A new therapeutic approach would reduce mortality from COVID-19

An international study led by Julián Pardo, a researcher at the University of Zaragoza and the IIS Aragón, opens the way to more effective therapies, by reducing inflammation and preventing respiratory failure.

The magazine in Cell Death Differentiation publishes the results of this research, co-directed by the CIBER Infectious Diseases area group (CIBERINFEC) in Aragon

An international study led from Aragon opens the way to most effective therapies in the treatment of COVID-19 by neutralizing FasL, a critical protein in the immune system, mitigating the effects of Acute Respiratory Distress Syndrome and reducing mortality. This research is co-directed by the CIBER Infectious Diseases area group (CIBERINFEC) in Aragon, led by the immunologist Julian Pardo, professor and researcher at the University of Zaragoza and the Aragón Health Research Institute (IIS Aragón) and Maykel Arias and Iratxe Uranga, of the IIS Aragón.

Published in the prestigious magazine Cell Death Differentiation, this work focuses on the discovery and applications of a new treatment model for COVID-19, a disease that, despite advances in vaccination, continues to present significant challenges worldwide, with a high number of deaths and comorbidities. . The research has been possible thanks to the development of a new SARS-CoV-2 virus adapted to mice, whose infection closely mimics COVID-19 in humans, thus paving the way for new therapeutic strategies.

New therapeutic approach

The team has discovered that overstimulation of the activity of FasL, a crucial molecule involved in the regulation of cell death and immunological homeostasis, leads to high destruction of lung cells, which produces inflammatory reactions and severe respiratory failure, situations commonly observed in patients. severe cases of COVID-19.

«We have revealed that the therapeutic blockade of FasL, using a molecule previously tested in cancer clinical trials, notably improves survival in mice, reducing inflammation and preventing respiratory failure caused by acute respiratory distress syndrome", one of the main causes of death in patients with COVID-19," says Julian Pardo, principal investigator of the “Immunotherapy, inflammation, infection and cancer” group at the University of Zaragoza, the Health Research Institute of Aragon (IIS Aragón) and CIBERINFEC.

Additionally, this therapeutic approach prevents lymphopenia or low blood counts of lymphocytes, potentially protecting against secondary infections. “This approach represents a paradigm shift in the treatment of COVID-19 since it does not focus on blocking inflammatory cytokines such as IL-6, IL-1 or TNF, which are the consequence and not the cause of inflammation.” , and it is also a more selective blockade than the use of corticosteroids,” says Dr. Pardo. The team is currently evaluating whether this lockdown could also be useful in preventing long COVID.

Recently, it has been developed an international clinical trial (ASUNCTIS: NCT04535674) to evaluate the effectiveness of FasL blockade in patients with COVID-19, where the IIS Aragón and the CIBERINFEC group have also participated, which could represent a crucial advance not only for this disease but also for other serious respiratory infections that cause similar symptoms, such as the flu.

This work also stands out for the international collaboration uniting research centers from Germany, Austria, Hungary, the United Kingdom and Spain, a team led by Henning Walczak (University of Cologne and University College London), Michael Bergmann (University Hospital of Vienna) and Julián Pardo (IIS Aragón/Universidad of Zaragoza), marking a milestone in the fight against COVID19 and opening new avenues for the treatment of infectious diseases. In addition, members of CIBERINFEC such as Iratxe Uranga-Murillo, Diego de Miguel and Maykel Arias have participated, along with Rebeca Sanz-Pamplona from CIBERESP and bioinformatics at the IIS Aragón, thus consolidating an innovative approach that could transform the treatment of serious respiratory infections.

Source: University of Zaragoza