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1.
Front Pharmacol ; 13: 813087, 2022.
Article in English | MEDLINE | ID: covidwho-1775746

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an acute respiratory disease with systemic complications. Therapeutic strategies for COVID-19, including repurposing (partially) developed drugs are urgently needed, regardless of the increasingly successful vaccination outcomes. We characterized two-dimensional (2D) and three-dimensional models (3D) to establish a physiologically relevant airway epithelial model with potential for investigating SARS-CoV-2 therapeutics. Human airway basal epithelial cells maintained in submerged 2D culture were used at low passage to retain the capacity to differentiate into ciliated, club, and goblet cells in both air-liquid interface culture (ALI) and airway organoid cultures, which were then analyzed for cell phenotype makers. Airway biopsies from non-asthmatic and asthmatic donors enabled comparative evaluation of the level and distribution of immunoreactive angiotensin-converting enzyme 2 (ACE2). ACE2 and transmembrane serine proteinase 2 (TMPRSS2) mRNA were expressed in ALI and airway organoids at levels similar to those of native (i.e., non-cultured) human bronchial epithelial cells, whereas furin expression was more faithfully represented in ALI. ACE2 was mainly localized to ciliated and basal epithelial cells in human airway biopsies, ALI, and airway organoids. Cystic fibrosis appeared to have no influence on ACE2 gene expression. Neither asthma nor smoking status had consistent marked influence on the expression or distribution of ACE2 in airway biopsies. SARS-CoV-2 infection of ALI cultures did not increase the levels of selected cytokines. Organotypic, and particularly ALI airway cultures are useful and practical tools for investigation of SARS-CoV-2 infection and evaluating the clinical potential of therapeutics for COVID-19.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306750

ABSTRACT

Background: There are limited data in paediatric populations evaluating whether chronic cardiorespiratory conditions are associated with increased risk of COVID-19. We aimed to compare the rates of chronic cardiac and respiratory disease in children testing positive (SARS-CoV-2[+]) compared to those testing negative (SARS-CoV-2[-]) at our institution. Method Prospective cohort with nested case-control study of all children tested by PCR for SARS-CoV-2 by nasopharyngeal/oropharyngeal sampling between March and October 2020. Children were identified prospectively via laboratory notification with age and sex-matching of SARS-CoV-2[+] to SARS-CoV-2[-] (1:2). Clinical data were extracted from the electronic medical record. Results In total, 179 SARS-CoV-2[+] children (44% female, median age 3.5 yrs, range 0.1 to 19.0 yrs) were matched to 391 SARS-CoV-2[-] children (42% female, median age 3.7 yrs, range 0.1 to 18.3 yrs). The commonest co-morbidities showed similar frequencies in the SARS-CoV-2[+] and [-] groups: asthma (n = 9, 5% vs n = 17, 4.4%, p = 0.71), congenital heart disease (n = 6, 3.4% vs n = 7, 1.8%, p = 0.25) and obstructive sleep apnoea (n = 4, 2.2% vs n = 10, 2.3%, p = 0.82). In the SARS-CoV-2 group, the prevalence of symptomatic disease was similar amongst children with and without cardiorespiratory comorbidities (n = 12, 75% vs n = 103, 57%, p = 0.35) who tested positive. A high proportion of children hospitalised with SARS-CoV-2 infection had cardiac comorbidities (23.8%). Conclusions In this single site dataset, rates of pre-existing cardiorespiratory disease were similar in SARS-CoV-2[+] and SARS-CoV-2[-] children. High rates of comorbid cardiac disease were observed amongst hospitalised children with COVID-19, warranting further research to inform public health measures and vaccine prioritisation.

