Despite the high clinical significance, there is limited knowledge of the management and treatment of COVID- 19. Patients with alcohol associated liver disease (ALD) and COVID-19 are at increased risk for severe disease, morbidity and mortality. There are also data that alcohol consumption increases during isolation, like that caused by social distancing measures enacted during the COVID-19 pandemic, therefore the incidence and severity of ALD is likely to increase. Current treatment approaches for patients with severe COVID-19 include antiviral agents and supportive care. In our preliminary and pilot studies we have observed sarcopenia or loss of skeletal muscle mass and impaired muscle strength in patients with ALD. Sarcopenia and accompanying contractile dysfunction contribute to longer hospital and intensive care stay, greater need for ventilatory support and poor outcomes in acute respiratory distress syndrome (ARDS), a hallmark of severe COVID-19. The ?cytokine storm? that occurs in patients with COVID-19 is accompanied by elevated circulating IL-6, and emerging data suggests that IL-6 inhibitors improve survival in patients with severe COVID-19. Despite the significant interest in IL-6 inhibitors with multiple ongoing clinical trials underway, these agents increase the risk for secondary infections (a common occurrence in COVID-19) and are contraindicated in those with significant elevated plasma transaminases. ?-hydroxy ?-methyl butyrate (HMB), a non-nitrogenous leucine metabolite with anabolic properties, also inhibits plasma IL-6 while improving muscle mass and contractile function. We therefore hypothesize that COVID-19 worsens clinical outcomes and muscle loss in ALD patients, and that reversal of muscle loss by HMB through an IL-6 dependent manner will improve clinical outcomes in ALD patients. This hypothesis will be tested through two interrelated, but independent specific aims: (1) establish the natural course of COVID-19 infection in patients with ALD by determining whether COVID-19 is more severe in ALD and whether COVID-19 worsens liver injury in ALD; (2) determine whether treatment with HMB improves the acute and long-term consequences of COVID-19 in terms of skeletal muscle mass, skeletal muscle function, and clinical outcomes in ALD patients. We will use clinical and biosamples to determine outcomes and responses to intervention targeting the skeletal muscle in these patients. We anticipate HMB will reduce inflammatory markers including circulating IL-6, improve clinical outcomes in-hospital, reverse sarcopenia, and improve long-term clinical outcomes. These human studies have the potential for immediate translation into clinical practice to rapidly improve immediate and long-term outcomes in ALD patients with COVID-19. These studies will supplement the applicant?s ongoing alcoholic hepatitis network grant supported by the NIAAA.
Patients with COVID-19 and comorbidities including alcohol associated liver disease (ALD) are at risk for severe illness and abrupt or sudden clinical deterioration with ventilatory failure. ?-hydroxy ?-methyl butyrate (HMB), a non-nitrogenous leucine metabolite with anabolic properties, increases muscle mass and contractile function and enhances immune function through IL-6 inhibitory dependent properties. We aim to study the natural course of COVID-19 in patients with ALD and test whether HMB can prevent ventilatory deterioration and improve short and long-term morbidity, mortality, and recovery from critical illness in symptomatic COVID-19 patients with ALD.
