The goal of this single center, double-blinded, placebo-controlled, and randomized Phase 1 trial is to determine if i.v. citicoline is safe and efficacious compared to i.v. saline/control in adults presenting with SARS CoV-2 infection complicated by acute hypoxemic respiratory failure. The main questions it aims to answer:

• Is citicoline safe in this patient population?
• Does citicoline have a benefit in terms of improving oxygenation?
• Does citicoline reduce overall severity of illness as reflected by standardized scales.

Patients will be assigned to i.v. treatment with citicoline or saline twice daily for 5 consecutive days. SpO2/FiO2 ratios will be recorded daily as per standard clinical practice to compare citicoline treatments at three different doses to placebo.

SCARLET is a single center, double-blinded, placebo-controlled, and randomized Phase 1 trial of i.v. citicoline in adult patients of any sex, gender, age, or ethnicity who are present with acute hypoxemic respiratory failure due to SARS CoV-2 infection. The goals are safety over a range of doses based on the number of treatment related adverse events as assessed by CTCAE v.5, and demonstration of efficacy as reflected by SpO2/FiO2 measured at day 3 in hospitalized COVID infected patients with acute hypoxemic respiratory failure, as defined by requiring at least 4 liters nasal cannula oxygen supplementation to maintain the SpO2 above 90%. The trial will enroll 20 patients per dose for 3 citicoline doses (1, 5, and 10 mg/kg/day) along with 20 placebo-treated controls.

1. The subject or their authorized representative must be able to understand and provide informed consent
2. Adult patients (≥18 years)
3. Laboratory-confirmed SARS-CoV-2 infection within the 10 days prior to randomization
4. Admitted to OSU East or OSU Main for acute respiratory failure (on at least 4 LPM oxygen)
5. C-reactive protein (CRP) > 32 mg/l
6. Adequate i.v. access available (either peripheral or central venous access)
7. Female subjects of childbearing potential must have a negative pregnancy test upon study entry

Exclusion Criteria:

1. Subjects who are unable or unwilling to give written informed consent or to comply with study protocol and who have no legal authorized representative available to give consent on their behalf
2. Individuals being treated with extracorporeal membrane oxygenation (ECMO)
3. Subjects who, in the clinicians estimation, will be unlikely to survive the protocol duration due to imminent and unavoidable risk of death
4. Individuals with hypertonia of the parasympathetic nervous system
5. Prisoners
6. Children (<18 years)
7. Women who may be pregnant, are pregnant, or have plans to become pregnant
8. Women who are breast feeding
9. Individuals with a known allergy to citicoline
10. Subjects that are taking medications that contain L-Dopa, centrophenoxine, or meclofenoxate
11. Subjects with past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the principal investigator (PI), may pose additional risks from participation in the study or that may impact the quality or interpretation of the data obtained from the study.