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      Impact of COVID-19 on people with cystic fibrosis

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          Abstract

          Early and detailed characterisation of coronavirus disease 2019 (COVID-19) has emerged principally through publications from China, where the disease was first identified. 1 As the pandemic spread to Lombardia, Northern Italy and then globally, 2 evaluating the impact on people with cystic fibrosis has become imperative, because the prevalence of this inherited condition is much higher in populations derived from Europe than in other populations. 3 Since the beginning of the outbreak in Lombardia, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported in ten patients with cystic fibrosis out of 42 161 people in the region known to have been infected. The number of infected patients in Lombardia make up a substantial proportion of the 101 739 total SARS-CoV-2 infections in Italy (according to available data on March 31, 2020). The Italian patients with cystic fibrosis were resident in endemic areas and acquired the infection from family members. These observations, as well as data from other European countries (five patients with cystic fibrosis in France have been reported to have SARS-CoV-2 infection, seven in the UK, five in Germany and three [one transplanted] in Spain) suggest few patients with cystic fibrosis, mainly adults, are becoming infected with SARS-CoV-19, without apparent effect on cystic fibrosis disease severity. From these data, it is not possible to identify factors that might be protective, for example use of long-term antibiotic therapy such as azithromycin. The few reported cases of SARS-CoV-2 infection in people with cystic fibrosis might reflect the efforts of families across Europe to minimise social contacts. This effort might be considered a success, but there is no room for complacency and the directive for social shielding of both the patient and family members remains clear and important. More data should be collected to better characterise the impact of COVID-19 on patients with cystic fibrosis. The European Cystic Fibrosis Society (ECFS) is supporting the collection and timely sharing of data from across Europe. The ECFS Patient Registry, in cooperation with national cystic fibrosis registries, has established a data collection and reporting system, contributing to an international harmonised dataset, to identify factors that predict severity of COVID-19. Viral respiratory tract infections are more severe in patients with cystic fibrosis than in the general population, with an increased risk of complications and a negative impact on lung function. During the 2009 influenza pandemic, H1N1 virus caused substantial morbidity in patients with cystic fibrosis, and in a subgroup with severe lung disease, H1N1 infection was associated with respiratory deterioration, mechanical ventilation, and even death.4, 5 The situation in Italy has been monitored carefully to inform management strategies and provide clear advice for patients with cystic fibrosis and their families. Consistent with the Italian Government, the Cystic Fibrosis Center in Milan promptly recommended self-isolation for these patients. Recommendations for preventive measures that were already established in this population, such as using face masks and practising adequate hand hygiene, were reinforced. The cystic fibrosis team in Milan cancelled routine clinic appointments to prevent unnecessary hospital visits and viral spread. Procedures such as respiratory function testing and bronchoscopy were put on hold. Phone calls and email contacts were used to monitor the clinical condition of patients and to provide psychological support immediately after the lockdown. These measures have subsequently been adopted by cystic fibrosis centres across Europe. There is no doubt that cancelling routine cystic fibrosis clinics and monitoring according to ECFS standards of care 3 will have a negative impact on the wellbeing of patients with cystic fibrosis over time. It is important that patients and their families are provided with tools to support self-monitoring during this period. This self-monitoring might include transmission to clinicians of spirometry and oxygen saturation data that are recorded at home. Support should also include the capacity to carry out respiratory culture at home and send to the laboratory securely. Home visits by health-care professionals present a risk of SARS-CoV-2 transmission and virtual clinics should be used to provide families with advice on all aspects of cystic fibrosis care management, including airway clearance and maintaining exercise. In case cystic fibrosis team members are seconded to work on the front line of tackling this pandemic, it is imperative that lines of communication remain open and that patients with cystic fibrosis do not feel isolated. For patients with more severe cystic fibrosis, access to lung transplantation might be compromised. People with cystic fibrosis have a phenotypic spectrum ranging from excellent respiratory health to chronic airways disease with productive cough and respiratory compromise. The clinical features of COVID-19 (dry cough, myalgia, and fever) are quite distinct from the symptoms of cystic fibrosis. Therefore, most COVID-19 in people with cystic fibrosis should be recognisable, but it is possible that mild disease might be labelled as within the normal spectrum of symptoms for that individual. A low threshold for testing is therefore needed in this population. Many isolated families are concerned about collection of medicines and food during this pandemic. Most countries have established systems to ensure deliveries to people who are isolated, often using volunteers, but as the pandemic progresses, maintaining these systems will be a priority for patients with cystic fibrosis and their families. A further concern is the halt to the development of new therapies for cystic fibrosis. 3 No new clinical trials are being initiated in Europe and recruitment of patients to ongoing trials is being stopped. Patients in existing trials are being supported by reducing study visits with the agreement of regulatory bodies such as the European Medicines Agency and by providing study medication to the home. 6 As national advice changes rapidly to respond to the pandemic, it is important that cystic fibrosis organisations place this advice in context and present information for patients and their families that is based on clear evidence and not conjecture. This pandemic is imposing an extraordinary level of stress on health services and the consequences include the trauma of witnessing so many deaths, even of young and healthy people, and the impact on the whole community of fear, isolation, and uncertainty for the future. Following the situation in Italy, a community-oriented plan for the next pandemic is clearly needed. 7 People with cystic fibrosis and their families have invested considerable time and energy to maintain good health and, now, on the cusp of remarkable new therapies to transform their condition, they face a global pandemic, the effect of which is unclear. Early data suggest that most patients with cystic fibrosis are doing an exceptional job avoiding SARS-CoV-19 infection, but they must remain dedicated to this task, as data are gathered from across Europe to better understand factors that affect the severity of COVID-19 in people with cystic fibrosis. For information from Italy on COVID-19 see https://www.salute.gov.it/nuovocoronavirus

