Immunological biomarkers of COVID-19 : response to vaccination and monoclonal antibody treatments in immunocompromised patients
COVID-19 has caused almost 7 million deaths worldwide with 768 million documented cases of SARS-CoV-2 infections. However, the burden of the pandemic could have been even higher without the development of effective COVID-19 treatments and vaccines in record time. The overarching goal of this thesis was to expend the knowledge about immune responses to COVID-19 and COVID-19 vaccination with the focus on understanding how host immune responses, especially the ones driven by cytokines, chemokines, and growth factors, pre-determine or affect the course of the disease and vaccination. As part of my doctoral thesis, I studied multiple cohorts of immunocompromised patients with COVID-19, or at high risk of developing COVID-19, with the overall aim to build immune-related signatures to predict either development of vaccination responses or responses to treatments, such as those with anti-SARS-CoV-2 monoclonal antibodies (mAb). Specifically, I explored post-vaccine immune responses in solid organ transplant (SOT) recipients and patients with solid and haematological malignancies and identified clinical and molecular signatures predictive of insufficient immune responses. Given the inability of some of these patients to develop sufficient antibody responses to COVID-19 vaccines, I assessed currently available treatment and prophylaxis options. Specifically, I evaluated the effect of mAb treatments and of host immune factors on Spike mutation development. Additionally, I studied neutralizing capacity of bamlanivimab, bamlanivimab/etesevimab, casirivimab/imdevimab, sotrovimab or tixagevimab/cilgavimab against SARS-CoV-2-CoV-2 variants of concern (VOCs). In conclusion, much like an orchestra, where the contributions of each instrument may seem minimal and indistinguishable among others, the influence of cytokines, chemokines and growth factors on COVID-19 is also subtle and may not be overtly noticeable, however, they play a crucial role in co-ordinating and orchestrating various immune responses important in COVID-19 disease and its prevention and treatment. Research findings described in this thesis utilise these variables to understand the molecular pathology of COVID-19 and hopefully would provide a lasting impact on ongoing efforts to combat this global health crisis and its aftermath.
Antwerp : University of Antwerp, Faculty of Medicine and Health Sciences , 2023
193 p.
Supervisor: Kumar-Singh, Samir [Supervisor]
Supervisor: Malhotra-Kumar, Surbhi [Supervisor]
Supervisor: Hotterbeekx, An [Supervisor]
Supervisor: Berkell, Matilda [Supervisor]
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Creation 26.10.2023
Last edited 07.11.2023
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