Termination due to challenges related to the operational feasibility of the study, taking into account the current epidemiology and declining hospitalization rates for severe COVID-19.

A Study to Learn About the Medicine Called Nirmatrelvir Used in Combination With Ritonavir in People with Weakened Immune Systems or at Increased Risk for Poor Outcomes who are Hospitalized Due to Severe COVID-19

Inclusion Criteria:

• Meeting 1 of the 2 categories of COVID-19 risk:
• Category A: Immunocompromised
• Category B: Non-Immunocompromised, but with ≥2 risk factors
• Onset of signs/symptoms attributable to COVID-19 ≤10 days prior to the day of randomization for non-immunocompromised participants (Category B).
• Confirmed SARS-CoV-2 infection as determined by Reverse transcription polymerase chain reaction (RT-PCR) or acceptable test method performed by a health care provider in any specimen collected within 48 hours prior to randomization.
• Hospitalized for inpatient care for the treatment of clinical manifestations of severe COVID-19.
• Requirement for oxygen supplementation (via nasal cannula, mask, non-invasive ventilation [NIV] or high flow oxygen) to maintain SpO2 ≥94% at the time of Screening and Randomization.

Exclusion Criteria:

• Critical illness, defined by ≥1 of the following:
• Requirement for mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at randomization, or likely to require intermittent mandatory ventilation (IMV) or ECMO within 12 hours of randomization .
• Multi-organ dysfunction/failure.
• Hemodynamically unstable, eg. septic shock, cardiac failure or requiring vasopressors.
• Participant not expected to survive 24 hours from time of randomization.
• History of severe chronic liver disease
• Receiving dialysis of any kind or severe renal impairment
• Use of nirmatrelvir/ritonavir as an outpatient to treat the current COVID-19 related illness ≤7 days of randomization

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.