Long COVID in Children: A Multidisciplinary Review.

Long COVID syndrome has emerged as a long-lasting consequence of acute SARS-CoV-2 infection in adults. In addition, children may be affected by Long COVID, with potential clinical issues in different fields, including problems in school performance and daily activities. Yet, the pathophysiologic bases of Long COVID in children are largely unknown, and it is difficult to predict who will develop the syndrome. In this multidisciplinary clinical review, we summarise the latest scientific data regarding Long COVID and its impact on children. Special attention is given to diagnostic tests, in order to help the physicians to find potential disease markers and quantify impairment. Specifically, we assess the respiratory, upper airways, cardiac, neurologic and motor and psychological aspects. Finally, we also propose a multidisciplinary clinical approach.

Recovering from COVID-19: psychological sequelae and post-traumatic growth six months after discharge.

Background: Clinical and scientific evidence has shown that a range of long-lasting symptoms can persist in the post-virological period. However, little is known about the psychological sequelae of patients hospitalized for coronavirus disease 2019 (COVID-19). Objective: This study aims to assess the prevalence of anxiety-depressive symptoms, post-traumatic stress disorder (PTSD), and post-traumatic growth among patients hospitalized for COVID-19 during the first wave of the pandemic 6 months after discharge, and to identify sociodemographic and clinical factors associated with psychological outcomes. Method: This cross-sectional cohort study enrolled recovered COVID-19 patients during a multidisciplinary follow-up screening. At 6 months post-discharge, participants underwent a remote assessment with the Mini-International Neuropsychiatric Interview Plus and completed the Hospital Anxiety and Depression Scale, PTSD Checklist for DSM-5, and Post-Traumatic Growth Inventory. Descriptive and regression analyses were conducted. Results: The sample was composed of 100 patients, mainly males (72%), with a mean ± SD age of 58.7 ± 11.8 years. Regarding psychological symptoms, 34% and 24% of patients, respectively, reported anxiety and depression over the clinical threshold, and 20% met the criteria for a possible PTSD diagnosis. Psychological symptoms were associated with the presence of a mood disorder in the patient's clinical history and having received a psychological consultation after discharge. Post-traumatic growth was associated with younger age and having received a psychological consultation after discharge. Conclusions: A high prevalence of anxiety and depressive symptoms, potentially indicative for a mood or anxiety disorder, and PTSD was confirmed among COVID-19 survivors after 6 months. Anxiety and depressive symptoms and PTSD were associated with a previous diagnosis of a mood disorder and having received psychological consultation. Post-traumatic growth was associated with younger age and having received psychological consultation. Tailored psychological interventions could help to elaborate the psychological suffering and foster post-traumatic growth after a traumatic experience such as COVID-19 hospitalization. HIGHLIGHTS: A high prevalence of psychological symptoms has been observed among COVID-19 survivors 6 months after hospitalization.Tailored psychological interventions could help to contain the psychological sequelae and facilitate post-traumatic growth.

Antecedentes: La evidencia clínica y científica reciente ha demostrado que una variedad de síntomas duraderos pueden persistir incluso en el periodo post-virológico. Sin embargo, poco se sabe sobre las secuelas psicológicas de los pacientes hospitalizados por COVID-19.Objetivo: Este estudio tiene como objetivo evaluar la prevalencia de síntomas ansioso-depresivos, Trastorno de Estrés Postraumático (TEPT) y crecimiento postraumático entre pacientes hospitalizados por COVID-19 durante la primera ola de pandemia seis meses después del alta e identificar los factores socio-demográficos y clínicos asociados con los resultados psicológicos.Método: Este estudio de cohorte transversal inscribió a pacientes recuperados de COVID-19 durante un tamizaje de seguimiento multidisciplinario. A los seis meses del alta, los participantes se sometieron a una evaluación remota con la Entrevista Neuropsiquiátrica Internacional Mini Plus y completaron la Escala de Depresión y Ansiedad Hospitalaria, la Lista de chequeo-5 para Trastorno de Estrés Postraumático y el Inventario de Crecimiento Postraumático. Se condujeron análisis de regresión y descriptivos.Resultados: La muestra se compuso de 100 pacientes, principalmente varones (72%), con una edad promedio de 58.7 años (DE=11.8). En cuanto a los síntomas psicológicos, 34% y 24% de los pacientes reportaron ansiedad y depresión por encima del umbral clínico y 20% reunía los criterios para un posible diagnóstico de TEPT. Los síntomas psicológicos se asociaron con la presencia de un trastorno del ánimo en la historia clínica del paciente y el haber recibido una consulta psicológica tras el alta. El crecimiento postraumático se asoció con ser más joven y haber recibido una consulta psicológica tras el alta.`Conclusiones: Se confirmó una alta prevalencia de síntomas ansiosos y depresivos, potencialmente indicativo de un trastorno del estado de ánimo y TEPT entre los sobrevivientes al COVID-19 después de seis meses. Los síntomas ansiosos y depresivos y el TEPT se asociaron con un diagnóstico previo de un trastorno del ánimo y haber recibido consulta psicológica. Se encontró que el crecimiento postraumático se asociaba con ser más joven y haber recibido consulta psicológica. Las intervenciones psicológicas "a la medida" podrían ayudar a elaborar el sufrimiento psicológico y fomentar el crecimiento postraumático tras una experiencia traumática como la hospitalización por COVID-19.

