PROJECT SUMMARY/ABSTRACT Acute respiratory distress syndrome (ARDS) is an often-fatal form of respiratory failure. Relevant to the recent coronavirus pandemic, the majority of patients with severe Coronavirus Disease of 2019 (COVID-19) develop ARDS and need mechanical ventilation and ICU admission, placing severe strains on the medical system. Use of mechanical ventilation (MV) during ARDS for cases such as COVID-19 is supportive until the infection has resolved which may take up to 20 days. While MV is useful for ventilation and supporting life, it causes severe atrophy of respiratory muscles that delays extubation. Furthermore, prolonged MV causes substantial morbidity and mortality (i.e. lung injury, pneumonia, laryngeal injury, etc.) Therefore, strategies to condition the respiratory muscles to prevent atrophy during intubation will likely decrease MV time, thereby decrease morbidity and mortality associated with MV, and decrease ventilator need and consumption of valuable resources. Strategies have been developed to condition or activate the diaphragm muscle during chronic high cervical spinal cord injury with implants that stimulate the phrenic nerve or diaphragm; however, such an invasive strategy is incompatible with the acute and temporary nature of ARDS. The main hurdle to accessing the neural network for breathing for therapeutic purposes is that the neural mechanisms controlling respiration reside deep in the brainstem, which is dangerous to access surgically. Recently, we elucidated a novel breathing pathway that can be modulated by stimulation of the spinal cord. We have compiled significant data demonstrating that this strategy can restore or augment breathing. The main objective of this project is to provide safety and feasibility data for this approach in patients with ARDS. The second objective is to provide proof of the concept that this strategy can improve respiratory function in ventilator-dependent patients and define the stimulation parameters that most effectively prevent respiratory muscle atrophy during MV. The deliverables for this project include establishing the safety and feasibility of transcutaneous spinal stimulation for respiratory rehabilitation in ARDS, preliminary efficacy data, refining the prototype design, and creating support for subsequent phases of device development.