Factors for severe outcomes following SARS-CoV-2 infection in people with cystic fibrosis in Europe

Andreas Jung; Annalisa Orenti; Fiona Dunlevy; Elina Aleksejeva; Egil Bakkeheim; Vladimir Bobrovnichy; Siobhán B Carr; Carla Colombo; Harriet Corvol; Rebecca Cosgriff; Géraldine Daneau; Deniz Dogru; Pavel Drevinek; Andrea Dugac Vukic; Isabelle Fajac; Alice Fox; Stojka Fustik; Vincent Gulmans; Satenik Harutyunyan; Elpis Hatziagorou; Irena Kasmi; Hana Kayserová; Elena Kondratyeva; Uroš Krivec; Halyna Makukh; Kestutis Malakauskas; Edward F McKone; Meir Mei-Zahav; Isabelle de Monestrol; Hanne Vebert Olesen; Rita Padoan; Tsitsino Parulava; Maria Dolores Pastor-Vivero; Luísa Pereira; Guergana Petrova; Andreas Pfleger; Liviu Pop; Jacqui G van Rens; Milan Rodic; Marc Schlesser; Valérie Storms; Oxana Turcu; Lukasz Woz Niacki; Panayiotis Yiallouros; Anna Zolin; Damian G Downey; Lutz Naehrlich

doi:10.1183/23120541.00411-2021

Factors for severe outcomes following SARS-CoV-2 infection in people with cystic fibrosis in Europe

ERJ Open Res. 2021 Dec 27;7(4):00411-2021. doi: 10.1183/23120541.00411-2021. eCollection 2021 Oct.

Authors

Andreas Jung^{1

2}, Annalisa Orenti^{3

2}, Fiona Dunlevy^{4

2}, Elina Aleksejeva⁵, Egil Bakkeheim⁶, Vladimir Bobrovnichy⁷, Siobhán B Carr^{8

9}, Carla Colombo¹⁰, Harriet Corvol¹¹, Rebecca Cosgriff¹², Géraldine Daneau¹³, Deniz Dogru¹⁴, Pavel Drevinek¹⁵, Andrea Dugac Vukic¹⁶, Isabelle Fajac^{17

18}, Alice Fox⁴, Stojka Fustik¹⁹, Vincent Gulmans²⁰, Satenik Harutyunyan²¹, Elpis Hatziagorou²², Irena Kasmi²³, Hana Kayserová²⁴, Elena Kondratyeva²⁵, Uroš Krivec²⁶, Halyna Makukh²⁷, Kestutis Malakauskas²⁸, Edward F McKone²⁹, Meir Mei-Zahav^{30

31}, Isabelle de Monestrol³², Hanne Vebert Olesen³³, Rita Padoan^{34

35}, Tsitsino Parulava³⁶, Maria Dolores Pastor-Vivero³⁷, Luísa Pereira³⁸, Guergana Petrova³⁹, Andreas Pfleger⁴⁰, Liviu Pop⁴¹, Jacqui G van Rens⁴, Milan Rodic⁴², Marc Schlesser⁴³, Valérie Storms⁴⁴, Oxana Turcu⁴⁵, Lukasz Woz Niacki⁴⁶, Panayiotis Yiallouros⁴⁷, Anna Zolin³, Damian G Downey^{48

