Dynamics of the Upper Respiratory Tract Microbiota and its Association with Mortality in COVID-19

Ren, Lili; Wang, Yeming; Zhong, Jiaxin; Li, Xia; Xiao, Yan; Li, Jie; Yang, Jing; Fan, Guohui; Guo, Li; Shen, Zijie; Kang, Lu; Shi, Leisheng; Li, Qiong; Li, Jizhou; Di, Lin; Li, Haibo; Wang, Conghui; Wang, Ying; Wang, Xinming; Zou, Xiaohui; Rao, Jian; Zhang, Li; Wang, Jianbin; Huang, Yanyi; Cao, Bin; Wang, Jianwei; Li, Mingkun

RATIONALE: Alteration of human respiratory microbiota had been observed in COVID-19. How the microbiota is associated with the prognosis in COVID-19 is unclear. OBJECTIVES: To characterize the feature and dynamics of the respiratory microbiota and its associations with clinical features in COVID-19 patients. Methods：We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 COVID-19 patients (including 39 deceased patients), and 95 healthy controls from the same geographic area. Meanwhile, the concentration of 27 cytokines and chemokines in plasma was measured for COVID-19 patients. MEASUREMENTS AND MAIN RESULTS: The upper respiratory tract (URT) microbiota in COVID-19 patients differed from that in healthy controls, while deceased patients possessed a more distinct microbiota, both on admission and before discharge/death. The alteration of URT microbiota showed a significant correlation with the concentration of proinflammatory cytokines and mortality. Specifically, Streptococcus-dominated microbiota was enriched in recovered patients, and show high temporal stability and resistance against pathogens. In contrast, the microbiota in deceased patients was more susceptible to secondary infections, and became more deviated from the normality after admission. Moreover, the abundance of S. parasanguinis on admission was significantly correlated with prognosis in non-severe patients (lower vs. higher abundance, odds ratio=7.80, [95% CI 1.70-42.05]). Conclusions：URT microbiota dysbiosis is a remarkable manifestation of COVID-19; its association with mortality suggests it may reflect the interplay between pathogens, symbionts, and the host immune status. Whether URT microbiota could be used as a biomarker for the diagnosis and prognosis of respiratory diseases merits further investigation. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).