Ageing is the biggest risk for poor outcomes due to COVID-19. Approximately 58% of those hospitalised in Ireland are aged >65 and many require ICU. Ventilator-induced diaphragm dysfunction (VIDD) and muscle wasting are found in critically ill patients within 24h of initiation of mechanical ventilation and can persist beyond 12 months.
Elevated cytokine levels, immunosenescence and muscle weakness are common in older people. COVID-19 patients with severe ARDS show increased IL6 levels and macrophage activation and are often administered drugs inducing muscle relaxation during ventilation, further increasing risk of muscle wasting in survivors. Therefore, COVID-19 critical illness, especially in older people, is likely to lead to premature frailty and long-term disability, loss of independence, further hospitalisation and increased morbidity and mortality.
There is no effective treatment for muscle wasting. Muscle loss leading to frailty is an increasing socio-economic and healthcare challenge in our ageing population and is likely to become a public health priority in the light of the current pandemic.
This patient-oriented proposal addresses a medical priority of treating ICU-related diaphragm and muscle weakness and establishing biomarkers of muscle loss and frailty in COVID-19 survivors to personalise and improve patient recovery. It builds on our work demonstrating that microRNAs improve muscle strength in vivo and the levels of circulating microRNAs are predictors of muscle health in critically ill patients. This proposal will validate the use of miR-181 and antago-oxi-miR-378 to maintain diaphragm and muscle function following mechanical ventilation. The combination of COVID-19 patient data with pre-clinical models will provide pre-clinical proof-of-principle for microRNA-based interventions and biomarkers for clinical development. The successful outcome of this project may improve patient recovery post-ICU for COVID-19, reducing pressure on the healthcare system, critical in the current pandemic and for our ageing population. This proposal is of interest to international clinical and pharmaceutical stakeholders.
