Compartmental Inflammation in Mechanically Ventilated Patients With COVID-19

Study Overview
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Brief Summary
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The aim of the present study is to examine the inflammatory response in the pulmonary compartment and blood of critically ill patients admitted to the ICU with COVID-19.

Detailed Description
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The mechanisms of the ARDS-like respiratory failure observed in patients with COVID-19 are currently unknown, but may be related to a distinct local immune response within the lung. In the present study, we will examine the cellular and humoral pulmonary immune response in mechanically ventilated patients admitted to the ICU with COVID-19 by examining immune cell profiles, cytokine patterns, and the complement pathway in bronchoalveolar lavage fluid, and relate it to the concomitant systemic inflammatory response. We will examine the patients on day 1-3 and 7-9 after ICU admission.

Official Title
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Early and Late Pulmonary and Systemic Inflammation in Critically Ill, Mechanically Ventilated Patients With Verified COVID-19

Conditions
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COVID-19, Respiratory Failure

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18y Mechanical ventilation Verified COVID-19 (throat swab or tracheal aspirate positive for SARS-CoV-2) ARDS according to the Berlin definition Exclusion Criteria: Untreated malignant tachycardia or bradycardia Suspected or verified intracranial hypertension (ICP > 15 mmHg) Unilateral lung ventilation Severe non-correctable coagulopathy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| White blood cell counts | Total white blood cells, neutrocytes, lymphocytes, and monocytes in bronchoalveolar lavage fluid and blood | Day 0 (subsequent to study inclusion in the ICU) | 
| White blood cell counts | Total white blood cells, neutrocytes, lymphocytes, and monocytes in bronchoalveolar lavage fluid and blood | Day 7 | 
| Lymphocyte populations | Cell populations and subpopulations evaluated by 10 colored flow cytometry (B cells, T cells, TCR subsets, Tregs/Th17, dendritic cells, myeloid cells and neutrophils) in bronchoalveolar lavage fluid and blood | Day 0 (subsequent to study inclusion in the ICU) | 
| Lymphocyte populations | Cell populations and subpopulations evaluated by 10 colored flow cytometry (B cells, T cells, TCR subsets, Tregs/Th17, dendritic cells, myeloid cells and neutrophils) in bronchoalveolar lavage fluid and blood | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytokines | Multiplex assay for measuring cytokines in bronchoalveolar lavage fluid and plasma (e.g. IL-1-beta, IL-1RA, IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-33, IL-35, TGF-beta, TNF-alpha, HMGB1) | Day 0 (subsequent to study inclusion in the ICU) | 
| Cytokines | Multiplex assay for measuring cytokines in bronchoalveolar lavage fluid and plasma (e.g. IL-1-beta, IL-1RA, IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-33, IL-35, TGF-beta, TNF-alpha, HMGB1) | Day 7 | 
| Lectin complement pathway | MBL, ficolin-1, ficolin-2, ficolin-3, and MASPs in bronchoalveolar lavage fluid and plasma | Day 0 (subsequent to study inclusion in the ICU) | 
| Lectin complement pathway | MBL, ficolin-1, ficolin-2, ficolin-3, and MASPs in bronchoalveolar lavage fluid and plasma | Day 7 | 
| Microorganisms | Growth of pathogenic microorganisms in body fluids (e.g. urine, blood, bronchoalveolar lavage fluid) | Up to 12 weeks | 
| Respiratory pathogens | Respiratory filmarray PCR for testing for pathogens | Day 0 (subsequent to study inclusion in the ICU) | 
| Respiratory pathogens | Respiratory filmarray PCR for testing for pathogens | Day 7 | 
| Ribosomal RNA in the airways | 16S ribosomal RNA (rRNA) and 18S rRNA PCR for bacterial or fungal pathogen identification in bronchoalveolar lavage fluid | Day 0 (subsequent to study inclusion in the ICU) | 
| Ribosomal RNA in the airways | 16S ribosomal RNA (rRNA) and 18S rRNA PCR for bacterial or fungal pathogen identification in bronchoalveolar lavage fluid | Day 7 | 
| Levels of SARS-CoV-2 in the airways | Semiquant PCR of SARS-CoV-2 in bronchoalveolar lavage fluid | Day 0 (subsequent to study inclusion in the ICU) | 
| Levels of SARS-CoV-2 in the airways | Semiquant PCR of SARS-CoV-2 in bronchoalveolar lavage fluid | Day 7 | 
| Surfactant in the airways | Measured in bronchoalveolar lavage fluid by fourier-transform infrared spectroscopy using the dipalmitoylphosphatidylcholine[DPPC]/spingomyelin[SM]) ratio | Day 0 | 
| Autoantibodies against type I IFNs in the airways | Measured in bronchoalveolarlavage fluid | Day 0 |