SARS-CoV-2 infection in beta thalassemia: Preliminary data from the Italian experience

Patients with pre\u2010existent chronic morbidities are likely to be more severely affected by SARS\u2010Cov2 infection, but no data are available regarding Thalassemic Syndromes (TS). Note, TS and hemoglobin variants represent, according to WHO, one of the most frequent causes of anemia, affecting more than 7% of the world population.1 Thalassemic Syndromes are classified in either transfusion\u2010dependent thalassemia (TDT) or non\u2010transfusion\u2010dependent thalassemia (NTDT). Infectious complications, mainly from bacteria, constitute a common cause of mortality and morbidity in TS. Stress erythropoiesis, iron overload, splenectomy and adrenal insufficiency among others may contribute to increase susceptibility to infection.2 To verify the impact of SARS\u2010CoV\u20102 infection on TS, we set\u2010up a specific survey by electronic Case Report Form (eCRF).3 Inclusion criteria require at least 15\u2009days of follow\u2010up from either the onset of symptoms or SARS\u2010CoV2 positivity. The survey was approved by Ethics Committee and eCRF was shared with the Centers of Italian Hemoglobinopathies Network. The \u201cSociet\ue0 Italiana Talassemie ed Emoglobinopatie\u201d (SITE), has estimated the presence in Italy of approximately 5000 TDT and 1900 NTDT patients.3 As of 10 April 2020, 11 cases of TS and COVID\u201019 have been collected (see supplementary information). All the reported patients are in Northern Italy, where the rate of infection is higher, reflecting the national epidemiology. The mean age is 44\u2009\ub1\u200911\u2009years (range 31\u201061\u2009years) and 55% (6/11) are females. Ten patients are TDT, and one is NTDT. All the patients have thalassemia associated comorbidities, eight are splenectomized, and one patient (#9 in the supplementary table) has pulmonary hypertension treated with sildenafil. The likely source of infection has been detected in 55% (6/11) of cases: two had contacts with COVID\u201019 positive subjects, and four had occupational exposure (three are nurses working in hospital or assisted living facilities). Three patients were asymptomatic. One patient (#3 in supplementary information) was admitted for high fever and bone marrow hypoplasia, lymphopenia, and agranulocytosis (on treatment with deferiprone) and tested positive at the third swab. Six out of 11 were hospitalized, but no one required mechanical ventilation. The patient with more severe symptoms who required more intensive ventilation support with continuous positive airway pressure (CPAP) has a history of diffuse large B\u2010cell lymphoma, treated with chemotherapy in the previous year, currently in complete remission. Of the six people admitted to the hospital, only three received supposedly specific treatment for COVID\u201019: one hydroxychloroquine (HCQ), one HCQ plus ritonavir/darunavir, and one HCQ plus anakinra. Patient #3 did not receive HCQ due to concomitant therapy with amiodarone and an increased risk of life\u2010threatening arrhythmia. The clinical course ranged from 10 to 29\u2009days. Ten patients have clinically recovered and are on a daily remote phone call follow\u2010up. Splenectomy which was present in 8/11 patients did not seem to affect the clinical course. Of note, except for the patient with myelosuppression, no increase in blood requirement was observed. When luspatercept treatment was halted in the NTDT patient, hemoglobin fell from 110 to 82 g/L, a value similar to the pre\u2010luspatercept period. Neither death nor severe SARS or signs of cytokines storm were observed in these 11 subjects, which may be surprising, taking into account the mean age and the presence of severe comorbidities. Our data, although preliminary, do not indicate increased severity of COVID\u201019 in TS. A larger number of cases needs to be collected to define the impact of this new infection and its outcome in these fragile patients

Patient Affected by Beta-Propeller Protein-Associated Neurodegeneration: A Therapeutic Attempt with Iron Chelation Therapy

Here, we report the case of a 36-year-old patient with a diagnosis of de novo mutation of the WDR45 gene, responsible for beta-propeller protein-associated neurodegeneration, a phenotypically distinct, X-linked dominant form of Neurodegeneration with Brain Iron Accumulation. The clinical history is characterized by a relatively stable intellectual disability and a hypo-bradykinetic and hypertonic syndrome with juvenile onset. Genetic investigations and T1 and T2-weighted MR images align with what is described in literature. The patient was also subjected to PET with 18-FDG investigation and DaT-Scan study. In reporting relevant clinical data, we want to emphasize the fact that the patient received a chelation therapy with deferiprone (treatment already used in other forms of NBIA with encouraging results), which, however, had to be interrupted because the parkinsonian symptoms worsened. Conversely, the patient has benefited from non-drug therapies and, in particular, from an adapted motor activity with assisted pedaling (method in the process of validation in treatments of parkinsonian syndromes), which started before the treatment with deferiprone and still continues

Recommendations for diagnosis and treatment of methemoglobinemia

Methemoglobinemia is a rare disorder associated with oxidization of divalent ferro-iron of hemoglobin (Hb) to ferri-iron of methemoglobin (MetHb). Methemoglobinemia can result from either inherited or acquired processes. Acquired forms are the most common, mainly due to the exposure to substances that cause oxidation of the Hb both directly or indirectly. Inherited forms are due either to autosomal recessive variants in the CYB5R3 gene or to autosomal dominant variants in the globin genes, collectively known as HbM disease. Our recommendations are based on a systematic literature search. A series of questions regarding the key signs and symptoms, the methods for diagnosis, the clinical management in neonatal/childhood/adulthood period, and the therapeutic approach of methemoglobinemia were formulated and the relative recommendations were produced. An agreement was obtained using a Delphi-like approach and the experts panel reached a final consensus >75% of agreement for all the questions