Better management of hospital resources in pandemic times through DNA measurement

For nearly two years, the COVID-19 pandemic has kept a firm grip on the world and caused many intensive care units to hit full capacity. It would help medical professionals tremendously if they could make a reliable prognosis the moment patients are hospitalized. A prognosis is especially useful when it comes to a targeted allocation of hospital resources. cfDNA screening could play an important role in the assessment of COVID-19 severity in patients.

Professor Perikles Simon has focused his research on cfDNA for many years. At the MEDICA trade fair, his presentation highlighted the values ​​this type of DNA provides and explained how these values ​​are used as a predictor of patient outcome in intensive care units. In this MEDICA.de interview, he tells us what cfDNA is and reveals how this method is already being used today.

Prof. Simon, your presentation at the MEDICA LABMED FORUM highlighted how cfDNA could be used in a COVID-19 context. But first, what is cfDNA?

Perikles Simon: cfDNA is cell-free DNA circulating in the bloodstream. Fifteen years ago, performance physiology and doping research naively believed most DNA is in the cell nucleus. But we also have "junk DNA" circulating in the blood. These days, liquid biopsy has become a popular method to detect the tissue source of this DNA. This is done based on the signature: with DNA from healthy cells, it can be an epigenetic signature, but it can also be a signature that suggests a tumor. If the DNA sequence of a gene is altered – such as in the case of an oncogene – it is specific to tumors.

We were explicitly interested in the release of DNA itself. This happens with any form of stress, both psychological and physical - all resulting in an increase in free circulating DNA in the blood. This attracted our attention because as sports physiologists, we are mainly interested in extreme situations such as complete exhaustion in athletes, but also the stress experienced by patients hospitalized with COVID-19 in the intensive care unit for four to six weeks. Obviously, these cases differ greatly in terms of stress levels, except for the one time when exhausted marathon runners arrive at the finish line. They temporarily exhibit significantly increased cfDNA levels, which drop quickly as the athletes recover, while our intensive care patients remain at this level of complete exhaustion for weeks. We can measure the corresponding markers such as cfDNA, hoping to predict disease severity.

Can you use cfDNA to predict disease severity in COVID-19 patients?

Simon: Researchers at the National Institute of Health already managed to do just that. When the patients were admitted to the hospital, the scientists determined they had no diseases other than COVID-19 and quantified their cfDNA on the day of admission – which is a good prognostic marker that predicts death or the need for mechanical ventilation. Better hospital resource management is thus made possible by quantifying cfDNA.

Our values likewise corresponded with the need for ventilation. We measured this in an intensive care setting along with our colleagues and determined that this can be a helpful planning tool. There is one caveat: you must quantify the DNA levels quickly. This year's MEDICA was well appointed in this respect, covering everything from basic research to problem solving: Driven by the analysis and monitoring of the COVID-19 pandemic, rapid DNA solutions have sprung up like mushrooms.

When will you be able to apply your research findings and what steps do you still have to take?

Simon: We recently received funding from the Federal Ministry of Education and Research. We are collaborating with the Fraunhofer Institute for Microtechnology and Microsystems (IMM) in Mainz, Bytec, R-Biopharm AG, and intensive care physicians in hope to develop a rapid analysis system. It's critical for us to get a whole blood assay to perform a DNA analysis, because we have recognized the importance of a pre-analysis: after the blood draw, there is often a certain nonchalance. After all, you now have your blood sample but technically you already affect the sample the moment you take it. The nature of the coagulation inhibitor and whether you perform a less invasive capillary blood sampling or venous blood sampling has a strong impact on the cfDNA levels – all this on top of concerns about the sample stability under realistic storage conditions in the clinical routine of an emergency room. Ideally, process steps should be reduced to an absolute minimum and deliver sensitive quantification of cfDNA directly via the full blood count – which is our goal. I predict it will take another five years of development to get there.

You studied cfDNA even prior to the pandemic. Did COVID-19 take you by surprise and prompted you to change your research focus?

Simon: As it happens, we had already switched before the outbreak. Our previous research method can detect gene doping in competitive sports, but it is incredibly complex. Given that athletes currently use conventional drugs for doping, use of the method was not sensible. That's why we started to measure indicators for colorectal cancer in the blood even pre-pandemic. One question we wanted to explore was whether someone with cancer releases more or fewer DNA fragments when he/she is physically active. The finding was that while the person releases DNA like all humans in response to stress, it is not DNA that comes from the tumor but stems from immune cells, while the circulating tumor DNA even dilutes, relatively speaking.

That is why DNA found in the bloodstream has been of great interest to us for quite some time. The COVID-19 pandemic has essentially validated and accelerated the issue, because we now know that these levels ​​are relevant as highly responsive stress markers. Some hospitalized COVID-19 patients have increased values that even competitive athletes will never achieve - these are cfDNA dimensions that suggest an enormously increased risk of thrombosis. That's because DNA is sticky, negatively charged, and binds positively charged proteins: Immune cells can eject their DNA, forming a "mesh" of sticky strands to capture and immobilize bacteria and viruses - but if they do this too much, they release too much genetic material, resulting in an increased risk of thrombosis. Our measurements are a great tool in these situations and can hopefully help improve prognosis and outcomes, as it facilitates better medical equipment and medication planning.

Let's take a look back at MEDICA: How did you like the trade fair?

Simon: It was great that we were able to attend MEDICA in person, because you could effortlessly visit all exhibition booths and engage with people. I was especially interested in the research facilities and the respective research undertaken by the individual countries. But it also broke my heart in a way because I know how crowded the MEDICA trade show floors usually are when there is no pandemic.