Pulmonary Inflammation in COVID-19 ARDS

Study Overview
=================
Brief Summary
-----------------
Patients older than 18 years of age, with COVID-19 related ARDS (C-ARDS) hospitalized in the ICU and invasively mechanically ventilated will be included in the study. This is an observational cohort study. After informed consent by the next of kin, and within the first 72 hours of invasive mechanical ventilation a blood and a Broncho Alveolar Lavage Fluid (BALF) sample will be collected. If the patients remain invasively mechanically ventilated a second and third blood and BALF sample will be collected every 7-10 days.

Detailed Description
-----------------
The main objective of the core study is to measure a number of biochemical, cellular and inflammatory mediators in the BALF of C-ARDS patients and evaluate their correlation with the course of disease in terms of respiratory mechanics, complications and outcomes. The mediators selected have been previously used in ARDS investigation to attempt prognostic and predictive enrichment. Patients hospitalized in the ICU following C-ARDS and requiring invasive mechanical ventilation will be candidates for enrollment. Patients enrolled in the study (Informed consent obtained from next of kin) will be subject to the realization of optic bronchoscopy within the first 72 h of mechanical ventilation to obtain BALF for analysis. A second and third bronchoscopy and sampling of BALF will be performed every 7-10 days if mechanical ventilation and the clinical conditions allow it. A sample of whole blood will be taken contemporary to each bronchoscopy in order to perform parallel measurements (lungs and peripheral blood). Patients will be followed up until hospital discharge. BALF samples will be divided to perform different analysis in the immunology, cytology and microbiology labs.

Official Title
-----------------
Pulmonary Inflammation Profiles in COVID-19 Related ARDS

Conditions
-----------------
ARDS Due to Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19 Acute Respiratory Distress Syndrome

Intervention / Treatment
-----------------
* Diagnostic Test: Bronchoalveolar lavage


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > 18 years old COVID-19 related ARDS Hospitalized in ICU Invasive mechanical ventilation Exclusion Criteria: Immunocompromised for previous condition transplanted patients Known pulmonary bacterial co-infection at the time of admission to the ICU Contraindication to the realization of Bronchoscopy (Itracranial Hypertension, severe hypoxaemia with P/F < 80, severe hemodynamic instability, severe arrhythmia, non correctable coagulopathy)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Bronchoalveolar lavage|Low volume Broncho alveolar lavage. During optic flexible bronchoscopy through the tracheal tube or the tracheostomy cannula a maximum of 4 aliquots of 20 ml normal saline will be instilled in a wedged position in the right medium lobe of the patients and then aspirated untill reaching a total of 25ml of fluid (BALF) for analysis|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Correlation of BALF and Blood mediators with ICU mortality | Up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory mechanics | Correlation of BALF and Blood mediators with respiratory mechanics during invasive mechanical ventilation | Day 0 (after study inclusion) and every day up to 3 months | 
| BALF PCR | Semiquant PCR of SARS-CoV-2 in bronchoalveolar lavage fluid, comparison with contemporary PCR in Blood | Day 0 (performance of first BALF sample) Day 8, Day 16 | 
| BALF characteristics | Cellular populations in BALF and their change over time | Day 0 (performance of first BALF sample) Day 8, Day 16 | 
| BALF cytoquines | Cytoquines in BALF and change over time | Day 0 (performance of first BALF sample) Day 8, Day 16 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ARDS, COVID-19, Broncho Alveolar Lavage, Pulmonary Inflammation, Mechanical Ventilation, Respiratory Mechanics