Children are affected by a broad spectrum of acute and chronic respiratory disorders. The number of children with respiratory disease is increasing, as are the complexity of disease pathophysiology and the management demands on pediatric pulmonologists. Despite slowing increasing numbers of board-certified pediatric pulmonologists, large areas of the country are underserved and there is a perception of an impending workforce crisis. There are multiple reasons for these concerns. A joint effort between the Pediatric Pulmonology Division Directors Association and Pediatric Pulmonary Training Directors Association was undertaken to address these issues.
Gene therapy is an attractive approach being intensively studied to prevent muscle deterioration in patients with Duchenne muscular dystrophy. While clinical trials are only in early stages, initial reports are promising for its effects on ambulation. Cardiopulmonary failure, however, is the most common cause of mortality in DMD patients, and little is known regarding the prospects for gene therapy on alleviating DMD-associated cardiomyopathy and respiratory failure. Here we review current knowledge regarding effects of gene therapy on DMD cardiomyopathy and discuss respiratory endpoints that should be considered as outcome measures in future clinical trials.
Abstract Background and Objectives: Better phenotyping of the heterogenous bronchiolitis syndrome may lead to targeted future interventions. This study aims to identify severe bronchiolitis profiles among hospitalised Australian Indigenous infants, a population at high-risk of bronchiectasis, using Latent Class Analysis (LCA). Methods: We included prospectively collected clinical, viral and nasopharyngeal bacteria data from 164 Indigenous infants hospitalised with bronchiolitis. We undertook multiple correspondence analysis (MCA) followed by LCA. The best-fitting model for LCA was based on adjusted Bayesian information criteria and entropy R2. Results: We identified five clinical profiles. Profile-A’s (23.8% of cohort) phenotype was previous preterm (90.7%), low birth-weight (89.2%) and weight-for-length z-score <-1 (82.7% from combining those with z-score between -1 and -2 and those in the z-score of <-2 group) previous respiratory hospitalisation (39.6%) and bronchiectasis on chest high-resolution computed tomography scan (35.4%). Profile-B (25.3%) was characterised by oxygen requirement (100%) and marked accessory muscle use (45.5%). Infants in profile-C (7.0%) had the most severe disease, with oxygen requirement and bronchiectasis in 100%, moderate accessory muscle use (85% vs 0-51.4%) and bacteria detected (93.1% vs 56.7-72.0%). Profile-D (11.6%) was dominated by rhinovirus (49.4%), mild accessory muscle use (73.8%) and weight-for-length z-score <-2 (36.0%). Profile-E (32.2%) included bronchiectasis (13.8%), RSV (44.0%), rhinovirus (26.3%) and any bacteria (72%). Conclusions: Using LCA in Indigenous infants with severe bronchiolitis, we identified 5 clinical profiles with one distinct profile for bronchiectasis. LCA can characterise distinct phenotypes for severe bronchiolitis and infants at risk for future bronchiectasis, which may inform future targeted interventions.
Introduction Childhood cancer survivors (CSs) might face an increased lifelong risk of lung function impairment. The Lung Clearance Index (LCI) has been described as being more sensitive than spirometry in the early stages of some lung diseases. The aim of this study was to evaluate this index in a cohort of patients with a history of childhood cancer for the first time. Materials and Methods We evaluated 57 off-treatment CSs aged 0–18 years old and 50 healthy controls (HCs). We used the multiple breath washout (MBW) method to study LCI and spirometry. Results CSs did not show any differences from the controls in ventilation homogeneity (LCI 6.78 ± 1.35 vs. 6.32 ± 0.44, P: ns) or lung function (FEV1 99.9 ± 11.3% vs. 103.0 ± 5.9% of predicted, P: ns; FVC 98.2 ± 10.3% vs. 101.1 ± 3.3% of predicted). LCI significantly correlated with the number of years since the last chemotherapy (r = 0.35, P < 0.05). Conclusions Our study describes the trend of LCI in a cohort of CSs and compares it with the results obtained from healthy controls. The results show that patients maintain both good values of respiratory function and good homogeneity of ventilation during childhood. Moreover, the LCI identifies the tendency toward pulmonary fibrosis, which is typical of adult CSs, at an earlier time than spirometry.
