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Invasieve pulmonale aspergillose geassocieerd aan ernstige virale infecties op intensieve zorgen

Boek - Dissertatie

Evidence of the last decades supports the establishment of severe influenza as an important risk factor for invasive pulmonary aspergillosis (IPA) development on intensive care units (ICU). Similar to influenza, invasive mould infections were observed in COVID-19 critically ill patients, though at a lower frequency and with more debate on the clinical relevance of the diagnosis. We therefore aimed to investigate IPA in ICU patients with severe viral respiratory failure, to strengthen current evidence arguing for viral-associated pulmonary aspergillosis (VAPA) inclusion in the ever-evolving list of risk factors for IPA development. Our antifungal prophylaxis chapter prospectively validated the frequent occurrence of influenza-associated pulmonary aspergillosis in ICU-admitted influenza patients. Moreover, early diagnostic evaluations identified that IAPA occurs very soon after or upon ICU admission, thereby arguing against a universal antifungal prophylaxis approach. With our histological investigation of VAPA, we identified tissue-based proof of invasive fungal disease similar in frequency and extent/pattern amongst critically ill influenza and COVID-19 cases, underscoring the invasive nature of IPA in both viral contexts. Shifting our attention to COVID-19 host responses in the final presented research data chapter, we used a multi-omics approach to investigate COVID-19 disease severity. A marked and disproportionate, myeloid-driven immunopathology was identified in ICU-admitted patients. Similar approaches towards unraveling host-pathogen interactions in the setting of CAPA (and VAPA) are now warranted. Overall, the data presented build a strong case for diagnostic awareness of IPA in ICU-admitted influenza and COVID-19 patients, with a need to further study differentiated management approaches, including targeted or universal prophylaxis. High-resolution multi-omics studies are necessary to further unravel the pathophysiology of VAPA.
Jaar van publicatie:2022
Toegankelijkheid:Open