Respiratory function and symptoms after acute COVID-19 infection in children and adolescents

Introduction/Aim: Significant long-term effects on both symptomatology and respiratory function have been recognised in adult populations after COVID-19 infection, termed 'Long COVID'. These have caused loss of productivity and increased need for healthcare services. This study aimed to measure symptoms and lung function in children and adolescents after acute COVID-19 infection Methods: Between June 1 and 31 October 2021 there were 144 children admitted to hospital across the Sydney Children's Hospital Network, Australia. Of these, 63 children were referred to the respiratory clinic with symptoms of ongoing cough, shortness of breath and fatigue, 3-6 months post COVID infection. 20 of these children performed reliable lung function. For these children, body plethysmography and double diffusion testing were performed within 3-6 months of their infection. The Liverpool respiratory questionnaire and PROMIS paediatric sleep questionnaires were also administered. Result(s): Of the 20 patients tested, 7 had COVID pneumonitis requiring hospitalisation during the acute illness. 6 of the 20 patients had significant persistent symptoms as measured by the Liverpool respiratory questionnaire, while none of the children had any significant sleep symptoms. All children had preserved spirometry within normal limits. Of note, 2 children with persistent respiratory symptoms had DLNO/DLCO ratio >1.15, suggesting pulmonary vascular disease. The same two children who had elevated DLNO / DLCO had high ventilator equivalents on CPET testing suggesting increased physiological dead space ventilation. Despite this, their peak aerobic capacity was within normal limits. There were no significant differences between the alpha and delta cohorts or between children treated at home vs those requiring hospitalisation during their infection. Conclusion(s): COVID-19 may cause long-lasting effects in children. In this cohort, all children maintained spirometry results within normal limits despite significant symptoms impacting daily activities. Double diffusion testing may shed some light on lung changes leading to persistent symptomatology after COVID infection.

The outcome of pulmonary function tests and high-resolution computed tomography of chest in post-coronavirus disease 2019-confirmed cases after 3 months of recovery

Background: Coronavirus disease (COVID-19) is a recently prevalent infectious disease that is caused by a virus from the coronavirus family and causes acute respiratory syndrome. It is a pandemic catastrophe that has affected more than 60 million people around the world and has caused about 1.5 million deaths, as reported by the WHO. This disease affects the respiratory system and leads to different forms of symptoms and signs. Pneumonia is a common cause for hospitalization, with most patients treated in hospital wards and others requiring ICU. Although the number of complete recoveries from COVID-19 has increased, there is still concern about complications associated with the disease that appear after recovery. The studies that have looked at past types and other forms of coronavirus epidemics, such as SARS have shown that some cases had respiratory complications from the infection after being full recovered, as 36 and 30% of the entire study population had clinical and high-resolution computed tomography (HRCT) changes at 3 and 6 months after recovery, respectively. Mostly, the abnormalities seen in pulmonary function test (PFT) results are sequelae of diffusion capacity defect. In recovered cases of Middle East respiratory syndrome, 36% of patients showed HRCT sequelae at follow-up of 6 weeks, because of fibrosis. Data on COVID-19 indicate that prolonged disease and persistent symptoms show post-PFT affection and follow-up radiographic changes after recovery from COVID-19 as interstitial pulmonary changes and a degree of pulmonary vasculopathy. In recovered cases of COVID-19, capacity of diffusion is the commonest defect in lung function, followed by the restrictive pattern defects on spirometry;both are related to the degree of severity of pneumonic COVID-19. PFTs (involving spirometry as well as diffusion capacity) are considered as routine follow-up examinations for some of the recovered cases, especially severe cases. Rehabilitation programs of the respiratory system are an option strategy that might be considered. This study aims to show changes in pulmonary function and HRCT of chest in post-COVID-19-infected patients to detect long-term effects on the lungs after 3 months as obstructive or restrictive, or both, lung diseases. Patients and Methods: The study was conducted on 100 confirmed PCR-positive COVID-19 cases that were admitted to Ain Shams University Isolation Hospitals, and the follow-up was performed in the outpatient clinic. PCR samples (Combined nasopharyngeal and oropharyngeal swab) were taken after 3 months from discharge of patients above the age of 18 years who become negative with clinical improvement. PFT [spirometry and diffusion for carbon monoxide (DLCO)] and chest HRCT were done. All patients' clinical data were recorded, and CT chest imaging data of these patients were correlated with the clinical data. Result(s): A total of 100 patients were included in this study, where males represented 58% and female represented 42%. The mean+/-SD age of cases in this study was 45.05 +/- 11.80 years and ranged from 20 to 79 years. CT chest severity score (SS) of abnormality in COVID-19-infectedd patients based on HRCT chest findings before and after 3 months from treatment showed a highly significant correlation (P=0.000). The results of PFT in the studied group after 3 months of discharge showed restrictive pattern in 14.9%, obstructive pattern in 17.8%, and both obstructive and restrictive patterns in 5.9% of the total number of cases. There was a significant correlation between DLCO abnormality findings and age of studied group (P=0.032), a significant correlation between abnormality findings on PFT and HRCT chest SS after discharge of the studied group (P0.001). There was a significant correlation between abnormality findings of DLCO and HRCT chest SS after 3 months of the studied group (P=0.000) and before treatment (P=0.001), whereas there was no significant correlation between other findings of PFT and HRCT chest SS after 3 months and before. There was a significant correlation between H

