Exploring Experimental Hematology: August 2025 (Volume 129)

Read the highlights from Inhibitory effects of SARS-CoV-2 spike protein and BNT162b2 vaccine on erythropoietin-induced globin gene expression in erythroid precursor cells from patients with β-thalassemia by Lucia Carmela Cosenza, Giovanni Marzaro, Matteo Zurlo, Jessica Gasparello, Cristina Zuccato, Alessia Finotti, and Roberto Gambari

In this issue of Simply Blood, we are highlighting a manuscript led by first author Lucia Carmela Cosenza conducted in the laboratory of Dr. Roberto Gambari at the Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy. This is the first study to demonstrate that both the SARS-CoV-2 spike (S) protein and BNT162b2 mRNA vaccine can inhibit fetal hemoglobin (HbF) production by and reduce γ-globin mRNA accumulation in β-thalassemic erythroid precursor cells (ErPCs).

Despite widespread vaccination efforts, COVID-19 remains a global health challenge. Emerging research suggests that the SARS-CoV-2 S-protein may contribute to side effects associated with mRNA vaccines such as BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). However, the impact of these vaccines on hematological disorders, especially on β-thalassemia has not been explored. In this study, Cosenza et al investigated the effect of SARS-Cov-2 S-protein and BNT162b2 vaccine on ErPCS isolated from β–thalassemia patients. ErPCS cells were exposed ex vivo to either SARS-Cov2 S-protein or BNT162b2 vaccine with or without erythropoietin. Cosenza et al. first confirmed that exposure to both SARS-Cov2 or BNT162b2 vaccine decreased total hemoglobin production with a pronounced effect on fetal hemoglobin (HbF). They also found a marked decrease in γ-globin mRNA in S-protein and BNT162b2 treated ErPCs.

In conclusion, these results suggest an inhibitory effect of S-protein and COVID19- vaccine on hemoglobin synthesis in β-thalassemia cells, aligning with broader concerns about the impact of SARS-Cov-2 on the hematopoietic system. 

Why this study matters

Since its emergence in late 2019, COVID-19 continues to affect individuals, causing dysregulated immune response. Recent studies highlight the impact of COVID-19 infection on hematopoiesis particularly alteration of hematopoietic stem and progenitor cells. However, studies on the short and long-term effect of spike protein and mRNA-based vaccines on hematological disorders are limited. Therefore, understanding the role of spike protein and COVID-vaccines on hematological disorders such as β-thalassemia would help manage the unexpected side-effects following COVID-19 mRNA vaccinations. 

Approaches used in this study

Erythroid precursor cells were obtained from six β-thalassemia patients with diverse genotypes via the β-Thalassemia Biobank. The authors used ex vivo and in silico approaches to test the effect of S-protein and BNT162b2 on fetal hemoglobin accumulation and affinity. They performed high-performance liquid chromatography to assess the effect of S-protein and BNT162b2 on hemoglobin production. Western blotting was used to measure γ-globin accumulation following ErPCs exposure with S-protein and BNT162b2. 

Why should you read this paper

The study offers a novel perspective on the effect of S-protein and COVID-19 vaccines on hematological disorders. By focusing on β-thalassemia patients, this study raises important questions about the long-term effects of S-protein and mRNA vaccines on hematopoietic system. The study encourages further exploration of effects of S-protein in β-thalassemia patients vaccinated with mRNA-based vaccines. Future studies in this field would lead to better pharmacologic strategies for patients with hematological disorders. 

Attached Figure:

Figure 4:  Effects of the BTN162b2 vaccine on hemoglobin accumulation and globin gene expression by treated ErPCs. (A,B) Effects on hemoglobin accumulation. ErPCs from patient#1 were either untreated (cultured with only EPO) (A) or exposed to the COVID- 19 BTN162b2 vaccine before culturing with EPO (B). The resulting HPLC patterns are shown. (C) Summary of the results obtained analyzing the accumulation of b-globin (white box) and g-globin (black box ) mRNAs in ErPCs from all the recruited patients treated with the COVID-19BTN162b2 vaccine. The data represent the average ±SD. ErPC = Erythroid precursor cells; EPO = erythropoietin; HPLC = high-performance liquid chromatography.

Read the Article

Blog post contributed by Kavita Bisht, PhD of the ISEH Publications Committee. 

Please note that the statements made by Simply Blood authors are their own views and not necessarily the views of ISEH. ISEH disclaims any or all liability arising from any author's statements or materials.