How can frontier science help fight the current COVID-19 outbreak? To find out, we talked to a range of ERC grantees who are working in the fields of molecular biology, virology, immunology, epidemiology, and network science. As it turns out, much of their work can be applied to the current situation and could help understand, predict and contain the outbreak.
We will add more news on ERC-funded research as they become available.
List of ERC-funded research projects related to coronavirus, epidemiology and virology as well as other relevant disciplines
HIV research helping to tackle the COVID-19 pandemic
Vaccination gives us protection against pathogens thanks to our B cells – a type of white blood cells that produce antibodies. My ERC-funded research project focuses on understanding how B cells obtain specific qualities needed to protect against HIV-1 and other viruses.
Quite a few insights from the study of HIV-1 could be applied to the current pandemic
HIV-1 and SARS-CoV-2 are two very different viruses and behave quite differently. However, every day we are learning new things about SARS-CoV-2. Even though HIV-1 and SARS-CoV-2 are both RNA viruses, SARS-CoV-2 is not as variable as HIV-1, which means it doesn’t mutate as often. However, we don’t know if a slightly different variant of the virus may appear at a later time, so it could become important to make a vaccine targeting the part of the virus that is least likely to change. We also need to understand how to make vaccines that give long-lasting immune responses. These are things I am also thinking a lot about in my research.
Quite a few insights from the study of HIV-1 could be applied to the current pandemic. In fact, many scientists that were a part of the initial HIV-1 epidemics are now engaging in this situation and I believe that they, together with non-HIV scientists, provide expertise that will help in handling this crisis. For one thing, the HIV epidemics and the long-term search for a vaccine against that virus have enabled scientists to optimise methods to study immunity and to gain information about the immune system that we would otherwise not have. For example, the identification of HIV-infected individuals with rare single B cells and their antibodies that are able to neutralise the virus efficiently has helped generate therapeutic antibodies that are being tested against HIV-1. The same workflow is now being applied in many labs around the world to generate therapeutic antibodies that could be used to treat COVID-19.
The vaccine work is unfolding at record speed
When it comes to a vaccine against SARS-CoV-2, the work is unfolding at record speed. A vaccine is normally first tested for safety and efficacy in animal models at a pre-clinical stage. Larger amounts are then produced for phase 1, 2 and 3 clinical testing of safety and efficacy in humans. Then it is mass-produced to meet the needs of the entire population. Due to safety, no step can be omitted, and usually these steps take place one at a time. However, in this situation some steps are being done in parallel to speed up the process. Several possible vaccines against SARS-CoV-2 are already being or will soon be tested in Phase 1 clinical trials in humans. However, it is difficult to predict exactly when we will have the first approved vaccine.
What we are experiencing now is a tough reminder that infections are real threats and that we need to be more prepared for next time something like this happens. It also shows just how important herd immunity is and that vaccines are the only safe way to achieve it.
Pia Dosenovic was awarded ERC Starting Grant in 2019.
Epidemics: Learning from the past
Our ERC project explored mechanisms of plague transmission to explain how plague spread in medieval times. Nineteenth century scholars discovered that rats and rat fleas could transmit plague to humans but there were some inconsistencies in that infection model. We tested the human-to-human transmission model mediated by human parasites (fleas and lice) with statistical analyses and proved that it is plausible. This finding can also be of help nowadays to tackle plague adequately. We observed how the Third Plague Pandemic in 1894 stopped in Europe at the middle of last century, in concomitance with the introduction of insecticide, but also of private baths, washing machines, the vacuum cleaner and other means to enforce personal and environmental hygiene. In other parts of the world, where reservoirs (e.g. infected wild rodents and their flees) are present, sporadic episodes of infection or epidemics are still recorded every year.
Plague circulated from one place to another due to trade and travel
To test the dynamics of plague in time and space, we analysed the DNA obtained from the teeth of more than 400 plague victims and we obtained genomes of the plague-causing bacteria (Y. pestis) which were placed on a phylogenetic tree. The outcomes of the analyses, interpreted in the context of historical information, support the hypothesis that plague was repeatedly imported into Europe from outside and that it was circulated from one place to another due to trade and travel, exactly as it happened at the time of the Third Pandemic. The biggest plague epidemic known to date, the Black Death itself (1346-1353) and the following wave (pestis secunda 1357-1366) seem to have found their origin not far from the Volga region and have followed the fur-trade routes to spread into Europe.
