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

Hussam Ghoti; Hala Zreid; Israa Ghoti; Arno R Bourgonje; Arjan Diepstra; Harry van Goor; Irit Avivi; Hisham Jeadi; Larissa E van Eijk; Günter Weiss

doi:10.1016/j.eclinm.2023.102096

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

EClinicalMedicine. 2023 Jul 26:62:102096. doi: 10.1016/j.eclinm.2023.102096. eCollection 2023 Aug.

Authors

Hussam Ghoti^{1

2}, Hala Zreid¹, Israa Ghoti³, Arno R Bourgonje⁴, Arjan Diepstra⁵, Harry van Goor⁵, Irit Avivi⁶, Hisham Jeadi¹, Larissa E van Eijk⁵, Günter Weiss⁷

Affiliations

¹ Department of Hematology, Al-Shifa Hospital, 51245, Gaza, Palestine.
² Hematology Clinic, National Health Services, 6818164, Tel Aviv, Israel.
³ Human Medicine, European University of Cyprus, 2404, Nicosia, Cyprus.
⁴ Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, Groningen, the Netherlands.
⁵ Division of Pathology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, Groningen, the Netherlands.
⁶ Hematology Division, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, 64239, Tel Aviv, Israel.
⁷ Department of Internal Medicine II, Medical University of Innsbruck, 6020, Innsbruck, Austria.

Abstract

Background: COVID-19 has raised special concern for patients with β-thalassemia major (β-TM) due to frequent comorbidities, regular blood transfusions, and iron overload. However, the exact implications of COVID-19 for patients with β-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 β-TM.

Methods: Patients with β-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 β-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 β-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 β-TM. Anti-SARS-CoV-2 IgG antibodies were significantly higher in symptomatic patients with β-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 β-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 β-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 β-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.

Keywords: COVID-19; Humoral immune response; Innate immune function; Iron; Iron chelation; Splenectomy; Vaccination; β–thalassemia major.