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

• Published in: Nature communications Vol. 12; no. 1; p. 6243
• Main Authors: Lloréns-Rico, Verónica, Gregory, Ann C., Van Weyenbergh, Johan, Jansen, Sander, Van Buyten, Tina, Qian, Junbin, Braz, Marcos, Menezes, Soraya Maria, Van Mol, Pierre, Vanderbeke, Lore, Dooms, Christophe, Gunst, Jan, Hermans, Greet, Meersseman, Philippe, Wauters, Els, Neyts, Johan, Lambrechts, Diether, Wauters, Joost, Raes, Jeroen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29-10-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 45/23; 49/91; 631/326/2565/107; 631/326/2565/2134; 692/420/254; Antibiotics; Bacteria; Community structure; Coronaviruses; COVID-19; COVID-19 - microbiology; Gastrointestinal Microbiome - genetics; Gastrointestinal Microbiome - physiology; Humanities and Social Sciences; Humans; Immune response; Immune system; Inflammation; Mechanical ventilation; Microbiomes; Microbiota; Microbiota - physiology; Microorganisms; multidisciplinary; Oxygen; Patients; Phenotypes; Respiratory tract; SARS-CoV-2 - pathogenicity; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Transcriptome - genetics; Ventilation; Ventilators; Viral diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-26500-8

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.
Here, the authors profile the respiratory microbiome of COVID-19 patients and link clinical practices, such as mechanical ventilation, with vast changes in the microbiota. In the lungs, oral bacteria are found physically associated with proinflammatory immune cells, thus possibly contributing to exacerbated immune responses in severe disease