Use of human lung tissue explants to analyse immunomodulatory approaches for the treatment of COVID-19 caused by the novel SARS-CoV-2 (CoIMMUNE)

COVID-19 is caused by the novel SARS-CoV-2 that has infected more than two million humans and caused over 150.000 deaths worldwide. A vaccine and treatments are not available, which urges the development of new treatments, strategies to limit viral replication and to reduce new infections. SARS-CoV-2 induces a biphasic immune imbalance, characterized by the lack of a proper innate immune response in the early phase and the development of hypercytokinemia in the later phase. Here, we propose that application of human IFN-a subtypes or inhibitors of the immune regulatory kinase p38 provide realistic strategies to achieve either activation of the innate immune response in the early and the reduction of overshooting responses in the late phase, respectively. For rapid translation into clinical treatments, repurposing of pre-evaluated drugs and the use of pre-clinical study models should be conducted. This project employs human lung tissue to provide the first pre-clinical assessment of the antiviral and immunomodulatory properties of human IFN-a subtypes to identify the best candidate(s) to reduce viral replication and limit viral trasmission. In addition, we will deliver a pre-clinical testing of three pre-developed p38 inhibitors to provide experimental evidence that the overshooting cytokine response can be rebalanced by p38 inhibition and IC50 values in human lung tissue to allow rapid application in COVID-19 patients. This project has the potential to identify new efficient treatment options for COVID-19 suitable for translation into clinical applications.