Dexamethasone is a critical drug for treating severe cases of COVID-19, but patients respond differently to it. Researchers from the German Center for Neurodegenerative Diseases (DZNE) and Charité — Universitätsmedizin Berlin have identified how this cortisone compound affects the impaired inflammatory response and which patients benefit from it using single-cell analyses, offering hope for more accurate prediction tools for various therapies and diseases. The study has been published in the scientific journal Cell.
In the treatment of severe COVID-19, the effectiveness of drugs can vary significantly from person to person. Scientists from DZNE and Charité — Universitätsmedizin Berlin have developed a method to better understand the molecular mechanisms underlying these differences. They examined how dexamethasone impacts patients with severe COVID-19 who show varied responses to the treatment.
Through single-cell analyses, they found that specific immune cells are responsible for the differing reactions observed. They also identified a way to predict early in the treatment whether an individual will respond positively to the therapy, a method that could be beneficial for treating other diseases as well.
Monocytes as Treatment Indicators
At the onset of the COVID-19 pandemic, it became evident that some individuals with severe cases experienced an overly aggressive immune response to the virus. Consequently, dexamethasone, a cortisone derivative used in treating various conditions to modulate the immune system, was administered. While many patients showed rapid improvement with dexamethasone treatment, others did not respond well, with some conditions deteriorating and leading to fatalities. The recent study sheds light on how the drug functions in cases where the treatment is effective.
Dr. Anna Aschenbrenner from DZNE, who led the study alongside Prof. Dr. Florian Kurth from Charité and their colleagues, explained, “Our findings indicate that the life-saving impact of dexamethasone is associated with the response of monocytes.” Monocytes are a type of white blood cell crucial to the immune system. Aschenbrenner further added, “While some monocytes responded positively to the treatment in patients who benefited from the therapy and survived the infection, the reasons behind this differing response remain unknown. However, it is known that dexamethasone’s efficacy varies among individuals with other diseases as well.”
Distinct Molecular Patterns
Back in 2020, during an early study on the immune response in severe cases of COVID-19, researchers from Bonn and Berlin identified an altered, abnormal monocyte “signature,” which essentially reflects the unique characteristics of these immune cells. The recent study demonstrated that dexamethasone treatment reversed these changes in cases where the therapy was effective. Florian Kurth from Charité’s Department of Infectious Diseases and Critical Care Medicine noted, “The monocytes’ response precedes health improvement by several days. Therefore, if the immune cells exhibit early positive response to dexamethasone, the treatment is likely to be effective. If not, additional medications can be considered to assist the patients.” However, further research is necessary before this new method can be implemented in clinical settings.
The researchers utilized single-cell sequencing to investigate these processes. Prof. Dr. Joachim Schultze, Director for Systems Medicine at DZNE and a lead author of the study, emphasized, “This method enables the detailed characterization of each individual cell. Analyzing cell signatures at this level provides insights into the body that were previously unattainable.” By examining blood samples from individuals with severe COVID-19 who received dexamethasone treatment at Charité, the researchers were able to determine that monocyte response serves as an indicator for the treatment outcome.
Innovative Approach for Targeted Drug Development
Prof. Dr. Leif Erik Sander, another principal investigator of the study and Director of Charité’s Department of Infectious Diseases and Critical Care Medicine and a research group leader at the Berlin Institute of Health, highlighted, “The significance of our results extends beyond COVID-19. By combining well-designed clinical trials with high-resolution molecular analyses, essential insights into the mechanisms of medications can be obtained. This approach could potentially identify predictive factors for therapy response in the early stages of testing new drugs, accelerating drug development and enabling personalized treatments in the future.”
Florian Kurth added, “I believe this strategy can be applied to other diseases as well. Depending on the condition and treatment, different cells may serve as indicators. Once these cells are identified through single-cell sequencing, simpler laboratory techniques can be used to detect the relevant cellular changes.”
The approach, known as “companion diagnostics” in research, involves concurrent molecular analyses alongside therapy. Anna Aschenbrenner sees the method’s application particularly relevant in infectious diseases, noting, “Immune cells play a critical role here and are easily accessible through blood samples. There is also potential for non-infectious systemic diseases like cancer or Alzheimer’s, which can manifest in changes in blood immune cells.”
