TY - JOUR
T1 - Lung Microbiota of Critically Ill Patients with COVID-19 Are Associated with Nonresolving Acute Respiratory Distress Syndrome
AU - Kullberg, Robert F. J.
AU - de Brabander, Justin
AU - Boers, Leonoor S.
AU - Biemond, Jason J.
AU - Nossent, Esther J.
AU - Heunks, Leo M. A.
AU - Vlaar, Alexander P. J.
AU - Bonta, Peter I.
AU - van der Poll, Tom
AU - ArtDECO Consortium and the Amsterdam UMC COVID-19 Biobank Study Group
AU - Duitman, JanWillem
AU - Bos, Lieuwe D. J.
AU - Wiersinga, W. Joost
N1 - Funding Information: Supported by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organization for Scientific Research) under VIDI grant 91716475 to W.J.W. and VENI grant 016.1860.046 to J.D.; and by an Amsterdam University Medical Centers Ph.D. scholarship to R.F.J.K. and fellowship to L.D.J.B. Publisher Copyright: Copyright © 2022 by the American Thoracic Society.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - 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, 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 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 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 nonresolving ARDS in COVID-19 and represent an important contributor to heterogeneity in COVID-19-related ARDS.
AB - 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, 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 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 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 nonresolving ARDS in COVID-19 and represent an important contributor to heterogeneity in COVID-19-related ARDS.
KW - COVID-19/complications
KW - Humans
KW - Lung/microbiology
KW - Microbiota/genetics
KW - RNA, Ribosomal, 16S/genetics
KW - Respiration, Artificial
KW - Respiratory Distress Syndrome
KW - Tumor Necrosis Factor-alpha
KW - artificial respiration
KW - critical illness
KW - host–microbial interactions
KW - lung microbiome
UR - http://www.scopus.com/inward/record.url?scp=85135829359&partnerID=8YFLogxK
U2 - https://doi.org/10.1164/rccm.202202-0274OC
DO - https://doi.org/10.1164/rccm.202202-0274OC
M3 - Article
C2 - 35616585
SN - 1073-449X
VL - 206
SP - 846
EP - 856
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 7
ER -