The evolving landscape of pulmonary arterial hypertension clinical trials

Although it is a rare disease, the number of available therapeutic options for treating pulmonary arterial hypertension has increased since the late 1990s, with multiple drugs developed that are shown to be effective in phase 3 randomised controlled trials. Despite considerable advancements in pulmonary arterial hypertension treatment, prognosis remains poor. Existing therapies target pulmonary endothelial dysfunction with vasodilation and anti-proliferative effects. Novel therapies that target proliferative vascular remodelling and affect important outcomes are urgently needed. There is need for additional innovations in clinical trial design so that all emerging candidate therapies can be rigorously studied. Pulmonary arterial hypertension trial design has shifted from short-term submaximal exercise capacity as a primary endpoint, to larger clinical event-driven trial outcomes. Event-driven pulmonary arterial hypertension trials could face feasibility and efficiency issues in the future because increasing sample sizes and longer follow-up durations are needed, which would be problematic in such a rare disease. Enrichment strategies, innovative and alternative trial designs, and novel trial endpoints are potential solutions that could improve the efficiency of future pulmonary arterial hypertension trials while maintaining robustness and clinically meaningful evidence.Copyright © 2022 Elsevier Ltd

Utility of Conventional but Late Pulmonary Artery Banding in Complex Cyanotic Congenital Heart Disease in a Toddler - A Single Case Scenario.

Newborns with untreated single ventricles develop pulmonary vascular diseases early in their lives. At that age, during the first eight weeks after birth, clinicians perform pulmonary artery (PA) banding to reduce the blood flow to the lung, decreasing the likelihood of future high vascular resistance or pressure. PA banding is also considered an initial stage in the process of single ventricle palliation procedures. We report a case of a 16-month-old toddler (7 kg) with room air saturation of 82%, diagnosed with tricuspid valve atresia, large atrial and ventricular septal defect, and hypoplastic right ventricle with severe pulmonary arterial hypertension. The baby underwent a successful surgical procedure of PA banding and was discharged after 13 days of hospital stay with a room air saturation of 89%. This case highlighted the benefit of PA banding beyond the stipulated period.

Evaluation of long-term sequelae by cardiopulmonary exercise testing 12 months after hospitalization for severe COVID-19.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is an important clinical tool that provides a global assessment of the respiratory, circulatory and metabolic responses to exercise which are not adequately reflected through the measurement of individual organ system function at rest. In the context of critical COVID-19, CPET is an ideal approach for assessing long term sequelae. METHODS: In this prospective single-center study, we performed CPET 12 months after symptom onset in 60 patients that had required intensive care unit treatment for a severe COVID-19 infection. Lung function at rest and chest computed tomography (CT) scan were also performed. RESULTS: Twelve months after severe COVID-19 pneumonia, dyspnea was the most frequently reported symptom although only a minority of patients had impaired respiratory function at rest. Mild ground-glass opacities, reticulations and bronchiectasis were the most common CT scan abnormalities. The majority of the patients (80%) had a peak O2 uptake (V'O2) considered within normal limits (median peak predicted O2 uptake (V'O2) of 98% [87.2-106.3]). Length of ICU stay remained an independent predictor of V'O2. More than half of the patients with a normal peak predicted V'O2 showed ventilatory inefficiency during exercise with an abnormal increase of physiological dead space ventilation (VD/Vt) (median VD/VT of 0.27 [0.21-0.32] at anaerobic threshold (AT) and 0.29 [0.25-0.34] at peak) and a widened median peak alveolar-arterial gradient for O2 (35.2 mmHg [31.2-44.8]. Peak PetCO2 was significantly lower in subjects with an abnormal increase of VD/Vt (p = 0.001). Impairments were more pronounced in patients with dyspnea. Peak VD/Vt values were positively correlated with peak D-Dimer plasma concentrations from blood samples collected during ICU stay (r2 = 0.12; p = 0.02) and to predicted diffusion capacity of the lung for carbon monoxide (DLCO) (r2 = - 0.15; p = 0.01). CONCLUSIONS: Twelve months after severe COVID-19 pneumonia, most of the patients had a peak V'O2 considered within normal limits but showed ventilatory inefficiency during exercise with increased dead space ventilation that was more pronounced in patients with persistent dyspnea. TRIAL REGISTRATION: NCT04519320 (19/08/2020).

