Are changes in skeletal muscle mitochondrial respiratory capacity responsible for lactate release and loss of vascular regulation in sepsis and COVID-19?

Lactate is an important energy source which is utilized by muscle, heart, and brain tissue. Blood lactate is frequently elevated in patients with sepsis or septic shock, where high lactate is predictive for mortality. In patients with COVID-19, however, even severe pneumonia is typically associated with only a small increase in lactate, and in these patients circulating lactate dehydrogenase (LDH; enzyme responsible for converting lactate to pyruvate) is elevated to the extent that it is related to disease severity and even mortality. These observations have led to the hypothesis that the muscle's ability to produce energy is impaired in sepsis but may be normal or even exaggerated in COVID-19. The results of this work may significantly change our perception of cardiovascular regulation in critically ill patients with sepsis and COVID-19 and may guide future therapies or prevent potentially harmful interventions; for example, excessive fluid administration with the purpose of normalizing lactate. The muscle's ability to utilize lactate and an explanation for the high LDH levels are not well described in COVID-19; therefore, by use of state-of-the-art research techniques, this study will explain where lactate is being taken up (muscle, heart, or lungs). This translational work may help explain the muscle fatigue experienced by COVID-19 and septic patients after critical illness. This study will utilize a high-quality research design with gold-standard measurement techniques in specific patients of interest with direct relevance to Canadian public health and treatment strategies for sepsis and COVID-19. As sepsis-induced multiple organ failure is a major cause of mortality and morbidity in critically ill patients, this study is necessary and of high importance. In view of the recent COVID-19 pandemic, the overwhelming strain on intensive care units worldwide places high priority for experimental studies that will optimize efficiency of critical care patient treatment.