[Article series] The experts behind Luxembourg's COVID-19 fight

Iris Behrmann, Head of the Department of Life Sciences and Medicine (DLSM) at the University of Luxembourg, is co-principal investigator of the COVID-19 research project "CovSerum: Early detection of COVID19-induced tissue damage and (hyper)inflammation from serum samples”. 

The project, funded by the Luxembourg National Research Fund (FNR), foresees the analysis of proteins present in serum samples from COVID-19 patients, with a specific focus on marker proteins for inflammation (“cytokines”) and for tissue damage.

Prof. Iris Behrmann explains the project “CovSerum” in more details. 

Could you tell us more about your background and expertise?

I joined the University of Luxembourg soon after its establishment in 2003 as professor for biochemistry. Since my PhD and post-doc time at the German Cancer Research Centre in Heidelberg and later as a group leader at the RWTH Aachen Medical school, I have been interested in inflammatory mediators called cytokines, which play important roles in our immune system as well as for cancer development. A main topic of our team, the Signal Transduction laboratory at Department of Life Sciences and Medicine, has been the understanding of how cytokines modulate the behavior of their target cells. This is mediated by signaling events involving enzymes called Janus kinases as well as STAT transcription factors and leads to the “switching on” of distinct sets of genes.

How is your expertise relevant in the current COVID context? 

Cytokines like the interferons are crucial to fight all kinds of infections including those caused by SARS-CoV2. For example, it could recently been shown that the risk of getting severe COVID-19 is increased in individuals with autoantibodies against interferons or with genetic defects in interferon signaling. However, “too much” of cytokines can be detrimental. Indeed, many patients with very severe COVID-19 suffer from a “cytokine storm”, a hyper-inflammation syndrome with often fatal consequences. The understanding of the role of cytokines in COVID-19 is therefore important, especially for working towards a therapy as reflected by these examples:

• Using cytokines as drugs: interferons have been applied to COVID-19 patients in (small scale) clinical studies. In particular as inhaled drugs, they may have the potential to restore the lung’s immune response and thereby accelerate recovery from disease.
• Cytokines can be prevented from binding to their target cells: some reports about the application of an antibody against the interleukin-6 receptor (Tocilizumab) to COVID-19 patients undergoing a cytokine storm have been very promising, although other clinical studies failed to prove a clear survival benefit.
• Stopping the signaling of cytokines in their target cells: With Baricitinib, a first Janus kinase inhibitor has recently been recommended for the (co)treatment of (certain) COVID-19 patients.

Due to the diversity of cytokines and their effects, which may help to control the disease or worsen it, the “right timing” of therapeutic interventions is likely important for success. 

What is your specific role in ongoing COVID projects?

In this project, we measure the level of a set of cytokines present in the blood of COVID-19 patients. Specifically, we analyse sera of patients enrolled in the Luxembourgish PrediCOVID cohort. This cohort comprises mostly patients with a mild disease as well as individuals who are asymptomatic, although tested positive for SARS-CoV2. 

Could you tell us more about your collaborators?

Dr. Mélanie Kirchmeyer performs the “multiplex cytokine ELISA” measurements. She rejoined my lab for the COVID project due to her expertise in this technology, gained in a previous FNR project on cytokines and liver cancer. Dr. Anthoula Gaigneaux crucially contributes to the data analysis in her role as biostatistician within DLSM.

The CovSerum project is coordinated by Dr. Gunnar Dittmar from the Quantitative Biology Unit at the LIH, also affiliated professor at DLSM. In his team, Dr. Daniel Perez Hernandez uses a mass spectrometry-based high-throughput proteomic technique, to analyze serum proteins of the COVID-19 samples on a broader scale. Thus, our complementary approaches will allow for a cross-comparison of the results obtained by both methods.

Our data on the circulating cytokines will be included into a larger immunological study of the patients enrolled in the PrediCOVID cohort, which is run by Dr. Feng He and Prof. Markus Ollert at the Department of Infection and Immunity of the LIH.