Antisense Therapy to Block the Kallikrein-kinin Pathway in COVID-19

Inclusion Criteria: 1. Patients with COVID-19 who need supplemental oxygen 2. Women must not be pregnant or breastfeeding, and must be surgically sterile or in the postmenopausal stage (without risk of becoming pregnant). 3. Men must be surgically sterile or abstinent or, if they are having sex with risk of pregnancy, the subject must use an effective method of contraception from the moment they sign the informed consent form until at least 24 weeks after the dose of the study drug (ISIS 721744 or placebo). Exclusion Criteria: 1. Patients on invasive mechanical ventilation or who may need mechanical ventilation for the next 24 hours. The use of non-invasive ventilation and/or a high-flow nasal catheter is permitted. 2. Patients with \> 10 days since symptom onset or more than 48h of oxygen use 3. Pregnancy, breast-feeding or risk of becoming pregnant 4. Hemodynamically unstable (use of vasoconstrictors, such as norepinephrine, at any dose) 5. Previous diagnosis of heart failure at functional class III or IV 6. Previous uncontrolled hypertension (more than 3 drug classes use at home) 7. Severe lung disease (use of home oxygen) 8. Age \< 18 and \> 80 years 9. Physician and family not committed to full life support and/or with severe existing illness with a life expectancy of less than 12 months 10. Refusal to accept informed consent and/or unwillingness to comply with all requirements of the study procedure and security monitoring