Background: Myeloid hyperinflammation leading to T-cell immune suppression and lymphocytopenia is a hallmark of severe COVID-19. Granulocyte macrophage-colony stimulating factor (GM-CSF) neutralization may prevent myeloid driven T-cell suppression leading to increased lymphocyte counts in patients with COVID-19. Given the dual mechanism of action, lenzilumab (anti-human GM-CSF monoclonal antibody) may reduce myeloid driven hyperinflammation and improve CD8+ antiviral T-cell responses directed at SARS-Cov-2 reducing the morbidity, mortality, need for invasive mechanical ventilation (IMV) and duration of hospitalization. Methods: Hospitalized subject with confirmed COVID-19 pneumonia and established risk factors for poor outcomes was treated in the ICU for 12 weeks using standard supportive care for chronic acute respiratory distress syndrome (ARDS). An emergency single-use investigational new drug application (IND) was approved for lenzilumab 600 mg, administered intravenously every eight hours for a total of three doses. Patient characteristics, clinical and laboratory outcomes, and adverse events were recorded through duration of hospitalization. Results: 77-year-old Caucasian male with past medical history of severe chronic obstructive pulmonary disease (COPD) with emphysema, coronary artery disease, type II diabetes, and obstructive sleep apnea admitted to ICU with fever, shortness of breath and confirmed SARS-CoV-2 infection. Patient was treated with standard supportive care including corticosteroids. Over the course of his ICU stay, the patient developed ARDS and on week 13, and after several unsuccessful attempts at oxygen weaning, lenzilumab was administered via emergency single use IND. One-week post lenzulimab therapy, oxygen demands decreased, lymphopenia appeared to improve and sixteen days post lenzulimab therapy, the patient was discharged home on 4L nasal cannula. No infusion-related or systemic side effects were noted. Conclusion: In a case of COVID-19 with multiple co-morbidities, refractory to corticosteroids, and deteriorating for several months, GM-CSF neutralization with lenzilumab appeared to reduce oxygen requirements, improve lymphopenia and accelerate time to recovery/discharge in a COVID-19 subject. A randomized, double-blind, placebo-controlled phase 3 clinical trial is ongoing to validate these findings (NCT04351152).