Clinical outcome and humoral immune responses of ß-thalassemia major patients with severe iron overload to SARS-CoV-2 infection and vaccination: a prospective cohort study.

Background: COVID-19 has raised special concern for patients with ß-thalassemia major (ß-TM) due to frequent comorbidities, regular blood transfusions, and iron overload. However, the exact implications of COVID-19 for patients with ß-TM remain uncertain. We aimed to explore the COVID-19 incidence and severity, and the serological response to SARS-CoV-2 infection and vaccination in patients with ß-TM. Methods: Patients with ß-TM (n = 105) and age-matched healthy controls, all individuals of all control groups were health care workers of the hospital, were prospectively enrolled at the haematology department of Al-Shifa hospital in the Gaza Strip from January 1st, 2021 to December 31st, 2021. Data on COVID-19 incidence and severity were analysed, with Alpha, Beta, and Delta SARS-CoV-2 variants dominating at that time. Anti-SARS-CoV-2 IgG antibody levels were measured and compared between study groups. Findings: Patients with ß-TM showed a higher incidence of SARS-CoV-2 infection than the general population (61.9% vs. 7.1%, p < 0.0001). Most patients with ß-TM had asymptomatic (70.8%) or mild disease (26.1%), with no fatalities recorded. COVID-19 illness was more severe among female than male patients with ß-TM. Anti-SARS-CoV-2 IgG antibodies were significantly higher in symptomatic patients with ß-TM than controls post-infection (geometric mean ÷ geometric standard deviation 1299.0 ÷ 3.3 vs. 555.7 ÷ 2.4 AU/mL, p = 0.009) and post-vaccination (8404.0 ÷ 3.9 vs. 2785.6 ÷ 5.0 AU/mL, p = 0.015). Similar responses were observed when comparing splenectomised to non-splenectomised (both asymptomatic and symptomatic) patients with ß-TM post-infection (595.4 ÷ 3.9 vs. 280.7 ÷ 3.5 AU/mL, p = 0.005) and post-vaccination (13,778.2 ÷ 3.2 vs. 4961.8 ÷ 4.1 AU/mL, p = 0.045). Interpretation: This distinctive ß-TM cohort exhibited a high susceptibility to SARS-CoV-2 infection but mild disease course. Our findings support favourable serological responses to SARS-CoV-2 infection and to vaccination in patients with ß-TM, indicating a potential interplay between iron availability and COVID-19-related immunity. Funding: This study was funded by Mr. Hosam and Wasim s. El Helou.

New Insights on ß-Thalassemia in the Palestinian Population of Gaza: High Frequency and Milder Phenotype Among Homozygous IVS-I-1 (HBB: c.92+1G>A) Patients with High Levels of Hb F.

ß-Thalassemia (ß-thal) is a very common disease in the Palestinian population of the Gaza Strip. We studied their mutation frequency and clinical features. Thirteen different mutations were identified. The most common mutation was IVS-I-1 (G>A) (HBB: c.92+1G>A), which was prevalent in 31.5% of the thalassemia alleles studied. The IVS-I-110 (G>A) (HBB: c.93-21G>A) mutation was found in 25.0% of the alleles. Homozygotes for the IVS-I-1 mutation had higher mean hemoglobin (Hb) levels, required less blood transfusions, and lower transferrin saturation than the homozygotes for the IVS-I-110 mutation. This milder phenotype was, most likely, the result of the persistent production of Hb F; it was 9-fold higher in absolute terms (g/dL) and 7.7-fold higher in relative terms (percentage of total Hb). About half of our IVS-I-1 patients carried the XmnI polymorphism, which is known to be associated with elevated Hb F levels.

Oxidative stress contributes to hemolysis in patients with hereditary spherocytosis and can be ameliorated by fermented papaya preparation.

In the present study, we questioned the role of oxidative stress in hereditary spherocytosis (HS), where red blood cells (RBC) have a shortened survival due to primary deficiency in membrane proteins. Using flow cytometry techniques, we showed that RBC derived from 17 HS patients of seven families generate more reactive oxygen species, membrane lipid peroxides, and less reduced glutathione than normal RBC. Following in vitro incubation of HS-RBC from seven patients with a fermentation bioproduct of Carica papaya (fermented papaya preparation (FPP)) with known antioxidative properties, oxidative stress markers were significantly reduced. Similar results were obtained following treatment with FPP for 3 months of 10 adult HS patients, as well as decreased tendency to undergo hemolysis. The hemoglobin levels increased by >1 g/dl, mean corpuscular hemoglobin concentration decreased by >1 g/dl, and the reticulocyte count decreased by 0.93%. Concomitantly, lactic dehydrogenase decreased by 17% and indirect bilirubin by 50%. A significant decrease in malonyldialdehyde was also detected. These data indicate that oxidative stress plays an important role in the pathophysiology of HS which can be ameliorated by an antioxidant such as FPP. Additional clinical trials with FPP and other antioxidants are warranted.