Impact and Sequelae of High Ventilatory Drive in Critically Ill COVID-19 Patients

Study Overview
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Brief Summary
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Critically ill COVID-19 patients with acute respiratory failure, in the intensive care unit (ICU), often feature high respiratory drive, determining large inspiratory efforts resulting in high pressures and global and regional over-distention, leading to lung injury. SARS-CoV-2 neurotropic-penetration in control centers in medulla oblongata might contribute to dysregulation and to excessively high respiratory drive observed in these patients. These pathophysiological conditions may often lead to the development of patient-ventilator asynchronies in aptients under mechanical ventilation, again leading to high tidal volumes and increased lung injury. These phenomena can contribute to prolonged duration of mechanical ventilation and ICU length of stay, but also can result in long term adverse outcomes like emotional/psychological and cognitive sequelae. All them compromising the quality of life of critically ill survivors after ICU discharge. The investigators will conduct a multicenter study in adult critically ill COVID-19 patients with hypoxemic respiratory failure, aiming to: 1) characterize incidence and clustering of high respiratory drive by developing algorithms, 2) apply artificial intelligence in respiratory signals to identify potentially harmful patient-ventilator interactions, 3) characterize cognitive and emotional sequelae in critically ill COVID-19 survivors after ICU discharge and 4) identify sets of genes and transcriptomic signatures whose quantified expression predisposed to asynchronies and cognitive impairment in critically ill COVID-19 patients.

Official Title
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Impact and Sequelae of High Ventilatory Drive in Critically Ill COVID-19 Patients With Acute Respiratory Failure Requiring High Flow Oxygen or Mechanical Ventilation: Mechanistic and Genomic Characterization Using Artificial Intelligence

Conditions
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COVID-19, Critical Illness, Hypoxemic Respiratory Failure, Neurocognitive Dysfunction, Mechanical Ventilation Complication

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults patients with hypoxemic respiratory failure. Admitted to ICU. Mechanical ventilation or high flow nasal cannula Exclusion Criteria: Neurologic patients with brainsteam affection.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COVID-19 Cohort<br>Patients with a diagnosis of moderate or severe pneumonia or ARDS secondary to COVID-19. | |
| Non COVID-19 Cohort<br>Patients with a diagnosis of moderate or severe pneumonia or ARDS not secondary to COVID-19. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory drive | To characterize the high respiratory drive phenomena in critically ill COVID-19 patients undergoing mechanical ventilation. | From day 1 at ICU until the day were the criteria of PaFi > 300 is met, up to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cluster of high respiratory drive | To describe the incidence and clustering of high respiratory drive throughout mechanical ventilation period by the development of specific algorithms. | From day 1 of mechanical ventilation until the day of mechanical ventilation discontinuation, up to 30 days | 
| Artificial intelligence algorithms | To apply artificial intelligence (machine learning, deep learning, pattern/image recognition and entropy) in physiologic respiratory signals to identify potentially harmful patient-ventilator interactions. | From day 1 of mechanical ventilation until the day of mechanical ventilation discontinuation, up to 30 days | 
| Neurocognitive disorders | To characterize cognitive and emotional sequelae in critically ill COVID-19 survivors at 1 month and 1 year after ICU discharge. | 1 month after ICU discharge and 1 year after ICU discharge | 
| Gene expression | Application of massive sequencing of gene expression and circulating micro-RNA in blood samples to identify sets of genes and c-miRNA whose quantified expression is related to ventilatory asynchronies and cognitive and emotional impairment in critically ill COVID-19 patients. | day 1 of ICU admission |