Avaliação da resposta imunológica pós-esquema de imunização contra COVID-19 em pacientes com doença falciforme

Abstract

Introduction: Sickle cell disease (SCD) is the most common hemoglobinopathy in the world, resulting from a mutation in the gene that encodes the beta chain of hemoglobin, leading to the formation of hemoglobin S (HbS). Patients exhibit chronic immunodeficiency associated with hyposplenism, persistent systemic inflammation, and defects in the cellular immune response—conditions that classify them as a high-risk group for severe complications from COVID-19 and as a priority group for vaccination. Objective: To evaluate the cellular immune response induced by COVID-19 vaccination in patients with sickle cell disease, through T- and B-cell immunophenotyping and measurement of circulating immune biomarkers. Methodology: A cross-sectional study conducted between 2021 and 2023 included 73 patients with sickle cell disease (50 SS and 23 Sβ) and 73 healthy controls treated at the HEMOAM Foundation in Manaus, Amazonas. Of the total patients, 73 completed the two-dose COVID-19 vaccination regimen with vaccines provided by the National Immunization Program: CoronaVac (n=27; 37.0%), Pfizer/BioNTech (n=27; 37.0%), AstraZeneca/Fiocruz (n=18; 24.7%), and Janssen (n=1; 1.4%). Complete blood counts were performed using the ADVIA 2120i system, T-lymphocyte immunophenotyping and B-lymphocyte quantification were conducted by flow cytometry, and cytokine, chemokine, and growth factor assays were performed using the Luminex technique. Statistical analyses were conducted using GraphPad Prism v.9.0 and RStudio software. Results: A significant reduction in red blood cell count, mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV) was observed in Sβ patients compared to the SS genotype. During vaso-occlusive crises in the SS group, significant leukocytosis and neutrophilia were observed. Immunophenotyping revealed a significant reduction in total CD3+, CD4+, and CD8+ T lymphocytes in patients with FV compared to the healthy control group, with marked depletion of naive and terminal effector memory (TEMRA) subpopulations, and expansion of central memory (TCM) and effector (TEM) cells. The profile of soluble mediators showed a marked elevation of IL-6, CCL3, CXCL10, and G-CSF in patients with SD compared to controls, with amplification during vaso-occlusive crises. Conclusion: This study comprehensively characterized the immunological profile of patients with sickle cell disease of the SS and Sβ genotypes in the context of COVID-19 vaccination, demonstrating significant immunological impairment with depletion of naive T cells, expansion of memory phenotypes, and dysregulated systemic inflammation. Such alterations may impact the quality and duration of the vaccine response in this population. Future studies should evaluate the correlation between immunological parameters and anti-Spike antibody titers to better understand vaccine efficacy in sickle cell disease.