Peginterferon lambda to treat outpatients with COVID‑19 to prevent severe disease: Focus on variants of concern

Feld, Jordan J | $994,420

Ontario University Health Network 2021 CIHR Operating Grant

The COVID‑19 pandemic continues to cause major problems globally. The appearance of multiple variants of concern (VOC) that spread more easily and cause more severe disease has led to surges of infection in Canada and abroad. There is concern that new variants may evade vaccine responses. The numbers of VOC have risen dramatically. In Toronto, VOC have increased from ~10% to >80% of all newly diagnosed cases of COVID‑19 in just 2 months with devastating effects on hospitalization, need for ICU care and mortality. To address the spread and health consequences of VOC, antiviral therapies unaffected by the sequence of the virus are urgently needed. Interferons are hormones that the body produces to fight off viral infections. They are the body’s first defense against most viral infections, so their activity does not depend on the sequence of the virus. We have previously shown that peginterferon lambda, a Type III interferon, with fewer side effects than other interferons, is very active against COVID-19. In our previous trial, treatment sped up clearance of the virus. We now propose to do a larger study with 610 people to see if peginterferon-lambda is effective against VOC and if it will prevent outpatients from requiring hospitalization. People with COVID‑19 with risk factors for severe disease will be randomized to get a single shot of peginterferon lambda under the skin or a matching placebo and we will assess whether treatment reduces the risk of hospitalization and leads to clearance of the virus more quickly than placebo. We will enroll 200 people in Toronto and will partner with a large group in Brazil where VOC are a major problem. The Brazilian team will enroll 410 people allowing us to evaluate treatment in 610 people to determine if peginterferon lambda is effective. We will also study in the lab how this treatment activates specialized immune cells to fight the virus with a particular focus on how it works against VOC.

With funding from the Government of Canada

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