Diverse epidemic infectious diseases caused Europe to tremble
The reason why the spread of plague in Europe has been much reduced is also to be found in the effective measures taken to prevent and contain the contagion. During the 19th century, diverse epidemic infectious diseases caused Europe to tremble, due to the introduction of steam locomotive and steamships, which started the process of globalisation. As a response, several International Health Conferences (Venice 1892, Dresden 1893, Paris 1894) were convened to find a consensus to prevent and combat contagion. The first International Health Conference on plague, took place shortly after two first plague cases were found on two ships from Bombay docked on the Thames. The measures suggested by the Conferences sought also to stem negative economic consequences: trade and travel from infected regions were not banned, but rigorous controls were carried out both in the country of origin and on arrival of trains and vessels.
Cooperation and solidarity between countries is important
To fight the plague, the best results have been achieved where rapid action has been taken to contain the contagion: quarantine and isolation of confirmed and suspected patients; intensified where cleaning and disinfection has been intensified; respect for where the dignity and needs of those affected or suspected; and the responsive cooperation of the citizens thanks to an intensive information campaign that accompanied the restrictive decrees, it has been possible to obtain the responsive cooperation of the citizens. Tracking the spread and reconstructing transmission chains helped to understand the mechanisms of introduction and dissemination and put suspicious cases into isolation. Delegations and medical commissions were sent from around the world to the epidemic foci to improve comprehension of the dynamics of spread and help combat it. At the international level, cooperation and solidarity between countries is important in order never to lower our guard against the spread of infections.
Barbara Bramanti was awarded ERC Advanced Grant in 2012.
Network medicine and the social network of the epidemic
How can network science help us control epidemics? All the models currently used to predict the spread of the virus, as well as to test effective interventions, are based on network science. The virus spreads through the social network, and via the travel network.
It is a network disease, hence you need to use network tools to develop strategies to control it.
Is our ERC funded project relevant in this context? Absolutely. The project is currently focusing on the dynamics of networks including diffusion through networks, like the spread of the coronavirus. The tools we hope to develop are expected to find their way into the toolset of network scientists tasked with modelling of the next epidemic outbreak.
Also, COVID-19 acts by perturbing the sub-cellular network of our cells, hence we need network science, and in particular the tools of network medicine, to find drugs that can be effective against it.
In this exceptional moment of need, we decided to turn the BarabasiLab's network medicine toolset to aid the hunt for a treatment for COVID-19. We will also forgo the usual guardedness of research, and post the results, as the arrive, here: https://t.co/HmzP1JfxWH. pic.twitter.com/Swui4OrYLW
— Albert-László Barabási (@barabasi) March 24, 2020
Albert-László Barabási, together with László Lovász and Jaroslav Nešetřil was awarded ERC Synergy Grant in 2018.
Trial of a possible COVID19 prophylactic treatment
Dr Mitjà is leading a trial of COVID19 antiviral treatment and prophylaxis.
The COVID-19 emergency warrants the urgent development of new strategies to protect high-risk people, close contacts and health-care workers. The reason is that those infected, in 14 days, will on average pass the virus to 15% - 20% of their contacts. Our current clinical trials exploit the same strategy we use in the ERC project on syphilis. We are trying to repurpose the drugs, which have already been approved, commercialised and are on the market, for the use against this coronavirus. We use in vitro and animal model data to find the best, cheapest and safest drugs, and then to test them in human clinical trials.
Se hace eco de nuestro ensayo clÃnico sobre la quimioprofilaxis para proteger contra SARS-CoV-2
Our clinical trail on chemoprophylaxis to protect against SARS-COV-2 infection is encoded pic.twitter.com/gAWK0dvAA3
â€” Oriol Mitja (@oriolmitja) March 19, 2020
This strategy is called post-exposure prophylaxis and is effective in preventing illness in a variety of microbial pathogens. We use an antiviral drug that has been shown to have an effect on coronavirus. The drug is called hydroxychloroquine. It inhibits the fusion of the virus in the host cell. Our hypothesis is that post-exposure prophylaxis with hydroxychloroquine administered to close contacts of an active case will reduce the incidence of contacts that develop the infection.
We are currently conducting a multi-centre clinical trial to evaluate the efficacy of these antiviral treatments and we will evaluate the reduction in transmissibility using a polymerase chain reaction test. Last week we started with the recruitment of patients and we expect to have the first results in about 3-4 weeks.
More on the research
If the results are positive it could be widely used in any all settings and have the potential to be a game changer in the fight against COVID-19 worldwide. The study is done in coordination with the WHO and five related trials around the world. I have always had interest in neglected tropical diseases and strategies to control the transmission of infectious diseases.
I used to conduct research on treponema pertenue which causes a disease that affects children in Africa and Oceania. I also developed a line of research on syphilis and other sexually transmitted infections. My ERC project aims to discover and repurpose drugs to treat syphilis. We are conducting studies to find new molecules that are effective against the bacteria that causes this disease as there is currently a shortage of new medicines to treat syphilis.
