Layman Summary COVID-19 is a new disease which is caused by a virus called the Corona virus. COVID-19 simply stands for Corona Viral Disease-2019 which is the year it was first recognised. There are currently no drugs approved to treat this disease. There have been a few suggestion that some drugs may be of benefit in this disease but this has yet to be confirmed. The World Health Organization is considering recommending four drugs, which have previously been used to treat other diseases, to treat patients with COVID-19 disease. These drugs are: • Chloroquine/hydroxychloroquine (used in treatment of malaria) • Lopinavir/ Ritonavir (used in treatment of HIV/AIDS) • Interferon beta 1a (used to boost the immune system) • Remdesivir (this has previously been tried for ebola treatment) Before approval of these drugs for treatment of COVID-19, an international study will be performed. The study will help to determine whether COVID-19 patients admitted to hospitals and treated with these drugs do any better or worse than those patients not treated with them. This study will also help to see if these patients will stay in hospitals for a longer or shorter duration than those not treated with these drugs. In addition, this study will assess whether these drugs reduce the need for intensive care unit or the need for a patient to be placed on a machine to help them breath. Any bad health effects in patients who will use these drugs will also be identified during the process of performing this study. Adults (above 18 years) who are in hospital because of COVID-19 disease will participate. The patients information will be recorded electronically. The patients will be put into 5 groups as follows: • One group for patients who are not receiving the new drugs • Other groups for patients who will receive each of the four drugs The patients will be observed until they are released from hospital or they die. After the study is completed, comparisons will be made between patients who received no drugs versus those who received one of these drugs to see if any particular group of patients did better than the other group.

Background: There is currently no approved anti-viral treatment for COVID-19. World Health Organisation (WHO) expert groups advised that four re-purposed drugs, Remdesivir, Lopinavir (given with Ritonavir, to slow hepatic degradation), Interferon (β1a), and chloroquine or hydroxychloroquine should be evaluated in an international randomised trial such as this. Objectives: The primary objective is to provide reliable estimates of any effects of these antiviral treatments on in-hospital mortality in patients with moderate and severe COVID. The secondary objectives are to assess any effects of these antiviral treatments on duration of hospitalisation and receipt of mechanical ventilation or requirement of intensive care as well as identification of any serious adverse drug reactions. Methodology: This is a randomised control trial involving adults ≥18years of age who are hospitalised with confirmed COVID-19 with no contraindication to any of the study drugs. Enrolment into the study will be done electronically. They will then be randomised between 5 treatment groups as follows: local standard of care alone, or local standard of care plus one of the following: Remdesevir daily infusion for 10days or chloroquine/ hydroxychloroquine two oral loading doses then twice daily dosing for 10days, lopinavir with ritonavir twice daily for fourteen days, lopinavir with ritonavir plus interferon daily for 6 days. Patients will then be followed up until time of discharge or death. Data will be collected on the duration of therapy, whether or not ICU care or ventilation was received as well as the date of death and discharge. Life threatening adverse reactions will be reported within 24 hours Statistical analysis will be carried out on an intention to treat basis. The primary analysis will assess any effects of treatment allocation on all cause mortality. Those with severe disease will be analysed separately from those with mild disease. Results: After the trial has ended and the results have been reported, anonymized data sharing will occur as per WHO policy.