Intensive Care Associated Complications and Outcome of Acute Respiratory Distress Syndrome Due to COVID-19

Study Overview
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Brief Summary
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COVID-19 patients with a severely symptomatic progression with development of an Acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 need prolonged intensive care treatment involving pharmacological immobilization, sedation and mechanical ventilation, leaving them at a very high risk for developing Critical illness myopathy (CIM). CIM is associated with increased mortality and significant consequences for recovery and the ability to return to normal daily life. Up to date, there are no studies investigating the mid- or long-term course of the novel COVID-19 disease. The present study therefore aims to evaluate the clinical outcome of patients with ARDS due to SARS-CoV-2 with special attention to the development of CIM and its underlying causes. To provide the possibility of early diagnosis of CIM, critically ill patients will be regularly screened for muscle membrane alterations using (Muscle velocity recovery cycles) MRVC measurements. The primary endpoint is the incidence of CIM in patients with ARDS due to SARS-CoV-2, diagnosed according to the current diagnostic criteria.

Detailed Description
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COVID-19 patients with a severely symptomatic progression with development of an ARDS due to SARS-CoV-2 need prolonged intensive care treatment involving pharmacological immobilization, sedation and mechanical ventilation, leaving them at a very high risk for developing CIM. CIM is associated with increased mortality and significant consequences for recovery and the ability to return to normal daily life. Up to date, there are no studies investigating the mid- or long-term course of the novel COVID-19 disease. The present study therefore aims to evaluate the clinical outcome of patients with ARDS due to SARS-CoV-2 with special attention to the development of CIM and its underlying causes. To provide the possibility of early diagnosis of CIM, critically ill patients will be regularly screened for muscle membrane alterations using MRVC measurements. Objective: The primary objective of this project is to prospectively evaluate the incidence and severity of CIM in patients with ARDS due to SARS-CoV-2. The secondary objectives of this project include: To assess the quality of life of patients with and without CIM after ARDS due to SARS-CoV-2. To monitor changes in muscle excitability parameters in critically ill patients with ARDS due to SARS-CoV-2 in relation to a later confirmed diagnosis of CIM according to the current standards. To explore underlying pathophysiological processes for CIM (mitochondrial dysfunction, medication e.g. Neuromuscular blocking agents (NMBA), sedative drugs, and metabolic (amino acids, inflammatory parameters)). Method: After enrolment in the study, patients will be examined for the first time within 24 hours after admission to the ICU, and follow-up visits will be performed at day 2, 5 and 10 or upon termination of therapy with NMBA, respectively. The endpoint will be at the clinical follow-up appointment.

Official Title
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Characterization of ARDS, Critical Illness Myopathy and Their Long-term Consequences in Patients With Covid-19 Disease: Effects of Inflammation, Mitochondrial Dysfunction and Plasma Concentrations of Various Sedative Drugs

Conditions
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COVID, Corona Virus Infection, Sars-CoV2

Intervention / Treatment
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* Procedure: Study Arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent as documented by a surrogate assessment by an independent physician Adult ICU Patients with ARDS due to SARS-CoV-2 requiring mechanical ventilation Exclusion Criteria: Age <18 years and > 80 years Pregnancy and breast feeding The presence of pre-existing: Known (at time of inclusion) Polyneuropathy, Known (at time of inclusion) Guillain-Barré syndrome, Known (at time of inclusion) Acute or chronic spinal cord lesion, Known (at time of inclusion) Myasthenia gravis, or Known (at time of inclusion) Myopathy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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

| Intervention/Treatment |
| --- |
|Procedure: Study Arm|First inpatient examination (within 24 hours after admission to ICU): Clinical examination Laboratory tests, Biobanking, Mitochondrial function testing Neurophysiological examination (MVRC recording) Follow-up inpatient examinations (day 2, 5 and 10 after admission): Clinical examination Laboratory tests, Biobanking, Mitochondrial functions testing Neurophysiological examination (MVRC recording) Day 10 only: Extended neurophysiological examination according to diagnostic criteria Day 10 only: Grading of muscle strength (Medical Research Council (MRC) system) Follow-up outpatient examination (after discharge from intensive care): Clinical examination Grading of muscle strength (MRC) Modified Rankin Scale (mRS) Barthel Scale Questionnaires (Short Form (36) Health Survey, Essener Questionnaire for Coping with a Disease and Beck's Depression Inventory II)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short Form (36) Health Survey (SF-36) | Short Form (36) Health Survey (SF-36) | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Mortality | 90 days | 
| Modified Rankin Scale (mRS) | Modified Rankin Scale (mRS); (0=no Symptoms at all, 6=dead) | 90 days | 
| Duration of mechanical ventilation in days | Duration of mechanical ventilation in days | 3 months | 
| Barthel Index | Barthel Index (80-100= patient should be able to live independently, <20=total dependence) | 3 months | 
| Beck's Depression Inventory II (BDI-II) | Beck's Depression Inventory II (BDI-II) | 3 months | 
| Essener Questionnaire for Coping with a Disease (EFK) | Essener Questionnaire for Coping with a Disease (EFK); (0=no burden of disease, 180-strong burden of disease) | 3 months | 
| Number of patients with Critical Illness Myopathy | Number of patients with Critical Illness Myopathy | day 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Corona, SARS-CoV2, ARDS, PICS