COVID-19 severity and complications associated with low diversity, dysbiosis and predictive metagenome features of the oropharyngeal microbiome.

Abstract Coronavirus 2 (SARS-CoV-2) infection and the resulting COVID-19 illness vary from asymptomatic disease, mild upper respiratory tract infection, pneumonia1, to a life-threatening multi-organ failure with case fatality rates ranging from 0.27–13.4%2,3. Despite increasing knowledge of the clinical and immunological features underlying COVID-191,4−6, biological variables explaining the course of infection and its severity remain elusive. At the entry site of SARS-CoV2, the oropharyngeal microbiome represents a hub integrating viral and immune signals at the start of the infection7–10. To evaluate the role of the oropharyngeal microbiome in COVID-19, we performed a multi-center, cross-sectional clinical study analyzing the oropharyngeal microbial metagenomes in healthy adults, patients with non-SARS-CoV-2 infections, or with mild, moderate and severe COVID-19 encompassing a total of 345 participants. Significantly reduced microbiome diversity and high dysbiosis were observed in hospitalized patients with severe COVID-19, which was further associated with a loss of microbial genes and metabolic pathways. In this cohort, diversity measures were also associated with need for intensive care treatments as major clinical parameters in COVID-19. We further applied random forest machine learning to unravel microbial features for segregating clinical outcomes in hospitalized cases, and observed oropharyngeal microbiome abundances of Haemophilus or Streptococcus species as most important features. These findings provide insights into the role of the oropharyngeal microbiome in SARS-CoV-2 infection, and may suggest new biomarkers for COVID-19 severity.