Patient Inclusion Criteria

Inclusion Criteria 1. Hospitalized subjects 18 to 85 years of age, inclusive 2. Able and willing to sign informed consent 3. Molecular (RT-PCR) diagnosis of SARS-CoV-2 infection 4. Moderate or Severe illness per NIH COVID-19 Treatment Guidelines: "Moderate" Illness: - Symptoms such as cough, fever, sore throat, malaise, myalgias, headache; and - Evidence of lower respiratory tract disease by clinical assessment and/or imaging; and - SpO2 >93% on room air at sea level "Severe" Illness, including any of the following: - Respiratory rate >30 breaths/minute; or - SpO2 ≤93% on room air at sea level; or - Ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300; or - Lung infiltrates >50% of pulmonary volume on imaging 5. Female subjects must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of investigational product 6. Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use adequate methods of contraception during the study and through 90 days after the last dose of study medication. Female subjects of childbearing potential are all those except subjects who are surgically sterile, who have medically documented ovarian failure, or who are at least 1 year postmenopausal. 1. For females: 2 of the following contraceptive methods, with at least 1 being a barrier method: - Hormonal contraceptives for at least 27 days before dosing - Intrauterine device (IUD) in place at least 27 days before dosing - Double-barrier methods (use of condom [male partner] with either diaphragm with spermicide or cervical cap with spermicide) from screening - Surgical sterilization of the partner (vasectomy at least 1 month before screening) - Female subjects must have a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of investigational product. 2. For males: Surgical sterilization (vasectomy at least 1 month before screening) or double barrier methods.

Patient Exclusion Criteria

1. 1. "Critical" Illness, per NIH COVID-19 Treatment Guidelines, including any of the following: - Respiratory failure; or - Septic shock; or - Multiple organ dysfunction 2. Subjects who require mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3. Participation in another clinical trial concurrently 4. Concurrent treatment with immunomodulators or anti-rejection drugs 5. Nursing women, pregnant women, women of childbearing potential who do not want adequate contraception 6. History of any of the following diseases or conditions: - Advanced or decompensated liver disease (including presence or history of bleeding varices, ascites, encephalopathy, or hepato-renal syndrome) - Inability to swallow tablets, or gastrointestinal disease which could interfere with the absorption of piclidenoson - Any malignancy within 5 years before screening; exceptions are superficial dermatologic malignancies (e.g., squamous cell or basal cell skin cancer treated with curative intent) - Cardiomyopathy, significant ischemic cardiac or cerebrovascular disease (including history of angina, myocardial infarction, or interventional procedure for coronary artery disease), or cardiac rhythm disorder - QTcF interval on an average of triplicate ECGs >450 milliseconds (msec) for males or >470 msec for females (except when QT prolongation is associated with right or left bundle branch block, in which case enrollment is allowed) - Any condition which increases proarrhythmic risk, including hypokalemia, hypomagnesemia, congenital Long QT Syndrome - Ongoing or planned use of a concomitant medication that is on the CredibleMeds list of drugs known to cause Torsades de Pointes unless the subject can be screened and monitored under the guidelines proposed by Giudicessi (2020) - Pancreatitis - Severe or uncontrolled psychiatric disorder, e.g., depression, manic condition, psychosis, acute and/or chronic cognitive dysfunction, suicidal behavior, and relapse of substance abuse - Active seizure disorder defined by either an untreated seizure disorder or continued seizure activity within the preceding year despite treatment with anti-seizure medication - Bone marrow or solid organ transplantation - Any serious condition that, in the opinion of the investigator, would preclude evaluation of response or make it unlikely that the contemplated course of therapy and follow-up could be completed 7. Any of the following abnormal laboratory tests: - Platelet count <90,000 cells/mm3 - Absolute neutrophil count (ANC) <1,500 cells/mm3 - Estimated creatinine clearance (CrCl) <50 mL/min by Cockroft-Gault formulation - Bilirubin level ≥2.5 mg/dL unless due to Gilbert's syndrome - AST or ALT level ≥3X the upper limit of normal - Serum albumin level <3.0 g/dL - International normalized ratio (INR) ≥1.5 (except subjects maintained on anticoagulant medications)