Are there too few samples for the many COVID-19 research projects? No, says Prof. Dr. Leif Erik Sander from the department for infectious diseases and pneumology at the Charité – Universitätsmedizin Berlin. Sander is currently conducting research into COVID-19 and is also a member of the Corona Research Board, which coordinates all COVID-19 research activities at the Charité. GBN spoke with him about his research and the associated biobanking as well as about his involvement in the research board.

What are you working on right now in terms of COVID-19?

Leif Erik Sander: Both at the Charité and throughout Berlin, we are working to characterise the disease’s progression among all patients infected with COVID-19. We are interested in patients’ possible underlying medical conditions and risk factors, for instance. We collect different types of samples from them every two days and analyse these. The Central Biobank at the Charité is responsible for storing the samples and for the entire biobanking. We are investigating the disease pathophysiology and seeking new biomarkers to better predict disease progression. We are also looking at the immune response to the virus: this seems to explain why some patients suffer more severe symptoms. Another goal is to develop new therapeutic approaches.

How large is the patient cohort now?

Sander: We’re up to 130 patients. All wards at the Charité treating COVID-19 patients are participating in the study, and other hospitals and locations in Berlin also wish to participate. Fortunately, the restrictions on public life mean that the number of patients at the Charité has now stabilised or even decreased slightly. However, I suspect that the number of cases will rise again in the coming weeks. Firstly because the restrictions have been relaxed and secondly quite simply because the epidemic is evolving.

Do you already have any preliminary findings to report?

Sander: In cooperation with Professor Ralser from the Institute of Biochemistry, we conducted proteomic investigations which have drawn our attention to a whole range of markers. Thanks to our broad-based approach, the cohort size was already sufficient for this despite still being relatively small at the time. We are now validating these markers in a second phase so that they can also be used as biomarkers in the hospital. The markers do not only provide information on the disease’s progression, though, but also on which directions we need to explore in terms of future therapies. For we must decide on certain strategies – at the Charité and nationwide – and cannot try out all approaches.

What other central research questions are there for you?

Sander: In my opinion, one of the most important questions is whether an infection with SARS-CoV-2 leads to lasting immunity and if this also provides protection for a long time. Whether this is the case or not will have a decisive impact on the future course of the pandemic. We are already working to determine which structures in the virus protective immunity is directed against and the reasons why immunity is not achieved. We may be able to determine a vaccination strategy from these findings, which can hopefully be developed quickly.

What do you think is important when collecting samples for COVID-19 studies?

Sander: A broad-based collection strategy is definitely advisable. Not only serum should be collected, but also different forms of plasma along with cellular components. It is important to also collect samples again when the patient has recovered from the illness. This will enable insights into their immunity later on, for example. In the past, there was a tendency to avoid preserving living cells from large disease or population cohorts. I think this is particularly important though. We started doing this from the very first patient in our cohort. We have frozen living blood cells every two days from the outset. We also have special buffers, which enable extremely good preservation of whole blood. Proteomic or flow cytometric analyses allow us to investigate the composition and activation profiles of the peripheral blood later on. We are also able to use modern single cell sequencing to decipher specific transcriptional signatures. I don’t think there has ever been anything comparable on such a large scale for other diseases or cohorts.

What other types of samples could prove interesting for future research questions?

Sander: The fine art of study design and biobanking involves keeping as many options open as possible for future analyses. That is why the broad-based collection strategy is so important. I think it is also useful to preserve tissue – I mean samples or perhaps even cells from the respiratory tract with this. It is relatively easy to obtain blood, but that is just one component.

Where do you see the biggest challenges for COVID-19 research in the coming weeks and months?

Sander: Firstly, I believe it is important to select the right therapies. What can we rapidly make available to as many people as possible to ensure that fewer patients become seriously ill or even die? Secondly, we need a vaccine – not at the end of next year, but rather far sooner. This will require a great deal of hard work and probably also unconventional approaches. I believe that all those involved in research have a duty and are called upon to work together to achieve this.

You are a member of the Charité’s Corona Research Board. How do you ensure a collaborative, coordinated approach within the hospital?

Sander: Our interdisciplinary board regularly discusses the projects of Charité researchers, who register these in a central database. We assess how promising the projects are, whether suitable patients are even available for them and how quickly they could be implemented. So while we spend quite a lot of time in meetings, it is time well spent because it ensures transparency within the Charité and we receive extensive input. It is really impressive to see what can be achieved when everyone works together.

Given the multitude of research activities, biobanks are sometimes concerned that competition could arise for research samples, which are not available in sufficient quantities. How do you handle this issue?

Sander: I have not yet had the impression that there are insufficient samples. The Corona Research Board receives a great many proposals for research projects. But with good coordination, we can manage with the samples that are available. If the board establishes that two researchers are planning similar projects, we attempt to bring these plans together. A multi-omic approach provides so much information that it is not necessary to measure individual parameters. This allows for a lot of information to be obtained even with relatively little material. And our basic prerequisite for participation is that findings are made public and available promptly. This is currently the task of the university hospitals.

Is there anything else you’d like to share with the biobanks from a researcher’s perspective?

Sander: Speed is crucial at the moment. Not prevailing over the competition, but rather sharing the knowledge gained. Large-scale initiatives are welcome, but it is questionable whether these can be implemented quickly enough to generate the knowledge that is urgently needed right now. I think the biobanks must first cooperate with their local scientific networks so that findings can be obtained as quickly as possible. Once the large networks and cohorts have been established, this will undoubtedly help us to understand the long-term effects of COVID-19, for example. But our main task still lies ahead in the coming weeks and months.

The interview was conducted by Verena Huth.