ABSTRACT
Background: Patients with red blood cell disorders (RBCD), are likely to be at increased risk of complications from SARS-Co-2 (Coid-19), but eidence in this population is scarce due to its low frequency and heterogeneous distribution. Aims: 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 seere outcomes. Methods: The ERN-EuroBloodNet registry was established in March 2020 by VHIR 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 waier of informed consent. Eligible patients had confirmed RBCD and COVID-19. Data collected included demographics, diagnosis, comorbidities, treatments, and COVID-19 symptoms and management. For analysis of COVID-19 seerity, two groups were established 1) Mild: asymptomatic or mild symptoms without clinical pneumonia and 2) Seere: pneumonia requiring oxygen/respiratory support and/or admission to intensie care unit. Continuous ariables were compared using the Wilcoxon rank-sum test or Kruskall Wallis test, while categorical ariables were analyzed using the Chi-square test or Fisher's Exact test. Releant factors influencing disease or seerity were examined by the logistic regression adjusted for age. Results: As of February 25, 2022, 42 medical centers from 10 EU countries had registered 428 patients: 212 Sickle cell disease (SCD), 186 Thalassemia major and intermedia (THAL). The mean age of SCD was lower (22y) than of THAL (39.4y). Splenectomy and comorbidities were higher in THAL (51.4% and 61,3%) than in SCD (16,3% and 46,8%) (p<0.001, p=0.004). Age and BMI correlated with COVID-19 seerity, as described in the general population (p=0.003, p<0.001). Fig 1 shows age distribution and COVID-19 seerity by disease seerity groups. The mean age for seere COVID-19 was lower in patients with seere SCD (SS/SB0 s SC/SB+: 23y s 67.5y) and THAL (major s intermedia: 43.5 s 51.3y) (p<0.001). Potential risk factors such as eleated ferritin, current chelation or history of splenectomy did not confer additional risk for deeloping seere COVID-19 in any patient group. Only diabetes as a comorbidity correlated with seerity grade in SCD (p=0.01) and hypertension in THAL (p=0.009). While seere 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 preious ACS or kidney disease in steady state. Oerall, 14,6% RBC patients needed oxygen/respiratory support, 4% were admitted to ICU with an oerall mortality rate of 1%, much lower than reported in other similar cohorts. Hospital Son Espases, Palma de Mallorca, Spain;54 Clinical Pharmacology Serice, Hospital Uniersitari Vall d'Hebron, Barcelona, Spain;55 Vall d'Hebron Institut de Recerca, Barcelona, Spain;56 Diision of Hematology and Oncology, Department of Internal Medicine, American Uniersity of Beirut Medical Center, Beirut, Lebanon;57 UOC Pediatric Hematology Oncology, Uniersity of Padoa, Padoa, Italy;58 Department of Haematology, Oxford Uniersity Hospitals NHS Foundation Trust, Oxford, United Kingdom;59 Translational Research in Child and Adolescent Cancer, Vall d'Hebron Institut de Recerca, Barcelona, Spain Background: Patients with red blood cell disorders (RBCD), are likely to be at increased risk of complications from SARS-Co-2 (Coid-19), but eidence in this population is scarce due to its low frequency and heterogeneous distribution. Aims: 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 seere outcomes. Methods: The ERN-EuroBloodNet registry was established in March 2020 by VHIR based on Redcap software in accordance with the Regulation (EU) 2016/679 on personal data. The local Research Ethics Committee confirm d that the exceptional case of the pandemic justifies the waier of informed consent. Eligible patients had confirmed RBCD and COVID-19. Data collected included demographics, diagnosis, comorbidities, treatments, and COVID-19 symptoms and management. For analysis of COVID-19 seerity, two groups were established 1) Mild: asymptomatic or mild symptoms without clinical pneumonia and 2) Seere: pneumonia requiring oxygen/respiratory support and/or admission to intensie care unit. Continuous ariables were compared using the Wilcoxon rank-sum test or Kruskall Wallis test, while categorical ariables were analyzed using the Chi-square test or Fisher's Exact test. Releant factors influencing disease or seerity were examined by the logistic regression adjusted for age. Results: As of February 25, 2022, 42 medical centers from 10 EU countries had registered 428 patients: 212 Sickle cell disease (SCD), 186 Thalassemia major and intermedia (THAL). The mean age of SCD was lower (22y) than of THAL (39.4y). Splenectomy and comorbidities were higher in THAL (51.4% and 61,3%) than in SCD (16,3% and 46,8%) (p<0.001, p=0.004). Age and BMI correlated with COVID-19 seerity, as described in the general population (p=0.003, p<0.001). Fig 1 shows age distribution and COVID-19 seerity by disease seerity groups. The mean age for seere COVID-19 was lower in patients with seere SCD (SS/SB0 s SC/SB+: 23y s 67.5y) and THAL (major s intermedia: 43.5 s 51.3y) (p<0.001). Potential risk factors such as eleated ferritin, current chelation or history of splenectomy did not confer additional risk for deeloping seere COVID-19 in any patient group. Only diabetes as a comorbidity correlated with seerity grade in SCD (p=0.01) and hypertension in THAL (p=0.009). While seere 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 preious ACS or kidney disease in steady state. Oerall, 14,6% RBC patients needed oxygen/respiratory support, 4% were admitted to ICU with an oerall mortality rate of 1%, much lower than reported in other similar cohorts. Summary/Conclusion: Results obtained so far show that seere COVID-19 occurs at younger ages in more aggressie forms of SCD and THAL. Current preentie approaches focus on age oer disease seerity. Our data highlights the risk of seere 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 ary 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 definitie risk factors can be reliably identified and used to guide management of patients with these rare disorders in the light of the ongoing pandemic. (Figure Presented).