Use of lung ultrasound in school-aged children with wheezing.

Background: There is limited information available on fast and safe bedside tools that could help clinicians establish whether the pathological process underlying cases of wheezing is due to asthmatic exacerbation, asthmatic bronchitis, or pneumonia. The study's aim was to characterize Lung Ultrasound (LUS) in school-aged children with wheezing and evaluate its use for their follow-up treatment. Materials and methods: We carried out a cross-sectional study involving 68 consecutive outpatients (mean age 9.9 years) with wheezing and suggestive signs of an acute respiratory infection. An expert sonographer, blinded to all subject characteristics, clinical course, and the study pediatrician's diagnosis, performed an LUS after spirometry and before BDT. The severity of acute respiratory symptoms was determined using the Pediatric Respiratory Assessment Measure (PRAM) score. Results: The LUS was positive in 38.2% (26/68) of patients [12 (46.1%) with multiple B-lines, 24 (92.3%) with consolidation, and 22 (84.6%) with pleural abnormalities]. In patients with pneumonia, asthmatic bronchitis, and asthma, the percentages of those patients with a positive LUS were 100%, 57.7%, and 0%, respectively. Of note, patients with a positive LUS were associated with an increased need for hospital admission (30.8% vs. 2.4%, p = 0.001), administration of oxygen therapy (14.6% vs. 0%, p = 0.009), oral corticosteroids (84.6% vs. 19.0%, p < 0.001), and antibiotics (88.5% vs. 11.9%, p < 0.001); and a higher median value of PRAM score (4.0 (2.0-7.0) vs. 2.0 (1.0-5.0); p < 0.001). Conclusions: Our findings would suggest the use of LUS as a safe and cheap tool used by clinicians to define the diagnosis of school-aged children with wheezing of unknown causes.

Feasibility and Clinical Outcomes of a Step Up Noninvasive Respiratory Support Strategy in Patients with Severe COVID-19 Pneumonia.

The best noninvasive respiratory strategy in patients with Coronavirus Disease 2019 (COVID-19) pneumonia is still discussed. We aimed at assessing the rate of endotracheal intubation (ETI) in patients treated with continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV) if CPAP failed. Secondary outcomes were in-hospital mortality and in-hospital length of stay (LOS). A retrospective, observational, multicenter study was conducted in intermediate-high dependency respiratory units of two Italian university hospitals. Consecutive patients with COVID-19 treated with CPAP were enrolled. Thoraco-abdominal asynchrony or hemodynamic instability led to ETI. Patients showing SpO2 ≤ 94%, respiratory rate ≥ 30 bpm or accessory muscle activation on CPAP received NIV. Respiratory distress and desaturation despite NIV eventually led to ETI. 156 patients were included. The overall rate of ETI was 30%, mortality 18% and median LOS 24 (17-32) days. Among patients that failed CPAP (n = 63), 28% were intubated, while the remaining 72% received NIV, of which 65% were intubated. Patients intubated after CPAP showed lower baseline PaO2/FiO2, lower lymphocyte counts and higher D-dimer values compared with patients intubated after CPAP + NIV. Mortality was 22% with CPAP + ETI, and 20% with CPAP + NIV + ETI. In the case of CPAP failure, a NIV trial appears feasible, does not deteriorate respiratory status and may reduce the need for ETI in COVID-19 patients.

