Skeletal Muscle Wasting in SARS-CoV-2 Infected ICU (Intensive Care Unit) Patients
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Cachexia
- Sponsor
- Hasselt University
- Enrollment
- 22
- Locations
- 1
- Primary Endpoint
- Skeletal muscle biopsy
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The SARS-CoV-2 pandemic causes a major burden on patient and staff admitted/working on the intensive care unit (ICU). Short, and especially long admission on the ICU causes major reductions in skeletal muscle mass (3-4% a day) and strength. Since it is now possible to reduce mortality on the ICU, short and long-term morbidity should be considered another principal endpoint after SARS-CoV-2 infection. Cachexia is defined as 'a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle mass'. Its clinical features are weight loss, low albumin, anorexia, increased muscle protein breakdown and inflammation. There is strong evidence that cachexia develops rapidly in patients hospitalized for SARS-CoV-2 infection, especially on the ICU. Several mechanisms are believed to induce cachexia in SARS-CoV-2. Firstly, the virus can interact with muscle cells, by binding to the angiotensin converting enzyme 2 (ACE-2). In vitro studies have shown the virus can cause myofibrillar fragmentation into individual sarcomeres, in addition to loss of nuclear DNA in cardiomyocytes. Similar results were found during autopsies. On a cellular level, nothing is known about the effects of SARS-CoV-2 infection on skeletal muscle cells. However, up to 19.4% of patients present with myalgia and elevated levels of creatine kinases (>200U/l), suggesting skeletal muscle injury. Moreover, patients with SARS-CoV-2 infection are shown to have elevated levels of C-reactive protein and other inflammatory cytokines which can all affect skeletal muscles. The above mentioned factors are not the only mediators by which skeletal muscle mass might be affected in SARS-CoV-2. There are other known factors to affect skeletal muscle mass on the ICU, i.e. immobilization and mechanical ventilation, dietary intake (anorexia) and inflammatory cytokines. SARS-CoV-2 infection in combination with bed rest and mechanical ventilation can lead to severe muscle wasting and functional decline resulting in long-term morbidity.
Until know there are no studies investigating acute skeletal muscle wasting in patients infected with SARS-CoV-2 and admitted to the ICU. As a result, there is a need of more in-depth understanding the effects of SARS-CoV-2 infection on muscle wasting. An optimal characterization of these effects may lead to improvement in morbidity and even mortality in the short and long term by the establishment of evidence-based rehabilitation programs for these patients.
Investigators
Frank Vandenabeele
Principal Investigator
Hasselt University
Eligibility Criteria
Inclusion Criteria
- •Age \>18 years
- •SARS-CoV-2 infection
- •Expected stay to ICU of \> 7 days
Exclusion Criteria
- •Spinal cord injury
- •Chronic use of corticosteroids before hospital admission
Outcomes
Primary Outcomes
Skeletal muscle biopsy
Time Frame: Day 7
A muscle biopsy of the m. vastus lateralis will be obtained at T4, after admission on ICU to evaluate the effects of SARS-CoV-2 infection and ICU admission on skeletal muscle fiber characteristics Muscle biopsy samples will be obtained using a minimally invasive (Bard® Mission® Core Biopsy Instrument (14G 10mm needle)) biopsy technique, under local anaesthesia
Electrophysiological test
Time Frame: Day 7
Electrophysiological test will be performed at T0 and T1. For nerve conduction studies, one standard motor and one sensory nerve will be evaluated in both upper and lower limbs unilaterally. We define reduced CMAP and SNAP when below the lower limit of normal in both nerves of both limbs. Needle electromyography in rest will be performed unilaterally in one standard proximal and distal muscle in both upper and lower limbs. Abundant SEA was defined as the presence of sustained fibrillation potentials and/or positive sharp waves in at least two muscles of at least two limbs.
Secondary Outcomes
- Mechanical ventilation and oxygen therapy(daily between baseline and day 7)
- Comorbidities(baseline)
- Dietary intake(daily between baseline and day 7)
- Duration from hospital admission to ICU admission(baseline)
- concommitted medication(daily between baseline and day 7)
- Skeletal muscle biopsy(Day 7)
- Blood sample analyses(daily between baseline and day 7)
- APACHE II score(day 7)
- Symptoms of disease onset and myalgia(baseline)