"Nevertheless, many continued hoping that the epidemic would soon die out and they and their families be spared. Thus they felt under no obligation to make any change in their habits as yet."
Albert Camus
The Plague, translated from the French by Stuart Gilbert
The current coronavirus pandemic demonstrates in an alarming way how important it is to understand and prepare for the fight against infectious diseases. As this is an integral part of the LifeTime roadmap, the initiative counts among its members actors at the forefront in the research on COVID-19. In a series of interviews, which will be regularly published here, we want to share with you the thoughts and recommendations of leading experts from LifeTime.
We learn from today so we can be prepared for tomorrow!
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"Our teams started work on the virus early on"

Interview with Prof. Dr. Jörg Vogel, Head of Department RNA Biology of bacterial infections, Helmholtz Institute for RNA-based Infection Biology

I run the HIRI, the Helmholtz Institute for RNA-based Infection Biology, which was founded a few years ago to better understand the role of RNA in infection. SARS-CoV-2 Corona is an RNA virus, it is infecting people around the world, and one of the most promising technologies for defeating this virus is mRNA vaccines. Several of our teams started work on the virus early on. For instance, Neva Caliskan investigates ribosomal frameshifting of SARS-CoV-2, trying to shed light on how the virus’ proteins are made. In line with the LifeTime innovative approach combining breakthrough technologies to understand and target human cells, Emmanuel Saliba is using single-cell RNA-seq to obtain time-resolved expression maps for individual infected cells. This can lead to the identification of new biomarkers and treatments enabling interception of the disease before it becomes too challenging. In short, the mission of our institute and the scientific interest of many of our researchers could not be closer to the COVID-19 pandemic.

We need to fully understand the course of the infection as well as the ensuing host response to help healthcare professionals to treat high-risk patients. The analysis of virus-host interactions on the single-cell level could be key, it would allow us to pinpoint molecular factors and cellular pathways for prioritizing drug targets. Most importantly, however: we need a vaccine soon. I think that this is the time for RNA therapeutics, in this very case mRNA vaccines, to show their full potential.

From previous RNA virus outbreaks, we know that the majority of novel RNA viruses are of animal origin. Databases of viral sequences from wild animals help us trace the natural reservoir by comparative analysis. This may help to predict or even prevent further outbreaks. In fact, the presence of a large reservoir of SARS-CoV-like viruses in horseshoe bats was identified as a major potential health threat more than a decade ago.

Furthermore, basic science into RNA viruses sets the frame for the identification of good antiviral targets, for instance, polymerases, proteases or envelope proteins. At the same time, this research helps us to identify good antigens for vaccines, which – in my view – are the most effective way forward to prevent such pandemics. Vaccines often only become available after the peak of an infection, however. It is thus of great importance to speed up their development especially in the field of RNA-based vaccines.

As said above already, I think that this is the time for mRNA vaccines to prove their enormous potential. It has taken decades of basic research to be able to make and deliver mRNAs — which are bulky molecules — to immune cells for those then to produce a viral protein of interest, with the hope that the patients become immune against the virus. Such mRNA vaccines promise to have many advantages over conventional vaccines: if everything works, they can be developed, tested and produced in much less time than what is currently standard.

Other RNA techniques such as single-cell RNA sequencing will help to monitor whether the vaccine works the way it should, and help us to understand why the virus in some people is more severe than in others. The same goes for testing the effects of antivirals. Using such data, we may understand better the determinants for virus entry in affected tissue.

The combination of these RNA sequencing techniques with advanced machine learning will in the future potentially allow us to predict disease outcomes and thus help healthcare professionals to stratify patients. In addition, we hope to identify RNA molecules, which are vital for the virus. In that case, we would have a unique opportunity to target the virus with specific compounds and enable the development of novel drugs.

In my view, the European Commission should increase science spending and in particular improve the monetary situation for infection research. Infectious diseases are too often considered a thing of the past, but we can now see before our eyes how a tiny virus can paralyze entire continents and cause human and economic losses of a scale that has had no liking in recent times. Importantly, funding of large scale trans-national consortia such as LifeTime is a crucial factor to foster the collaboration of researchers and clinicians in this area in Europe. Connection and coordination across all the necessary research fields is key to win the current fight while making sure we build the infrastructure ensuring preparedness for any future pandemics.

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"We need to better understand how human beings and their immune system fight this virus"

Interview with Prof. Dr. Joachim Schultze, Director, Platform for Single Cell Genomics and Epigenomics German Center for Neurodegenerative Diseases (DZNE e.V.)

There is no doubt that most of us, who have lived a normal life for the last decades, have not experienced such a dramatic situation. This coronavirus is dangerous, it spreads very fast and with the enormous mobility of our modern times, we now have to learn that this virus travels around the world in days and weeks, not months. Furthermore, since this crisis is not only a medical crisis, but comes with secondary effects on our economies, our whole societies, we probably cannot even estimate its true magnitude as of today. Clearly, we need to rethink many things, once we have managed the acute phase of this crisis and this does not only include life and medical sciences, this will include almost all parts of our modern lives.

