Interferon (IFN) lambda is one of the fundamental responses of the innate immune system. Peginterferon lambda is a long-acting form that has been studied extensively in human trials in viral hepatitis, confirming it safety and tolerability. It is particularly attractive for consideration in the use of acute respiratory illness due to the high expression of the lambda receptor in lung epithelia. We propose to evaluate peginterferon-lambda in ambulatory patients with mild to moderate COVID-19.

In this study, individuals who attend an Assessment Centre/Emergency Department to be swabbed for COVID-19 and deemed well enough for home isolation will be informed about the study. There will be two major routes of recruitment. Where feasible, a rapid point-of-care (POC) laminar flow based COVID-19 test (the Abbott PanBio) will be performed and those who do not have a POC test at the assessment centre will be tested by PCR.

Interested participants who contact study staff will be confirmed to have a positive COVID-19 test. Once confirmed will be further screened for eligibility criteria by research study staff. After review, a consent form will be emailed to the participant and informed consent will be obtained through witnessed telephone consent from the participant or a substitute decision maker (SDM). Participants who consent will be randomized to receive a single subcutaneous injection of Peginterferon lambda 180µg or saline placebo.

Patients will be followed remotely with visits. In addition, participants will also attend outpatient clinic for swabs and blood work for routine laboratory and inflammatory markers on Days 7 and 14 with the primary endpoint being the time to SARS-CoV-2 RNA negativity and the proportion with COVID-19 related emergency room assessment >6 hours, hospitalization or death by Day 28. Numerous secondary endpoints will be evaluated as well.

Safety data will be reviewed by the Data Safety and Monitoring Committee after the first 50% of randomized participants complete 14 days of follow-up after treatment.

Inclusion Criteria:

1. Adult 18 years of age or older.

2. Symptomatic and within 7 days of symptom onset.

3. High risk for severe disease (as defined by one or more of the following):

   1. Age >50
   2. Diabetes mellitus requiring therapy
   3. Hypertension on medication
   4. BMI >30 kg/m2
   5. Cardiovascular disease
   6. Asthma requiring chronic controller medication
   7. Symptomatic respiratory disease
   8. Immunosuppressed patients (to maximum of 10mg prednisone daily +/- other immunosuppressive agents)
   9. Documented fever (>38C)
   10. One or more of the following symptoms: cough, shortness of breath (SOB), pleuritic chest pain and/or myalgias (to a maximum of 25% of enrollment)

4. Discharged to home isolation.

5. Willing and able to provide informed consent (including by substitute decision maker).

6. Willing and able to follow-up by phone or videoconference.

7. Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use adequate methods of contraception during the study and through 90 days after the last dose of study medication. Female patients of childbearing potential are all those except patients who are surgically sterile, who have medically documented ovarian failure, or who are at least 1 year postmenopausal.

Exclusion Criteria:

1. Pregnancy (or positive urine pregnancy test) or lactating.

2. More than 14 days following completion of SARS-CoV-2 vaccition series

3. The following pre-existing medical conditions:

   1. Known cirrhosis with any history of decompensation (ascites, variceal bleeding or hepatic encephalopathy)
   2. Known chronic kidney disease with estimated creatinine clearance < 30 mL/minute or need for dialysis
   3. Uncontrolled severe psychiatric disorder - schizophrenia, bipolar disorder, depression with prior suicidality
   4. Uncontrolled seizures or seizure in the prior 1 month
   5. Any other underlying medical (cardiac, liver, renal, neurological, respiratory) or psychiatric condition that in the view of the investigator would preclude use of peginterferon lambda

4. Known alcohol or drug dependence that in the opinion of the investigator would impair study participation.

5. Known prior intolerance to interferon treatment.

6. Enrolment in another clinical trial testing an antiviral agent or receipt of an antiviral agent for COVID-19 in the past 7 days.

7. Use of investigational, off-label therapy for COVID-19, or unproven therapy for COVID-19.