PhD defence K.C.P. (Katrijn) Daenen

Below is a brief summary of the dissertation:

COVID-19 can trigger severe (hyper)inflammation, leading to high morbidity and mortality, particularly in patients developing acute respiratory distress syndrome (ARDS). Corticosteroids, notably dexamethasone, are standard therapy, but the benefit of high-dose corticosteroids remains uncertain. This thesis investigates the efficacy, timing, and outcome predictors of high-dose corticosteroid therapy in critically ill, hospitalized COVID-19 patients.

In the multicenter SELECT study, high-dose corticosteroids (>6mg dexamethasone or equivalent) were compared with standard-dose therapy in non-ICU and ICU cohorts. In non-ICU patients, high-dose therapy did not reduce mortality and increased risk in patients with BMI >30kg/m² or CRP <200mg/L. In ICU patients with ARDS, high-dose corticosteroids were generally associated with higher mortality, especially in males, obese patients, and patients with lower CRP or SOFA scores, though early initiation (<24 hours of start mechanical ventilation) mitigated harm without clear benefit. A study in Suriname showed no significant effect of high-dose therapy on mortality or superinfections in a resource-limited setting.

Causal mediation analyses identified CRP, D-dimer, and IL-6 as key mediators of corticosteroid-associated mortality. Biomarker dynamics, particularly NLR, predicted mortality in ARDS patients receiving high-dose therapy. Systematic review of ARDS mortality prediction models revealed moderate performance, with no model achieving both robust discrimination and calibration.

Overall, high-dose corticosteroids offer no benefit over standard-dose therapy in severe COVID-19, and may increase mortality in specific subgroups. Biomarker-guided treatment and early identification of high-risk patients are important for personalized care and optimal outcomes in COVID-19 ARDS.