Immune Modulators for Treating COVID-19

Inclusion Criteria:

1. Admitted to a hospital or awaiting admission in the ED with symptoms suggestive of
COVID-19.

2. Subject (or legally authorized representative) provides informed consent prior to
initiation of any study procedures.

3. Subject (or legally authorized representative) understands and agrees to comply with
planned study procedures.

4. Male or non-pregnant female adults ≥18 years of age at time of enrollment.

5. Has laboratory-confirmed (within 14 days prior to enrollment) SARS-CoV-2 infection as
determined by PCR or other commercial or public health assay in any specimen.

6. Ongoing illness of any duration, and at least one of the following:

- Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR

- Blood oxygen saturation (SpO2) ≤94% on room air, OR

- Requiring supplemental oxygen, OR

- Requiring mechanical ventilation or ECMO.

7. Women of childbearing potential must agree to either abstinence or use of at least one
primary form of contraception not including hormonal contraception from the time of
screening through Day 60.

8. Agrees to not to participate in another interventional trial for the treatment of
COVID-19 through Day 60.

Exception 1: Participant may co-enroll in ACTIV-4 (ACTIV-4A and ACTIV-4C). Exception 2:
Participants in ACTIV-2 who have been hospitalized may be enrolled in ACTIV-1 as long as
ACTIV-2 study therapy has been discontinued. They will remain in ACTIV-2 follow-up.

Exception 3: If participant is already participating in a COVID-19 vaccine trial but
develops COVID-19 disease that requires hospitalization, participant is eligible for this
study, assuming all other inclusion/exclusion criteria are met.

Exclusion Criteria:

1. ALT or AST >10 times the upper limit of normal.

2. Estimated glomerular filtration rate (eGFR) <30 mL/min (including patients receiving
hemodialysis or hemofiltration).

Exception: Participants with an eGFR <30 mL/min may enroll as long as their renal
insufficiency has been stable without renal replacement therapy for ≥1 month and they
are not current candidates for renal replacement therapy. These participants will not
receive remdesivir.

3. Neutropenia (absolute neutrophil count <1000 cells/μL) (<1.0 x 103/μL or <1.0 GI/L).

4. Lymphopenia (absolute lymphocyte count <200 cells/μL) (<0.20 x 103/μL or <0.20 GI/L)

5. Pregnancy or breast feeding.

6. Anticipated discharge from the hospital or transfer to another hospital which is not a
study site within 72 hours.

7. Known allergy to any study medication.

8. Received cytotoxic or biologictargeted immune-modulator treatments (such as
anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab], anti-IL-17, or T-cell
or B-cell targeted therapies ([e.g., rituximab), tyrosine kinase], JAK inhibitors
[including baricitinib,], TNF inhibitors, or interferon) within 4 weeks or 5
half-lives prior to screening., whichever is longer. Steroid dependency, defined as
need for prednisone at a dose >10 mg (or equivalent) for >1 month within 2 weeks of
screening, is exclusionary. Note Exception 1: Dexamethasone (at a dose of 6 mg per day
for up to 10 days) is permitted for the treatment of COVID-19 in patients who are
already mechanically ventilated and in patients who require supplemental oxygen at
screening, but who are not mechanically ventilated in accordance with national
guidelines. Note Exception 2: Infusion of convalescent plasma given for treatment of
COVID-19 while on-study is also allowed.

Exception 3: Monoclonal antibody therapy given for COVID-19 treatment at any time
prior to enrollment is also allowed.

9. BasedKnown or suspected history of untreated tuberculosis (TB). TB diagnosis may be
suspected based on medical history and concomitant therapies that would suggest TB
infection, have suspected clinical diagnosis of current active tuberculosis (TB) or,
if. Participants are also excluded if they have known, latent TB treated for less than
4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history
only, no screening required).

10. Based on medical history and concomitant therapies that would suggest infection,Known
or suspected serious, active bacterial, fungal, or viral (infection (excepting
SARS-CoV-2 and including, but not limited to, active HBV, HCV, or HIV/AIDS). with the
latter defined as a CD4 count <200 or an unsuppressed HIV viral load), or other
infection (besides COVID-19) that in the opinion of the investigator could constitute
a risk when taking investigational product.

Note: Broad-spectrum empiric antibiotic usage does not exclude participation.

11. Have received any live vaccine (that is,or live attenuated) within 3 months before
screening, or intend to receive a live vaccine (or live attenuated) during the study.
Note Exception: Use of prior non-live (inactivated) vaccinations is allowed for all
participants, including any vaccine for COVID-19.

12. Severe hepatic impairment (defined as liver cirrhosis Child stage C).

13. CurrentKnown severe heart failure (New York Heart Association [NYHA] III-IV).) or
new-onset left-systolic or global cardiac dysfunction in the setting of COVID-19.

Exception: Right-sided heart dysfunction or pulmonary hypertension thought related to
COVID-19 is permitted.

14. In the Investigator's judgment, the patient has any advanced organ dysfunction that
would not make participation appropriate.