The effects of commonly used drugs on the alveolar homeostasis during SARS-CoV-2 infection

Abstract: "The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) causes besides asymptomatic courses, in many cases severe progression including pneumonia with high mortality rates. Up to now, no vaccines or efficient therapeutic strategies are available. Many clinical approaches focus on repurposing of approved therapeutics against other diseases. However, efficacy of these compounds on viral infection or even harmful secondary effects in context of SARS-CoV-2 infection is sparsely investigated. Similarly, adverse events of commonly used therapeutics against lifestyle diseases are unknown. Major problems correlated to COVID-19 are lung tissue damage, dysregulation of the innate immune response and abnormal coagulation parameters. To investigate processes that maintain lung homeostasis, we have established a human alveolus-on-a-chip model, which is composed of epithelial-cells and endothelial-cells as well as macrophages. By use of this system, the alveolar homeostasis, which is easily dysbalanced by infections, can be examined. We will investigate (a) the replication efficacy of SARS-CoV-2 isolates in epithelial and endothelial cells, (b) the effects of infection on innate immune response (c) the barrier integrity and regulation of vascular coagulation and fibrinolysis system and (d) the effects of commonly used therapeutics on SARS-CoV-2 infection that also act on the vascular system. We expect complex insights into the pathophysiology of SARS-CoV-2 infection on the different cell types that are involved in the disease development."; Research Type: discovery; Study population: not applicable