We profiled the upper and lower respiratory tract of COVID-19 patients admitted to the UZ Leuven hospital in Belgium during the first wave of the pandemic. In the upper respiratory tract cohort, we observed that clinical practices, such as mechanical ventilation, are linked to vast changes in microbiota composition, and should be considered as potential confounders in future studies of respiratory microbiome in disease. In the lower respiratory tract cohort, we analyzed single-cell RNA-seq data to find microbial signatures in these patients. We found that bacteria in the lower respiratory tract can be found physically associated with specific pro-inflammatory immune cells, and thus potentially contribute to the exacerbated immune responses in severe COVID-19 disease.

The 16S raw data and metadata of patients enrolled in this study has been deposited in the EGA repository under controlled access and can be found at: https://ega-archive.org/studies/EGAS00001004951. The code used to generate the results presented in the manuscript is available at: https://github.com/raeslab/covid19_respiratory_microbiome.