The main aim of this study is to evaluate the efficacy of S-217622 versus placebo among outpatient adults with mild and moderate COVID-19 starting intervention within 3 days of symptom onset.

Inclusion Criteria:

• Documentation of laboratory-confirmed active SARS-CoV-2 infection, as determined by a nucleic acid (for example, reverse-transcriptase PCR) or antigen test from any respiratory tract specimen (for example, oropharyngeal, NP or nasal swab, or saliva) collected ≤72 hours (3 days) prior to randomization.
• Participants are expected to begin study intervention ≤3 days from self-reported date of onset of any of the COVID-19-related symptoms from the following list:
• Cough
• Shortness of breath or difficulty breathing
• Feeling feverish
• Chills
• Fatigue
• Body pain or muscle pain or aches
• Diarrhea
• Nausea
• Vomiting
• Headache
• Sore throat
• Nasal obstruction or congestion
• Nasal discharge
• Loss of taste
• Loss of smell
• One or more of the following signs/symptoms present within 24 hours prior to randomization:
• Cough
• Shortness of breath or difficulty breathing
• Feeling feverish
• Chills
• Fatigue
• Body pain or muscle pain or aches
• Diarrhea
• Nausea
• Vomiting
• Headache
• Sore throat
• Nasal obstruction or congestion
• Nasal discharge
• Participants at higher risk of progression to severe COVID-19 are defined as follows:
• Age ≥65 years
• Age ≥18 with 1 of the following:
• Obesity (body mass index [BMI] ≥30 kilograms per square meter [kg/m^2]). Note: BMI is rounded to the nearest whole number, for example 29.5 kg/m^2 is rounded to 30 kg/m^2.
• Diabetes mellitus
• Hypertension requiring daily prescribed therapy
• Cardiovascular disease (requiring daily prescribed therapy or congenital heart disease)
• Chronic lung disease (for example, chronic obstructive pulmonary disease, moderate to severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension) requiring daily prescribed therapy
• Chronic kidney disease, defined as known current kidney impairment with a creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR) <60 milliliters (mL)/minute (min)/1.73 square meter (m^2) within the past 12 months prior to randomization, as long as the participant does not have known CrCl <30 mL/min by Cockcroft-Gault or require dialysis
• Down syndrome
• Sickle cell disease
• One of the following immunocompromising conditions or immunosuppressive treatments:
• Receiving chemotherapy or other therapies for cancer
• Hematologic malignancy (active or in remission)
• History of a hematopoietic stem cell or a solid organ transplant
• Human immunodeficiency virus infection: not on antiretroviral therapy or with cluster of differentiation 4+ cell count <200 cells per cubic millimeter
• Combined primary immunodeficiency disorder
• Taking immunosuppressive medications (for example, drugs to suppress rejection of transplanted organs or to treat rheumatologic and gastrointestinal conditions, such as anti-tumor necrosis factor agents, mycophenolate, and rituximab).

Note: Current use of some corticosteroids is exclusionary, due to concern for possible drug-drug interaction (DDI) with S-217622.

Exclusion Criteria:

• History of hospitalization for the current SARS-CoV-2 infection (that is, prior hospitalization for a prior episode of SARS-CoV-2 infection is allowable)
• For the current SARS-CoV-2 infection, any positive SARS-CoV-2 molecular (nucleic acid) or antigen test from any respiratory tract specimen (for example, oropharyngeal, NP, or nasal swab, or saliva) collected ˃72 hours (3 days) prior to randomization. Participants with reinfection, defined as prior SARS-CoV-2 infection that began >90 days prior to the current onset of symptoms with interval resolution of symptoms are eligible as long as the current infection has not been present for more than 3 days prior to randomization.
• Current need for hospitalization or immediate medical attention in the opinion of the investigator
• Current use of any medications prohibited with the study intervention. Individuals who have used Paxlovid or any other oral, inhaled, or injectable medication intended to treat the current SARS-CoV-2 infection before randomization are excluded. After randomization, locally available SARS-CoV-2 treatment (including but not limited to molnupiravir, mAbs, outpatient IV remdesivir, convalescent plasma, inhaled budesonide, favipiravir, and fluvoxamine) will be permitted, as long as there are no concerns for DDIs.

Note: Paxlovid use for a prior episode of COVID-19 is permitted.

• Receipt of any investigational treatments for the current episode of SARS-CoV-2 at any time prior to randomization is exclusionary. Note: This does not include drugs approved for other uses and taken for those indications or COVID-19 vaccines. Note: Use of locally authorized or approved therapies to prevent COVID-19, such as mAbs given solely to prevent COVID-19, are not exclusionary.
• Any co-morbidity requiring surgery within 7 days prior to randomization or that is considered life threatening in the opinion of the investigator within 28 days prior to randomization
• Known allergy/sensitivity or any hypersensitivity to components of S-217622 or placebo for S-217622
• Known (within 12 months prior to randomization) renal impairment defined as CrCl <30 mL/min by Cockcroft-Gault or requiring dialysis
• Known history of cirrhosis or liver decompensation (including ascites, variceal bleeding, or hepatic encephalopathy)
• Participants who have used any of the following drugs within 14 days prior to randomization:
• Strong cytochrome P453A inducer
• Products containing St. John's Wort