Frequency of COVID-19 Antibodies in Patients With Hereditary Hematological Diseases
Frequency of COVID-19 Antibodies in Patients With Hereditary Hematological Diseases
In Italy there are about 5000 patients with dependent transfusion thalassemia (source Italian
 Thalassemia and Hemoglobinopathies - SITE) and a smaller number, currently not definable, of
 patients with sickle cell anemia in chronic transfusion.

 A recent study in the Lombardy region identified the positivity of anti-Covid-19 antibodies
 in 4.5-7% of asymptomatic donors (Valenti L et al). As already known, a preliminary study
 conducted in Italy (Motta I et al, Hussain FA et al, Taher A et al) reported only 11 cases of
 symptomatic infection all with benign evolution. Currently there are 15 reported cases (12
 thalassemias and 3 sickle cell anemias). 75% of the cases have been identified in Lombardy.

 Our hypothesis is that in a percentage of polytransfused patients a transmission of the virus
 may have developed that stimulated the production of protective antibodies. This could be an
 explanation of the low contagiousness and severity of the infection in polytransfused
 patients. Currently no data are available for this purpose.

 This study will be conducted in collaboration with the Microbiology Unit and involves the
 determination of SARS-CoV-2 antibodies (anti-s1 and s2) by CLIA method with a high
 sensitivity (94.7%) and specificity (98.5%).
INTRODUCTION In Italy there are about 5000 patients with dependent transfusion thalassemia
 (source Italian Thalassemia and Hemoglobinopathies - SITE) and a smaller number, currently
 not definable, of patients with sickle cell anemia in chronic transfusion.

 These patients, as patients with chronic diseases, many of which also splenectomized, are
 generally considered to be at greater risk of infection and complications in the event of an
 infection.

 However, preliminary studies in patients with thalassemia and sickle cell anemia do not seem
 to confirm these assumptions about the COVID-19 pandemic (Motta I et al, Hussain FA et al,
 Taher A et al). On the basis of these data, it was hypothesized that the chronic inflammatory
 background, the hemolytic and anemic status of these patients could have a favorable and
 protective influence on the risk of fatal COVID-19 infections (Roy NBA et al).

 A recent study in the Milan area identified the positivity of anti-Covid-19 antibodies in
 4.4-10.8% of asymptomatic donors (Valenti L et al).

 TARGETS In this study, the presence of COVID-19 IgG antibodies will be assessed in all
 transfusion dependent patients affected by thalassemia, Blackfan-Diamond anemia, sickle cell
 anemia and other chronic anemias, related to the ASST-Monza Rare Disease Center, S. Gerardo
 and all residents in the provinces of Monza-Brianza, Como, Lecco, Varese and Milan. Of these
 patients, 15% experienced potentially suspect symptoms of infection, albeit mildly overall,
 but only 5 patients performed the nasal swab which tested positive in one case.

 The study should be considered as a pilot and preliminary study since no data are available.
 The primary objective is to define the transfusion risk as a source of contact with the virus
 in patients subject to multiple transfusions (every 2-3 weeks for a total of about 300 units
 of blood used per month). Based on the results, further information on the exposure of these
 patients to COVID-19 infection may be obtained.

 DESIGN This is a study with use of biological material. All patients suffering from
 hereditary transfusion anemias or who have undergone recurrent transfusion procedures
 belonging to the Rare Disease Center of ASST Monza will be enrolled in the study. The
 patients will be enrolled in the study when consent is obtained. A serum sample will be
 analyzed for anti-COVID-19 antibodies and if the result is positive, the nasal swab will be
 performed. If the outcome of the swab is positive, the patient must undergo quarantine and
 follow the national protocol. Only demographic data will be collected and only the value of
 antibodies to COVID-19 as biochemical data.

 METHODS Serological test is based on the identification of COVID-19 antibodies (anti-s1 and
 -s2) by CLIA method. It has a high sensitivity (97.4%) and specificity (98.%). Although the
 test has a high concordance value (> 95%), it is not possible to consider if the positive
 subjects have neutralizing antibodies for the virus. In the case of a positive test, the
 molecular test for diagnostic confirmation is provided.

 The analysis will be carried out at the ASST-Monza Microbiology Laboratory - S. Gerardo
 Hospital (Primary: Dr. Annalisa Cavallero) and an aliquot of serum will be kept at the
 Cytogenetics and Medical Genetics Laboratory for 1 year after the end of the study.

 EXPECTED RESULTS Based on the few data available in Italy, the investigator foresees 5-10% of
 positive subjects.

 SAMPLE SIZE AND STATISTICAL ANALYSIS All 81 transfusion dependent patients belonging to the
 Rare Disease Center of ASST-Monza, S. Gerardo Hospital will be included in the study and for
 this reason a formal calculation of sample size has not been performed.

 The statistical analysis will be substantially descriptive and it will use appropriate
 central tendency and dispersion measures for quantitative variables, while absolute and
 relative frequencies will be used for qualitative variables. The estimates of the primary
 endpoint relating to the percentage of transfusion-dependent patients tested positive will be
 reported with their respective 95% confidence intervals.
Inclusion Criteria:

 -  Patients with inherited dependent transfusion anemias (thalassemia major and
 intermediate, sickle cell anemia and Blackfan-Diamond anemia) or undergoing recurrent
 transfusion procedures (erythro-exchange in sickle cell anemia), belonging to the Rare
 Disease Center - ASST-Monza, Hospital S Gerardo.

 -  Age greater than or equal to 18 years.

 Exclusion Criteria:

 -  No exclusion criteria are expected apart from patients' refusal to participate in the
 study.