RATIONALE Bacterial lung microbiota are correlated with lung inflammation and acute respiratory distress syndrome (ARDS), and altered in severe 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 non-resolving 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 COVID-19 patients. All patients had ARDS and underwent bronchoscopy with bronchoalveolar lavage (BAL). Lung microbiota were profiled using 16S rRNA gene sequencing and qPCR targeting the 16S and 18S rRNA genes. Key features of lung microbiota (bacterial and fungal burden, α-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 COVID-19 patients were analyzed. Patients with increased lung bacterial and fungal burden were less likely to be extubated (subdistribution hazard ratio 0.64 [95% CI 0.42-0.97], p=0.034 and 0.59 [95% CI 0.42-0.83], p=0.0027 per log10 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-α) were associated with the microbial burdens. CONCLUSIONS Bacterial and fungal lung microbiota are related to non-resolving ARDS in COVID-19, and represent an important contributor to heterogeneity in COVID-19-related ARDS. 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/).
Lung Microbiota of Critically Ill COVID-19 Patients are Associated with Non-Resolving Acute Respiratory Distress Syndrome.