DisCoVeRy is a randomized controlled trial among adults (≥18-year-old) hospitalized for
COVID-19. This study is an adaptive, randomized, open or blinded, depending on the drug to be
evaluated, clinical trial to evaluate the safety and efficacy of possible therapeutic agents
in hospitalized adult patients diagnosed with COVID-19. The study is a multi-centre/country
trial that will be conducted in various sites in Europe with Inserm as sponsor. The study
will compare different investigational therapeutic agents to a control group managed with the
SoC including corticosteroids and anticoagulants. There will be interim monitoring to allow
early stopping for safety and to introduce new therapies as they become available. If one
therapy proves to be superior to others in the trial, this treatment may become part of the
SoC for comparison(s) with new experimental treatment(s).

In previous versions of the DisCoVeRy protocol, remdesivir, lopinavir/ritonavir with or
without interferon ß-1a and hydroxychloroquine were evaluated as potential treatments for
COVID-19. These treatments have been discontinued based on analyses review by both DSMC/DSMB,
the Solidarity Executive Group and the DisCoVeRy steering committee.

This version of the protocol, therefore, describes a randomized blinded placebo-controlled
trial among adults (≥18-year-old) hospitalized for COVID-19 that randomly allocates them (1:1
ratio) between 2 arms: SoC + placebo versus SoC + AZD7442.

Randomization will be stratified by region (according to the administrative definition in
each country), antigenic status (positive or negative) obtained from the result of a rapid
antigen test on nasopharyngeal swab performed at enrolment and vaccination initiation (yes if
at least one injection of any vaccine against SARS-CoV-2 was reveived prior to enrolment
whatever the delay or no).

The primary analyses will be conducted on patients with antigen-positive results. A positive
antigenic test is evidence of high viral shedding consistent with a recently started or
uncontrolled infection. Overall, the number of antigen-negative patients will be at most 30%
of all included subjects. The number of patients with vaccination (partly or fully) will be
limited to 20% of all participants, split evenly between antigen positive and antigen
negative patients (i.e. vaccinated patients can make up at most 20% of antigene positive
patients and 20% of antigene negative patients). Sensitivity analyses will be performed in
all patients, stratified by antigenic status and vaccination initiation.

A global independent data and safety monitoring board (DSMB) monitors interim data to make
recommendations about early study closure or changes to conduct, including adding or removing
treatment arms. However, the current version of the protocol does not allow for efficacy or
futility analysis, and the ability to add trial arms will be limited by the study being
blinded and placebo-controlled during the investigation of AZD7442.

All subjects will undergo a series of efficacy and safety assessments, including laboratory
assays.

Subjects will be assessed at baseline, and at Days 3, 8 and 15 while hospitalized. Patients
will be contacted by phone at Day 15 for evaluation of the Primary Endpoint if they have been
discharged prior to Day 15-, and 14-days following hospital discharge for efficacy
assessment.

Further follow-up assessments will be organized at Days 29, 90, 180, 365 and 456.

If discharged from the hospital, days 29 and 90 assessments will be organized as outpatients'
consultations for all. For Days 180 and 365 assessments, a subset of 25% of patients enrolled
in centers with available resources and selected at Day 90 will be evaluated during a medical
consultation, while the other will be contacted by phone. For Day 456, all patients will be
contacted by phone.

Nasopharyngeal swabs (NP) or lower respiratory tract samples will be obtained at baseline
(Day 1 pre-treatment) and at Days 3, 8, 15 (while hospitalized) and 29 (while hospitalized
or, if discharged from the hospital, in the outpatient setting).

Blood samples will be obtained at baseline (Day 1 pre-treatment) and at Days 3, 8, 15 (while
hospitalized), at Days 29 and 90, and at Days 180 and 365 (for the subset of patients
evaluated during a medical consultation at these times).

Thoracic computed tomography (CT)-scan will be obtained at baseline, depending on the
centre's imagery capacities.