Background: High frequency (HF) oscillatory ventilation has been shown to improve CO2 clearance in premature infants. In a previous in vitro lung model with normal lung mechanics we demonstrated significantly improved CO2 washout by HF oscillation of bubble CPAP (BCPAP). Objective: To examine CO2 clearance in a premature infant lung model with abnormal lung mechanics via measurement of end-tidal CO2 levels (EtCO2) while connected to HF oscillated BCPAP. Design/Methods: A 40mL premature infant lung model with either: normal lung mechanics (NLM): compliance 1.0 mL/cmH2O, airway resistance 56 cmH2O/(L/s); or abnormal lung mechanics (ALM): compliance 0.5 mL/cmH2O, airway resistance 136 cmH2O/(L/s), was connected to BCPAP with HF oscillation at either 4,6,8,10 or 12 Hz. EtCO2 was measured at BCPAPs of 4,6 and 8 cmH2O and respiratory rates (RR) of 40,60 and 80 breaths/min and 6mL tidal volume. Results: HF oscillation decreased EtCO2 levels at all BCPAPs, RRs, and oscillation frequencies for both lung models. Overall mean±SD EtCO2 levels decreased (p<0.001) from non-oscillated baseline by 19.3±10.2% for NLM vs. 14.1±8.8% for ALM. CO2 clearance improved for both lung models (p<0.001) as a function of oscillation frequency and RR with greatest effectiveness at 40-60 breaths/min and HF at 8-12 Hz. Conclusions: In this in-vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO2 clearance as compared to non-oscillated BCPAP for both NLM and ALM. The significant improvement in CO2 clearance in an abnormal lung environment is an important step towards clinical testing of this novel respiratory support modality.
Background: The novel coronavirus disease (Covid-19) can progress with mild to moderate or self-limiting clinical findings in children. The aim of this study was to investigate the disease features of Covid-19 in Turkish children. Methods: Children diagnosed by the method of RT-PCR for Covid-19 at the Dicle University Department of Pediatric, between April and June 2020, were evaluated. Hospital records were investigated retrospectively. Results: One hundred and five patients children with the mean age of 108.64±65.61 were enrolled in this study. The most common cause of transmission in pediatric patients was contacting with a family member diagnosed with COVID-19 (n=91, 86.7%).The most common admission complaints were dry cough (n=17, 16.2%), fever (n=16, 15.2%), lassitude and fatigue (n=14, 13.3%) respectively. More than 95 % of all children with Covid-19 had asymptomatic, mild, or moderate cases. CRP was identified only independent factor associated with long duration of hospitalization. Conclusion: The results of this study show preliminary results of a study investigating the effect of Covid-19 on Turkish children. A clear understanding of the local epidemiology of corona virus infections and identification of risk factors is critical for the successful implementation of the prevention and control program.
This letter is meant to inform the community of pediatricians/pediatric intensivists that we suspect SARS-CoV-2 to cause life-threatening bronchiolitis in infants and we therefore suggest maintaining a high level of suspicion of COVID-19, irrespective of an initially negative SARS-CoV-2 RT-PCR testing, when other causes of bronchiolitis are unidentifiable in young children.
The first drug specific for cystic fibrosis (CF) was approved in 1993, and since then several other drugs have been approved. Median predicted survival in people with CF has improved from approximately 30 years to 44.4 years over that same period. In 2020, highly-effective modulators of the cystic fibrosis transmembrane conductance regulator became available to approximately 90% of people with CF ages 12 years and older. These transformative therapies will surely reduce morbidity and further extend longevity. The drug development pipeline is filled with therapies that address most aspects of CF disease. As survival and CF therapies have advanced, and the complexity of CF care increases, the process of drug development has become more sophisticated. In addition, detecting meaningful changes in clinical outcomes has become more difficult as the health status of people with CF improves. Design of clinical trials in CF has become more complex, and innovative approaches are required to continue to advance drug development. This review provides a general overview of drug development from the pre-clinical phase through Phase IV. Special considerations with respect to CF are integrated into the discussion of each phase of drug development. The dawn of a new era has arrived for people with CF. As CF care evolves, drug development must continue to evolve as well, until a one-time cure is available to all people with CF.