This is probably one of the few bright spots, I think that the international scientific and medical communities has never been faster, connecting basic and translational researchers, together with clinicians, and pulling things together. Currently in the spotlight are the many attempts to develop new vaccines against the infection and similarly important is the search for new drugs inhibiting the virus or reducing clinical symptoms. These efforts need to be supported and accelerated as much as we can.

But we also need to understand that the only thing that can fight the virus in absence of vaccines and drugs is the human immune system. Unfortunately, we do not know enough about the immune response against this new virus. We also do not understand why the immune system seems to work in most patients, those with few symptoms, and why it fails so miserably in those with severe symptoms and those who died. This knowledge can be used to help select which currently available drugs or therapies would benefit patients and help reduce the pressure on health systems, while the search for a vaccine or drugs inhibiting the virus is ongoing. Here the expertise and the scientific and technological power of the members of LifeTime could really help to decipher the interaction of this virus with their host, namely us human beings. Using the LifeTime’ approach would  help identify individuals at risk of developing severe symptoms and guide treatments based on identified biomarkers, while at the same time  conduct research to systematically identify new drug targets and vaccine strategies.

LifeTime was initially designed to shape the path towards precision medicine in Europe by bringing together the best brains to determine within a decade how we can leverage our technological and scientific advances for medicine. From the beginning, it was clear that infectious diseases would play an important part in this program, because LifeTimers were convinced from the beginning that infections are a major threat to our citizens’ health, and can lead to lifelong effects after the acute infection.  As a short term response to this pandemic,  members of LifeTime are also involved in ramping up testing capacities for viral diagnostics, because they have the technical capacity and the respective knowledge, as well as identifying how current patients can be treated. LifeTime itself is designed to identify  cellular and molecular biomarkers that can also guide the development of innovative precise treatments based on the understanding of diseases over time in many patients.

While the project was planned for a decade, LifeTimers are also engaged actively in projects to better understand the course of this devastating infectious disease right now. We have been already working hard to adapt our plans to cope with the much more urgent situation we are facing now. We are already asking ourselves: how can we leverage our novel technologies and approaches to faster learn about this disease now? As this crisis will not be gone in a couple of days or weeks, LifeTime members are preparing for tackling the many open questions of this disease that we will have to understand during the next months and that would help to address similar outbreaks in the future.

I am convinced that the search for vaccines, for faster diagnostics tools and curative treatments is of the highest priority. And we fully support our national governments and the European Commission pursuing exactly this goal.

But we need to remember that there is still no guarantee that these searches will be all successful. As I eluded to already, at the moment, the only system fighting this virus efficiently is our human immune system and it will be of utmost importance to understand all these complex interactions between the virus, immune cells and other cells within our body that decide between cure and immunity on the one hand and devastating disease and death on the other hand. At the moment, we do not know enough about this battle and this is exactly what the members of LifeTime want to achieve with novel and innovative technologies that allow us to monitor these complex mechanisms over time in high-resolution.

So, we also need projects that address questions such as which immune cells and immune mediators are involved in the immune response against SARS-CoV-2, when are these operative? Which molecular mechanisms are involved? How do these cells interact with non-immune cells in their environment? What influences the natural history of the disease? Can we manipulate the immune system to change the outcome of the patient? And if so, can we transform this knowledge into new immunotherapies? We will generate lots and lots of data, clinical data, research data, genomics data. Can we utilize the most cutting-edge mathematics, data science, and artificial intelligence to help us make sense of this avalanche of data and be more successful in intercepting the disease? These are some of the burning questions to be answered, but there are many more.

Currently we are in the very acute phase of the pandemics and saving lives with classical methods on intensive care units is of highest priority. But even there, it will be important to guide treatment plans and strategies by a better understanding of the pathophysiology of the disease. So even for these situations it is important to apply cutting edge science and technology to better understand COVID-19.

We also can learn from China where the acute situation seems to be over, but the overall crisis is certainly not yet over. For example, we do not know if enough people have been infected and developed immunity. We also do not know how long immunity lasts and whether this immunity can be boosted by re-infections. So even in this phase, we need to develop programs that monitor how the immune system copes with viruses such as SARS-Cov-2 over time. This is something LifeTime was built for.

And lastly, even if we overcome SARS-Cov-2 completely, humankind needs to prepare for the appearance of similar viruses in the future. History and our virologists taught us this already, and they were right. So, it is worth every effort, to invest in programs such as LifeTime that build the foundation for very strong science, cutting-edge technology development and that bring expertise from many institutions across Europe together to tackle current and future threats on all our people’s health.