Usefulness of Lung Ultrasound in Paediatric Respiratory Diseases.

Respiratory infection diseases are among the major causes of morbidity and mortality in children. Diagnosis is focused on clinical presentation, yet signs and symptoms are not specific and there is a need for new non-radiating diagnostic tools. Among these, lung ultrasound (LUS) has recently been included in point-of-care protocols showing interesting results. In comparison to other imaging techniques, such as chest X-ray and computed tomography, ultrasonography does not use ionizing radiations. Therefore, it is particularly suitable for clinical follow-up of paediatric patients. LUS requires only 5-10 min and allows physicians to make quick decisions about the patient's management. Nowadays, LUS has become an early diagnostic tool to detect pneumonia during the COVID-19 pandemic. In this narrative review, we show the most recent scientific literature about advantages and limits of LUS performance in children. Furthermore, we discuss the major paediatric indications separately, with a paragraph fully dedicated to COVID-19. Finally, we mention potential future perspectives about LUS application in paediatric respiratory diseases.

Distinct Mechanical Properties of the Respiratory System Evaluated by Forced Oscillation Technique in Acute Exacerbation of COPD and Acute Decompensated Heart Failure.

Discriminating between cardiac and pulmonary dyspnea is essential for patients' management. We investigated the feasibility and ability of forced oscillation techniques (FOT) in distinguishing between acute exacerbation of COPD (AECOPD), and acute decompensated heart failure (ADHF) in a clinical emergency setting. We enrolled 49 patients admitted to the emergency department (ED) for dyspnea and acute respiratory failure for AECOPD, or ADHF, and 11 healthy subjects. All patients were able to perform bedside FOT measurement. Patients with AECOPD showed a significantly higher inspiratory resistance at 5 Hz, Xrs5 (179% of predicted, interquartile range, IQR 94-224 vs. 100 IQR 67-149; p = 0.019), and a higher inspiratory reactance at 5 Hz (151%, IQR 74-231 vs. 57 IQR 49-99; p = 0.005) than patients with ADHF. Moreover, AECOPD showed higher heterogeneity of ventilation (respiratory system resistance difference at 5 and 19 Hz, Rrs5-19: 1.49 cmH2O/(L/s), IQR 1.03-2.16 vs. 0.44 IQR 0.22-0.76; p = 0.030), and a higher percentage of flow limited breaths compared to ADHF (10%, IQR 0-100 vs. 0 IQR 0-12; p = 0.030). FOT, which resulted in a suitable tool to be used in the ED setting, has the ability to identify distinct mechanical properties of the respiratory system in AECOPD and ADHF.

Effects of Air Stacking on Dyspnea and Lung Function in Neuromuscular Diseases.

OBJECTIVE: To investigate whether the decrease in dyspnea in neuromuscular diseases after air stacking (AS) occurs mostly in patients with decreased inspiratory muscle force and ensuing chest wall restriction or heterogeneous ventilation across the lungs. DESIGN: Interventional, before-after study. SETTING: A neurorehabilitation inpatient and outpatient center. PARTICIPANTS: Fifteen consecutive adult patients affected by neuromuscular diseases (N=15). INTERVENTIONS: AS treatment. MAIN OUTCOME MEASURES: Patients had vital capacity (VC) and sniff nasal inspiratory pressure (SNIP) measured. We measured Borg score, oxygen saturation, and ventilation heterogeneity across the lung as estimated from the difference between respiratory resistance at 5 and 19 Hz (R5-19) with the forced oscillation technique before and 5, 30, 60, and 120 minutes after applying AS. RESULTS: Before AS, Borg score was significantly related to R5-19 (r2 0.46, P<.05) but not to VC % predicted, SNIP % predicted, and time since symptom onset. After AS, average Borg score gradually decreased (P=.005), whereas inspiratory flow resistance at 5 Hz, R5-19, and inspiratory reactance at 5 Hz tended to improve, despite not reaching statistical significance. The decrease in dyspnea at 60 and 120 minutes after AS significantly correlated with baseline R5-19 (r2 0.49, P<.01 and r2 0.29, P<.05, respectively), but not with VC % predicted, SNIP % predicted, time since symptom onset, and clinical severity score for patients affected by amyotrophic lateral sclerosis. CONCLUSIONS: These findings suggest that dyspnea in neuromuscular diseases is related to heterogeneous ventilation rather than inspiratory muscle force and/or lung volumes decrease. Restoring ventilation distribution across the lungs with AS appears to improve dyspnea.