ABSTRACT
Background: ERN-EuroBloodNet was established in 2017 as the European Reference Network on Rare Hematological Disorders (RHDs) bringing together nationally recognized centres of excellence with the goal of promoting EU best health care in RHDs. ERN-EuroBloodNet has been recently enlarged integrating 103 HCP from 24 EU-MS. Aims: ERN-EuroBloodNet was conceived to contribute to innovative, efficient and sustainable health systems and facilitate access to better and safer healthcare for EU citizens while decreasing the cross-border health barriers. Methods: Since 2017, ERN-EuroBloodNet established the state-of-the art of RHD allowing the implementation of transversal and disease-specific strategies, where actions on very rare RHD were prioritized. Results: Profile. 182 expert profiles were created freely accessible. Expert centers follow 65,000 RHD patients and treat 5,000 new patients per year, while 24 patients requested support for cross-border health assistance. Expertise. The need to improve access to next-generation sequencing for non-oncological RHD and bone marrow transplantation for sickle cell disease (SCD) was identified. Also, significant disparities in the clinical practice of primary vitreoretinal lymphoma were found and we demonstrated that less than 30% of children with SCD benefit from adequate annual stroke risk monitoring. Guidelines. A repository of 68 Clinical Practice Guidelines (CPG) classified on quality of evidence and consensus approach was created. Recommendations for diagnosis and treatment of methemoglobinemia was published in collaboration with EHA. A CPG on Adult Burkitt Lymphoma is under development. Next topics focus long-term complications in hemoglobinopathies and patients' pathways&summary. Education. ERN-EuroBloodNet Webinars were launched for professionals with 26 Thursdays Webinars and 3 EBAH accredited Topic on Focus on Cutaneous Lymphoma, Thrombotic Microangiopathies, and Bone Marrow Failures. A collaboration was established for EHA & ERN-EuroBloodNet Spotlight on Castleman Disease. For patients, 3 Topic on Focus were launched for Myelodysplastic syndromes, SCD, and Cutaneous lymphoma. Past webinars are available at EuroBloodNet EDU Youtube channel. Preceptorships on SCD will be launched soon. Telemedicine. 43 complex cases have been inter-professionally discussed in the Clinical Patient Management System with 21 outcome reports delivered. Registries. 184 Registries were identified through the European Rare Blood Diseases Platform (ENROL), endorsed by the EHA. The ENROL project, which includes rare anemias, dendritic cell leukemia and von Villebrand's disease pilots, aims to collect exhaustive and therefore epidemiological data for RHDs. The final objective is a possibility of EU health planningl and the promotion of research by identifying cohorts of patients. ERNEuroBloodNet launched the collaborative platform on patients with red blood cells and COVID-19 containing so far 373 patients. Collaborations. collaborative research projects were encouraged like EC-funded projects i.e., genomics and personalized medicine in hematological diseases (GenoMed4All) and the properties and viability of erythrocytes (EVIDENCE), or the International Hemoglobinopathy Research Network (INHERENT) for genomic and phenotypic correlations. Summary/Conclusion: The implementation of well-defined strategies but above all adapted to the specific and not yet covered needs of RHD has led to the realization of concrete projects. This has laid the foundations to strengthen health systems in the field of RHD and allow them to flourish under the new EU4Health programme.