Prevention of the immunopathology induced by SARS-CoV-2

SARS-CoV-2 infected patients develop pneumonia, which in severe cases leads to fatal respiratory failure and acute respiratory distress syndrome. Currently there are no drug therapies available for COVID-19. Respiratory syndrome severity and vascular permeability are related to local inflammation, lung damage and cell death. Coronaviruses by counteracting the host immune defense contribute in disequilibrium between inflammation and antiviral response. The loss of lymphocytes also characterizes SARS-CoV-2 infection and is linked to a worst prognosis. Thus, immunopathology is critical in determining the outcome of COVID-19 infection. Therefore, therapeutic strategies aiming at reducing inflammation and tissue injury and sustaining immune defense may reduce COVID-19 pathology. In the context of this application, we combined the expertise of virologists, molecular biologists and immunologists to evaluate the therapeutic potential of a series of compounds previously demonstrated to modulate inflammation and cell death. We will benefit from an animal respiratory Biosafety Level 3 laboratory dedicated for the manipulation of highly infectious viral material. This will offer the opportunity to analyze tissues that are of difficult access in patients, as well the impact of these compounds against SARS-CoV-2 variants. This program, in addition to generating knowledge of how these compounds prevent the pathological response to SARS-CoV-2 infection in a relevant animal model, will allow the identification of new biomarkers that may be helpful in predicting patients at higher risk to develop a fatal disease and long-term COVID-19.