Both 5q-linked spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are fatal monogenic neuromuscular disorders caused by loss-of-function mutations. SMA is an autosomal recessive disorder affecting motor neurons that is typically caused by homozygous whole-gene deletions of SMN1. DMD is an X-linked recessive muscle disease most often due to exon deletions, but also duplications and smaller sized variants within the DMD gene. Gene replacement therapy offers the opportunity to correct the underlying genetic defect by the introduction of a functional gene. We review the transformative work from clinical trials to United States Food and Drug Administration approval of onasemnogene abeparvovec-xioi in SMA and its application in clinical practice and the early results of microdystrophin delivery in DMD. We also review the introduction of antisense oligonucleotides to alter pre-mRNA splicing to promote exon inclusion (as in nusinersen in SMA) or exclusion (as in eteplirsen in DMD) into neuromuscular therapeutics. There are multiple promising novel genetically mediated therapies on the horizon, which in aggregate point towards a hopeful future for individuals with SMA and DMD.
To the editor, Chronic eosinophilic pneumonia (CEP) is an idiopathic disease rarely reported in children1,2. It typically occurs in non-smoking, middle age females and the diagnosis requires exclusion of systemic or primary eosinophilic lung diseases1,2. The triad of pulmonary symptoms (usually for >2 weeks), abnormal chest radiographic findings and eosinophilia in the blood and/or pulmonary tissue in the absence of an alternative etiology is highly suggestive of CEP. Patients may present with cough (90-93%) dyspnea (50-90%), fever (77-87%), night sweats (23%), weight loss (57-75%), rhinitis or sinusitis (6-24%), chest pain (8-16%), hemoptysis (8-10%), and weakness/fatigue1,2. An asthma phenotype is present in roughly a third to 3/4 of patients. Bilateral peripheral consolidative infiltrates are seen on chest radiograph (CXR) with computed tomography (CT) showing peripheral airspace disease and reactive hilar adenopathy1,2. Peripheral eosinophilia is almost universal with cell counts routinely higher than 1000/mm3 and more than half of patients also have an elevated IgE2. Eosinophilia on the bronchoalveolar lavage (BAL) ranges from 12 to 95% with a mean of 58%2. The triad of pulmonary symptoms, radiographic findings and eosinophilia in CEP typically respond to prednisone within a few days2. Initial doses range from 0.5 to 1mg/kg/day and may be tapered after clinical/radiographic improvement. Duration of therapy depends on the response and is highly variable, with a mean of 19 months but a range of 0.5 to 96 months1. Relapse is common, occurring in up 50% of patients2. While the pathogenesis of CEP is not fully understood, the underlying mechanism undoubtedly involves eosinophils and likely shares inflammatory pathways with asthma, which is why it may be amenable to treatment with novel biologic therapies approved for asthma. Although there are case reports of patients with CEP who were treated with either omalizumab or mepolizumab, there are no reports of treatment with dupilumab3. However, there is a report of a patient possibly experiencing CEP as a consequence of dupilumab4. We present the case of an 11-year-old, previously healthy, African American female who presented with fever, cough, dyspnea, chest pain and decreased appetite of 3 months duration. Her past medical history was significant for pneumonia three months prior that failed to resolve with antibiotics. She was subsequently prescribed albuterol and treated as an outpatient with a working diagnosis of asthma. Her symptoms persisted and she was ultimately hospitalized with chronic pneumonia of unclear etiology. Her family and social histories were unremarkable. She strongly denied vaping or inhalant abuse. Her physical exam was remarkable for bilateral coarse crackles, signs of respiratory distress and reproducible chest pain. Her CXR showed bilateral consolidative opacities and her CT demonstrated bilateral lymphadenopathy and multilobar consolidation (see Figures 1 &2). Her initial lab work was remarkable for a white blood cell count of 10,000/µL (3.84-9.84/µL) with 10% (0-4%) peripheral eosinophilia, erythrocyte sedimentation rate of 103 mm/hr (0-15mm/hr), and C reactive protein of 7mg/dL (0.00-0.50mg/dL). She was treated with 14 days of antibiotics without clinical improvement. During the course of follow up her FEV1 declined > 35% and she developed a severe persistent asthma phenotype. She was evaluated for tuberculosis, allergic bronchopulmonary