Title: Covid-19 model of acute sarcopenia recovery: investigating immune-muscle interactions.
Funder: The Academy of Medical Sciences

Abstract: The overarching aim of the study is to differentiate between individuals recovering from Covid-19 well and those recovering poorly and consider the differences related to muscle health and the interaction between the immune system and muscle regeneration. Covid-19 has had unprecedented effects over the last 6 months; it has resulted in significant mortality and morbidity including acute sarcopenia. Acute sarcopenia is defined as the changes in muscle mass and function within 28 days of a significant physiological stressor event. In collaboration with the PHOSP-COVID study I will conduct scientific experiments to determine the differences in muscle structure, regeneration and immune function between individuals who recover well from Covid-19 and those who recover poorly, showing evidence of frailty. Individuals in the PHOSP-COVID study will be extensively clinically characterised at 3 and 12 months post discharge from hospital. Muscle biopsies will be carried out in two selected groups of individuals: a cohort of individuals who have recovered well and a cohort of individuals who have not recovered well. Recovery will be described using sarcopenia, frailty and quality of life measures. Experimental analysis will focus on three key areas: muscle architecture, macrophage-muscle interaction and, local and systemic inflammatory environment. Muscle tissue will be stained appropriately to analyse cross-sectional area, proportion of type 1 and 2 fibres and muscle regeneration potential. mRNA expression of macrophage derived factors promoting muscle regeneration, pro and anti-inflammatory markers will be measured both in muscle tissue and serum. Immunostaining will be used to describe macrophage phenotype within the muscle.

Lay abstract: Covid-19 has had an unprecedented effect on life over the last 6 months. Primarily a disease of the respiratory system it also has multiple other health impacts. This has resulted in both a significant number of deaths and individuals with long-term, ongoing, health issues. One of these issues is ‘acute sarcopenia’. Acute sarcopenia is a term that describes loss of muscle mass and strength over a short period of time usually connected with illness or bed-rest. In collaboration with the PHOSP-COVID study, a study established to understand and improve long term health outcomes in Covid-19, we wish to investigate the differences between individuals who recover well from Covid-19 and those who do not. We will focus our investigation on muscle health in particular the muscle’s ability to regenerate and this relationship with the immune system. We will use available data from the PHOSP-COVID study to determine who to conduct more in depth analysis on including a muscle biopsy. We will conduct a number of experiments on the muscle tissue to decide whether there is a structural difference in the muscle of people who recover well from Covid-19 and those that don’t. We will also investigate the concentration of a protein secreted by immune cells within the muscle that promotes regeneration of the muscle and also the number and type of immune cells. We hope that we will be able to determine the differences in immune function and muscle regeneration in individuals with Covid-19 with good recovery and poor recovery.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: INFECTION;MUSCULOSKELETAL