluated, 13 (1.7%) presented olfactory impairment at a mean follow-up since the acute infection of more than three months. Parents' answers showed that they were worried about their children's health, in particular they wanted to know if and when they would recover and if these disorders would have long-term consequences. They also wanted to share their experiences, in order to help other people who are experiencing the same disorders in everyday life. Our study highlights that smell disorders can significantly upset children's eating habits and everyday activities. Furthermore, these findings suggest that future research should try to better understand the mechanisms causing loss of smell in COVID-19 patients and find the most appropriate treatment.

Recovering or Persisting: The Immunopathological Features of SARS-CoV-2 Infection in Children.

BACKGROUND: The profile of cellular immunological responses of children across the spectrum of COVID-19, ranging from acute SARS-CoV-2 infection to full recovery or Long COVID, has not yet been fully investigated. METHODS: We examined and compared cytokines in sera and cell subsets in peripheral blood mononuclear cells (B and regulatory T lymphocytes) collected from four distinct groups of children, distributed as follows: younger than 18 years of age with either acute SARS-CoV-2 infection (n = 49); fully recovered from COVID-19 (n = 32); with persistent symptoms (Long COVID, n = 51); and healthy controls (n = 9). RESULTS: In the later stages after SARS-CoV-2 infection, the cohorts of children, both with recovered and persistent symptoms, showed skewed T and B subsets, with remarkable differences when compared with children at the onset of the infection and with controls. The frequencies of IgD+CD27- naïve B cells, IgD+IgM+ and CD27-IgM+CD38dim B cells were higher in children with recent infection than in those with an older history of disease (p < 0.0001 for all); similarly, the total and natural Tregs compartments were more represented in children at onset when compared with Long COVID (p < 0.0001 and p = 0.0005, respectively). Despite the heterogeneity, partially due to age, sex and infection incidence, the susceptibility of certain children to develop persistent symptoms after infection appeared to be associated with the imbalance of the adaptive immune response. Following up and comparing recovered versus Long COVID patients, we analyzed the role of circulating naïve and switched B and regulatory T lymphocytes in counteracting the evolution of the symptomatology emerged, finding an interesting correlation between the amount and ability to reconstitute the natural Tregs component with the persistence of symptoms (linear regression, p = 0.0026). CONCLUSIONS: In this study, we suggest that children affected by Long COVID may have a compromised ability to switch from the innate to the adaptive immune response, as supported by our data showing a contraction of naïve and switched B cell compartment and an unstable balance of regulatory T lymphocytes occurring in these children. However, further prospective immunological studies are needed to better clarify which factors (epigenetic, diet, environment, etc.) are involved in the impairment of the immunological mechanisms in the Long COVID patients.

Orbito-Frontal Cortex Hypometabolism in Children With Post-COVID Condition (Long COVID): A Preliminary Experience.

We describe 3 children with new-onset neurocognitive problems after coronavirus disease 2019 (COVID-19), that showed, at the brain [18F]-fluorodeoxyglucose positron emission tomography/computed tomography, hypometabolism in the left orbito-frontal region. The voxel-wise analysis confirmed a cluster of hypometabolic voxels in this region with a peak at -18/46/-4mm (179 voxels, T-Score 8.1). These findings may explain neurocognitive symptoms that some children develop after COVID-19 and require further investigations.

COVID-19 review shows that benefits of vaccinating children and adolescents appear to outweigh risks of post-vaccination myopericarditis.

AIM: Myopericarditis after COVID-19 vaccination were the most serious adverse events reported in children over 5 years of age. We want to summarise these cases, describing their incidence, clinical features, diagnostic pathways, therapeutic strategies and outcome. METHODS: A systematic review of the literature was conducted until 20 March 2022 by bibliographic electronic databases. We included all reports of post-vaccination myopericarditis in children aged between 5 and 18 years. RESULTS: All reported cases had elevated serum Troponin levels, associated with electrocardiogram changes, but often with normal echocardiogram. Cardiac magnetic resonance images always showed typical alterations. The pathogenetic mechanism is still unknown. Myocarditis following post-COVID vaccination is more frequent in boys with an average age of about 15 years. Treatment involves the usage of non-steroidal anti-inflammatory drugs, and the average hospitalisation is about 3 days. The long-term consequences are not yet known, so these patients should be studied in a cardiological follow-up and abstention from physical activity should be recommended. CONCLUSION: The benefits of COVID-19 vaccination in children and adolescents appear to outweigh the risk of developing post-vaccination myopericarditis. We can also speculate a possible approval of vaccination in children under 5 years for the coming winter.

Epidemiology, Microbiology and Severity of Bronchiolitis in the First Post-Lockdown Cold Season in Three Different Geographical Areas in Italy: A Prospective, Observational Study.