aspergillosis, helminth infection, eosinophilic granulomatosis with polyangitis, sarcoidosis, and immunodeficiency however her work up was negative. She underwent bronchoscopy, which demonstrated significant bilateral lower airway casts that were 93% eosinophilic. She was treated with high dose prednisone for 4 weeks and improved for a few months, however her symptoms returned. She continued oral prednisone intermittently for approximately 22 months without improvement and was deemed refractory to therapy. Repeat imaging during that time demonstrated persistent opacities and she developed bronchiectasis. Repeat bronchoscopies revealed return of mucoid impactions. Throughout her course, she continued to have eosinophilia in the blood (ranging from 0.4 to 13%) and on BAL (ranging from 9-93%). She was then treated with pulse methylprednisolone and daily cyclosporine in an attempt to gain clinical remission which resulted in modest improvement of symptoms. She continued daily cyclosporine with the addition of dupilumab every 2 weeks for 6 months. Following the addition of dupilumab significant clinical and radiographic improvement were noted within 2 weeks. Her cyclosporine was subsequently weaned without recurrence of symptoms and she remains symptom free with marked improvement in her Chest X-ray findings for over 12 months on subcutaneous dupilumab injections q 2 weeks. Dupilumab is an injectable humanized IgG4 monoclonal antibody, approved for home use in patients with eosinophilic or steroid dependent asthma, which targets IL-4α receptors and inhibits IL-4 and IL-13 binding. It has been shown to reduce the frequency of asthma exacerbations, improve FEV1 and reduce oral steroid use in patients with severe asthma5. This is the first report of dupilumab as a therapy to treat CEP and the first report of monoclonal antibody therapy to treat CEP in a pediatric patient. Dupilumab may be an alternative for CEP that is refractory to corticosteroids or that requires prolonged therapy. It may also be a more convenient therapy compared to other monoclonal antibodies available to patients because it can be administered at home. References1. Jederlinic PJ, Sicilian L, Gaensler EA. 1988. Chronic eosinophilic pneumonia. A report of 19 cases and a review of the literature. Medicine (Baltimore). 67(3):154-162.2. Marchand E, Reynaud-Gaubert M, Lauque D, Durieu J, Tonnel AB, Cordier JF. 1998. Idiopathic chronic eosinophilic pneumonia. A clinical and follow-up study of 62 cases. The groupe d'etudes et de recherche sur les maladies "orphelines" pulmonaires (germ"o"p). Medicine (Baltimore). 77(5):299-312.3. Lin RY, Santiago TP, Patel NM. 2019. Favorable response to asthma-dosed subcutaneous mepolizumab in eosinophilic pneumonia. J Asthma. 56(11):1193-1197.4. Menzella F, Montanari G, Patricelli G, Cavazza A, Galeone C, Ruggiero P, Bagnasco D, Facciolongo N. 2019. A case of chronic eosinophilic pneumonia in a patient treated with dupilumab. Ther Clin Risk Manag. 15:869-875.5. Castro M, Rabe KF, Corren J, Pavord ID, Katelaris CH, Tohda Y, Zhang B, Rice MS, Maroni J, Rowe P et al. 2020. Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma. ERJ Open Res. 6(1).
We read the letter to the editor “B-lines score: artifacts as a sign of neonatal specific disease?” by Quarato et al. and we are pleased by the interest aroused by our article “Neonatal lung ultrasonography score after surfactant in preterm infants: A prospective observational study” published on your journal. This study included preterm neonates with respiratory distress syndrome (RDS), requiring non-invasive ventilation and surfactant. The aim of our citated study was to asses changes of a validated neonatal lung ultrasonography score (nLUS) after surfactant treatment. Our data demonstrate a lowering of the nLUS 2h and 12h after surfactant treatment. In their letter to the editor Quarato et al. expressed criticism about the nLUS score validation and about the utility of the Lung Ultrasound (LUS) as a diagnostic tool. They conclude that “LUS can be used only for diagnosing minimal pleural effusion and, at least, as complementary imaging, in addiction to chest radiographs (CR), for monitoring the reduction of subpleural pneumonitic consolidations under therapy”. Our citated study hasn’t focused on validation of the nLUS score or on LUS as a diagnostic tool for neonatal RDS, so we don’t get how Quarato’s concerns can be addressed to our paper. Nevertheless, finding the debate about nLUS or LUS in the neonatal field an occasion to promote an improving in the care of the preterm babies, we will discuss objections raised in Quadrato’s work, point by point.
