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https://www.arca.fiocruz.br/handle/icict/63969
CELLULAR RESPONSE IN SEVERE ADVERSE EVENTS AFTER COVID-19 VACCINATION
Author
Affilliation
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia.em imunobiológicos (Bio-manguinhos). Rio de Janeiro, RJ, Brasil.
Abstract
Introduction: Vaccination is the most effective prevention against SARS-CoV-2 infection and COVID-19
vaccines meet strict safety requirements. Although, severe adverse events (SAE) following COVID-19
vaccination were reported, such as Vaccine-induced immune thrombotic thrombocytopenia (VITT),
Guillain- Barré syndrome (GBS) and others. Pharmacovigilance studies are important to ensure vaccine
safety and reduce the negative impact of vaccine hesitancy on immunization programs.
Objectives: To understand the underlying mechanisms of SAE following COVID-19 vaccination by
analyzing the immunologic profile of vaccinated individuals.
Methodology: Peripheral blood mononuclear cells (PBMC) were isolated from 32 SAE cases
(CAAE: 58916622.0.0000.5262), comprising VITT (n=14), SBG (n=13), myelitis (n=3), ADEM (n=2)
pathologies. PBMC responses were stimulated for 16 hours using a mix of peptides from SARS-CoV-2
Spike glycoprotein. Seven healthy vaccinated individuals were included as controls. A flow cytometry
panel was used to characterize PBMC subpopulations, including lymphocytes and NK cells, from cases
and controls and Kruskal-Wallis and Dunn’s tests were performed (p<0.05). Furthermore, inflammatory
markers were quantified in stimulated PBMC supernatant from cases and compared to controls using non-
parametric unpaired t-test (p<0.05).
Results: A lower frequency of activated CD8+T cells (CD3+CD8+CD38+) was found in cases of SAE
(1.15%) when compared to healthy individuals (5.78%), while no changes in the percentage of activated
CD4+T cells (CD3+CD4+CD38+), activated monocytes (CD14+HLADR+), and NK cells (CD56+) were
observed between the two groups. In a more accurate analysis, the SAE group was stratified by clinical
outcome (VITT and SBG) and a lower percentage of NK cells was seen in the VITT group but not in
the GBS group. Moreover, a lower concentration of IL-4, IL-6, IL-7 and GM-CSF was detected in the
supernatant of PBMCs from SAE cases.
Conclusion: Our findings indicate that individuals with SAE exhibited a decreased functional response
of CD8+T lymphocytes which are crucial for the antiviral cellular response. This immunophenotypic
pattern suggests a reduced production of cytokines associated with the cellular response. As a perspective,
we intend to evaluate through RNAseq the correlation between immunodeficiency and the occurrence of
SAE.
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