Thesis Towards precision medicine for (long) COVID, 2025, Baalbaki

Towards precision medicine for (long) COVID
Perspectives on pharmacotherapy and molecular mechanisms

N. Baalbaki

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Abstract
This thesis shed light on the complex and heterogeneous nature of (long) COVID. It contributed to the characterization of both acute COVID-19 and long COVID patients and the identification of individuals at risk of developing chronic lung damage.

It covered research ranging from pharmacokinetic and pharmacodynamic studies on the repurposing of imatinib to target endothelial dysfunction in COVID-19, to the characterization of the P4O2 long COVID cohort, contributing to our understanding of its associated cellular and molecular profiles.

This cohort included long COVID patients aged 40-65, mostly hospitalized with moderate disease severity, who predominantly experienced persistent respiratory, neurological, and fatigue symptoms and showed signs of ongoing pulmonary abnormalities at 3-6 months post-COVID. Transcriptomic analysis identified inflammatory nasal and blood profiles.

This thesis provided novel insights into the nasal epithelium of long COVID patients, revealing upregulated SMURF1 expression in the nasal epithelium of patients with pulmonary radiological abnormalities. Additionally, it demonstrated decreased wound healing potential, barrier dysfunction and hypersensitivity of the nasal epithelium along with the involvement of the IFN-γ and IL-1β axis.

The findings of this thesis highlight the need for continued inter- and multidisciplinary research to fully understand this (post-)viral condition and to explore clinical interventions, emphasizing our responsibility as researchers to continue solving the (long) COVID puzzle. The lessons learned from the COVID-19 pandemic and its lingering consequences can serve as a model for approaching future health crises, as we work towards tailored treatments for both immediate symptoms and long-term health outcomes in precision medicine for (post-)viral conditions.

Link (Thesis) [Some sections accessible, some embargoed until 28 February 2027]