Novel therapies are desperately needed for treatment of COVID-19 patients. At present, there are no proven interventions to prevent progression of the disease or to rapidly treat patients with COVID-19 related respiratory failure. Data on the original coronavirus -SARS pneumonia suggested that high dose (>160ppm) inhaled Nitric Oxide could have beneficial effects also on COVID-19, due to the genomic similarities between these two coronaviruses (1-3). This study will test whether high dose inhaled nitric oxide is safe and can reverse virus burden and respiratory failure in patients on mechanical ventilation.

Inclusion Criteria:

1. Confirmed infection with COVID-19 positive RT-PCR tracheal aspirate prior to treatment
2. Use of mechanical ventilation with or without ECMO
3. Male or female ages > 18 years
4. < 14 days from symptom initiation to study enrolment and < 7 days from intubation to study enrolment

Exclusion Criteria:

1. Patients on other interventional clinical trials
2. Subjects diagnosed with congestive or unstable heart disease including heart failure, left ventricular dysfunction (LVEF < 40 %) or myocardial damage, severe pulmonary hypertension and/or unstable hypertension
3. Subjects diagnosed with immunodeficiency
4. Hematology: patients with clinically significant anemia e.g. Hemoglobin < 100 and thrombocytopenia e.g. Platelets < 75
5. Subjects with clinically significant history of, or active bleeding including active pulmonary or gastrointestinal bleeding
6. Hepatic Function: Patients with abnormal liver function defined as any two of the following ALT >3x ULN, AST >3x ULN, Total bilirubin < 1.5 X ULN
7. Patient receiving drugs that have a contraindication with NO e.g. use of a nitric oxide donor agent such as nitroglycerin or drugs known to increase methemoglobin such as lidocaine, prilocaine, benzocaine or dapsone at screening as relevant to the proposed study population
8. Pregnancy
9. Subjects with a known hypersensitivity to methylene blue, subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency
10. Known or suspected thalassemia, sickle cell disease, or other conditions associated with poor oxygen carrying capacity