Clinical practices underlie COVID-19 patient respiratory microbiome composition and its interactions with the host

Author:

Lloréns-Rico VerónicaORCID,Gregory Ann C.,Van Weyenbergh Johan,Jansen SanderORCID,Van Buyten Tina,Qian JunbinORCID,Braz Marcos,Menezes Soraya Maria,Van Mol PierreORCID,Vanderbeke LoreORCID,Dooms Christophe,Gunst JanORCID,Hermans Greet,Meersseman Philippe,Van Herck Yannick,Wilmer Alexander,Casaer Michael,Rex Stephen,Lorent Nathalie,Yserbyt Jonas,Testelmans Dries,Thevissen Karin,Wauters Els,Neyts JohanORCID,Lambrechts DietherORCID,Wauters Joost,Raes JeroenORCID,

Abstract

AbstractUnderstanding the pathology of COVID-19 is a global research priority. Early evidence suggests that the respiratory microbiome may be playing a role in disease progression, yet current studies report contradictory results. Here, we examine potential confounders in COVID-19 respiratory microbiome studies by analyzing the upper (n = 58) and lower (n = 35) respiratory tract microbiome in well-phenotyped COVID-19 patients and controls combining microbiome sequencing, viral load determination, and immunoprofiling. We find that time in the intensive care unit and type of oxygen support, as well as associated treatments such as antibiotic usage, explain the most variation within the upper respiratory tract microbiome, while SARS-CoV-2 viral load has a reduced impact. Specifically, mechanical ventilation is linked to altered community structure and significant shifts in oral taxa previously associated with COVID-19. Single-cell transcriptomics of the lower respiratory tract of COVID-19 patients identifies specific oral bacteria in physical association with proinflammatory immune cells, which show higher levels of inflammatory markers. Overall, our findings suggest confounders are driving contradictory results in current COVID-19 microbiome studies and careful attention needs to be paid to ICU stay and type of oxygen support, as bacteria favored in these conditions may contribute to the inflammatory phenotypes observed in severe COVID-19 patients.

Funder

Fonds Wetenschappelijk Onderzoek

European Molecular Biology Organization

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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