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

Verónica Lloréns-Rico, Ann C. Gregory, Johan Van Weyenbergh, Sander Jansen, Tina Van Buyten, Junbin Qian, Marcos Braz, Soraya Maria Menezes, Pierre Van Mol, Lore Vanderbeke, Christophe Dooms, Jan Gunst, Greet Hermans, Philippe Meersseman, Els Wauters, Johan Neyts, Diether Lambrechts, Joost Wauters and Jeroen Raes ()
Additional contact information
Verónica Lloréns-Rico: Rega Institute, KU Leuven
Ann C. Gregory: Rega Institute, KU Leuven
Johan Van Weyenbergh: Rega Institute, KU Leuven
Sander Jansen: Rega Institute, KU Leuven
Tina Van Buyten: Rega Institute, KU Leuven
Junbin Qian: Zhejiang University School of Medicine
Marcos Braz: Rega Institute, KU Leuven
Soraya Maria Menezes: Rega Institute, KU Leuven
Pierre Van Mol: Laboratory of Translational Genetics, Department of Human Genetics, KU Leuven
Lore Vanderbeke: Immunology and Transplantation, KU Leuven
Christophe Dooms: University Hospitals Leuven
Jan Gunst: Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven
Greet Hermans: Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven
Philippe Meersseman: Laboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven
Els Wauters: University Hospitals Leuven
Johan Neyts: Rega Institute, KU Leuven
Diether Lambrechts: Laboratory of Translational Genetics, Department of Human Genetics, KU Leuven
Joost Wauters: Laboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven
Jeroen Raes: Rega Institute, KU Leuven

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Understanding 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.

Date: 2021
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DOI: 10.1038/s41467-021-26500-8

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