Objective An analysis of the SARS-CoV-2 pandemic impact in the Spanish Gaucher Disease (GD) community is presented here. Patients & methods The Spanish GD foundation (FEETEF) surveyed 113 GD patients from March 30 to April 27; all patients provided a verbal consent. Results 110 surveys were analyzed. The median age was 47 years old (y.o.), 31 patients were ≥ 60 y.o.; and 34% of patients reported comorbidities. 46% (51/110) of patients were treated by enzyme replacement therapy (ERT), 48 of them at hospitals; 45.1% (45/110) were on substrate reduction therapy (SRT) and 9% (10/110) receive no therapy. 25% (11/48) of ERT-hospital-based patients reported therapy interruptions, while SRT-patients did not report missing doses. No bone crises were reported. However, 50% (55/110) of patients reported being worried about their predisposition to a severe SARS-COV-2 infection and 29% (16/55) of them took anxiolytics or antidepressants for this. While 6 patients reported to have contact with an infected person, another two confirmed SARS-CoV-2 infections were reported in splenectomyzed patients, one of them (a 79-year-old diabetic) died. Conclusions One quarter of the patients treated at hospitals reported dose interruptions. Home-based therapy may need to be considered in order to minimize the impact of the COVID-19 pandemic.

Background Since enzyme replacement therapy for Gaucher disease (MIM#230800) has become available, both awareness of and the natural history of the disease have changed. However, there remain unmet needs such as the identification of patients at risk of developing bone crisis during therapy and late complications such as cancer or parkinsonism. The Spanish Gaucher Disease Registry has worked since 1993 to compile demographic, clinical, genetic, analytical, imaging and follow-up data from more than 400 patients. The aims of this study were to discover correlations between patients’ characteristics at diagnosis and to identify risk features for the development of late complications; for this a machine learning approach involving correlation networks and decision trees analyses was applied. Results A total of 358 patients, 340 type 1 Gaucher disease and 18 type 3 cases were selected. 18% were splenectomyzed and 39% had advanced bone disease. 81% of cases carried heterozygous genotype. 47% of them were diagnosed before the year 2000. Mean age at diagnosis and therapy were 28 and 31.5 years old (y.o.) respectively. 4% developed monoclonal gammopathy undetermined significance or Parkinson Disease, 6% cancer, and 10% died before this study. Previous splenectomy correlates with the development of skeletal complications and severe bone disease (p = 0.005); serum levels of IgA, delayed age at start therapy (> 9.5 y.o. since diagnosis) also correlates with severe bone disease at diagnosis and with the incidence of bone crisis during therapy. High IgG (> 1750 mg/dL) levels and age over 60 y.o. at diagnosis were found to be related with the development of cancer. When modelling the decision tree, patients with a delayed diagnosis and therapy were the most severe and with higher risk of complications. Conclusions Our work confirms previous observations, highlights the importance of early diagnosis and therapy and identifies new risk features such as high IgA and IgG levels for long-term complications.

Background : Since enzyme replacement therapy for Gaucher disease (MIM#230800) has become available, both awareness of and the natural history of the disease have changed. However, there remain unmet needs such as the identification of patients at risk of developing bone crisis during therapy and late complications such as cancer or parkinsonism. The Spanish Gaucher Disease Registry has worked since 1993 to compile demographic, clinical, genetic, analytical, imaging and follow-up data from more than 400 patients. The aims of this study were to discover correlations between patients’ characteristics at diagnosis and to identify risk features for the development of late complications; for this a machine learning approach involving correlation networks and decision trees analyses was applied. Results : A total of 358 patients, 340 type 1 Gaucher disease and 18 type 3 cases were selected. 18% were splenectomyzed and 39% had advanced bone disease. 81% of cases carried heterozygous genotype. 47% of them were diagnosed before the year 2000. Mean age at diagnosis and therapy were 28 and 31.5 years old (y.o.) respectively. 4% developed monoclonal gammopathy undetermined significance or Parkinson Disease, 6% cancer, and 10% died before this study. Previous splenectomy correlates with the development of skeletal complications and severe bone disease (p=0.005); serum levels of IgA, delayed age at start therapy (>9.5 y.o. since diagnosis) also correlates with severe bone disease at diagnosis and with the incidence of bone crisis during therapy. High IgG (>1750mg/dL) levels and age over 60 y.o. at diagnosis were found to be related with the development of cancer. When modelling the decision tree, patients with a delayed diagnosis and therapy were the most severe and with higher risk of complications. Conclusions : Our work confirms previous observations, highlights the importance of early diagnosis and therapy and identifies new risk features such as high IgA and IgG levels for long-term complications.

Background : The SARS-CoV-2 infection activates both innate and adaptive immune responses and induces an exaggerated cytokine storm leading to causes septic shock, acute respiratory distress syndrome, and/or multiple organ failure in critically ill patients. The knowledge of this dysregulated immune response is not well explained. One hypothesis is that the response of macrophages and neutrophils to infection is disproportionate, resulting in overproduction of cytokines and activation of neutrophils leading to the most severe complications of infection, including the production of multiple microthrombi and endothelial damage. Aim of the study: To evaluate the activation levels of macrophage biomarkers as well as indicators of the development of neutrophil extracellular traps (NET) in the first phase of infection in hospitalized patients with COVID19. Patients and Methods: We selected dry blood spot from a total of 60 previously identified SARS-CoV-2 infected subjects. Plasma samples were provided by the Aragon Health System Biobank's collection and were extracted within 5 days of symptom onset. Plasma from 60 healthy controls were used to stablish the control range for NETosis determination. The study was authorized by the Ethics Committee of the Aragon Health System and complies with the European General Data Protection Regulation (GDPR 2016/679) and LO 3/2018. Demographic characteristics, clinical manifestations, follow-up during hospitalization, associated comorbidities, and thrombotic complications were obtained from the database. Chitotriosidase activity (ChT), YKL40 chitinase and CCL18/PARC cytokine were measured as markers of macrophage activation. Myeloperoxidase (MPO), Neutrophil Elastase (NE), and S100A8/S100A9 Heterodimer (MPR) were immuno-quantified, levels of circulating free DNA (cfDNA) were measured as well as the presence of DNAsases by fluorimetry as indicators of Netosis. For the comparative analysis, we stratified patients by age groups and disease severity and used the Mann-Whitney U test for statistical comparison, considering a p-value < 0.05 as statistically significant. Results : A statistically significant increase in ChT (p=0.032) and CCL18/PARC (p=0.0001) was observed in the patients´ group. A comparative study with clinical variables and other inflammation markers as ferritin, D-dimer will be shown upon acceptance. Concerning NET markers, we found a statistically significant increase in MPO, NE, and MRP in COVID-19 patients (p=0.0001; p=0.0290; p=0.0001 respectively), as well as a statistically significant decrease in DNAsa (p=0.0001). No differences in cfDNA levels were observed. The table shows the median (quartile1-quartile3) for each marker in the control group and in the patient group. Conclusions : In this study, biomarkers of macrophage activation do not appear to be more sensitive than the indicators of inflammation in routine clinical practice (ferritin, D-dimer). Clinical cases of severe COVID-19 disease show an excessive NET formation, which contributes to vascular damage and the development of thrombosis. This work was supported by a research grant from FEETEG Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.