This study is an adaptive, randomized, open-label, controlled clinical trial, in collaboration with countries around the world through the World Health Organization.

Subjects will be randomized, across one, two, three or up to four separate randomizations, to receive either standard-of-care products or the study medication plus standard of care, while being hospitalized for COVID-19.

Randomization WHO: Imatinib vs Infliximab vs Artesunate vs Standard of care

Randomization Dex: Dexamethasone vs Standard of care

Randomization LSALT: LSALT Peptide vs Standard of care

Hospitalized subjects will require blood sampling for screening and on days 1 and 5.

Inclusion Criteria:

Each participant must meet all of the following inclusion criteria to participate in this study:

1. ≥ 18 years of age
2. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen, within 14 days prior to randomization.
3. Hospitalized at a participating centre
4. Primary reason for hospitalization or subsequent in-hospital illness is because of acute COVID19 infection
5. First admission for acute COVID19

In addition, there will be the below intervention-specific inclusion:

Randomization WHO will have no other specific inclusion criteria.

Randomization LSALT will have no other specific inclusion criteria.

Randomization Dex will have the following specific inclusion criteria

1. On 10 days of steroid course and
2. Receiving any supplemental oxygen for 10 days

Exclusion Criteria:

All participants meeting any of the following exclusion criteria at baseline will be excluded from participation in this study:

1. Anticipated transfer to another hospital, within 72 hours, which is not a study site
2. Expected to not survive beyond 24 hours
3. Receiving one of the study drugs at time of enrolment

In addition, there will be the below intervention-specific exclusions:

Randomization WHO:

These will be drug-specific exclusions; patients will still be eligible for randomization in Randomization WHO to the other available study drugs (in randomization WHO or subsequent randomizations).

Artesunate:

1. Known hypersensitivity to artesunate

Imatinib:

1. Pregnant or breastfeeding;
2. Known hypersensitivity to imatinib;
3. Liver transaminases (either ALT or AST) > 5x upper limit of normal

Infliximab:

1. Known moderate or severe heart failure, per treating clinician, defined as New York Heart Association (NYHA) class III or IV
2. Known or suspected active tuberculosis
3. Known hypersensitivity to infliximab

Randomization LSALT:

1. Known hypersensitivity or prior use of LSALT peptide.
2. Pregnant or breastfeeding

Randomization Dex:

1. Receiving glucocorticoids for a specific, non-COVID-19 indication

As per World Health Organization policies on data sharing in a Public Health Emergency, any clinical trial outcome data will be shared at the earliest possible opportunity. In addition, given the nature of this protocol, being performed across regions, the DSMB may access other regions trials, and possibly recommend alterations in study design based on accumulating data, through a centralized data repository being built under the auspices of the World Health Organization.

Data Sharing for Secondary Research Data from this study may be used for secondary research. All of the individual subject data collected during the trial will be made available after de-identification through expert determination. The SAP and Analytic Code will also be made available. This data will be available immediately following publication, with no end date, as part of data sharing requirements from journals and funding agencies.

Unknown and variable

Endpoint assessment