Development of a Predictive Serologic Test for Cytopathogenic Autoantibodies in COVID‑19 Patients

Rottapel, Robert K | $215,475

Ontario University Health Network 2020 CIHR Operating Grant

Patients infected with the SARS-COV2 virus experience large variation in their clinical outcome. Most patients are asymptomatic or have mild symptoms while a smaller fraction of individuals develop devastating organ damage with fatal results. Currently, we have little insight into the factors that contribute to these dramatically different clinical outcomes. This proposal seeks to develop a test that will predict patients who may develop poor outcomes by measuring the emergence of antibodies that are destructive to tissues. These « destructive » antibodies are called autoantibodies. Normally our immune system generate antibodies protect us from viral and bacterial infections. We present preliminary data derived from a small cohort of COVID‑19 patients that demonstrates the presence of autoantibodies in as many as 40% of infected patients. In some case these autoantibodies are present at high concentration. We will measure the presence of autoantibodies prospectively in a cohort of 150 patients that react against human lung cells, blood vessel cells and heart cells. The presence of these autoantibodies will then be correlated with the clinical course of Covid-19 infected patients. We will use well established mass spectroscopy methodologies to identify the proteins on human cells that are recognized by these autoantibodies. We will determine if purified autoantibodies from patients cause cell damage or death. Lastly, we will raise antibodies in mice directed against the proteins recognized by COVID‑19 autoantibodies and determine if they cause injury to lung, heart, or blood vessels in animals. These efforts will allow us to develop a test to identify the emergence of autoantibodies in COVID‑19 patients that will aid in stratification and the application of anti-viral therapeutics for those patients predicted to have unfavourable outcomes.

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