In February 2020, a pandemic began with the first patients in China and then all over the world.
Since then, more than 217 million people worldwide have been infected with the new SARS Cov-2 virus and more than 4.5 million people have died from the infection. After initial euphoria over rapidly developed vaccines, it now appears that the occurrence of mutations and the fact that even vaccinated people can transmit the virus mean that there is no end in sight to the pandemic.
In particular, the fourth wave in Israel and the USA, where more than 60% of the population has already been doubly vaccinated, shows the need for therapy.
Approximately 5% of infected patients show a severe course of the disease and in some cases must be treated in intensive care units. A cytokine storm triggered by the infection is particularly threatening.
Studies have shown that the acute-phase protein alpha-1 antitrypsin (AAT) plays a decisive role in this process. AAT prevents the virus from docking to the ACE 2 receptor and thus prevents infection of the host cell. Clinical studies show that patients who do not respond to the infection with a sufficient release of AAT are more likely to have a fatal outcome. Furthermore, therapy with intravenous AAT has been shown to be effective against Covid-19. However, it is known that only about 2% of the administered AAT dose actually reaches the lungs.
Early on, the use of mesenchymal stem cells (MSCs) was considered for their immunomodulatory properties in the setting of a Covid-19 infection.
A prospective study conducted in Miami showed that 91% of patients with severe Covid-19 disease survived, compared with 42% in the control group.
The cytokine storm responsible for the fatal courses of Covid-19 disease resembles the immunological process in the context of a graft-versus-host reaction after bone marrow transplantation. For this disease pattern, a mesenchymal stem cell producing alpha-1 antitrypsin (MSC-AAT) was developed. This MSC-AAT potentiates both properties (immunomodulation of MSC and reduction of cytokine storm by AAT) in one cell.
MSCs are known to accumulate in the lungs after intravenous administration. The lung, as the primary entry site for the SARS-Cov-2 virus and one of the most severely affected organs during infection, thus represents the first target for effective therapy against Covid-19.
In preclinical studies, we showed that MSC-AAT accumulates in the lung, where it releases AAT, such that even an increase in the systemic AAT concentration could be observed. In addition, therapy with MSC-AAT in various models led to an increase in regulatory T cells, a reduction in proinflammatory cytokines, an improvement in lung function, and the repair of damaged lung tissue.
Therefore, MSC-AAT should be a promising therapy for patients with a severe course of Covid-19 disease, regardless of the causative viral mutant.