• Simon Feys, Martina Cardinali-Benigni, Hanne Moon Lauwers, Cato Jacobs, Annelies Stevaert, Samuel M Gonçalves, Cristina Cunha, Yves Debaveye, Greet Hermans, Jannes Heylen, Stephanie Humblet-Baron, Katrien Lagrou, Lenn Maessen, Philippe Meersseman, Marijke Peetermans, Alvaro Redondo-Rios, Laura Seldeslachts, Marick R Starick, Karin Thevissen, Greetje Vande Velde, Christophe Vandenbriele, Lore Vanderbeke, Alexander Wilmer, Lieve Naesens, Frank L van de Veerdonk, Johan Van Weyenbergh, Toni Gabaldón, Joost Wauters, and Agostinho Carvalho.
• KU Leuven University Hospitals Leuven, Leuven, Belgium.
• Am. J. Respir. Crit. Care Med. 2024 Jun 12.

RationaleThe influence of the lung bacterial microbiome, including potential pathogens, in patients with influenza- or COVID-19-associated pulmonary aspergillosis (IAPA or CAPA) is yet to be explored.ObjectivesTo explore the composition of the lung bacterial microbiome and its association with viral and fungal infection, immunity and outcome in severe influenza versus COVID-19 with or without aspergillosis.MethodsWe performed a retrospective study in mechanically ventilated influenza and COVID-19 patients with or without invasive aspergillosis in whom bronchoalveolar lavage (BAL) for bacterial culture (with or without PCR) was obtained within two weeks after ICU admission. Additionally, 16S rRNA gene sequencing data and viral and bacterial load of BAL samples from a subset of these patients, and of patients requiring non-invasive ventilation, were analyzed. We integrated 16S rRNA gene sequencing data with existing immune parameter datasets.Measurements And Main ResultsPotential bacterial pathogens were detected in 20% (28/142) of influenza and 37% (104/281) of COVID-19 patients, while aspergillosis was detected in 38% (54/142) of influenza and 31% (86/281) of COVID-19 patients. A significant association between bacterial pathogens in BAL and 90-day mortality was found only in influenza patients, particularly IAPA patients. COVID-19 but not influenza patients showed increased pro-inflammatory pulmonary cytokine responses to bacterial pathogens.ConclusionsAspergillosis is more frequently detected in lungs of severe influenza patients than bacterial pathogens. Detection of bacterial pathogens associates with worse outcome in influenza patients, particularly in those with IAPA, but not in COVID-19 patients. The immunological dynamics of tripartite viral-fungal-bacterial interactions deserve further investigation. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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