Analysis of the correlation of immune response with clinical outcome for Plasmodium and SARS-CoV-2 infections in Rwanda
(2024)
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- Abstract
- Over a century after the discovery of the causative agent of malaria, it still wreaks a devastating global health concern. Most death occurs in sub-Saharan Africa, especially in children under five years old. On the other hand, the impact of COVID-19 in Africa has been a big concern since the pandemic began. However, a low incidence of COVID-19 cases and their severity and mortality have been reported in many African countries, many of which are known to be endemic for malaria. COVID-19 exhibits similarities in clinical presentation and empirical treatment with malaria. In both conditions, disease severity is likely influenced by immune responses directed against the pathogen, which are critical for clearance and protection but may also cause immunopathology. Thus, understanding the dynamic and function of immune responses during malaria and COVID-19 infections is essential for disease prevention and treatment. In this thesis, we studied comprehensive cytokine profiles and T cell transcription gene expression in SARS-CoV-2 and malaria patients vis-à-vis disease outcomes. The aim was to document immune markers that can help predict disease severity. We found that the upregulation of pro-inflammatory cytokines (IFNγ, IL-6) in COVID-19 and malaria patients was strongly associated with the severity of the disease. On the other hand, we observed that patients with mild clinical presentation of malaria had high levels of latent TGFβ1 and TGFβ3 in plasma, which were nearly undetected in severe cases. Moreover, a selective upregulation of IL-9 and mRNA FoxP3 in patients with mild malaria was observed (Paper I). Similarly, longitudinal cytokine kinetics of patients infected with SARS-CoV-2 2 identified a string of low IL-9 and High IFNγ/ IL-9 ratios in the plasma of patients who succumbed to COVID-19 compared to those who recovered (Paper II). Together, these results suggest that stimulating regulatory T cells through TGFβ- and IL-9 is paramount to an effective and balanced protective immunity in Malaria and COVID-19 infection. In addition, the findings of this study have suggested that cytokines could be an essential biomarker for predicting disease severity.
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Citations
Ndoricyimpaye, E. L. (2024). Analysis of the correlation of immune response with clinical outcome for Plasmodium and SARS-CoV-2 infections in Rwanda. https://hdl.handle.net/2078.5/216900