-Author name in bold denotes the presenting author
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Clinically Relevant Abstract denotes an abstract that is clinically relevant.

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4058 ERN-EuroBloodNet European Registry of Patients Affected by Red Blood Cell Disorders and COVID-19Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 904. Outcomes Research—Non-Malignant Conditions: Poster III
Hematology Disease Topics & Pathways:
Sickle Cell Disease, Adults, Thalassemia, Hemoglobinopathies, Diseases, Pediatric, Young Adults, Study Population, Clinical Practice (e.g. Guidelines, Health Outcomes and Services, and Survivorship, Value; etc.)
Monday, December 13, 2021, 6:00 PM-8:00 PM

Pablo Velasco, MD, Prof1,2*, Filomena Longo, MD3*, Andrea Piolatto, MSc4*, Eduardo J. Bardón-Cancho, MD5,6,7*, Beatriz Ponce-Salas, MD8*, Pagona Flevari, MD, PhD9*, Ersi Voskaridou, MD, PhD9*, Bart J. Biemond, MD, PhD10, Erfan Nur, MD, PhD10,11, Polyxeni Delaporta, PhD12*, Tatiana Besse-Hammer, MD13*, Anna Ruiz-Llobet, MD14*, Simona Raso, MD15*, Anna Spasiano, MD16*, Maria Elena Guerzoni, MD17*, David Beneitez-Pastor, MD18,19,20,21*, Laurence Dedeken, MD22, Alessia Pepe, MD, PhD23*, Rosamaria Rosso, MD24*, Joachim B. Kunz, MD25*, Mariane de Montalembert, MD, PhD26*, Saveria Campisi, MD27*, Andreas Glenthøj, MD, PhD28, Paula Gonzalez Urdiales, MD29,30*, Fleur Samantha Benghiat, MD, PhD31*, Marie-Agnès Azerad, MD32*, Christopher J. Saunders, MD33*, Teresa Ferreira Faria, MD34*, Tommaso Casini, MD35*, Sabrina Bagnato, MD36*, Ann Van de Velde, MD, PhD37*, Veerle Labarque, PhD, MD38*, Elisa Bertoni, MD39*, An Van Damme40, Michael D. Diamantidis, MD, PhD, MSc41, Roberta Russo, PhD42,43*, Eftichia Stiakaki, MD, PhD, Prof44*, Alessandra Quota, MD45*, Soteroula Christou, MD46*, Maria Jose Teles, MD47,48,49,50,51*, Ioannis Lafiatis, BSc, MD52*, Jean-Louis Kerkhoffs, MD, PhD53, María Argüello Marina, MD54*, Mikael Lorite, MD55*, Alexis Rodriguez, MD56,57*, Achille Iolascon, MD, PhD42,43, Ali T. Taher, MD, PhD, FRCP58, Raffaella Colombatti, MD, PhD59, Noemi Roy, MD, PhD60 and Maria del Mar Mañú Pereira, Bsc, PhD61*

