Rationale: Alteration of human respiratory microbiota had been observed in coronavirus disease (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 patients with COVID-19. Methods: We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 patients with COVID-19 (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 patients with COVID-19. Measurements and Main Results: The upper respiratory tract (URT) microbiota in patients with COVID-19 differed from that in healthy controls, whereas 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 showed 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 norm after admission. Moreover, the abundance of S. parasanguinis on admission was significantly correlated with prognosis in nonsevere 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 diagnosis and prognosis of respiratory diseases merits further investigation.

中文翻译：

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上呼吸道微生物群的动态及其与 COVID-19 死亡率的关系。

理由：在冠状病毒病 (COVID-19) 中观察到人类呼吸道微生物群的改变。微生物群如何与 COVID-19 的预后相关尚不清楚。目的：描述 COVID-19 患者呼吸道微生物群的特征和动态及其与临床特征的关联。方法：我们对来自同一地理区域的 192 名 COVID-19 患者（包括 39 名已故患者）和 95 名健康对照者的 588 份纵向口咽拭子标本进行了元转录组测序。同时，测量了 COVID-19 患者血浆中 27 种细胞因子和趋化因子的浓度。测量和主要结果：COVID-19 患者的上呼吸道 (URT) 微生物群与健康对照组不同，而死者在入院时和出院/死亡前都拥有更独特的微生物群。URT微生物群的改变与促炎细胞因子浓度和死亡率显着相关。具体而言，以链球菌为主的微生物群在康复患者中富集，并表现出高度的时间稳定性和对病原体的抵抗力。相比之下，已故患者的微生物群更容易受到继发感染，入院后变得更加偏离常态。此外，入院时副血链球菌的丰度与非重症患者的预后显着相关（丰度较低与较高，优势比，7.80；95% CI，1.70-42.05）。结论：URT微生物群失调是COVID-19的显着表现；它与死亡率的关联表明它可能反映了病原体、共生体和宿主免疫状态之间的相互作用。URT微生物群是否可以用作呼吸系统疾病诊断和预后的生物标志物值得进一步研究。