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

Kullberg, Robert F. J.; Brabander, Justin de; Boers, Leonoor S.; Biemond, Jason J.; Nossent, Esther J.; Heunks, Leo; Vlaar, Alexander P.J.; Bonta, Peter I.; Poll, Tom van der; Duitman, JanWillem; Bos, Lieuwe; Wiersinga, W. Joost; Saris, Anno; Vries, Heder de; Meijboom, Lilian J.; Blok, Siebe G.; Schuurman, Alex R.; Reijnders, Tom D.Y.; Vallejo, Juan J. García; Bontkes, Hetty J.; Lutter, René; Bogaard, Harm Jan; Bruin, Sanne de; Koning, Rutger; Agtmael, Michiel A. van; Algera, Anna Geke; Baarle, Frank E.H.P. van; Bax, Diane; Beudel, Martijn; Bomers, Marije; Botta, Michela; Bree, Godelieve J. de; Bugiani, Marianna; Bulle, Esther; Chouchane, Osoul; Cloherty, Alex; Elbers, Paul; Fleuren, Lucas M.; Geerlings, Suzanne E.; Geerts, Bart F.; Geijtenbeek, T.B.H.; Girbes, Armand R. J.; Goorhuis, A.; Grobusch, Martin P.; Hafkamp, Florianne; Hagens, Laura A.; Hamann, Jörg; Harris, Vanessa; Hemke, Robert; Hermans, Sabine; Hollmann, Markus W.; Horn, Johanna; Hovius, Joppe W.; Jong, Menno D. de; Mourik, Niels van; Nellen, Jeannine; Paulus, Frederique; Peters, Elizabeth; Preckel, Benedikt; Raasveld, S.J.; Schinkel, Michiel; Schultz, Marcus J.; Sigaloff, Kim C.E.; Smit, Marry R.; Stijnis, Cornelis; Stilma, Willemke; Teunissen, Charlotte E.; Thoral, Patrick; Tsonas, A.M.; Valk, Marc van der; Veelo, Denise P.; Vugt, Michèle van; Wouters, Dorien; Zwinderman, A. H.; Brouwer, Matthijs C.; Beek, Diederik van de

doi:10.1164/rccm.202202-0274oc

Cited by 31 publications

(33 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, for Staphylococcus and Haemophilus the cut-offs were less reliable. This is in line with results from a similar comparison in invasively ventilated COVID-19 patients [ 43 ]. This could be a result of reduced taxonomic resolution of 16s sequencing: limited to genus rather than species level.…”

Section: Discussionsupporting

confidence: 92%

Composition and diversity analysis of the lung microbiome in patients with suspected ventilator-associated pneumonia

et al. 2022

View full text Add to dashboard Cite

Background Ventilator-associated pneumonia (VAP) is associated with high morbidity and health care costs, yet diagnosis remains a challenge. Analysis of airway microbiota by amplicon sequencing provides a possible solution, as pneumonia is characterised by a disruption of the microbiome. However, studies evaluating the diagnostic capabilities of microbiome analysis are limited, with a lack of alignment on possible biomarkers. Using bronchoalveolar lavage fluid (BALF) from ventilated adult patients suspected of VAP, we aimed to explore how key characteristics of the microbiome differ between patients with positive and negative BALF cultures and whether any differences could have a clinically relevant role. Methods BALF from patients suspected of VAP was analysed using 16s rRNA sequencing in order to: (1) differentiate between patients with and without a positive culture; (2) determine if there was any association between microbiome diversity and local inflammatory response; and (3) correctly identify pathogens detected by conventional culture. Results Thirty-seven of 90 ICU patients with suspected VAP had positive cultures. Patients with a positive culture had significant microbiome dysbiosis with reduced alpha diversity. However, gross compositional variance was not strongly associated with culture positivity (AUROCC range 0.66–0.71). Patients with a positive culture had a significantly higher relative abundance of pathogenic bacteria compared to those without [0.45 (IQR 0.10–0.84), 0.02 (IQR 0.004–0.09), respectively], and an increased interleukin (IL)-1β was associated with reduced species evenness (rs = − 0.33, p < 0.01) and increased pathogenic bacteria presence (rs = 0.28, p = 0.013). Untargeted 16s rRNA pathogen detection was limited by false positives, while the use of pathogen-specific relative abundance thresholds showed better diagnostic accuracy (AUROCC range 0.89–0.998). Conclusion Patients with positive BALF culture had increased dysbiosis and genus dominance. An increased caspase-1-dependent IL-1b expression was associated with a reduced species evenness and increased pathogenic bacterial presence, providing a possible causal link between microbiome dysbiosis and lung injury development in VAP. However, measures of diversity were an unreliable predictor of culture positivity and 16s sequencing used agnostically could not usefully identify pathogens; this could be overcome if pathogen-specific relative abundance thresholds are used.