Management of Patients With Pulmonary Hypertension in COVID-19 Pandemic

The new coronavirus (COVID-19) epidemic caused by SARS-CoV-2 has emerged as perhaps the biggest medical problem of our century. Although COVID-19 mainly affects the lungs, it also affects many organs, especially the cardiovascular system. Pulmonary hypertension (PH) is a pulmonary vascular disease described by pulmonary arterial vasoconstriction and remodeling, which may lead to an increased pulmonary artery pressure with varying clinical course and severity depending on the etiology and eventually to right heart failure. Because of associated comorbidities, patients with PH are likely to face a potential risk of severe complications and mortality and unfortunately, they may have worse outcomes than other patients. The COVID-19 pandemic has brought us new and different challenges in the follow-up and treatment processes of patients with PH. For patients admitting to the hospital, it is important to balance the risk of exposure to COVID-19 with ongoing care and treatment services. However, the COVID-19 outbreak has brought serious challenges to PH centers to weigh the risks and benefits of diagnostic research, including potential exposure to COVID-19, and the timing of initiation of PH-specific treatment in high-risk patients. In this article, the management of PH patients during the COVID-19 pandemic;problems encountered in diagnosis, clinical follow-up and treatment processes;the different difficulties experienced during hospitalizations have been compiled.

Variation in Lung Function in Pediatric and Adolescent Population Post SARS-COV-2 Infection: Pediatric Pulmonary Practice Experience

Introduction: In our study, we are reporting pulmonary function testing (PFT) changes post recovery from SARS-CoV-2 infection in the pediatric and adolescents. This is a unique paper which may shed light on a matter of utter importance that has been poorly reported in the literature. Studies reviewing SARS-CoV-2 infection PFT, mostly from adult, had shown obstructive and restrictive impairment, small airway dysfunction, and decreased diffusion capacity for carbon monoxide (DLCO), which gives an overall assessment of the lung's ability of gas exchange likely due to SARS-CoV-2 triggered pulmonary vasculopathy. Restrictive pattern and decreased DLCO were the most frequently impaired PFT parameter. Method: This is a single-site retrospective charts review of children and adolescents, ages 6 to 22 years old, who presented to pediatric pulmonology outpatient after having a SARS-CoV-2 infection. They were either managed in the hospital and had at least one pulmonary symptom or they were managed as outpatient. Results: In our case series of 33 patients, mean age was 16.8 years, the majority were seen as an outpatient (78.7%, 26/33). PFT results were interpreted using ATS standard, 4 PFT were suboptimal, mean time from SARSCoV- 2 infection and PFT was 4.3 months. Among patients with optimal PFT, 72.4% (21/29) had abnormal PFT (table 1). Subjects with PFT changes, 9 previously healthy subjects had PFT changes post- SARS-CoV-2, compared to 12 patients who had history of asthma. All hospitalized patients had measured DLCO except one whom DLCO wasn't measured. Among all hospitalized patients, whose pulmonary imaging exhibited ground glass opacities, 2 patients had normal DLCO (42.8%, 2/6). The rate of low DLCO was higher inpatient than outpatient cases (42.9% vs. 4.5%, p<0.0369) with mean DLCO 71.2% predicted. All hospitalized patients with decreased DLCO had elevated lactate dehydrogenase (LDH) and D-dimer.The most common co-morbid conditions noted to have were asthma (55%, 16/29) and obesity/overweight (51.7%, 15/29). Subjects who were hospitalized, 71% (5/7) required supplemental oxygen;most common chest imaging findings were bilateral ground-glass opacity, or patchy infiltrates. LDH was elevated in 71% (5/7) whereas D-dimer was elevated in 85.7% (6/7). All received steroids, and 85.7% (6/7) received remdesivir. Conclusion: SARS-CoV-2 related pulmonary complications remains a topic of research and is poorly studied in pediatric population. Impaired DLCO could correlate imaging findings However;we didn't find that association in our report, which is limited by low sample size. PFT may be useful as an objective measure for post-COVID infection follow up. (Figure Presented).

