Quantitative SARS-CoV-2 RT-PCR and Bronchoalveolar Cytokine Concentrations Redefine the COVID-19 Phenotypes in Critically Ill Patients
RATIONALE: Recent studies suggest that both hypo- and hyperinflammatory acute respiratory distress syndrome (ARDS) phenotypes characterize severe COVID-19-related pneumonia. The role of lung Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) viral load in contributing to these phenotypes remains unknown.
OBJECTIVES: To redefine COVID-19 ARDS phenotypes when considering quantitative SARS-CoV-2 RT-PCR in the bronchoalveolar lavage of intubated patients. To compare the relevance of deep respiratory samples versus plasma in linking the immune response and the quantitative viral loads.
METHODS: Eligible subjects were adults diagnosed with COVID-19 ARDS who required mechanical ventilation and underwent bronchoscopy. We recorded the immune response in the bronchoalveolar lavage and plasma and the quantitative SARS-CoV-2 RT-PCR in the bronchoalveolar lavage. Hierarchical clustering on principal components was applied separately on the 2 compartments' datasets. Baseline characteristics were compared between clusters.
MEASUREMENTS AND RESULTS: Twenty subjects were enrolled between August 2020 and March 2021. Subjects underwent bronchoscopy on average 3.6 days after intubation. All subjects were treated with dexamethasone prior to bronchoscopy, 11 of 20 (55.6%) received remdesivir and 1 of 20 (5%) received tocilizumab. Adding viral load information to the classic 2-cluster model of ARDS revealed a new cluster characterized by hypoinflammatory responses and high viral load in 23.1% of the cohort. Hyperinflammatory ARDS was noted in 15.4% of subjects. Bronchoalveolar lavage clusters were more stable compared to plasma.
CONCLUSIONS: We identified a unique group of critically ill subjects with COVID-19 ARDS who exhibit hypoinflammatory responses but high viral loads in the lower airways. These clusters may warrant different treatment approaches to improve clinical outcomes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Journal of intensive care medicine - (2024) vom: 17. Apr., Seite 8850666231217707 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Vazquez Guillamet, M Cristina [VerfasserIn] |
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Date Revised 17.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1177/08850666231217707 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM371185726 |
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| 500 | |a Date Revised 17.04.2024 | ||
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| 500 | |a Citation Status Publisher | ||
| 520 | |a RATIONALE: Recent studies suggest that both hypo- and hyperinflammatory acute respiratory distress syndrome (ARDS) phenotypes characterize severe COVID-19-related pneumonia. The role of lung Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) viral load in contributing to these phenotypes remains unknown | ||
| 520 | |a OBJECTIVES: To redefine COVID-19 ARDS phenotypes when considering quantitative SARS-CoV-2 RT-PCR in the bronchoalveolar lavage of intubated patients. To compare the relevance of deep respiratory samples versus plasma in linking the immune response and the quantitative viral loads | ||
| 520 | |a METHODS: Eligible subjects were adults diagnosed with COVID-19 ARDS who required mechanical ventilation and underwent bronchoscopy. We recorded the immune response in the bronchoalveolar lavage and plasma and the quantitative SARS-CoV-2 RT-PCR in the bronchoalveolar lavage. Hierarchical clustering on principal components was applied separately on the 2 compartments' datasets. Baseline characteristics were compared between clusters | ||
| 520 | |a MEASUREMENTS AND RESULTS: Twenty subjects were enrolled between August 2020 and March 2021. Subjects underwent bronchoscopy on average 3.6 days after intubation. All subjects were treated with dexamethasone prior to bronchoscopy, 11 of 20 (55.6%) received remdesivir and 1 of 20 (5%) received tocilizumab. Adding viral load information to the classic 2-cluster model of ARDS revealed a new cluster characterized by hypoinflammatory responses and high viral load in 23.1% of the cohort. Hyperinflammatory ARDS was noted in 15.4% of subjects. Bronchoalveolar lavage clusters were more stable compared to plasma | ||
| 520 | |a CONCLUSIONS: We identified a unique group of critically ill subjects with COVID-19 ARDS who exhibit hypoinflammatory responses but high viral loads in the lower airways. These clusters may warrant different treatment approaches to improve clinical outcomes | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ARDS | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a cycle threshold | |
| 650 | 4 | |a phenotyping | |
| 700 | 1 | |a Vazquez Guillamet, Rodrigo |e verfasserin |4 aut | |
| 700 | 1 | |a Rjob, Ashraf |e verfasserin |4 aut | |
| 700 | 1 | |a Reynolds, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Parikh, Bijal |e verfasserin |4 aut | |
| 700 | 1 | |a Despotovic, Vladimir |e verfasserin |4 aut | |
| 700 | 1 | |a Byers, Derek E |e verfasserin |4 aut | |
| 700 | 1 | |a Ellebedy, Ali H |e verfasserin |4 aut | |
| 700 | 1 | |a Kollef, Marin H |e verfasserin |4 aut | |
| 700 | 1 | |a Mudd, Philip A |e verfasserin |4 aut | |
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