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          Most cited references 5

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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            COVID-19 and Italy: what next?

            Summary The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already taken on pandemic proportions, affecting over 100 countries in a matter of weeks. A global response to prepare health systems worldwide is imperative. Although containment measures in China have reduced new cases by more than 90%, this reduction is not the case elsewhere, and Italy has been particularly affected. There is now grave concern regarding the Italian national health system's capacity to effectively respond to the needs of patients who are infected and require intensive care for SARS-CoV-2 pneumonia. The percentage of patients in intensive care reported daily in Italy between March 1 and March 11, 2020, has consistently been between 9% and 11% of patients who are actively infected. The number of patients infected since Feb 21 in Italy closely follows an exponential trend. If this trend continues for 1 more week, there will be 30 000 infected patients. Intensive care units will then be at maximum capacity; up to 4000 hospital beds will be needed by mid-April, 2020. Our analysis might help political leaders and health authorities to allocate enough resources, including personnel, beds, and intensive care facilities, to manage the situation in the next few days and weeks. If the Italian outbreak follows a similar trend as in Hubei province, China, the number of newly infected patients could start to decrease within 3–4 days, departing from the exponential trend. However, this cannot currently be predicted because of differences between social distancing measures and the capacity to quickly build dedicated facilities in China.
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              Influenza A/H1N1 in patients with cystic fibrosis in Italy: a multicentre cohort study.

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                Author and article information

                Contributors
                Journal
                Lancet Respir Med
                Lancet Respir Med
                The Lancet. Respiratory Medicine
                Elsevier Ltd.
                2213-2600
                2213-2619
                15 April 2020
                15 April 2020
                Affiliations
                [a ]Cystic Fibrosis Regional Reference Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Department of Pathophysiology and Transplantation, 20122 Milan, Italy
                [b ]Respiratory Medicine and National Cystic Fibrosis Reference Center, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris, Institut Cochin, INSERM U1016, Paris, France
                [c ]Pediatric Pulmonology and Cystic Fibrosis Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain
                [d ]Cystic Fibrosis Centre, Children's Hospital, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
                [e ]Department of Pediatrics, Justus-Liebig-University, Giessen, Germany
                [f ]INSERM U1151, Institut Necker Enfants Malades, National Cystic Fibrosis Reference Center (paediatric site), Hôpital Necker Enfants Malades, Assistance Publique Hôpitaux de Paris Paris, ERN-Lung, Université de Paris, France
                [g ]Department of Women's and Children's Health, University of Liverpool, Institute in the Park, Alder Hey Children's Hospital, Liverpool, UK
                Article
                S2213-2600(20)30177-6
                10.1016/S2213-2600(20)30177-6
                7159857
                © 2020 Elsevier Ltd. All rights reserved.

                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.

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