In this study we propose to treat 560 patients with ramipril or placebo for 14 days. After an initial evaluation for COVID-19 status, medical history, and symptom assessment, patients will receive either 2.5 mg/day of ramipril or placebo. Patients' symptoms and study endpoints will be monitored at regular intervals. After 14 days, patients will undergo a laboratory assessment and an end-of-treatment follow-up visit at day 28. The primary endpoints of successful therapy will be improved survival, reductions in ICU admissions, and/or reductions in use of mechanical ventilator support.

Ramipril has not been studied in SARS-CoV-2 infected patients. In this study we propose to treat 560 patients with ramipril or placebo for 14 days. After an initial evaluation for COVID-19 status, medical history, and symptom assessment, patients will receive either 2.5 mg/day of ramipril or placebo. Patients' symptoms and study endpoints will be monitored at regular intervals. Additional follow-up will be performed at day 28. As an exploratory objective, biomarkers of the RAAS axis will also be monitored. The primary endpoints of successful therapy will be improved survival, reductions in ICU admissions, and/or reductions in use of mechanical ventilator support. Secondary endpoints will be the proportion of patients needing continued hospitalization, time to mortality, time to ICU admission, time to discharge from hospital, proportion of patients developing hypotension and needing pressor support, and proportion of patients developing septic shock.

Inclusion Criteria:

• Age ≥ 18 years
• Willing and able to provide written informed consent prior to performing study procedures
• Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test ≤ 5 days before randomization OR Clinical presentation consistent with COVID-19 infection (fever or cough or shortness of breath) with positive IgM serology
• Currently hospitalized or in an emergency department
• Peripheral capillary oxygen saturation (SpO2) ≥ 93% on room air at screening

Exclusion Criteria:

• Participation in any other clinical trial of an experimental treatment for COVID-19 (use of hydroxycholoroquine or compassionate use of choloroquine or azithromycin is allowed)
• Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 is prohibited < 24 hours prior to study drug/placebo dosing
• Requiring mechanical ventilation at screening
• Requiring ICU care at admission
• NSAID use within 12 hours of randomization or requiring continued NSAID use during this trial
• Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 X upper limit of normal (ULN)
• Estimated GFR < 40 mL/min
• History of serum creatinine ≥ 2 mg/dl in the previous 28 days
• Systolic BP < 100 mm hg or diastolic BP < 65 mm hg
• Hypersensitivity to ACEI
• History of angioedema
• Outpatient use of ACE inhibitor or Angiotensin II receptor blocker in the last 7 days
• History of renal artery stenosis
• Serum potassium ≥ 5.1 mEq/L
• Pregnancy or breastfeeding
• Use of aliskiren, amifostine, lithium, sacubitril within 7 days

28 Days