Lung epithelial and myeloid innate immunity in influenza-associated or COVID-19-associated pulmonary aspergillosis: an observational study

When disaster strikes fungi take control

“…Using state-of-the-art techniques, including transcriptomics and proteomics on the bronchoalveolar lavage samples of more than 100 critically ill patients with influenza or COVID-19 with or without aspergillosis and RNAScope and spatial transcriptomics on the in vivo tracheobronchial biopsy samples from two patients with IAPA and two patients with CAPA, the authors identified a multilevel breach in antifungal immunity in patients with VAPA. 9 First, they observed a downregulation of numerous genes with antifungal effector functions in patients with VAPA, implicating impairments in macrophages, monocytes, and neutrophils; the authors also found that patients with CAPA had significantly lower neutrophil cell fractions than did patients with COVID-19 only. Second, they visualised SARS-CoV-2induced epithelial barrier disruption, facilitating tissue-invasive CAPA.…”

“…Finally, the concentrations of several profibrotic growth factors were significantly increased in the bronchoalveolar lavage fluid from patients with IAPA versus influenza only and from patients with CAPA versus COVID-19 only, potentially contributing to the higher mortality observed in patients with VAPA versus monoinfections. 9 Feys and colleagues should be applauded for their study that provides the foundation for future, functional research on the pathophysiology of VAPA. The identified multilevel breach in antifungal immunity, affecting the integrity of the epithelial barrier, the capacity to phagocytise and kill Aspergillus spores, and the ability to destroy Aspergillus hyphae, might also have implications for clinical management, including diagnosis (eg, novel diagnostic or prognostic biomarkers) and treatment (eg, the use of recombinant IFNγ as an adjuvant to antifungal treatment), which needs to be investigated in future studies.…”

“…In The Lancet Respiratory Medicine , Simon Feys and colleagues 9 report results from the first study to use human lower respiratory tract samples to investigate epithelial and myeloid innate immunology in patients with influenza-associated pulmonary aspergillosis (IAPA) or CAPA. Using state-of-the-art techniques, including transcriptomics and proteomics on the bronchoalveolar lavage samples of more than 100 critically ill patients with influenza or COVID-19 with or without aspergillosis and RNAScope and spatial transcriptomics on the in vivo tracheobronchial biopsy samples from two patients with IAPA and two patients with CAPA, the authors identified a multilevel breach in antifungal immunity in patients with VAPA.…”

“…Using state-of-the-art techniques, including transcriptomics and proteomics on the bronchoalveolar lavage samples of more than 100 critically ill patients with influenza or COVID-19 with or without aspergillosis and RNAScope and spatial transcriptomics on the in vivo tracheobronchial biopsy samples from two patients with IAPA and two patients with CAPA, the authors identified a multilevel breach in antifungal immunity in patients with VAPA. 9 …”

“…Finally, the concentrations of several profibrotic growth factors were significantly increased in the bronchoalveolar lavage fluid from patients with IAPA versus influenza only and from patients with CAPA versus COVID-19 only, potentially contributing to the higher mortality observed in patients with VAPA versus monoinfections. 9 …”