A Study to Learn About the Study Medicine Ibuzatrelvir in Adults With COVID-19 Who Are Severely Immunocompromised

This is a Phase 3, randomized, actively controlled, double-blinded, double-dummy, superiority study to evaluate the efficacy and safety of ibuzatrelvir alone and in combination with remdesivir IV compared to remdesivir IV alone for the treatment of symptomatic COVID-19 in severely immunocompromised adult participants who are non-hospitalized or are hospitalized for observation or study intervention administration but do not require supplemental oxygen for COVID-19.

The purpose of this clinical trial is to learn about a study medicine called Ibuzatrelvir for the possible treatment of COVID-19 in immunocompromised patients. Immunocompromised patients with COVID-19 have more difficulty fighting infections and are at risk for persistent infections and progression to severe illness. This patient population may benefit from extended antiviral treatment durations, or a combination of antiviral therapies. This study will evaluate the efficacy and safety of ibuzatrelvir with and without remdesivir compared with remdesivir alone for the treatment of symptomatic COVID-19 in adult participants who are severely immunocompromised. The study is seeking adult male and female participants who: * Have a confirmed COVID-19 infection * Are severely immunocompromised due to blood cancers, organ transplant, certain medications or therapies * Have experienced the onset of signs or symptoms of COVID-19 within the past 5 days and are currently experiencing at least one of them. All of the participants in this study will receive active treatment for COVID-19, and will be randomized to one of three treatment arms. One-third will received remdesivir, one-third will receive ibuzatrelvir, and one third will receive both remdesivir and ibuzatrelvir. Ibuzatrelvir will be taken by mouth twice daily, and remdesivir is given as an IV infusion daily. Placebos that look like the study medicines but do not have any medication will be given to make the 3 treatment arms appear to be the same. The study will compare the experiences of people receiving ibuzatrelvir with and without remdesivir to those of the people who only received remdesivir for COVID-19. This will help decide if ibuzatrelvir is safe and effective. Participants will attend about 10 study visits over 24 weeks. During this time, they will have: * visits at the study clinic * blood work * swabs of the nose that are collected in the clinic and also by participants at home * questionnaires

Inclusion Criteria: 1. 18 years of age or older at screening who are non-hospitalized or hospitalized for observation or with the intent of administering the study intervention. 2. Confirmed SARS-CoV-2 infection as determined by RAT (or other locally approved test) collected within 2 days prior to randomization. Initial onset of symptoms attributable to COVID-19 within 5 days prior to the day of randomization and at least 1 of the specified symptoms attributable to COVID-19 present on the day of randomization. 3. Severely immunocompromised due to: * Solid organ or islet cell transplant recipient who is receiving immunosuppressive therapy; * Active hematologic malignancy (eg, chronic lymphocytic leukemia, non-Hodgkin lymphoma, multiple myeloma, acute leukemia); * Receipt of CAR-T-cell therapy or HCT either within 2 years of transplantation or who are receiving immunosuppressive therapy; * Currently receiving or recently received B-cell depleting therapies (eg, rituximab), where the immunosuppressive effect is still ongoing. Exclusion Criteria: 1. Severe COVID-19, or current need for supplemental oxygen for treatment of COVID-19. 2. Receiving dialysis or have current kidney failure (ie, eGFR consistently \<15 mL/min/1.73 m2) 3. Active liver disease 4. History of hypersensitivity or other contraindication to any of the components of the study interventions, as determined by the investigator 5. Suspected or confirmed concurrent active systemic infection other than COVID-19 that may interfere with the evaluation of response to the study intervention. 6. Life expectancy less than 30 days at study entry due to an underlying condition, in the judgement of the investigator. 7. Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. 8. Has received any other antiviral for the treatment of the current COVID-19 infection 9. Current use of any prohibited concomitant medication(s) or unwillingness or inability to use a required concomitant medication(s). 10. Current or previous administration of an investigational product (drug or vaccine) within 30 days (or as determined by local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer). Authorized or products with conditional approval are not considered investigational. 11. Prior participation in this trial or any clinical trial of ibuzatrelvir. 12. Females who are pregnant, breastfeeding, or who are planning to become pregnant within the timeframe of the study. 13. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.