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Am J Respir Crit Care Med ; 2022 May 26.
Article in English | MEDLINE | ID: covidwho-1865207


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 (

Antibiotics (Basel) ; 11(2)2022 Feb 08.
Article in English | MEDLINE | ID: covidwho-1697083


The understanding of the gut microbiome in health and disease has shown tremendous progress in the last decade. Shaped and balanced throughout life, the gut microbiome is intricately related to the local and systemic immune system and a multitude of mechanisms through which the gut microbiome contributes to the host's defense against pathogens have been revealed. Similarly, a plethora of negative consequences, such as superinfections and an increased rate of hospital re-admissions, have been identified when the gut microbiome is disturbed by disease or by the iatrogenic effects of antibiotic treatment and other interventions. In this review, we describe the role that probiotics may play in the intensive care unit (ICU). We discuss what is known about the gut microbiome of the critically ill, and the concept of probiotic intervention to positively modulate the gut microbiome. We summarize the evidence derived from randomized clinical trials in this context, with a focus on the prevention of ventilator-associated pneumonia. Finally, we consider what lessons we can learn in terms of the current challenges, efficacy and safety of probiotics in the ICU and what we may expect from the future. Throughout the review, we highlight studies that have provided conceptual advances to the field or have revealed a specific mechanism; this narrative review is not intended as a comprehensive summary of the literature.