A recent study published in the prestigiousProceedings of the National Academy of Sciences by a team of researchers at the University of Colorado Anschutz Medical Campus significantly improved the understanding of a key component of the immune system during COVID-19: the interferon response.
Interferons (IFNs) are coding proteins produced by a host cell to activate antiviral defenses within the body. If the immune response, including the production of IFNs, is unable to clear the virus, and the immune system continues to fight. However, a prolonged and exacerbated immune response can cause organ damage and even death.
The collaboration team led by Joaquin Espinosa, the PhD, and the executive director of the University of Colorado School of Medicine used blood samples and data from patients who had been diagnosed with COVID-19 in a series of experiments. This large dataset has been created on the COVIDome Explorer portal, a user-friendly platform that has grown by 1500+ users across 60+ countries since its publication in November 2020.
The development of the COVIDome dataset was modeled after the Crnic InstituteHuman Trisome Project (HTP) which was launched in 2016, and is one of the world''s largest research aimed at understanding co-occurring conditions of Down syndrome. Notably, individuals with Down syndrome are at a high risk of developing severe COVID-19.
This research is the first of its kind in the use of a deep multi-omics approach to investigate the use of 12 different IFNs in COVID-19 patients. These latest findings are evidence from previous research and provide a new model for performing the pathology of COVID-19.
We were able to measure 12 different IFNs and track their activity during COVID-19 by defining associations with thousands of RNAs, proteins, antibodies, and immune cells measured in the same blood samples. There are no other statistics that have compared that many different measurements to 12 different IFNs in this way, according to the lead author of the paper. Matthew Galbraith, an associate research professor at the University of Colorado, is the director of the Data Sciences Program at the Crnic Institute.
According to Kelly Sullivan, a PhD and a professor of Medicine at the University of Colorado, there are clear implications in the results that resolve ongoing controversies in COVID-19 research. Part of the controversy is based on the assumption that all IFNs work fairly similar, but we found significant specialization in IFN action, with different IFNs being associated with different pathological processes.
These findings have significant therapeutic implications, because both pro and anti-IFN therapies have been tested in COVID-19, with mixed results. This work indicates that it is more complicated, as not all IFNs are created equal, and that different IFN subtypes will likely modulate the patient''s disease stage and the outcome of the therapy. According to Tell Bennett, the researcher and director of theColorado Clinical and Translational Sciences Institute''s independent analysis and analysis expertise.
The FDA has approved the emergency use authorization for baricitinib for patients with severe COVID-19. Baricitinib is a janus kinase inhibitor (JAK inhibitor) that suppresses the action of IFNs and other inflammatory processes. However, it is not clear which patients might benefit the most from this therapy, and why suppressing the immune response in this way is often beneficial. Dr. Espinosa believes that this study will help to better understand how to deal severe
Elena Hsieh, MD, who specializes in pediatric allergies and immunology at Childrens Hospital Colorado and is a member of the internationalCOVID Human Genetic Effort, believes these findings provide additional insight into the future future. I believe this research would help identify a predictive marker about who is at risk for severe COVID-19 and who isnt. If physicians could do a multi-IFN test to measure the specific IFN signatures along the course of COVID-19, and determine which patients at a
During COVID-19, follow-up mechanistic experiments will be necessary to fully define the implications of specialized IFN actions, but this work provides a solid foundation for future research aimed at better prevention and treatment of infectious diseases globally.