Investigating the Impact of COVID-19 Infection on Skeletal Muscle
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Covid19
- Sponsor
- University of Nottingham
- Locations
- 1
- Primary Endpoint
- The difference in mitochondrial function between levels of ventilation support required in COVID-19 patients
- Status
- Withdrawn
- Last Updated
- 2 years ago
Overview
Brief Summary
With the recent worldwide outbreak of the COVID-19 infection and the huge impact it has had upon lives in the UK, it is key to increase knowledge on the impact of the virus on the body. Certain aspects of the virus' characteristics are also poorly understood: The reason behind the variation in response between individuals, and the long-term impacts of infection upon the body. It is already known from previous research that muscle-health plays an important role in health, with other illnesses known to have an impact upon muscle health. A large number of studies have investigated the relationship between muscle and health, with an increasing focus upon the impact upon the mitochondria within the muscle cells. Mitochondria are the energy-producing component of a cell and are vital not just for the muscle-cells but for the body as a whole.
The researchers hope that by investigating the impact of COVID-19 infection upon human skeletal muscle, the question of why individuals have different responses to the infection and the mechanism of the longer-term impact of infection can be answered. This added knowledge will then, hopefully, be able to guide therapy targets in the future.
Detailed Description
Since the outbreak of the COVID-19 pandemic worldwide, there have been over 50,000 deaths and over 1million infections in the UK alone. It has been widely reported that infection with COVID-19 leads to large variation between individuals, a large number appear asymptomatic or mild flu-like symptoms compared to a percentage requiring intensive care support and for some, the infection is ultimately fatal. The reason behind this variation is not yet fully understood. With COVID-19 likely to have a lasting impact within the UK and on the NHS, any research that improves our knowledge upon the effect of the infection has the possibility to improve therapy targets and hopefully improve patient outcomes. With how novel the COVID-19 pathogen is, little is currently known about the potential long-term impacts of infection upon individuals. There are currently many reports of longer-term syndromes following infection with COVID-19 including loss of smell and myalgia. The researchers hope that investigating the impact upon patients over the 12-months following their infection will gather information on the long-term impacts and potentially find evidence of the reason for these longer-term symptoms. With skeletal muscle being one of the largest components of the human body, any impact upon its function is likely to have a significant impact upon an individual. With it being vital for not only locomotion but also in energy production for the body. The researchers hypothesize that changes within the skeletal muscle may account for some of the impacts of COVID-19 infection. The investigators hope that by investigating changes in muscle structure, muscle mitochondrial function, and neurological supply to the muscle they can identify a future therapy target to improve outcomes from COVID-19 infection. To investigate this, this study plans to recruit participants with confirmed COVID-19 infection requiring varying levels of oxygen support (Oxygen therapy only n=12, Non-invasive ventilation n=12) and a control group of non-covid community-acquired pneumonia requiring oxygen therapy (n=12). All groups will undergo the same investigations, and no interventions will form part of the study. Investigations will be carried out at 24-72hours of acute hospital admission, with follow-up assessments at 6-months and 12-months post-discharge. The assessments performed will include: muscle biopsy of the vastus lateralis muscle, an ultrasound scan of the vastus lateralis muscle, voluntary and stimulated iEMG of VL, and hand-grip strength analysis.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Confirmed COVID-19 infection as confirmed by PCR swab, or being treated for non-COVID-19 community acquired pneumonia
- •A minimum of oxygen treatment required for 24hours.
- •Capacity to give informed and written consent
Exclusion Criteria
- •A BMI \<16.5 or \>35 kg/m2
- •Active cardiovascular disease:
- •Significant arrhythmia
- •Recent acute coronary event
- •Cerebrovascular disease:
- •Recent stroke
- •Respiratory disease including:
- •Pulmonary hypertension
- •Significant COPD
- •Uncontrolled asthma
Outcomes
Primary Outcomes
The difference in mitochondrial function between levels of ventilation support required in COVID-19 patients
Time Frame: each of the 3 time points assessed: the acute admission, as well as in the recovery phases - 6 month and 12 month follow up
Assessment of skeletal muscle mitochondrial oxidative phosphorylation rate assessed using high-resolution respirometer between the 2 groups of ventilatory support in COVID-19 patients (Oxygen only support, non-invasive ventilation). Expressed as a ratio of maximal oxygen consumption.
The changes in mitochondrial function during the recovery period from COVID-19
Time Frame: Comparison over the 3 time periods: acute admission, 6month and 12 month follow up
Assessment of skeletal muscle mitochondrial oxidative phosphorylation rate using high-resolution respirometer expressed as a percentage change over the time period in each group
The difference in mitochondrial function between COVID-19 infection and control group
Time Frame: This will be assessed in each of the 3 time points: the acute admission assessment, as well as in the recovery period of 6-month and 12-month follow up
Assessment of skeletal muscle mitochondrial oxidative phosphorylation rate between COVID-19 associated illness and Control group (non-covid community-acquired pneumonia). This will be assessed by measuring oxygen consumption using a high-resolution respirometer and expressed as a ratio of maximal rate.
Secondary Outcomes
- The difference in muscle macroscopic structure between the groups(This will be assessed in each of the 3 time points: the acute admission assessment, as well as in the recovery period of 6-month and 12-month follow up)
- Difference in the neurological supply of skeletal muscle(This will be assessed in each of the 3 time points: the acute admission assessment, as well as in the recovery period of 6-month and 12-month follow up)
- Difference in muscle function(This will be assessed in each of the 3 time points: the acute admission assessment, as well as in the recovery period of 6-month and 12-month follow up)