At the peak of COVID-19 age and disease severity but not comorbidities are predictors of mortality: COVID-19 burden in Bergamo, Italy.

BACKGROUND: Findings from February 2020, indicate that the clinical spectrum of COVID-19 can be heterogeneous, probably due to the infectious dose and viral load of SARS-CoV-2 within the first weeks of the outbreak. The aim of this study was to investigate predictors of overall 28-day mortality at the peak of the Italian outbreak. METHODS: Retrospective observational study of all COVID-19 patients admitted to the main hospital of Bergamo, from February 23 to March 14, 2020. RESULTS: Five hundred and eight patients were hospitalized, predominantly male (72.4%), mean age of 66±15 years; 49.2% were older than 70 years. Most of patients presented with severe respiratory failure (median value [IQR] of PaO2/FiO2: 233 [149-281]). Mortality rate at 28 days resulted of 33.7% (N.=171). Thirty-nine percent of patients were treated with continuous positive airway pressure (CPAP), 9.5% with noninvasive ventilation (NIV) and 13.6% with endotracheal intubation. 9.5% were admitted to Semi-Intensive Respiratory Care Unit, and 18.9% to Intensive Care Unit. Risk factors independently associated with 28-day mortality were advanced age (≥78 years: odds ratio [OR], 95% confidence interval [CI]: 38.91 [10.67-141.93], P<0.001; 70-77 years: 17.30 [5.40-55.38], P<0.001; 60-69 years: 3.20 [1.00-10.20], P=0.049), PaO2/FiO2<200 at presentation (3.50 [1.70-7.20], P=0.001), need for CPAP/NIV in the first 24 hours (8.38 [3.63-19.35], P<0.001), and blood urea value at admission (1.01 [1.00-1.02], P=0.015). CONCLUSIONS: At the peak of the outbreak, with a probable high infectious dose and viral load, older age, the severity of respiratory failure and renal impairment at presentation, but not comorbidities, are predictors of 28-day mortality in COVID-19.

Measuring vital capacity in amyotrophic lateral sclerosis: Effects of interfaces and reproducibility.

BACKGROUND: Deterioration of vital capacity (VC) in amyotrophic lateral sclerosis (ALS) signifies disease progression and indicates need for non-invasive ventilation. Weak facial muscles consequent to ALS, with resulting poor mouth seal, may interfere with the accuracy of VC measurements. OBJECTIVES: To determine whether different interfaces affect VC measurements in ALS patients and whether the interface yielding the largest VC produces an even higher VC when re-measured after one week (learning effect). To explore the relationship between optimal interface VC and sniff nasal pressure (SNIP), a measurement of global inspiratory muscle strength. METHODS: Thirty-five patients (17 bulbar and 18 spinal ALS) were studied. Three interfaces (rigid-cylindrical, flanged, oronasal mask) were tested. One week after the first visit, VC was recorded using the optimal interface. SNIP recordings were also obtained. RESULTS: In the bulbar ALS group, median (interquartile range) VC with the flanged mouthpiece was 8.4% (3.9-15.5) larger than with the cylindrical mouthpiece (p < 0.001). VC values with oronasal mask were intermediate to VC with the other two interfaces. In spinal ALS, flanged mouthpiece VC was 4.6% (2.3-7.5) larger than with oronasal mask (p < 0.0006). The latter was 4.5% (0.6-5.2) smaller than with the cylindrical mouthpiece (p = 0.002). In both groups, VC during the second visit was greater than during the first visit (p < 0.025). SNIPs were logarithmically related to VC values recorded with the flanged mouthpiece. CONCLUSION: A flanged mouthpiece yields the largest values of VC in patients with bulbar and spinal ALS.

Respiratory dysfunction in Parkinson's disease: a narrative review.

