PhD defence R.S.G. (Roos) Sablerolles

Below is a brief summary of the dissertation:

This dissertation investigates clinical, pharmacological, and immunological questions that emerged during different phases of the COVID-19 pandemic, with the aim of contributing to optimal patient care and improved preparedness for future public health crises.
Part I describes the background, rationale, and objectives of the dissertation.
Part II presents results from the international, multicenter COvid MEdicaTion (COMET) study, a retrospective observational cohort study conducted during the first wave of the COVID-19 pandemic across 63 hospitals in 11 European countries. Prior use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers before hospital admission was not associated with an adverse clinical course, supporting continuation of these medications. Chronic oral anticoagulant use was associated with higher in-hospital mortality and a lower likelihood of ICU admission, potentially explained by underlying comorbidities, the interaction between COVID-19-associated coagulopathy and systemic inflammation, and differences in clinical decision-making. Frailty, assessed using the Clinical Frailty Scale (CFS), was strongly associated with in-hospital mortality, independent of age and other clinical factors. Although the CFS appears to be a useful predictor of hospital mortality, its interpretation in younger patients requires caution, as functional limitations in this group do not necessarily reflect age-related frailty.
Part III describes the SWITCH study, a randomized controlled trial in healthcare workers primed with a single dose of the Janssen vaccine (Ad26.COV2.S). Heterologous mRNA-based booster vaccination induced stronger humoral and cellular immune responses than homologous adenovirus-based boosting.
Part IV describes the SWITCH ON study, which evaluated the immunogenicity of a bivalent BA.1 mRNA booster vaccination in healthcare workers primed with Janssen or an mRNA vaccine. The BA.1 booster induced rapid recall of immunological memory and increased antibody and T-cell responses. Neutralizing antibody responses against Omicron subvariants remained lower than against the ancestral virus, consistent with immune escape and amplification of pre-existing memory responses (immune imprinting), without a clear BA.1-specific neutralization preference.
Part V, the general discussion, places these findings in a broader clinical and scientific context and highlights the importance of integrated research approaches and robust infrastructures for future pandemic preparedness.