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      Clinical characteristics of SARS-CoV-2 infection in children with cystic fibrosis: an international observational study

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      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 4 , 11 , 12 , 13 , 14 , 4 , 15 , 16 , 17 , 18 , 19 , 4 , 20 , 2 , 1 , 21 , # , 1 , 21 , # , *
      Journal of Cystic Fibrosis
      The Author(s). Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.
      COVID-19, cystic fibrosis, children

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          Abstract

          Background

          The presence of co-morbidities, including underlying respiratory problems, has been identified as a risk factor for severe COVID-19 disease. Information on the clinical course of SARS-CoV-2 infection in children with cystic fibrosis (CF) is limited, yet vital to provide accurate advice for children with CF, their families, caregivers and clinical teams.

          Methods

          Cases of SARS-CoV-2 infection in children with CF aged less than 18 years were collated by the CF Registry Global Harmonization Group across 13 countries between 1 February and 7 August 2020.

          Results

          Data on 105 children were collated and analysed. Median age of cases was ten years (interquartile range 6-15), 54% were male and median percentage predicted forced expiratory volume in one second was 94% (interquartile range 79-104). The majority (71%) of children were managed in the community during their COVID-19 illness. Out of 24 children admitted to hospital, six required supplementary oxygen and two non-invasive ventilation. Around half were prescribed antibiotics, five children received antiviral treatments, four azithromycin and one additional corticosteroids. Children that were hospitalised had lower lung function and reduced body mass index Z-scores. One child died six weeks after testing positive for SARS-CoV-2 following a deterioration that was not attributed to COVID-19 disease.

          Conclusions

          SARS-CoV-2 infection in children with CF is usually associated with a mild illness in those who do not have pre-existing severe lung disease.

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          Most cited references37

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            A Novel Coronavirus from Patients with Pneumonia in China, 2019

            Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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              Remdesivir for the Treatment of Covid-19 — Final Report

              Abstract Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. Methods We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. Results A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). Conclusions Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)
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                Author and article information

                Journal
                J Cyst Fibros
                J Cyst Fibros
                Journal of Cystic Fibrosis
                The Author(s). Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.
                1569-1993
                1873-5010
                3 December 2020
                3 December 2020
                Affiliations
                [1 ]Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
                [2 ]Cystic Fibrosis Trust, London, UK
                [3 ]Division of Paediatric Pulmonology, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, South Africa
                [4 ]Cystic Fibrosis Foundation, Bethesda, Maryland, USA
                [5 ]Respiratory Medicine and National Reference CF Center, AP-HP Hôpital Cochin, Paris, France
                [6 ]Université de Paris, Institut Cochin, Inserm U-1016, Paris, France
                [7 ]Royal Brompton Hospital and Imperial College London, UK
                [8 ]Department of Pulmonology, Hospital de Pediatria JP Garrahan, Buenos Aires, Argentina
                [9 ]CF Regional Reference Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Italy
                [10 ]Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, Assistance Publique Hôpitaux de Paris (APHP), Hôpital Trousseau, Service de Pneumologie Pédiatrique, Paris, France
                [11 ]Department of Medicine and Pediatrics, University of Washington, Seattle, Washington
                [12 ]Pediatric Pulmonary and Sleep Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
                [13 ]Department of Pulmonology and Children's Research Centre, University Children's Hospital Zurich, Zurich, Switzerland
                [14 ]Laboratory of Genetic Epidemiology, Research Centre for Medical Genetics, Moscow, Russian Federation
                [15 ]Instituo Nacional del Tórax, Santiago, Chile
                [16 ]Pediatric Pulmonology and Cystic Fibrosis Unit, Hospital Clinico Universitario Virgen de la Arrixaca, Murcia, Spain
                [17 ]Stockholm Cystic Fibrosis Centre Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden
                [18 ]Universities of Giessen and Marburg Lung Center, German Center of Lung Research, Justus‐Liebig‐University Giessen, Giessen, Germany
                [19 ]Cystic Fibrosis Unit, Cruces University Hospital, Bilbao, Spain
                [20 ]Pediatric Pulmonology Unit, Instituto da Criança do Hospital das Clínicas da FMUSP, São Paulo, São Paulo, Brazil
                [21 ]Paediatric Respiratory Medicine, Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
                Author notes
                [* ]Corresponding author: Malcolm Brodlie, MRC Clinician Scientist/Honorary Consultant in Paediatric Respiratory Medicine, Level 3, Clinical Resource Building, Great North Children's Hospital, Queen Victoria Road, Newcastle upon Tyne, UK, NE1 4LP. Tel: +44 191 2336161.
                [#]

                Equal contribution

                Article
                S1569-1993(20)30931-0
                10.1016/j.jcf.2020.11.021
                7713571
                33309057
                91794e13-9eb5-4295-80d7-6c7f3d8203b1
                © 2020 The Author(s). Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 27 November 2020
                : 29 November 2020
                Categories
                Article

                Genetics
                covid-19,cystic fibrosis,children
                Genetics
                covid-19, cystic fibrosis, children

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