The presence of respiratory symptoms in Parkinson's disease (PD) has been known since the first description of the disease, even though the prevalence and incidence of these disturbances are not well defined. Several causes have been reported, comprising obstructive and restrictive pulmonary disease and changes in the central ventilatory control, and different pathogenetic mechanisms have been postulated accordingly. In our review, we encompass the current knowledge about respiratory abnormalities in PD, as well as the impact of anti-Parkinsonian drugs as either risk or protective factors. A description of putative pathogenetic mechanisms is also provided, and possible treatments are discussed, focusing on the importance of recognising and treating respiratory symptoms as a key manifestation of the disease itself. A brief description of respiratory dysfunctions in atypical Parkinsonism, especially α-synucleinopathies, is also provided.

Inpatient Care during the COVID-19 Pandemic: A Survey of Italian Physicians.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease that is of great global public health concern. OBJECTIVE: We explored the clinical management of inpatients with COVID-19 in Italy. METHODS: A self-administered survey was sent by email to Italian physicians caring for adult patients with COVID-19. A panel of experts was selected according to their clinical curricula and their responses were analyzed. RESULTS: A total of 1,215 physicians completed the survey questionnaire (17.4% response rate). Of these, 188 (15.5%) were COVID-19 experts. Chest computed tomography was the most used method to detect and monitor COVID-19 pneumonia. Most of the experts managed acute respiratory failure with CPAP (56.4%), high flow nasal cannula (18.6%), and non-invasive mechanical ventilation (8%), while an intensivist referral for early intubation was requested in 17% of the cases. Hydroxychloroquine was prescribed as an antiviral in 90% of cases, both as monotherapy (11.7%), and combined with protease inhibitors (43.6%) or azithromycin (36.2%). The experts unanimously prescribed low-molecular-weight heparin to patients with severe COVID-19 pneumonia, and half of them (51.6%) used a dose higher than standard. The respiratory burden in patients who survived the acute phase was estimated as relevant in 28.2% of the cases, modest in 39.4%, and negligible in 9%. CONCLUSIONS: In our survey some major topics, such as the role of non-invasive respiratory support and drug treatments, show disagreement between experts, likely reflecting the absence of high-quality evidence studies. Considering the significant respiratory sequelae reported following COVID-19, proper respiratory and physical therapy programs should be promptly made available.

Clinical Use and Barriers of Thoracic Ultrasound: A Survey of Italian Pulmonologists.

INTRODUCTION: Thoracic ultrasound is accurate in the diagnosis of a wide range of respiratory diseases. Yet the extent of its use is unknown. Through a national survey, we aimed to explore the clinical use of thoracic ultrasound and the barriers to the diffusion of the technique in Italy. METHODS: Accademia di Ecografia Toracica (AdET) developed a self-administered survey which was sent by email to Italian pulmonologists via national scientific societies and networks. RESULTS: Of the 2010 physicians invited, 514 completed the survey (26% response rate). According to 99% of responders, thoracic ultrasound had a relevant clinical role. Seventy-nine percent of the responders used thoracic ultrasound at least once a month. The main settings were: 53% pulmonology ward, 15% outpatient clinic, 15% interventional pulmonology room, 10% internal medicine ward, 4% respiratory intensive care units, and 9% other. Thoracic ultrasound was primarily used: (1) with both diagnostic and interventional aims (72%), (2) as diagnostic imaging (17%), and (3) as guidance for interventional procedures (11%). The main clinical applications were: (1) diagnosis and management of pleural effusion, (2) pneumothorax, (3) pneumonia, (4) cardiac failure, and (5) acute dyspnea. Twenty-one percent of the responders do not use thoracic ultrasound. The main reported bar-riers were: (1) availability of an ultrasound system (52%), (2) lack of protected time and training (22%), and (3) use of the technique by other specialists (15%). CONCLUSION: Thoracic ultrasound is widely used by Italian pulmonologists and considered a clinically relevant tool. The availability of dedicated ultrasound systems seems to be a major limit of the use of the technique.

