We have previously provided the first genetic evidence that Angiotensin converting enzyme 2 (ACE2) is the critical receptor for SARS-CoV and that ACE2 protects multiple tissues from organ damage (Imai et al., Nature 2005; Kuba et al., Nature 2005). ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19.

The primary site of SARS-CoV-2 infection is the lung, which then becomes a source for viral spread to other tissues such as the heart, kidney and intestine (Ling et al., Chin Med J 2020; Young et al., JAMA 2020). Based on size constraints, it seems that the SARS-CoV-2 virus must directly infect blood vessel cells to spread to secondary tissues. Studying the molecular mechanisms of SARS-CoV-2 infection in blood vessels is therefore important for the understanding of disease pathogenesis, patient care, and virus transmission - critical information required for the containment of this pandemic. We have previously developed vascular organoids from human induced pluripotent stem cells (Wimmer et al., Nature 2019; Wimmer et al., Nature Protocols 2019); and our recent study shows that human recombinant soluble ACE2 (hrsACE2, APN01) significantly reduced SARS-CoV-2 infections of human organ-like tissues (Monteil et al., Cell 2020).

Together with an international network of tissue engineers, SMEs (e.g. Apeiron developing ACE2 for therapy), and virologists we aim to dissect, at the single cell level, the pathogenesis of SARS-CoV-2 infections in human vascular organoids in the presence and absence of hrsACE2, which is undergoing clinical testing for COVID19 patients. Since diabetic patients belong to a particular vulnerable COVID-19 risk group, we will also compare diabetic blood vessels (Wimmer et al., Nature 2019) to their healthy counterparts in terms of viral infection, ACE2 expression, and its inhibition by hrsACE2.

Project number COV20-002

Vienna Science and Technology Fund