Grant: Operating Grant: COVID-19 - Transmission dynamics/animal host/modeling

Despite efforts to contain COVID-19, the potential for a global pandemic necessitates the rapid evaluation of strategies for prevention of COVID-19 in close contacts of new cases. Lab data, animal models and early clinical data suggest that a drug commonly used to treat HIV, called Kaletra, may have activity against COVID-19 and its closely related "cousin" coronaviruses, SARS and MERS. Kaletra is currently being tested in clinical trials in China for treatment. This drug has been safely used for over two decades in HIV treatment and also in post-exposure prophylaxis (PEP) for un-infected people with high-risk exposures. We propose a study that will address the immediate need for prevention interventions by testing whether or not giving Kaletra PEP to contacts exposed to COVID-19 will stop them from getting the disease. We expect to test this in three key groups of exposed contacts: the frail elderly in nursing/retirement homes, frontline health workers, and household/community contacts. Our trial employs a commonly used approach in vaccination studies called a ring design, which also allows us to collect detailed information about the natural history of the infection in exposed contacts. In addition to testing the effectiveness of our specific intervention, the master protocols and procedures developed can be used to test other prevention interventions including both medications and vaccines, once they become available. This ring design was a key part of the successful eradication of smallpox, and the evaluation of the vaccine used for Ebola. We will identify a ring of exposed close contacts around index cases and randomize these rings to a 14-day course of Kaletra PEP or a placebo control and will test contacts systematically to see if they develop COVID-19. Our study team members of Canadian experts on the frontlines with SARS, MERS, H1N1, Ebola, and HIV, are well connected to coordinate with existing clinical trials networks both in Canada and internationally.