ERN-EuroBloodNet Registry on Patients with Rare Red Blood Cell Defects and COVID-19

ERN-EuroBloodNet European Collaborative Platform to Share COVID-19 Data in Patients with Red Blood Cell Disorders in Real Time

Patients with red blood cell disorders (RBCDs), such as Sickle cell disease (SCD) and Thalassemia, are chronic, life-threatening conditions that can become multi-organ complications over time, and are likely at an increased risk of COVID-19-related complications. Patients at the highest risk include the elderly (>50 in our population), those with a history of respiratory or cardiac disease and those with other comorbidities. Several patients affected by RBCDs undergo splenectomy as therapeutic option to improve their level of hemoglobin concentration. Splenectomized patients, or in the case of SCD with functional hyposplenism, are more vulnerable to bacterial infections / superinfections after viral infection. Acute pulmonary syndrome (ACS) is the main cause of morbidity in SCD in middle-high income countries, and is often triggered by infectious events. Currently, there is no literature on the subject. Thus, any recommendation available comes from the experience gained with previous Coronaviruses infections. Accordingly, the correct treatment and management of infection by Coronavirus SARS-COV-2 (COVID-19) in patients affected by RBCDs may be challenging given the rapid spread of the pandemic and limited literature so far, especially in some countries. Accordingly, there is an urgent need to pool evidence in a unique repository on patients affected by RBCDs and COVID-19 in order to reach critical numbers to facilitate the medical decision making process across Europe.

The Registry on patients with rare RBCDs and COVID-19 is an initiative conceived in the core of the European Reference Network on Rare Hematological Diseases (ERN-EuroBloodNet, FPA 739541, www.eurobloodnet.eu) aiming at supporting medical practice of COVID-19 in these patients by gathering evidence on pediatric and adult COVID-19 confirmed cases in RBCDs across Europe.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease; Hemoglobinopathies; Sickle Cell Anemia; Beta-Thalassemia; Sickle Beta Thalassemia; Alpha-Thalassemia; Beta Thalassemia Intermedia; Beta Thalassemia Major; Spherocytosis, Hereditary; Sickle Cell Hemoglobin C; Elliptocytosis, Hereditary; Stomatocytosis; Sickle-Cell; Hemoglobinopathy; Sickle Cell Hemoglobin D; Sickle Cell-Hemoglobin E Disease; Dominant Beta-Thalassemia; Hereditary Persistence of Fetal Hemoglobin Thalassemia; Delta-Beta Thalassaemia; Haemoglobin C-Beta-Thalassaemia Syndrome; Hemoglobin E-Beta Thalassemia; Hemoglobin H Disease; Hemoglobin Barts Hydrops; Enzyme Disorder; Anemia; Membranes; Disorder
• Intervention / Treatment: Other: Non applicable, is a patient registry

Detailed Description

The Registry on patients with rare red blood cell disorders (RBCDs) and COVID-19 is an initiative conceived in the core of the European Reference Network on Rare Hematological Diseases (ERN-EuroBloodNet, FPA 739541, www.eurobloodnet.eu) aiming at supporting medical practice of COVID-19 in these patients by gathering evidence on pediatric and adult COVID-19 confirmed cases in RBCDs across Europe.

Primary objective of the registry is to pool evidence on the clinical management and outcomes of patients affected by red blood cell disorders and COVID-19 for supporting daily medical practice while enabling inter-professional consultation of complex cases. Secondary objective includes the performance of observational studies in the different cohorts of patients, including Sickle Cell Disease, Thalassaemia, Enzymopathies and Membranopathies patients in pediatric and or adult stages.

The network of hospitals that will be created from this registry will hold regular meetings to analyze the data that are being introduced and to discuss possible measures against COVID-19 based on them. The collaboration will continue with the development of observational studies that will give the necessary evidence to make recommendations for COVID-19 management in hematological patients.

METHODOLOGY

Inclusion criteria include both pediatric and adults patients with confirmed COVID-19 and affected by a rare anaemia disorder due to a red blood cell defect. Data set elements include:

• Demographics: country of living, sex, age (only year of birth)
• Data related to Red blood cell disorder: diagnosis, co-morbidities, treatments, splenectomy, blood transfusion requirement.
• Data related to COVID-19: date and method for diagnosis, severity grade, clinical manifestations i.e. pneumonia, symptoms days, acute events, treatments, days of hospitalization, days at intensive care unit, sequela, death.

The registry has been developed by Vall d'Hebron Research Institute using Redcap, a secure web application for building and managing online databases. Individual patients' data will be gathered in a codified way.

ETHICS AND GDPR COMPLIANCE

The processing of personal data is conducted fully respecting the Regulation (EU) 2016/679 (General Data Protection Regulation), including legal basis and special requirements and safeguards to ensure the safety and the confidentiality of the data subjects.

The Research Ethics Committee of the Vall d'Hebron's Hospital has confirmed that this exceptional case justifies the waiver of informed consent.

PROCESSING OF THE DATA

The patient's information included in the database is pseudonymised by single codification. The minimization principle of data protection is followed (i.e. only year of age is collected, no identified data is collected, and only clinical data of the health care is collected). The medical doctors at each center have a coding table in which the code can be linked to the patient's personal information. This table is safely guarded by the medical doctor and never leaves the center. All the information stored in the database is pseudonymised.

