Multicenter Randomized Double-blind Placebo-controlled Study to Investigate Azvudine in Symptomatic Adults With COVID-19 at Increased Risk of Progressing to Severe Illness

Inclusion Criteria:

• (1) An age of 18 years or over (inclusive); (2) Not more than five days since thedevelopment of COVID-19 symptoms, and positive for nucleic acid or antigen test forCOVID-19 within five days before enrollment; (3) Presence of at least one symptomrelated to COVID-19 infection at the time of enrollment; (4) Agreement to practiceeffective birth control (for females of child-bearing potential); (5) Presence of atleast one high risk factor for severe COVID-19 infection:

• Age ≥ 60 years;

• BMI>25；

• Fever (body temperature ≥ 38℃) for ≥ 3 days;

• Current smokers (still being smoking within 30 days beforeenrollment and have used at least 100 cigarettes up to date);

• Immunosuppressive diseases, including but not limited to:myelosuppression or organ transplantation or primaryimmunodeficiency disease; prolonged use ofimmunosuppressive agents (≥ 20 mg/d for at least 14 days inthe case of prednisone within the last 30 days); biologictherapy (such as infliximab, etc.); use of immunomodulators (including but not limited to methotrexate, azathioprine,etc.); radiotherapy and/or chemotherapy for anymalignancies within 90 days (for chest radiotherapy, thistime interval should be more than 6 months);

• Chronic lung disease (such as asthma requiringintervention daily, bronchiectasis, COPD, pulmonaryhypertension, OSAS, interstitial lung disease, etc.);

• Hypertension; ⑧ Cardiovascular diseases (previously diagnosed as myocardial infarction orstroke, TIA (transient ischemic attack), cardiacinsufficiency, angina pectoris requiring nitratetherapy, CABG, post-PCI, post-carotidendarterectomy and aortic bypass surgery, etc.); ⑨ Type 1 or type 2 diabetes; ⑩ Neurodevelopmental abnormalities (such ascerebral palsy, Down's syndrome) or other geneticor metabolic syndromes and severe congenitalmalformations; ⑪ Active tumors (excluding localized skincancer); ⑫ No vaccination against COVID-19

Exclusion Criteria:

• (1) Known or suspected allergy to the components of Azvudine Tablets; (2) Patientsdiagnosed as severe or critical COVID-19 infection (Severe: 1. shortness of breathwith RR ≥ 30 breaths/min; 2. oxygen saturation ≤ 93% when inhaling air at rest; 3.partial pressure of arterial oxygen (PaO2) / fraction of inspired oxygen (FiO2) ≤ 300 mmHg; 4. progressive worsening of clinical symptoms, and obvious lesionprogression > 50% on lung images within 24 to 48 hours. Critical: 1. respiratoryfailure, requiring mechanical ventilation; 2. shock; 3. concomitant organ failure,requiring care in ICU); (3) Patients with severe liver disease (total bilirubin [TBIL] ≥ 2 × upper limit of normal (ULN), alanine aminotransferase (ALT) andaspartate aminotransferase (AST) ≥ 3 × ULN; (4) Patients with severe renalinsufficiency (glomerular filtration rate ≤ 60 mL/min/1.73 m2) or currently oncontinuous renal replacement therapy, hemodialysis, and/or peritoneal dialysis; (5)Patients with malabsorption syndrome or any other condition compromisinggastrointestinal absorption, or patients requiring parenteral nutrition or withdifficulty in taking the investigational product orally; (6) Known HIV infection; (7) Presence of diabetic ketosis or hyperosmolar hyperglycemic state (HHS); (8)Total neutrophil count < 750 cells/L; (9) Pregnant or lactating women or those whoplan to have a child during participation in this study and within six months afterthe end of this study; (10) Currently participating in another clinical trial orcurrently using another investigational product; (11) Presence of other activeinfections (must be etiologically confirmed) in addition to COVID-19 infection; (12)Presence of any comorbidities requiring hospitalization and/or a surgical procedurewithin 7 days prior to the start of this study or a comorbidity consideredlife-threatening within 30 days prior to the start of this study; (13) Patients whohave received or are expected to receive convalescent plasma for COVID-19; (14)Previous treatment with anti-viral agents that have been proved to be effectiveagainst COVID-19, including but not limited to Nirmatrelvir/Ritonavir orMolnupiravir (this criterion does not apply to use of glucocorticoids for reasonsother than COVID-19); (15) Other conditions that make it inappropriate for theparticipant to take part in this trial at the investigator's discretion.