Background: Elevated Pre-discharge capillary blood gas partial pressure of carbon dioxide (pCO2) has been associated with increased adverse events including readmission. This study aimed to determine if pre-discharge pCO2 or 36-week pCO2 was associated with increased respiratory readmissions or other pulmonary healthcare utilization in the year after NICU discharge for infants with BPD discharged with home oxygen, using a standardized outpatient oxygen weaning protocol. Methods: This was a secondary cohort analysis of infants born <32 weeks gestational age with BPD, referred to our Pulmonary clinic for home oxygen therapy either from our level IV NICU or local level III NICUs between 2015-17. Infants with major non-respiratory comorbidities were excluded. Subject information was obtained from electronic health records. Results: Of 125 infants, 120 had complete 1-year follow-up. Twenty three percent of infants experienced a respiratory readmission after NICU discharge. There was no significant association between pre-discharge or 36-week pCO2 and respiratory readmissions, emergency room visits, new or increased bronchodilators or diuretics. Higher 36-week pCO2 was associated with a later corrected age when oxygen was discontinued (<6 months, median 54 mm Hg, Interquartile range (IQR) 51-61; 6-11 months, median 62 mm Hg IQR 57-65; ≥12 months, median 66 mm Hg, IQR 58-73; p=0.006). Conclusions: Neither pre-discharge pCO2 nor 36-week pCO2 was associated with one-year respiratory readmissions. Higher pCO2 at 36 weeks was associated with longer duration of home oxygen. Neonatal illness measures like 36-week pCO2 may be useful in communicating expectations for home oxygen therapy to families.
Objectives: Although albuterol, the most frequently used bronchodilator, has been traditionally and generally delivered via nebulization (NEB) with compressed air/oxygen, the benefits of metered‐dose inhalers with a spacer (MDI+S) have been widely recognized as an alternative method for albuterol administration. The aim of this systematic review was to compare the response to albuterol delivered through NEB with albuterol delivered through MDI+S in pediatric patients with asthma exacerbations. Methods: We conducted an electronic search in MEDLINE/PubMed, EMBASE, Ovid and ClinicalTrials. To be included in the review, a study had to a randomized clinical trial comparing albuterol delivered via NEB versus MDI+S; and had to report the rate of hospital admission (primary outcome), or any of the following secondary outcomes: oxygen arterial saturation, heart rate (HR), respiratory rate, the pulmonary index score (PIS), adverse effects, and need for additional treatment. Results: Fifteen studies (n=2057) met inclusion criteria. No significant differences were found between the two albuterol delivery methods in terms of hospital admission (RR 0.89; 95% CI 0.55 to 1.46; I2=32%; p=0.65). There was a significant reduction in the PIS score (MD -0.63; 95% CI -0.91 to -0.35; I2=0%; p < 0.00001), and a significantly smaller increase in HR (better) (MD -6.47; 95% CI -11.69 to -1.25; I2=0%; p=0.02) when albuterol was delivered through MDI+S than when it was delivered through NEB. Conclusions: This review showed a significant reduction in the PIS and a significantly smaller increase in HR when albuterol was delivered through MDI+S than when it was delivered through NEB.
The difference in morbidity and mortality between adult and pediatric COVID-19 infections is dramatic. Understanding pediatric-specific acute and delayed immune responses to SARS-CoV-2 is critical for the development of vaccination strategies, immune-targeted therapies, and treatment and prevention of MIS-C. The goal of this review is to highlight research developments in understanding of the immune responses to SARS-CoV-2 infections, with a specific focus on age-related immune responses.