1Pediatric Oncology and Hematology, Vall d'Hebron Hospital Universitari, Barcelona, Spain
2Pediatric Department, UAB ( Universitat Autònoma de Barcelona) College, Barcelona, Spain
3Department of Clinical and Biological Sciences, University of Torino, Orbassano (To), Italy
4Department of Clinical and Biological Sciences, Department of Clinical and Biological Sciences, University of Turin, Orbassano, To, Italy
5Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
6Pediatric Hematology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
7Instituto Investigación Sanitaria Gregorio Marañón, Madrid, Spain
8Onco-Hematología Infantil, Hospital General Universitario Gregorio Marañón, Madrid, Spain
9Center of Excellence in Rare Haematological Diseases-Haemoglobinopathies, Laiko General Hospital, Athens, Greece
10Department of Hematology, Amsterdam University Medical Centers, Amsterdam, Netherlands
11Department or Blood Cell Research, Sanquin Research, Amsterdam, Netherlands
12First Department of Pediatrics, National and Kapodistrian University of Athens, 'Aghia Sophia' Children's Hospital, Athens, Greece
13URC, CHU Brugmann, Brussels, Belgium
14Paediatric Haematology Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain
15Department of Hematology and Rare Diseases, V Cervello, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
16Malalttie Rare del Globulo Rosso, AORN A. Cardarelli, Naples, Italy
17Pediatric Unit, Department of Medical and Surgical Sciences of Mothers, Children and Adults, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy
18Translational Research Group in Rare Anemia Disorders, Vall d'Hebron Institut de Recerca, Barcelona, Spain
19Hematology Department, Vall d'Hebron Hospital Universitari, Barcelona, Spain
20Experimental Hematology Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
21Vall d'Hebron Hospital Universitari, ERN-EuroBloodNet, Barcelona, Spain
22Hôpital Universitaire des Enfants Reine Fabiola (ULB), Brussels, Belgium
23Fondazione Toscana G. Monasterio per la ricerca medica e di sanità pubblica, Pisa, Italy
24Thalassemia and Heamoglobinophaties, Policlinico Universitario G. Rodolico, Catania, Italy
25University Hospital Heidelberg, Heidelberg, Germany
26Hôpital Necker, Paris, France
27Ospedale Umberto I, Siracusa, Italy
28Department of Hematology, Rigshospitalet, Copenhagen, Denmark
29Pediatric oncology and hematology department, Hospital Universitario Cruces, Barakaldo, Spain
30Instituto de investigación Biocruces Bizkaia, Barakaldo, Spain
31CUB Erasmus hospital, Brussels, Belgium
32Hematology, CHU Liège Citadelle site, Liège, Belgium
33Hospital dos Capuchos, Centro Hospitalar e Universitário Lisboa Central, Lisbon, Portugal
34Pediatric Department, Hospital Fernando Fonseca, Amadora, Portugal
35Pediatric OncoHematology, Meyer Children Hospital, Florence, Italy
36Thalassemia, Ospedale Civile, Lentini, Italy
37Hematology, University Hospital Antwerp, Edegem, Belgium
38Pediatric Hemato-Oncology, University Hospitals Leuven, Leuven, Belgium
39Oncohaematology and BMT Unit, ASST Spedali Civili di Brescia, Brescia, Italy
40Paediatric Hémato-oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
41Thalassemia and Sickle Cell Disease Unit, Department of Hematology, General Hospital of Larissa, Larissa, Greece
42Department of Molecular Medicine and Medical Biotechnology, University Federico II, Naples, Italy
43CEINGE – Advanced Biotechnologies, Naples, Italy
44Pediatric Hematology-Oncology Department, University of Crete, University Hospital of Heraklion, Heraklion, Greece
45UOSD Thalassemia, V.Emanuele Hospital, Gela, Italy
46Thalassemia Clinic, Archbishop Makarios III Hospital, Nicosia, Cyprus
47Clinical Pathology, Centro Hospitalar e Universitário de São João, Porto, Portugal
48Clinical Hematology, Centro Hospitalar e Universitário do Porto, Porto, Portugal
49Anemia Working Group Portugal, Porto, Portugal
50Institute for the Health Research and Innovation (i3S), Porto, Portugal
51Hematology Working Group of the Portuguese Society of Clinical Pathology, Porto, Portugal
52General Hospital of Mytilini, Mytilini, Greece
53Hematology, HagaZiekenhuis, The Hague, Netherlands
54Hematology, Hospital Príncipe de Asturias, Madrid, Spain
55Department of pediatric Hematology, Hospital Son Espases, Palma de Mallorca, Spain
56Clinical Pharmacology Service, Hospital Universitari Vall d’Hebron, Barcelona, Spain
57Vall d'Hebron Institut de Recerca, Barcelona, Spain
58Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
59UOC Pediatric Hematology Oncology, University of Padova, Padova, Italy
60Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
61Translational Research in Child and Adolescent Cancer, Vall d'Hebron Institut de Recerca, Barcelona, Spain

PV, NR and MMP contributed equally

Introduction

Patients with red blood cell disorders (RBCD), chronic life threating multisystemic disorders in their severe forms, are likely to be at increased risk of complications from SARS-Cov-2 (Covid-19), but evidence in this population is scarce due to its low frequency and heterogeneous distribution. ERN-EuroBloodNet, the European Reference Network in rare hematological disorders, established a European registry to determine the impact of COVID-19 on RBCD patients and identify risk factors predicting severe outcomes.

Methods

The ERN-EuroBloodNet registry was established in March 2020 by Vall d'Hebron Research Institute based on REDcap software in accordance with the Regulation (EU) 2016/679 on personal data. The local Research Ethics Committee confirmed that the exceptional case of the pandemic justifies the waiver of informed consent. The ERN-EuroBloodNet registry on RBCD and COVID-19 is endorsed by the European Hematology Association (EHA).

Eligible patients had confirmed RBCD and COVID-19. Data collected included demographics, diagnosis, comorbidities, treatments, and COVID-19 (severity grade, clinical manifestations, acute events, treatments, hospitalization, intensive care unit, death).

For analysis of COVID-19 severity, two groups were established 1) Mild: asymptomatic or mild symptoms without clinical pneumonia and 2) Severe: pneumonia requiring oxygen/respiratory support and/or admission to intensive care unit. Continuous variables were compared using the Wilcoxon rank-sum test or Kruskall Wallis test, while categorical variables were analyzed using the Chi-square test or Fisher’s Exact test. Relevant factors influencing disease or severity were examined by the logistic regression adjusted for age.

Results

As of June 2021, 42 medical centers from 10 EU countries had registered 373 patients: 191 Sickle cell disease (SCD), 156 Thalassemia major and intermedia (THAL) and 26 other RBCD. 84% of the SCD patients were reported by Spain, Belgium, Italy and The Netherlands and 92% of the THAL patients by Italy and Greece.

