In this Current Opinion, we highlight the importance of the material properties of tissues and how alterations therein, which influence epithelial-to-mesenchymal transitions, represent an important layer of regulation in a number of diseases and potentially also play a critical role in host-pathogen interactions. In light of the current SARS-CoV-2 pandemic, we here highlight the possible role of lung tissue stiffening with ageing and how this might facilitate increased SARS-CoV-2 replication through matrix-stiffness dependent epithelial-to-mesenchymal transitions of the lung epithelium. This emphasizes the need for integrating material properties of tissues in drug discovery programs.