Soluble Signals to Improve Endothelial Integrity in the Lung

Disorders in pulmonary vascular integrity are a prominent feature in many lung diseases, including acute respiratory distress syndrome (ARDS), capillary leak syndrome, and COVID19. Paracrine signals are enriched in the lung and are critically important in regulating the homeostasis of the functional pulmonary microvasculature. Here, we employed single-cell RNA-sequencing (scRNAseq) to study ligand and receptor interactions in the native human lung microvascular niche, and identified soluble factors that are critical in endothelial integrity. The scRNAseq data reveals a total of 47 cell populations consisting of five vascular endothelial subtypes in human lungs, including general capillary EC, aerocyte capillary EC (EC aCap), arterial EC, pulmonary venous EC, and systemic venous EC. Using EC aCap as a signal receiving core (Receptors) and the putative adjacent cell types (alveolar fibroblast, ATI, ATII, pericyte, plasma cell, etc.) in the EC aCap niche as senders (Ligands), we identified that SLIT2-ROBO4, ANGPT1-TIE1, ADM-RAMP2, VEGFD-KDR, and BMP5-BMPR2 are the top specific and abundant pairs in the niche. Immunostaining and ELISA assays confirmed their spatial information and secretion level. Furthermore, upon treatment with these ligands, real-time resistance recorded using an electric cell-substrate impedance sensing (ECIS) system revealed that VEGFD, ANGPT1 (angiopoietin 1), and ADM (adrenomedullin) could markedly increase the electrical resistance of human lung microvascular, arterial, and venous endothelial cells, suggesting their strong impact on the endothelial barrier function. Deciphering the cell-cell soluble signals that improve endothelial integrity in human lungs lays the foundation for uncovering the pathogenesis of pulmonary vascular disorders and the development of ex vivo functional lung vasculature.

Abstracts of the 2021 Annual Conference of the Canadian Paediatric Society

The proceedings contain 122 papers. The topics discussed include: educational impact of targeted neonatal echocardiography (TNE) on neonatal-perinatal medicine (NPM) subspecialty residents;extremely low gestational age neonates and resuscitation: perspectives of Canadian neonatologists;neurodevelopmental outcomes of extremely preterm infants with late-onset bacterial sepsis according to type of bacteria;efficacy of pharmacologic therapy for patent ductus arteriosus closure in preterm newborns according to their gestational age-specific Z-score for birth weight;food insecurity during COVID-19 in a Canadian academic pediatric hospital;the burden of bronchopulmonary dysplasia and pulmonary vascular disease in premature infants;high spontaneous ductal closure even at the extreme of prematurity;exploring the impact of COVID-19 on families of children with developmental disabilities: a community-based formative study;a qualitative study of factors that helped prepare athletes for special Olympics sport programs;and impact of catheter choice on procedural success of minimally invasive surfactant therapy.

Observational study of clinico-radiological follow-up of COVID-19 pneumonia: a district general hospital experience in the UK.

BACKGROUND: The British Thoracic Society (BTS) recommends that all patients admitted with COVID-19 pneumonia should have a chest X-ray (CXR) and clinical follow-up at 6 or 12 weeks, depending on the disease severity. Little data is available on long-term CXR follow-up for moderate and severe COVID-19 pneumonia. This study aims to evaluate compliance with clinico-radiological follow-up of patients recovering from COVID-19 pneumonia at a local hospital in the UK, as per the BTS guidance, and to analyse radiological changes at clinical follow-up at 12 weeks, in order to risk-stratify and improve patient outcomes. METHODS: This is a single-centre retrospective audit of 255 consecutive COVID-19 positive patients admitted to a local hospital in the UK over 5 months between May and October 2020. All CXRs and clinic follow-up at 12 ± 8 weeks were checked on an electronic database. RESULTS: Over one in two (131/255) patients had CXR evidence of COVID-19 pneumonia during the initial hospital admission. Half of the patients (60/131) died before CXR or clinic follow-up. Fifty-eight percent (41/71) of the surviving patients had a follow-up CXR, and only two developed respiratory complications- one had residual lung fibrosis, another a pulmonary embolism. Eighty-eight percent (36/41) of the patients had either resolution or improved radiological changes at follow-up. Most patients who had abnormal follow-up CXR were symptomatic (6/8), and many asymptomatic patients at follow-up had a normal CXR (10/12). CONCLUSIONS: Although there were concerns about interstitial lung disease (ILD) incidence in patients with COVID-19 pneumonia, most of our patients with COVID-19 pneumonia had no pulmonary complications at follow-up with CXR. This emphasises that CXR, a cost-effective investigation, can be used to risk-stratify patients for long term pulmonary complications following their COVID-19 pneumonia. However, we acknowledge the limitations of a low CXR and clinic follow-up rate in our cohort.