4.
Pediatr Pulmonol ; 56(12): 3664-3668, 2021 12.
Article in English | MEDLINE | ID: covidwho-1384289

ABSTRACT

BACKGROUND: There are limited data in pediatric populations evaluating whether chronic cardiorespiratory conditions are associated with increased risk of coronavirus disease 2019 (COVID-19). We aimed to compare the rates of chronic cardiac and respiratory disease in children testing positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2[+]) compared with those testing negative (SARS-CoV-2[-]) at our institution. METHOD: Prospective cohort with nested case-control study of all children tested by polymerase chain reaction (PCR) for SARS-CoV-2 by nasopharyngeal/oropharyngeal sampling between March and October 2020. Children were identified prospectively via laboratory notification with age and sex-matching of SARS-CoV-2[+] to SARS-CoV-2[-] (1:2). Clinical data were extracted from the electronic medical record. RESULTS: In total, 179 SARS-CoV-2[+] children (44% females, median age 3.5 years, range: 0.1-19.0 years) were matched to 391 SARS-CoV-2[-] children (42% female, median age 3.7 years, range: 0.1-18.3 years). The commonest comorbidities showed similar frequencies in the SARS-CoV-2[+] and [-] groups: asthma (n = 9, 5% vs. n = 17, 4.4%, p = 0.71), congenital heart disease (n = 6, 3.4% vs. n = 7, 1.8%, p = 0.25) and obstructive sleep apnoea (n = 4, 2.2% vs. n = 10, 2.3%, p = 0.82). In the SARS-CoV-2[+] group, the prevalence of symptomatic disease was similar among children with and without cardiorespiratory comorbidities (n = 12, 75% vs. n = 103, 57%, p = 0.35). A high proportion of children hospitalized with SARS-CoV-2 infection had cardiac comorbidities (23.8%). CONCLUSIONS: In this single site data set, rates of pre-existing cardiorespiratory disease were similar in SARS-CoV-2[+] and SARS-CoV-2[-] children. Rates of symptomatic infection were similar between children with and without cardiorespiratory comorbidity. High rates of comorbid cardiac disease were observed among hospitalized children with COVID-19 warranting further research to inform vaccine prioritization.


Subject(s)
COVID-19 , SARS-CoV-2 , Case-Control Studies , Child , Child, Preschool , Comorbidity , Female , Humans , Male , Prospective Studies
5.
Curr Opin Pulm Med ; 27(6): 544-553, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1371767

ABSTRACT

PURPOSE OF REVIEW: At many institutions, the Covid-19 pandemic made it necessary to rapidly change the way services are provided to patients, including those with cystic fibrosis (CF). The purpose of this review is to explore the past, present and future of telehealth and virtual monitoring in CF and to highlight certain challenges/considerations in developing such services. RECENT FINDINGS: The Covid-19 pandemic has proven that telehealth and virtual monitoring are a feasible means for safely providing services to CF patients when traditional care is not possible. However, both telehealth and virtual monitoring can also provide further support in the future in a post-covid era through a hybrid-model incorporating traditional care, remote data collection and sophisticated platforms to manage and share data with CF teams. SUMMARY: We provide a detailed overview of telehealth and virtual monitoring including examples of how paediatric and adult CF services adapted to the need for rapid change. Such services have proven popular with people with CF meaning that co-design with stakeholders will likely improve systems further. In the future, telehealth and virtual monitoring will become more sophisticated by harnessing increasingly powerful technologies such as artificial intelligence, connected monitoring devices and wearables. In this review, we harmonise definitions and terminologies before highlighting considerations and limitations for the future of telehealth and virtual monitoring in CF.


Subject(s)
COVID-19 , Cystic Fibrosis , Telemedicine , Adult , Artificial Intelligence , Child , Cystic Fibrosis/therapy , Humans , Pandemics , SARS-CoV-2
7.
BMJ Open ; 11(1): e044491, 2021 01 31.
Article in English | MEDLINE | ID: covidwho-1060011

ABSTRACT

INTRODUCTION: Children born moderate to late preterm (MLP, 32-36 weeks' gestation) account for approximately 85% of all preterm births globally. Compared with children born at term, children born MLP are at increased risk of poor neurodevelopmental outcomes. Despite making up the largest group of preterm children, developmental outcomes of children born MLP are less well studied than in other preterm groups. This study aimed to (1) compare neurodevelopmental, respiratory health and brain magnetic resonance imaging (MRI) outcomes between children born MLP and term at 9 years of age; (2) examine the differences in brain growth trajectory from infancy to 9 years between children born MLP and term; and in children born MLP; (3) examine the relationship between brain development and neurodevelopment at 9 years; and (4) identify risk factors for poorer outcomes at 9 years. METHODS AND ANALYSIS: The "LaPrem" (Late Preterm MRI Study) study is a longitudinal cohort study of children born MLP and term controls, born at the Royal Women's Hospital in Melbourne, Australia, between 2010 and 2013. Participants were recruited in the neonatal period and were previously followed up at 2 and 5 years. This 9-year school-age follow-up includes neuropsychology, motor and physical activities, and lung function assessments, as well as brain MRI. Outcomes at 9 years will be compared between birth groups using linear and logistic regressions. Trajectories of brain development will be compared between birth groups using mixed effects models. The relationships between MRI and neurodevelopmental outcomes, as well as other early predictors of poor 9-year outcomes, will be explored using linear and logistic regression. ETHICS AND DISSEMINATION: This study was approved by the human research ethics committee at the Royal Children's Hospital, Melbourne, Australia. Study outcomes will be disseminated through peer-reviewed publications, conference presentations and social media.


Subject(s)
Brain , Lung Diseases , Premature Birth , Australia/epidemiology , Brain/diagnostic imaging , Brain/growth & development , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant, Newborn , Longitudinal Studies , Lung Diseases/etiology , Pregnancy , Premature Birth/epidemiology , Prospective Studies , Schools
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