Observational Study for Patients With Hemoglobinopathies and Rare Inherited Anemia and Covid 19

The COVID-19 pandemic is causing many deaths around the world, putting a strain on health
services. Patients with pre-existing chronic diseases are most affected by SARS-COV2
infection. Italy is one of the countries most involved. Thalassaemia, drepanocytosis, other
hemoglobinopathies and inherited anemias are widespread in italy and the mediterranean area.
Thalassaemia syndromes are characterized by different clinical forms with mutations in globin
genes that cause the reduction or complete absence of synthesis of the globin chain.
Transfusion therapy remains the basis of thalassaemia management. Based on the extent of the
severity of anemia and clinical presentation, thalassaemia was classified as
transfusion-dependent (TDT) and non-transfusion-dependent (NTDT). Transfusion inevitably
contributes to iron overload, which is associated with secondary morbidity, including organ
damage, especially heart, liver, bone tissue, and endocrine glands. In ntdt, comorbility is
mainly related to chronic anemia and increased gastrointestinal iron adsorption.

Other inherited anaemias include a large group of pathologies such as: hyporegenerative
anaemias, such as congenital diseritropoietic anaemia and diamond-blackfan anemia; anaemies
from deficiency of red blood cell membrane proteins due to altered membrane structure, such
as hereditary spherocytosis and hereditary ellipsocytosis, and impaired membrane transport
function, such as hereditary stomatocytosis; anaemies due to enzymatic deficiency, the most
frequent of which are pyruvate deficiency kinase and glucose-6 phosphate dehydrogenase;
sideroblastic anaemias and all other hereditary microcytic anaemies such as irida. All these
anemias are characterized by high phenotypic heterogeneity but in most cases chronic
hemolytic anemia, iron overload and addiction transfusion are found (as a percentage of a
variable of cases). Transfusion therapy remains the basis of the management of these anaemias
along with splenectomy (not practicable in all these classes of anemia). As with thalassaemia
syndromes, in such anaemias, we find secondary morbidity, such as heart, liver, and endocrine
damage resulting from both chronic anemia and iron overload.

Infectious complications are a common cause of mortality and one of the main causes of
morbidity in all these pathologies. The greater quantitative and functional quantities, the
involve t and b lymphocytes, production of immunoglobulins, neutrophils and macrophages,
chemotaxis and phagocytosis, as well as the complement system. Excess iron can alter the
immune balance in favour of the growth of infectious organisms. Other factors include
multiple transfusions, associated with constant allo-antigenic stimulation. A large
percentage of adult patients are splenectomized and risk complications related to splenectomy
such as capsuled bacterial infections and immune system changes; low levels of zinc, another
immune regulator; iron chelation therapy, which predisposes to serious yersinia-like
infections. The circulation of abnormal erythrocytes is the cause of another permanent immune
stimulus. In addition, particularly in elderly patients, the coexistence of adrenal
hypofunction makes the response to sepsis less effective.

However, we have no information on the vulnerability of patients with thalassaemia,
drepanocytosis, other hemoglobinopathies and hereditary anemias to SARS-COV2 infection. In
order to obtain more information useful to increase our knowledge, a retrospective survey has
been planned.

The main objective of this project is the evaluation of patients with thalassaemia,
drepanocytosis, other hereditary hemoglobinopathies and anaemias affected by SARS-COV2 to:

1. obtain clinical and epidemiological data that may dare information on a possible
increased vulnerability of these patients to SARS-COV2;

2. share therapeutic approaches considering the lack of information about treatment.

This is an italian study of observational, pharmacological, non-interventional,
retrospective, prospective and multicenter, non-profit cohort. Patients diagnosed with
thalassaemia, drepanocytosis, other hemoglobinopathies and hereditary anaemia positive to the
SARS-COV2 virus will be enlisted. Patient data from reference centers will be introduced into
the card via a web service.

The scientific committee of the project has discussed and approved a set of data that will be
collected by local centers and that will feed the data collection database.

The study will be launched in every Italian center that requires participation. The Italian
Society of Thalassaemia and Hemoglobinopathies (SITE) in its role as a scientific reporting
company for pathology and the Foranemia Foundation, a non-profit organization, makes
available to the center of microcitemie, coordinator of the study, a special web space for
online data collection assuming the costs.