Clinical outcome and humoral immune responses of β-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 beta-thalassemia major (beta-TM) due to frequent comorbidities, regular blood transfusions, and iron overload. However, the exact implications of COVID-19 for patients with beta-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 beta-TM. Methods Patients with beta-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 beta-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 beta-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 beta-TM. Anti-SARS-CoV-2 IgG antibodies were significantly higher in symptomatic patients with beta-TM than controls post-infection (geometric mean divided by geometric standard deviation 1299.0 divided by 3.3 vs. 555.7 divided by 2.4 AU/mL, p = 0.009) and post-vaccination (8404.0 divided by 3.9 vs. 2785.6 divided by 5.0 AU/mL, p = 0.015). Similar responses were observed when comparing splenectomised to non-splenectomised (both asymptomatic and symptomatic) patients with beta-TM post-infection (595.4 divided by 3.9 vs. 280.7 divided by 3.5 AU/mL, p = 0.005) and post-vaccination (13,778.2 divided by 3.2 vs. 4961.8 divided by 4.1 AU/mL, p = 0.045). Interpretation This distinctive beta-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 beta-TM, indicating a potential interplay between iron availability and COVID-19-related immunity. Copyright (c) 2023 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).