show abstract

Section: Discussionsupporting

confidence: 92%

Composition and diversity analysis of the lung microbiome in patients with suspected ventilator-associated pneumonia

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Making data publicly available for reanalysis and meta-analysis would allow for standardization across studies. A minority of studies make sufficient data available (e.g., Gupta et al, Kullberg et al [53,54]).…”

Section: Inconsistent Analytical Techniquesmentioning

confidence: 99%

Alterations in the respiratory tract microbiome in COVID-19: current observations and potential significance

2022

View full text Add to dashboard Cite

SARS-CoV-2 infection causes COVID-19 disease, which can result in consequences ranging from undetectable to fatal, focusing attention on the modulators of outcomes. The respiratory tract microbiome is thought to modulate the outcomes of infections such as influenza as well as acute lung injury, raising the question to what degree does the airway microbiome influence COVID-19? Here, we review the results of 56 studies examining COVID-19 and the respiratory tract microbiome, summarize the main generalizations, and point to useful avenues for further research. Although the results vary among studies, a few consistent findings stand out. The diversity of bacterial communities in the oropharynx typically declined with increasing disease severity. The relative abundance of Haemophilus and Neisseria also declined with severity. Multiple microbiome measures tracked with measures of systemic immune responses and COVID outcomes. For many of the conclusions drawn in these studies, the direction of causality is unknown—did an alteration in the microbiome result in increased COVID severity, did COVID severity alter the microbiome, or was some third factor the primary driver, such as medication use. Follow-up mechanistic studies can help answer these questions.

show abstract

“…Colonization data were not collected in this study, but it could be logical to hypothesize that patients with fungal infections might have a healthcare associated change in microbiota due to antibiotics, immunosuppressants, and exposure to multi-drug resistant pathogens of the ICU. There are plenty data in the literature on the role of microbiota in the respiratory diseases and suggestions that increased bacterial and fungal burden might be associated with worse outcome in COVID-19 patients [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Fungal Infections in the ICU during the COVID-19 Era: Descriptive and Comparative Analysis of 178 Patients

Koukaki

Rovina

Tzannis

et al. 2022

JoF

View full text Add to dashboard Cite

Background: COVID-19-associated fungal infections seem to be a concerning issue. The aim of this study was to assess the incidence of fungal infections, the possible risk factors, and their effect on outcomes of critically ill patients with COVID-19. Methods: A retrospective observational study was conducted in the COVID-19 ICU of the First Respiratory Department of National and Kapodistrian University of Athens in Sotiria Chest Diseases Hospital between 27 August 2020 and 10 November 2021. Results: Here, 178 patients were included in the study. Nineteen patients (10.7%) developed fungal infection, of which five had COVID-19 associated candidemia, thirteen had COVID-19 associated pulmonary aspergillosis, and one had both. Patients with fungal infection were younger, had a lower Charlson Comorbidity Index, and had a lower PaO2/FiO2 ratio upon admission. Regarding health-care factors, patients with fungal infections were treated more frequently with Tocilizumab, a high regimen of dexamethasone, continuous renal replacement treatment, and were supported more with ECMO. They also had more complications, especially infections, and subsequently developed septic shock more frequently. Finally, patients with fungal infections had a longer length of ICU stay, as well as length of mechanical ventilation, although no statistically significant difference was reported on 28-day and 90-day mortality. Conclusions: Fungal infections seem to have a high incidence in COVID-19 critically ill patients and specific risk factors are identified. However, fungal infections do not seem to burden on mortality.

show abstract

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

Cited by 31 publications

References 51 publications

Composition and diversity analysis of the lung microbiome in patients with suspected ventilator-associated pneumonia

Composition and diversity analysis of the lung microbiome in patients with suspected ventilator-associated pneumonia

Alterations in the respiratory tract microbiome in COVID-19: current observations and potential significance

Fungal Infections in the ICU during the COVID-19 Era: Descriptive and Comparative Analysis of 178 Patients

Contact Info

Product

Resources

About