The aim of this study was to understand the epidemiology, disease severity, and microbiology of bronchiolitis in Italy during the 2021-2022 cold season, outside of lockdowns. Before COVID-19, the usual bronchiolitis season in Italy would begin in November and end in April, peaking in February. We performed a prospective observational study in four referral pediatric centers located in different geographical areas in Italy (two in the north, one in the center and one in the south). From 1 July 2021 to 31 January 2022, we collected all new clinical diagnoses of bronchiolitis in children younger than two years of age recording demographic, clinical and microbiological data. A total of 657 children with a clinical diagnosis of bronchiolitis were enrolled; 56% children were admitted and 5.9% required PICU admission. The first cases were detected during the summer, peaking in November 2021 and declining into December 2021 with only a few cases detected in January 2022. RSV was the commonest etiological agent, while SARS-CoV-2 was rarely detected and only since the end of December 2021. Disease severity was similar in children with RSV vs. non-RSV bronchiolitis, and in those with a single infectious agent detected compared with children with co-infections. The 2021-2022 bronchiolitis season in Italy started and peaked earlier than the usual pre-pandemic seasons, but had a shorter duration. Importantly, the current bronchiolitis season was not more severe when data were compared with Italian published data, and SARS-CoV-2 was rarely a cause of bronchiolitis in children younger than 24 months of age.

Association between Coagulation Profile and Clinical Outcome in Children with SARS-CoV-2 Infection or MIS-C: A Multicenter Cross-Sectional Study.

Limited data on the coagulation profile in children affected by the SARS-CoV-2 infection are available. We aimed to evaluate the role of d-dimers as predictors of poor outcomes in a pediatric population affected by the SARS-CoV-2 infection or multisystem inflammatory syndrome (MIS-C). We performed a retrospective cross-sectional multicenter study. Data from four different centers were collected. Laboratory tests, when performed, were collected at the time of diagnosis, and 24, 48, 72, 96, 120 and beyond 120 h from diagnosis; blood counts with formula, an international normalized ratio (INR), activated partial thromboplastin time (aPTT), D-dimers and fibrinogen values were collected. Data regarding clinical history, management and outcome of the patients were also collected. Three hundred sixteen patients with a median age of 3.93 years (IQR 0.62-10.7) diagnosed with COVID-19 or MIS-C were enrolled. Fifty-eight patients (18.3%) showed a severe clinical outcome, 13 (4.1%) developed sequelae and 3 (0.9%) died. The univariate analysis showed that age, high D-dimer values, hyperfibrinogenemia, INR and aPTT elongation, and low platelet count were associated with an increased risk of pediatric intensive care unit (PICU) admission (p < 0.01). Three multivariate logistic regressions showed that a d-dimer level increase was associated with a higher risk of PICU admission. This study shows that D-dimer values play an important role in predicting the more severe spectrum of the SARS-CoV-2 infection, and was higher also in those that developed sequelae, including long COVID-19.

Classification of Lung Disease in Children by Using Lung Ultrasound Images and Deep Convolutional Neural Network.

Bronchiolitis is the most common cause of hospitalization of children in the first year of life and pneumonia is the leading cause of infant mortality worldwide. Lung ultrasound technology (LUS) is a novel imaging diagnostic tool for the early detection of respiratory distress and offers several advantages due to its low-cost, relative safety, portability, and easy repeatability. More precise and efficient diagnostic and therapeutic strategies are needed. Deep-learning-based computer-aided diagnosis (CADx) systems, using chest X-ray images, have recently demonstrated their potential as a screening tool for pulmonary disease (such as COVID-19 pneumonia). We present the first computer-aided diagnostic scheme for LUS images of pulmonary diseases in children. In this study, we trained from scratch four state-of-the-art deep-learning models (VGG19, Xception, Inception-v3 and Inception-ResNet-v2) for detecting children with bronchiolitis and pneumonia. In our experiments we used a data set consisting of 5,907 images from 33 healthy infants, 3,286 images from 22 infants with bronchiolitis, and 4,769 images from 7 children suffering from bacterial pneumonia. Using four-fold cross-validation, we implemented one binary classification (healthy vs. bronchiolitis) and one three-class classification (healthy vs. bronchiolitis vs. bacterial pneumonia) out of three classes. Affine transformations were applied for data augmentation. Hyperparameters were optimized for the learning rate, dropout regularization, batch size, and epoch iteration. The Inception-ResNet-v2 model provides the highest classification performance, when compared with the other models used on test sets: for healthy vs. bronchiolitis, it provides 97.75% accuracy, 97.75% sensitivity, and 97% specificity whereas for healthy vs. bronchiolitis vs. bacterial pneumonia, the Inception-v3 model provides the best results with 91.5% accuracy, 91.5% sensitivity, and 95.86% specificity. We performed a gradient-weighted class activation mapping (Grad-CAM) visualization and the results were qualitatively evaluated by a pediatrician expert in LUS imaging: heatmaps highlight areas containing diagnostic-relevant LUS imaging-artifacts, e.g., A-, B-, pleural-lines, and consolidations. These complex patterns are automatically learnt from the data, thus avoiding hand-crafted features usage. By using LUS imaging, the proposed framework might aid in the development of an accessible and rapid decision support-method for diagnosing pulmonary diseases in children using LUS imaging.