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: Sickle cell disease (SCD) is frequently complicated by painful vaso-occlusive crises (VOCs) often resulting in healthcare utilization including hospital admission. A vaso-occlusive crisis (VOC) can be induced by multiple factors including infection, exposure to cold, physical exercise, dehydration and stress. Given the current SARS-CoV-2 pandemic, we hypothesized that SARS-CoV-2 (even without symptoms of upper airway infection) might play a major causal role in VOC. However, our data suggests that COVID-19 is not a frequent provoking factor for clinical VOCs during the pandemic. Methods: In order to test this hypothesis, consecutive SCD patients presenting to the emergency department in our centre with symptoms compatible with VOC between March 16 th 2020 and March 16 th 2021, were tested for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR) of nasopharyngeal swabs irrespective of respiratory symptoms. Given the limited sensitivity of the RT-PCR in SARS-CoV-2 high incidence groups, low-dose non-contrast chest CT-scans were initially performed in addition to the RT-PCR.In addition, data comprised of temperature, oxygen saturation and laboratory results, was collected through chart review, from the visit at the emergency department. Presentations of SCD patients with a proven prior SARS-CoV-2 infection were excluded. Results: In total 122 VOCs in 70 adult SCD patients, presenting to the emergency department between March 16 th 2020 and March 16 th 2021, were evaluated. (Figure 1) Five presentations in two individual patients were excluded due to a prior RT-PCR proven SARS-CoV-2 infection. Furthermore, 13 presentations in six patients were excluded due to non-protocol adherence (not obtaining a RT-PCR at presentation). In total 104 episodes of VOC in 62 patients with SCD were prospectively analyzed on SARS-CoV-2 by RT-PCR irrespective of respiratory symptoms. In 104 consecutive presentations, five presentations tested positive on SARS-CoV-2 (4.8%). Only one of these five patients presented with respiratory symptoms in addition to the symptoms of a VOC and one patient was diagnosed with acute chest syndrome (ACS). Five of the 99 presentations of patients with a negative SARS-CoV-2 PCR, presented with respiratory symptoms. In this group, seven patients developed an ACS during admission. From March 16 th till May 31 st 2020, routine CT-scans were performed, in 23 out of 27 presentations with a VOC at the emergency department in addition to the RT-PCR in order to increase the diagnostic accuracy. In 19 of these presentations, that were tested negative for SARS-COV-2, no CT-abnormalities suggestive for COVID-19 were found. One of four CT-scans performed in patients with a positive RT-PCR, showed abnormalities that were not specific for COVID-19. Conclusion: In conclusion, we found a low incidence of SARS-CoV-2 infections in our cohort of consecutive SCD patients presenting with VOCs in 12 months during the COVID-19 pandemic. This suggests that COVID-19 is not a frequent provoking factor for clinical VOCs during the pandemic and may even be considered a coincidental finding given the low incidence and the fact that only one of the five patients with a positive RT-PCR presented with pulmonary symptoms. [Formula presented] Disclosures: Nur: Celgene: Speakers Bureau;Roche: Speakers Bureau;Novartis: Research Funding, Speakers Bureau.
ABSTRACT
[Formula presented] 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 p wer 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. [Formula presented] 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. 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.