∙ The main inclusion criteria include but are not limited to the following:

• Is an individual of any sex/gender, ≥18 years of age

• Has documentation of SARS-CoV-2 infection with sample collection ≤4 days prior to randomization

• Has initial onset of signs/symptoms attributable to COVID-19 for ≤4 days prior to the day of randomization and ≥2 of the following signs/symptoms attributable to COVID-19 on the day of randomization: cough, sore throat, nasal congestion, shortness of breath or difficulty breathing with exertion, muscle or body aches, fatigue, fever \>38.0°C or chills, nausea or vomiting or diarrhea, change in sense of smell or change in sense of taste, or headache

• Has ≥1 of the following characteristics or medical conditions associated with the highest risk of severe illness from COVID-19:

‣ Advanced age of ≥75 years of age

⁃ Immunocompromised

⁃ Neurocognitive or physical disability

⁃ Has ≥3 characteristics or medical conditions which increase the risk of severe illness due to COVID-19 (e.g., chronic lung disease, obesity with body mass index (BMI) ≥35, diabetes)

• Is unable or unwilling to receive treatment with nirmatrelvir/ritonavir (NMV/r) due to 1 or more of the following:

‣ Is receiving drug(s) highly dependent on cytochrome P450 3A (CYP3A) for clearance and for which elevated concentrations are associated with serious and/or life-threatening consequences or drug(s) with a clinically significant drug-drug interaction for which co-administration is not possible

⁃ Is receiving potent CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance

⁃ Has severe hepatic impairment

⁃ Has experienced prior adverse reactions or hepatotoxicity to NMV/r that would preclude future use

⁃ Has known or suspected NMV/r resistance

⁃ Has uncontrolled HIV infection

⁃ NMV/r is not approved/authorized in the participant's country or it is not accessible to participant (e.g., drug shortage)

⁃ Is unwilling to receive treatment with NMV/r

∙ Inclusion note: Participants may receive remdesivir as standard of care in addition to molnupiravir or placebo. If remdesivir is available and clinically appropriate per local clinical practice, investigators will aim to ensure that those who are most vulnerable to severe COVID-19 receive timely access to remdesivir as standard of care on this study.