Lung Microbiota of Critically Ill Patients with COVID-19 Are Associated with Nonresolving Acute Respiratory Distress Syndrome

被引：34

作者：

Kullberg, Robert F. J. ^{[1
]}

de Brabander, Justin ^{[1
]}

Boers, Leonoor S. ^{[2
,3
]}

Biemond, Jason J. ^{[1
]}

Nossent, Esther J. ^{[4
]}

Heunks, Leo M. A. ^{[2
]}

Vlaar, Alexander P. J. ^{[2
,3
]}

Bonta, Peter, I ^{[4
]}

van Der Poll, Tom ^{[1
,5
]}

Duitman, JanWillem ^{[4
,6
]}

Bos, Lieuwe D. J. ^{[2
,3
,4
]}

Wiersinga, W. Joost ^{[1
,5
]}

机构：

[1] Univ Amsterdam, Amsterdam Univ Med Ctr, Ctr Expt & Mol Med, Meibergdreef 9,Room T1-234, NL-1105 AZ Amsterdam, Netherlands

[2] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Intens Care Med, Amsterdam, Netherlands

[3] Univ Amsterdam, Amsterdam Univ Med Ctr, Lab Expt Intens Care & Anesthesiol, Amsterdam, Netherlands

[4] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Pulm Med, Amsterdam, Netherlands

[5] Univ Amsterdam, Amsterdam Univ Med Ctr, Div Infect Dis, Amsterdam, Netherlands

[6] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Expt Immunol, Amsterdam, Netherlands

来源：

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE | 2022年 / 206卷 / 07期

关键词：

lung microbiome; host-microbial interactions; critical illness; artificial respiration; MODELS;

D O I：

10.1164/rccm.202202-0274OC

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

Rationale: Bacterial lung microbiota are correlated with lung inflammation and acute respiratory distress syndrome (ARDS) and altered in severe coronavirus disease (COVID-19). However, the association between lung microbiota (including fungi) and resolution of ARDS in COVID-19 remains unclear. We hypothesized that increased lung bacterial and fungal burdens are related to nonresolving ARDS and mortality in COVID-19. Objectives: To determine the relation between lung microbiota and clinical outcomes of COVID-19-related ARDS. Methods: This observational cohort study enrolled mechanically ventilated patients with COVID-19. All patients had ARDS and underwent bronchoscopy with BAL. Lung microbiota were profiled using 16S rRNA gene sequencing and quantitative PCR targeting the 16S and 18S rRNA genes. Key features of lung microbiota (bacterial and fungal burden, alpha-diversity, and community composition) served as predictors. Our primary outcome was successful extubation adjudicated 60 days after intubation, analyzed using a competing risk regression model with mortality as competing risk. Measurements and Main Results: BAL samples of 114 unique patients with COVID-19 were analyzed. Patients with increased lung bacterial and fungal burden were less likely to be extubated (subdistribution hazard ratio, 0.64 [95% confidence interval, 0.42-0.97]; P = 0.034 and 0.59 [95% confidence interval, 0.42-0.83]; P = 0.0027 per log(10) increase in bacterial and fungal burden, respectively) and had higher mortality (bacterial burden, P = 0.012; fungal burden, P = 0.0498). Lung microbiota composition was associated with successful extubation (P = 0.0045). Proinflammatory cytokines (e.g., tumor necrosis factor-alpha) were associated with the microbial burdens. Conclusions: Bacterial and fungal lung microbiota are related to nonresolving ARDS in COVID-19 and represent an important contributor to heterogeneity in COVID-19-related ARDS.

引用

页码：846 / 856

页数：11

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