The mean age of SCD was lower (22.5y) than of THAL (39.6y) with pediatric population accounting for 50.5% in SCD and 9% in THAL (p <0.001). Splenectomy and comorbidities were higher in THAL (51.3% and 65.8%) than in SCD (16% and 48.1%) (p<0.001, p=0.002).

Age and BMI correlated with COVID-19 severity, as described in the general population (p=0.002, p<0.001). Fig 1 shows age distribution and COVID-19 severity by disease severity groups. The mean age for severe COVID-19 was lower in patients with severe SCD (SS/SB0 vs SC/SB+: 23.3y vs 67.5y) and THAL (major vs intermedia: 43.5 vs 51.3y) (p<0.001).

Potential risk factors such as elevated ferritin, current chelation or history of splenectomy did not confer additional risk for developing severe COVID-19 in any patient group. Only diabetes as a comorbidity correlated with severity grade in SCD (p=0.011) and hypertension in THAL (p=0.014). While severe COVID-19 infection in SCD was associated with both ACS (p<0.001) and kidney failure requiring treatment (p=0.001), this was not predicted by a history of previous ACS or kidney disease in steady state.

Overall, 14.8% RBC patients needed oxygen/respiratory support, 4.4% were admitted to ICU with an overall mortality rate of 0.8% (no deaths were registered in pediatric age), much lower than reported in other similar cohorts.

Discussion

Results obtained so far show that severe COVID-19 occurs at younger ages in more aggressive forms of SCD and THAL. Current preventive approaches (shielding, vaccinations) focus on age over disease severity. Our data highlights the risk of severe COVID-19 infection in some young patients, particularly those with SS/SB0 SCD, suggesting that immunization should be considered in this pediatric group as well.

Results between similar sized cohorts of RBCD patients vary between each other and those presented here, highlighting the importance of collecting all of these small cohorts together to ensure adequate statistical power so that definitive risk factors (eg. age, genotype, comorbidities) can be reliably identified and used to guide management of patients with these rare disorders in the light of the ongoing pandemic.

Disclosures: Longo: Bristol Myers Squibb: Honoraria; BlueBird Bio: Honoraria. Bardón-Cancho: Novartis Oncology Spain: Research Funding. Flevari: PROTAGONIST COMPANY: Research Funding; ADDMEDICA: Consultancy, Research Funding; BMS: Research Funding; IMARA COMPANY: Research Funding; NOVARTIS COMPANY: Research Funding. Voskaridou: BMS: Consultancy, Research Funding; IMARA: Research Funding; NOVARTIS: Research Funding; ADDMEDICA: Consultancy, Research Funding; GENESIS: Consultancy, Research Funding; PROTAGONIST: Research Funding. Biemond: GBT: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Novo Nordisk: Honoraria; Celgene: Honoraria; Sanquin: Research Funding. Nur: Celgene: Speakers Bureau; Roche: Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Beneitez-Pastor: Agios: Honoraria; Alexion: Honoraria; Novartis: Honoraria; Forma Therapeutics: Honoraria. Pepe: Chiesi Farmaceutici S.p.A: Other: no profit support; Bayer S.p.A.: Other: no profit support. de Montalembert: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Addmedica: Membership on an entity's Board of Directors or advisory committees; BlueBirdBio: Membership on an entity's Board of Directors or advisory committees; Vertex: Membership on an entity's Board of Directors or advisory committees. Glenthøj: Agios: Consultancy; Novo Nordisk: Honoraria; Novartis: Consultancy; Alexion: Research Funding; Bluebird Bio: Consultancy; Bristol Myers Squibb: Consultancy; Saniona: Research Funding; Sanofi: Research Funding. Benghiat: Novartis: Consultancy; BMS: Consultancy. Labarque: Novartis: Consultancy; Bayer: Consultancy; Sobi: Consultancy; NovoNordisk: Consultancy; Octapharma: Consultancy. Van Damme: Pfizer: Consultancy; Shire: Consultancy; Bayer: Consultancy. Diamantidis: Genesis Pharma: Honoraria; Uni-Pharma: Honoraria; Bristol Myers Squibb: Consultancy; IONIS Pharmaceuticals: Research Funding; NOVARTIS, Genesis Pharma SA: Research Funding. Kerkhoffs: Sanofi: Research Funding; Terumo BCT: Research Funding. Iolascon: Celgene: Other: Advisory Board; Bluebird Bio: Other: Advisory Board. Taher: Vifor Pharma: Consultancy, Research Funding; Agios Pharmaceuticals: Consultancy; Ionis Pharmaceuticals: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Colombatti: Novartis: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novonordisk: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees; Addmedica: Membership on an entity's Board of Directors or advisory committees; BlueBirdBio: Research Funding. Mañú Pereira: Novartis: Research Funding; Agios Pharmaceuticals: Research Funding.

*signifies non-member of ASH