Comparison of the Respiratory Tractmicrobiome in Hospitalized COVID-19 Patients with Different Disease Severity

Background: Little is known about the characteristics of respiratory tract microbiome in Coronavirus disease 2019 (COVID-19) inpatients with different severity. Methods: A cross-sectional study was conducted to characterize respiratory tract microbial communities of 69 COVID-19 inpatients from 64 nasopharyngeal swabs and 5 sputum specimens using 16S ribosomal RNA (rRNA) gene V3-V4 region sequencing. The bacterial profiles were used to find potential biomarkers by the two-step method, the combination of random forest model and the linear discriminant analysis effect size (LEfSe), and explore the connections with clinical characteristics by Spearman’s rank test.Results: Compared with mild COVID-19 patients, severe patients had significantly decreased bacterial diversity (Pvalues were less than 0.05 in the alpha and beta diversity) and relative lower abundance of opportunistic pathogens, including Actinomyces, Prevotella, Rothia, Streptococcus, Veillonella. Eight potential biomarkers including Treponema, Lachnoanaerobaculum, Parvimonas, Selenomonas, Alloprevotella, Porphyromonas, GemellaandStreptococcus were found to distinguish the mild COVID-19 patients from the severe COVID-19 patients. The genera of Actinomyces andPrevotella were negatively correlated with age and inpatient days. Intensive Care Unit (ICU) admission, neutrophil count (GRA) and lymphocyte count (LYMPH) were significantly correlated with different genera in the two groups. In addition, there were a positive correlation between Klebsiella and white blood cell count (WBC) in two groups.Conclusion: The respiratory tract microbiome had significant difference in COVID-19 patients with different severity. The value of the respiratory tract microbiome as predictive biomarkers for COVID-19 severity merits further exploration.