49

50}, Lutz Naehrlich^{3

51

50}

Affiliations

¹ Paediatric Pulmonology, University Children's Hospital Zurich, Zurich, Switzerland.
² Co-first authors.
³ Dept of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Epidemiology and Biometry G.A. Maccacaro, University of Milan, Milan, Italy.
⁴ European Cystic Fibrosis Society, Karup, Denmark.
⁵ Dept of Pneumology, Children's Clinical University Hospital, Rīga Stradinš University, Riga, Latvia.
⁶ Dept of Paediatrics, Norwegian Cystic Fibrosis Registry, Oslo University Hospital, Oslo, Norway.
⁷ Belarusian Republic Children's Center of Pulmonology and Cystic Fibrosis, Pulmonary Department, 3rd City Children's Clinical Hospital, Minsk, Belarus.
⁸ Dept of Respiratory Paediatrics, Royal Brompton Hospital, London, UK.
⁹ NHLI, Imperial College, London, UK.
¹⁰ Dept of Pathophysiology and Transplantation, Cystic Fibrosis Reference Center of Lombardia Region, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
¹¹ Pediatric Pulmonology Dept and Cystic Fibrosis Center, Sorbonne Université, Centre de Recherche Saint-Antoine, Inserm UMR_S938, Assistance Publique-Hôpitaux de Paris, Hôpital Trousseau, Paris, France.
¹² Cystic Fibrosis Trust, London, UK.
¹³ Sciensano, Epidemiology and Public Health, Health Services Research, Brussels, Belgium.
¹⁴ Cystic Fibrosis Registry of Turkey, Ankara, Turkey.
¹⁵ Dept of Medical Microbiology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
¹⁶ University Hospital Centre Zagreb, Cystic Fibrosis Centre - Paediatrics and Adults, Zagreb, Croatia.
¹⁷ Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
¹⁸ AP-HP, Hôpital Cochin, Service de Physiologie et Explorations Fonctionnelles, Paris, France.
¹⁹ Centre for Cystic Fibrosis, University Children's Hospital, Skopje, North Macedonia.
²⁰ Dutch Cystic Fibrosis Foundation (NCFS), Baarn, The Netherlands.
²¹ Yerevan University CF Centre, Muratsan Hospital, Yerevan, Armenia.
²² Cystic Fibrosis Unit, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
²³ Dept of Paediatrics, "Mother Thereza" Hospital Center, Tirana, Albania.
²⁴ Cystic Fibrosis Centre, University Hospital of Bratislava, Bratislava, Slovakia.
²⁵ Clinical Research Dept of Cystic Fibrosis "Research Centre for Medical Genetics", Moscow, Russian Federation.
²⁶ Dept of Paediatric Pulmonology, University Children's Hospital, Ljubljana University Medical Centre, Ljubljana, Slovenia.
²⁷ Institute of Hereditary Pathology, Ukrainian National Academy of Medical Sciences, Lviv, Ukraine.
²⁸ Adult Cystic Fibrosis Center, Dept of Pulmonology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
²⁹ St Vincent's University Hospital & University College Dublin School of Medicine, Dublin, Ireland.
³⁰ Pulmonary Institute, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
³¹ Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
³² Stockholm CF Centre, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
³³ Dept of Pediatrics and Adolescent Medicine, Cystic Fibrosis Center, Aarhus University Hospital, Aarhus, Denmark.
³⁴ Dept of Paediatrics, Cystic Fibrosis Regional Support Centre, University of Brescia, Brescia.
³⁵ Scientific Board of Italian CF Registry, Rome, Italy.
³⁶ I. Tsitsishvili Children's Clinic, CF Centre, Tblisi, Georgia.
³⁷ Pediatric Pneumology and Cystic Fibrosis Unit, Osakidetza, Hospital Universitario Cruces, Bizkaia, Spain.
³⁸ Centre for Cystic Fibrosis, Hospital de Santa Maria, Lisbon, Portugal.
³⁹ Pediatric Clinic, Alexandrovska University Hospital, Medical University, Sofia, Bulgaria.
⁴⁰ Dept of Pediatrics and Adolescent Medicine, Division of Pediatric Pulmonology and Allergology, Medical University of Graz, Graz, Austria.
⁴¹ Victor Babes University of Medicine and Pharmacy Timisoara, National Cystic Fibrosis Centre, Timisoara, Romania.
⁴² National Centre for Cystic Fibrosis, Mother and Child Health Institute of Serbia "Dr Vukan Čupić", Belgrade, Serbia.
⁴³ Dept of Pulmonology, Hôpital Robert Schuman, Luxembourg, Luxembourg.
⁴⁴ Cystic Fibrosis Europe, Brussels, Belgium.
⁴⁵ Dept of Pediatrics, Ambulatory Cystic Fibrosis and Other Rare Diseases Center, Institute for Maternal and Child Healthcare, State University of Medicine and Pharmacy "Nicolae Testemitanu", Chisinau, Republic of Moldova.
⁴⁶ Dziekanow Paediatric Hospital, Cystic Fibrosis Centre, Institute of Mother and Child, Warsaw, Poland.
⁴⁷ Medical School, University of Cyprus, Nicosia, Cyprus.
⁴⁸ Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK.
⁴⁹ Regional Respiratory Centre, Belfast City Hospital, Belfast, UK.
⁵⁰ Co-senior authors.
⁵¹ Universities of Giessen and Marburg Lung Center, German Center of Lung Research, Justus-Liebig-University Giessen, Giessen, Germany.

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with cystic fibrosis (pwCF) can lead to severe outcomes.

Methods: In this observational study, the European Cystic Fibrosis Society Patient Registry collected data on pwCF and SARS-CoV-2 infection to estimate incidence, describe clinical presentation and investigate factors associated with severe outcomes using multivariable analysis.

Results: Up to December 31, 2020, 26 countries reported information on 828 pwCF and SARS-CoV-2 infection. Incidence was 17.2 per 1000 pwCF (95% CI: 16.0-18.4). Median age was 24 years, 48.4% were male and 9.4% had lung transplants. SARS-CoV-2 incidence was higher in lung-transplanted (28.6; 95% CI: 22.7-35.5) versus non-lung-transplanted pwCF (16.6; 95% CI: 15.4-17.8) (p≤0.001).SARS-CoV-2 infection caused symptomatic illness in 75.7%. Factors associated with symptomatic SARS-CoV-2 infection were age >40 years, at least one F508del mutation and pancreatic insufficiency.Overall, 23.7% of pwCF were admitted to hospital, 2.5% of those to intensive care, and regretfully 11 (1.4%) died. Hospitalisation, oxygen therapy, intensive care, respiratory support and death were 2- to 6-fold more frequent in lung-transplanted versus non-lung-transplanted pwCF.Factors associated with hospitalisation and oxygen therapy were lung transplantation, cystic fibrosis-related diabetes (CFRD), moderate or severe lung disease and azithromycin use (often considered a surrogate marker for Pseudomonas aeruginosa infection and poorer lung function).

Conclusion: SARS-CoV-2 infection yielded high morbidity and hospitalisation in pwCF. PwCF with forced expiratory volume in 1 s <70% predicted, CFRD and those with lung transplants are at particular risk of more severe outcomes.