Global and Regional Diagnostic Accuracy of Lung Ultrasound Compared to CT in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: Lung CT is the reference imaging technique for acute respiratory distress syndrome, but requires transportation outside the intensive care and x-ray exposure. Lung ultrasound is a promising, inexpensive, radiation-free, tool for bedside imaging. Aim of the present study was to compare the global and regional diagnostic accuracy of lung ultrasound and CT scan. DESIGN: A prospective, observational study. SETTING: Intensive care and radiology departments of a University hospital. PATIENTS: Thirty-two sedated, paralyzed acute respiratory distress syndrome patients (age 65 ± 14 yr, body mass index 25.9 ± 6.5 kg/m, and PaO2/FIO2 139 ± 47). INTERVENTIONS: Lung CT scan and lung ultrasound were performed at positive end-expiratory pressure 5 cm H2O. A standardized assessment of six regions per hemithorax was used; each region was classified for the presence of normal aeration, alveolar-interstitial syndrome, consolidation, and pleural effusion. Agreement between the two techniques was calculated, and diagnostic variables were assessed for lung ultrasound using lung CT as a reference. MEASUREMENTS AND MAIN RESULTS: Global agreement between lung ultrasound and CT ranged from 0.640 (0.391-0.889) to 0.934 (0.605-1.000) and was on average 0.775 (0.577-0.973). The overall sensitivity and specificity of lung ultrasound ranged from 82.7% to 92.3% and from 90.2% to 98.6%, respectively. Similar results were found with regional analysis. The diagnostic accuracy of lung ultrasound was significantly higher when those patterns not reaching the pleural surface were excluded (area under the receiver operating characteristic curve: alveolar-interstitial syndrome 0.854 [0.821-0.887] vs 0.903 [0.852-0.954]; p = 0.049 and consolidation 0.851 [0.818-0.884] vs 0.896 [0.862-0.929]; p = 0.044). CONCLUSIONS: Lung ultrasound is a reproducible, sensitive, and specific tool, which allows for bedside detections of the morphologic patterns in acute respiratory distress syndrome. The presence of deep lung alterations may impact the diagnostic performance of this technique.

Management of Chronic Respiratory Failure in Interstitial Lung Diseases: Overview and Clinical Insights.

Interstitial lung diseases (ILDs) may be complicated by chronic respiratory failure (CRF), especially in the advanced stages. Aim of this narrative review is to evaluate the current evidence in management of CRF in ILDs. Many physiological mechanisms underlie CRF in ILDs, including lung restriction, ventilation/perfusion mismatch, impaired diffusion capacity and pulmonary vascular damage. Intermittent exertional hypoxemia is often the initial sign of CRF, evolving, as ILD progresses, into continuous hypoxemia. In the majority of the cases, the development of CRF is secondary to the worsening of the underlying disease; however, associated comorbidities may also play a role. When managing CRF in ILDs, the need for pulmonary rehabilitation, the referral to lung transplant centers and palliative care should be assessed and, if necessary, promptly offered. Long-term oxygen therapy is commonly prescribed in case of resting or exertional hypoxemia with the purpose to decrease dyspnea and improve exercise tolerance. High-Flow Nasal Cannula oxygen therapy may be used as an alternative to conventional oxygen therapy for ILD patients with severe hypoxemia requiring both high flows and high oxygen concentrations. Non-Invasive Ventilation may be used in the chronic setting for palliation of end-stage ILD patients, although the evidence to support this application is very limited.

ERS statement on chest imaging in acute respiratory failure.

Chest imaging in patients with acute respiratory failure plays an important role in diagnosing, monitoring and assessing the underlying disease. The available modalities range from plain chest X-ray to computed tomography, lung ultrasound, electrical impedance tomography and positron emission tomography. Surprisingly, there are presently no clear-cut recommendations for critical care physicians regarding indications for and limitations of these different techniques.The purpose of the present European Respiratory Society (ERS) statement is to provide physicians with a comprehensive clinical review of chest imaging techniques for the assessment of patients with acute respiratory failure, based on the scientific evidence as identified by systematic searches. For each of these imaging techniques, the panel evaluated the following items: possible indications, technical aspects, qualitative and quantitative analysis of lung morphology and the potential interplay with mechanical ventilation. A systematic search of the literature was performed from inception to September 2018. A first search provided 1833 references. After evaluating the full text and discussion among the committee, 135 references were used to prepare the current statement.These chest imaging techniques allow a better assessment and understanding of the pathogenesis and pathophysiology of patients with acute respiratory failure, but have different indications and can provide additional information to each other.