To the editor,Following the online podcast recorded the 31 March 2020 by the International Committee of the American Thoracic Society Pediatrics Assembly and recently published in Pediatric Pulmonology1, we have interesting discussion with my international colleagues about the likelihood of acute bronchiolitis caused by SARS-CoV-2 infection in absence of RSV co-infection. Here, we report 2 cases of COVID-19 in infants < 3 months old admitted to our paediatric unit. The infants presented fever and neurological symptoms and after a short period, acute bronchiolitis.Case 1 : A term-born boy with unremarkable history was admitted to the emergency department with poorly tolerated high fever (38.8°C) and rhinitis. The parents, who had no history of asthma or allergy, showed clinical signs suggesting SARS-CoV-2 infection. RT-PCR for SARS-CoV-2 on a nasopharyngeal swab was positive for the father and the grandfather, who was hospitalized in the intensive care unit. Neurologic examination of the infant revealed lethargy and hypotonia with a bulging anterior fontanelle. The respiratory condition and clinical examination findings including hemodynamics were normal.The first blood test showed isolated lymphopenia (lymphocyte count 1.56 x109/L; normally 4-6x109/L) without modification of biological inflammatory parameters, as assessed by normal levels of C-reactive protein (CRP) and procalcitonin (PCT). Spinal fluid analysis, cytobacteriological urine analysis and blood culture were negative. RT-PCR of a nasopharyngeal swab was positive for SARS-CoV-2 but negative for respiratory syncytial virus (RSV) and influenza virus (IV). The patient received fluid volume expansion(20 ml/Kg of 0.9% sodium chloride solution) together with antibiotic treatment (cefotaxime, amoxicillin and gentamicin at meningeal doses) for 24 hr, that was stopped with a positive RT-PCR test for SARS-CoV-2 and negative blood culture. Favourable clinical outcome was obtained shortly thereafter, allowing the infant to return home 2 days later.Ten days later, the child returned with acute bronchiolitis. Respiratory symptoms included polypnea, shortness of breath, wheezing and hypoxia (SpO2< 92 %). Lung ultrasonography revealed signs of interstitial syndrome with thickened and irregular pleural line associated with confluent B lines and small multifocal subpleural consolidations. RT-PCR for RSV and IV remained negative. Treatment associated supplemental oxygen and enteral nutrition for 6 days. A second episode of acute bronchiolitis occurred 1 month later, but a RT-PCR test for SARS-CoV-2 was negative. The chest X-ray was normal. The child remained hospitalized for 5 days with enteral nutrition support but did not require oxygen supplementation. Long-term treatment with inhaled daily corticosteroids (fluticasone) was introduced.Case 2 : A term-born eutrophic male with otherwise unremarkable neonatal history was referred for poorly tolerated high fever at age 2 months. Both parents had clinical signs of COVID-19 but were not tested (a member of the family had a positive test). The neurologic examination revealed lethargia and hypotonia in the child; the respiratory condition and clinical examination findings including hemodynamics were normal. The first blood test showed lymphopenia (lymphocyte count: 1.86 x109/L; normally 4-6x109/L)without modification of biological inflammatory parameters. Cytobacteriological examination of urine and blood culture were negative and spinal fluid analysis was not performed. RT-PCR testing of a nasopharyngeal swab was positive for SARS-CoV-2 but negative for RSV and IV. The patient did not receive any antibiotics. On day 3 after admission, the respiratory condition progressively worsened, with retraction, wheezing, increased respiratory rate at 80/min and hypoxia (SpO2 < 92%) requiring supplemental oxygen together with enteral nutrition for 3 days. The chest X-ray was normal, and no lung ultrasonography was performed. The infant was returned to the emergency department 2 weeks later with a non-severe wheezing episode and was discharged at home.These 2 cases of COVID-19 in infants hospitalized for poorly tolerated high fever and neurological symptoms in whom acute bronchiolitis developed at a delay of 2 to 8 days suggest that SARS-CoV-2 infection may cause acute bronchiolitis in absence of viral co-infection such as RSV. Pneumonia is the most common diagnosis among symptomatic children with COVID-191. High-resolution CT scan usually shows ground-glass opacities or bilateral lung consolidations, especially in the periphery, and lung ultrasonography, as in our case 1, reveals signs of lung involvement. In contrast, to the best of our knowledge, acute bronchiolitis due to SARS-CoV-2 infection has never been reported. The wheezing episodes described in our patients were likely due to SARS-CoV-2 infection for the following reasons: first, RT-PCR tests for RSV and IV were always negative in both children, and second, the epidemic season for both viruses was over and the lockdown in France was still active at the time of the cases. Finally, previous study of virus repartition in positive respiratory samples from infants with acute bronchiolitis detected close to a 5% frequency of coronaviruses OC43 and 229E2. Moreover, a recent experimental model of COVID-19 in ferrets showed lung lesions compatible with bronchiolitis3. Our patients showed bronchiolitis symptoms several days after those of COVID-19, which may explain the lack of wheezing episodes reported in the literature. Case 2 was diagnosed with recurrent wheezing presumably due to SARS-CoV-2 infection. RSV as well as rhinovirus bronchiolitis is a risk factor for recurrent wheezing and asthma4,5,but little is known about the long-term impact of SARS-CoV-2 infection in lung function trajectory, which emphasizes the need to follow these children. Whether the infection in symptomatic or asymptomatic infants may predispose to recurrent wheezing or asthma remains to be determined.
Long isolation period for suspected child cases was proposed based in one case. New evidence suggests that children are not as dangerous as they seemed, as a vehicle for this infection. We must be cautious when making recommendations for a disease that affects millions of people, based on just one case.