With the outbreak of the COVID-19 pandemic, the search for specific forms of therapy began. Especially severe courses with multiorgan failure and the resulting long-term damage pose a particular challenge. The better understanding of immunological correlations in the context of the infection allowed the identification of specific infection pathways of the virus into the body cells as well as mechanisms in the development of a fatal cytokine release syndrome (CRS). Early clinical studies with mesenchymal stem cells could show a side-effect free modulating effect on this excessive immune reaction. In the severely affected regions of Northern Italy, coincidence with a latent congenital alpha-1 antitrypsin deficiency was observed. In vitro experiments demonstrated an anti-infective and immunoregulatory effect of alpha-1-antitrypsin. Low plasma levels of this acute phase protein appear to play a central role in the development of severe and fatal disease. The combination of both principles in a genetically engineered stem cell with the ability to express alpha-1-antitrypsin seems logical. This cell therapy with its specific effect could be used especially in patients with a severe course of disease and a cytokine release syndrome.