• Study Type: Observational
• Enrollment (Actual): 684

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Vall D'hebron Institut De Recerca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients both pediatric and adults with confirmed COVID19 and affected by a rare anaemia disorder due to a red blood cell defect according to the following ORPHA codes for rare diseases:

• 68364 Hemoglobinopathy
• 275752 Sickle Cell Disease and related diseases
• 848 Beta-thalassemia
• 846 Alpha-Thalassaemia
• 98363 Rare hemolytic anemia
• 98369 Rare constitutional hemolytic anemia due to an enzyme disorder
• 98364 Rare constitutional hemolytic anemia due to a red cell membrane anomaly

Description

Inclusion Criteria:

• Patients both pediatric and adults with confirmed COVID-19 and affected by a rare anaemia disorder due to a red blood cell defect

Study Plan

How is the study designed?

Number of groups / cohorts

8

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pediatric Sickle cell disease patients infected by COVID-19; Sickle cell diagnosed patients (<18 years old) infected by COVID-19	Other: Non applicable, is a patient registry; Non applicable, is a patient registry
Adult Sickle cell disease patients infected by COVID-19; Sickle cell diagnosed patients (≥18 years old) infected by COVID-19	Other: Non applicable, is a patient registry; Non applicable, is a patient registry
Pediatric Thalassemia patients infected by COVID-19; Thalassemia-diagnosed patients (<18 years old) infected by COVID-19	Other: Non applicable, is a patient registry; Non applicable, is a patient registry
Adult Thalassemia patients infected by COVID-19; Thalassemia-diagnosed patients (≥18 years old) infected by COVID-19	Other: Non applicable, is a patient registry; Non applicable, is a patient registry
Pediatric Enzymopathy patients infected by COVID-19; Enzymopathy-diagnosed patients (<18 years old) infected by COVID-19	Other: Non applicable, is a patient registry; Non applicable, is a patient registry
Adult Enzymopathy patients infected by COVID-19; Enzymopathy-diagnosed patients (≥18 years old) infected by COVID-19	Other: Non applicable, is a patient registry; Non applicable, is a patient registry
Pediatric Membranopathy patients infected by COVID-19; Membranopathy-diagnosed patients (<18 years old) infected by COVID-19	Other: Non applicable, is a patient registry; Non applicable, is a patient registry
Adult Membranopathy patients infected by COVID-19; Membranopathy-diagnosed patients (<18 years old) infected by COVID-19	Other: Non applicable, is a patient registry; Non applicable, is a patient registry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Management and Outcomes in Patients with Red Blood Cell Disorders and COVID-19	• COVID-19 clinical manifestations and required treatment in each cohort (Sickle Cell Disease, Thalassemia, Enzymopathies, and Membranopathies)..	Through study completion, an average of 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Analysis in Different Cohorts of Patients with Red Blood Cell Disorders and COVID-19:	Descriptive analysis of demographic and baseline disease characteristics in each cohort (Sickle Cell Disease, Thalassemia, Enzymopathies, and Membranopathies).; COVID-19 clínical manifestations in each cohort.; Identification of preventive measures and risk factors related to severe COVID-19 in each cohort	Through study completion, an average of 3 years

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Collaborators: Hospital General Universitario Gregorio Marañon; Universitaire Ziekenhuizen KU Leuven; UMC Utrecht; Guy's and St Thomas' NHS Foundation Trust; University Hospital Heidelberg; Azienda Ospedaliera di Padova; University Hospital Freiburg; San Luigi Gonzaga Hospital; Brno University Hospital; Palacky University; University Hospital, Gentofte, Copenhagen; Oxford University Hospitals NHS Trust; Erasme University Hospital; European Georges Pompidou Hospital; Hospital Vall d'Hebron; Hôpital Necker-Enfants Malades; Centro Hospitalar e Universitário de Coimbra, E.P.E.; Aghia Sophia Children's Hospital of Athens; Cyprus Institute of Neurology and Genetics; Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello; General Hospital of Athens Elpis; Institute of Hematology and Blood Transfusion, Czech Republic; Children's Health Ireland; Amsterdam UMC
• Investigators: Principal Investigator: María del Mar Mañú Pereira, PhD, Vall d'Hebron Institut de Recerca, Barcelona (Spain) and ERN-EuroBloodNet; Principal Investigator: Pablo Velasco Puyó, MD, Vall d'Hebron University Hospital, Barcelona (Spain)

Publications and helpful links

Helpful Links

• European Commission website section on European Reference Networks
• Registry platform
• ERN-EuroBloodNet Collaborative Platform on Red Blood Cell and COVID-19 patients section
• ERN-EuroBloodNet website
• Directive 95/46/EC of the European Parliament and of the Council of 24 October 1995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2020
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: February 17, 2023
• First Submitted That Met QC Criteria: February 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: COVID-19; Hemoglobin; Sickle cell disease; Sickle Cell Anemia; Beta-Thalassemia; Hemoglobinopathy; Beta Thalassemia Major; Alpha-Thalassemia; Sickle cell-beta-thalassemia; Sickle cell-hemoglobin; Beta Thalassemia Intermedia; Delta-Beta Thalassaemia; Rare hemolytic anemia; Hereditary Spherocytosis; Hereditary Elliptocytosis; Hereditary Stomatocytosis
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Hematologic Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; COVID-19; Anemia, Sickle Cell; Thalassemia; beta-Thalassemia; Anemia; alpha-Thalassemia; Hemoglobinopathies; Hemoglobin SC Disease; Elliptocytosis, Hereditary; Spherocytosis, Hereditary
• Other Study ID Numbers: VHI-ERN-2020-00; PR(AG)215/2020 (Other Identifier: Ethics Committee Vall d'Hebron Universitary Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No