Compartmental Inflammation in Mechanically Ventilated Patients With COVID-19 (COV2ICU-DK)

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; Respiratory Failure

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen
    • Hvidovre, Copenhagen, Denmark, 2650
      • Dept. of Intensive Care 542, University Hospital Hvidovre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Mechanically ventilated COVID-19 patients with ARDS included within 3 days of ICU admission

Description

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

Study Plan

How is the study designed?

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	ICU mortality	Up to 6 months
Mortality II	In hospital mortality	Up to 6 months
Blood markers of inflammation	C-reactive protein, procalcitonin, ferritin	Daily assessment in the ICU up to 12 weeks
Infiltrates on conventional chest x-ray	Number of participants with unilateral infiltrates or bilateral infiltrates and/or air bronchogram	Up to 12 weeks

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Investigators: Principal Investigator: Ronni R Plovsing, MD, PhD, Dept. of Intensive Care, University Hospital Hvidovre, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2020
• Primary Completion (Actual): January 10, 2022
• Study Completion (Actual): January 10, 2022

Study Registration Dates

• First Submitted: April 13, 2020
• First Submitted That Met QC Criteria: April 19, 2020
• First Posted (Actual): April 21, 2020

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: January 10, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Inflammation; Respiratory Insufficiency
• Other Study ID Numbers: COV2ICU-DK; H-20023159 (Other Identifier: Research Ethical Committee of The Capital Region of Denmark); R349-2020-540 (Other Grant/Funding Number: The Lundbeck Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No