Pulmonary hypertension and right ventricular involvement in hospitalised patients with COVID-19.

OBJECTIVE: To assess the prevalence, characteristics and prognostic value of pulmonary hypertension (PH) and right ventricular dysfunction (RVD) in hospitalised, non-intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). METHODS: This single-centre, observational, cross-sectional study included 211 patients with COVID-19 admitted to non-ICU departments who underwent a single transthoracic echocardiography (TTE). Patients with poor acoustic window (n=11) were excluded. Clinical, imaging, laboratory and TTE findings were compared in patients with versus without PH (estimated systolic pulmonary artery pressure >35 mm Hg) and with versus without RVD (tricuspid annular plane systolic excursion <17 mm or S wave <9.5 cm/s). The primary endpoint was in-hospital death or ICU admission. RESULTS: A total of 200 patients were included in the final analysis (median age 62 (IQR 52-74) years, 65.5% men). The prevalence of PH and RVD was 12.0% (24/200) and 14.5% (29/200), respectively. Patients with PH were older and had a higher burden of pre-existing cardiac comorbidities and signs of more severe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (radiological lung involvement, laboratory findings and oxygenation status) compared with those without PH. Conversely, patients with RVD had a higher burden of pre-existing cardiac comorbidities but no evidence of more severe SARS-CoV-2 infection compared with those without RVD. The presence of PH was associated with a higher rate of in-hospital death or ICU admission (41.7 vs 8.5%, p<0.001), while the presence of RVD was not (17.2 vs 11.7%, p=0.404). CONCLUSIONS: Among hospitalised non-ICU patients with COVID-19, PH (and not RVD) was associated with signs of more severe COVID-19 and with worse in-hospital clinical outcome. TRIAL REGISTRATION NUMBER: NCT04318366.

Assessment of Small Pulmonary Blood Vessels in COVID-19 Patients Using HRCT.

RATIONALE AND OBJECTIVES: Mounting evidence supports the role of pulmonary hemodynamic alternations in the pathogenesis of COVID-19. Previous studies have demonstrated that changes in pulmonary blood volumes measured on computed tomography (CT) are associated with histopathological markers of pulmonary vascular pruning, suggesting that quantitative CT analysis may eventually be useful in the assessment pulmonary vascular dysfunction more broadly. MATERIALS AND METHODS: Building upon previous work, automated quantitative CT measures of small blood vessel volume and pulmonary vascular density were developed. Scans from 103 COVID-19 patients and 107 healthy volunteers were analyzed and their results compared, with comparisons made both on lobar and global levels. RESULTS: Compared to healthy volunteers, COVID-19 patients showed significant reduction in BV5 (pulmonary blood volume contained in blood vessels of <5 mm2) expressed as BV5/(total pulmonary blood volume; p < 0.0001), and significant increases in BV5-10 and BV 10 (pulmonary blood volumes contained in vessels between 5 and 10 mm2 and above 10 mm2, respectively, p < 0.0001). These changes were consistent across lobes. CONCLUSION: COVID-19 patients display striking anomalies in the distribution of blood volume within the pulmonary vascular tree, consistent with increased pulmonary vasculature resistance in the pulmonary vessels below the resolution of CT.

COVID-19 pandemic and troponin: indirect myocardial injury, myocardial inflammation or myocarditis?

The initial mechanism for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the binding of the virus to the membrane-bound form of ACE2, which is mainly expressed in the lung. Since the heart and the vessels also express ACE2, they both could become targets of the virus. However, at present the extent and importance of this potential involvement are unknown. Cardiac troponin levels are significantly higher in patients with more severe infections, patients admitted to intensive care units or in those who have died. In the setting of COVID-19, myocardial injury, defined by an increased troponin level, occurs especially due to non-ischaemic myocardial processes, including severe respiratory infection with hypoxia, sepsis, systemic inflammation, pulmonary thrombosis and embolism, cardiac adrenergic hyperstimulation during cytokine storm syndrome, and myocarditis. At present, there are limited reports on definite diagnosis of myocarditis caused by SARS-CoV-2 in humans and limited demonstration of the virus in the myocardium. In conclusion, although the heart and the vessels are potential targets in COVID-19, there is currently limited evidence on the direct infection of the myocardium by SARS-CoV-2. Additional pathological studies and autopsy series will be very helpful to clarify the potentiality of COVID-19 to directly infect the myocardium and cause myocarditis.