Oriol Mitjà was awarded ERC Starting Grant in 2019.
Using computational models to predict the spread of coronavirus
Due to the increasing mobility of people on a global scale, infectious diseases now spread rapidly and frequently reach epidemic, and in the case of the current COVID-19 virus, even pandemic proportions. How can the spread of such epidemics be better predicted, anticipated and controlled?
I work in computational epidemiology, a new scientific discipline that brings together mathematics, statistics, computational sciences and epidemiology. This novel combination of different scientific disciplines and methods enables us, among other things, to collect and integrate massive datasets on historical epidemics with which to develop computational models. Such models can then be used to provide reliable, detailed and accurate predictions of the spread of future epidemics.
We are working around the clock to help manage the current health crisis
As part of the ERC-funded EPIFOR project, which ran from 2008-2013, together with my team I have developed an array of computational tools that could provide accurate predictions of future viral outbreaks, enabling a timely and efficient response to the threat. The aim was to enhance our ability to control the transmission of a disease, to better target interventions and to understand more about its effects on large populations.
During the lifetime of the project, we faced two emerging epidemics – the 2009 H1N1 pandemic (or swine flu) and the MERS-CoV epidemic – so we were able to concretely test our innovative approaches in real-life situations. These experiments confirmed the significant capabilities of the computational models developed and provided useful patterns on the potential future spread of infectious diseases.
Today I am research director at INSERM (French National Institute for Health and Medical Research), where we are working around the clock as part of a multi-disciplinary team to help manage the health crisis caused by the COVID-19 outbreak. Our work is supported by several other H2020 projects; however, the computational models and other tools developed during the EPIFOR project laid the foundation for this work and are proving to be instrumental. Over the course of the last couple of months, we have produced several important papers, using computational models to predict the spread of the disease and the expected impact of mitigation measures being implemented all over Europe.
Vittoria Colizza was awarded the ERC Starting Grant in 2007.
Fighting the disinformation pandemic
Covid-19 is keeping people indoors, forcing us to social distance to try and contain the virus SARS-CoV-2. But while we sit at home, another aspect of this diseaseis proving rather "viral".
The spread of fake news linked to its nature, propagation and cure seems as inevitable as it is damaging. Philip Howard, director of the the Oxford Internet Institute and ERC grantee talks to us about who stands to benefit from this different type of pandemic, why it occurs, and how we can behave to prevent untrustworthy information from circulating.
Developing SARS-CoV-2 antiviral drugs
'We are a molecular biology group at the International Institute of Molecular and Cell Biology in Warsaw. In our work, we predominantly use two methods: protein crystallography and recently also cryo-electron microscopy. The two methods allow us to visualise molecules which are the gears of each living cell at the level of single atoms. This in turn allows us to understand how these molecules function in health and disease.
To understand how molecules function in health and disease
The ERC grant was the main source of funding for our group for several years. It was thus instrumental in consolidating our research potential and also allowed us to explore medically relevant aspects of the atomic structures of proteins. For example, as a part of our ERC project we studied a protein that is in involved in the maintenance of the genetic information, which prevents mutations and cancer. Using protein crystallography we defined for the first time the atomic structure of this protein and its mechanism of action. Defects in this protein in humans lead to severe genetic diseases and we proposed the basis of these defects at the atomic level.
ERC grant was instrumental in consolidating our research potential
The information about the atomic structure of biological molecules is also instrumental in the design of new drugs. These are usually small molecules that specifically stick to a particular protein and block it. Over the last six years a subdivision of our group collaborated closely with the pharmaceutical industry on numerous projects in which we determined three-dimensional atomic structures of proteins with bound potential drugs. Such structures are invaluable in understanding how potential drugs work and in rational computational improvement of their properties.
Now we will contribute our research potential to the [coronavirus] project
We will now contribute our research potential to the project which aims at developing drugs for combating the new SARS-CoV-2 virus. We are part of large consortium EXSCALATE4CoV coordinated by an Italian company Dompe, which aims at developing substances that can be developed into antiviral drugs. The first step is a powerful computational search for candidate substances. The found chemicals will be next characterised experimentally and we will be involved in the determination of the atomic structures of viral proteins with bound candidate substances identified through the search. This information can be used to further optimise the initial compounds to develop them into antiviral drugs.'
Marcin Nowotny was awarded ERC Starting Grant in 2011.
The basic science of immunity
'I’m a physicist and I study the adaptive immune system. This is the army of cells that protects us from attacks, for example from viruses. They have specialised receptors that can recognise and respond to different pathogens. We have around the same number of receptors as there are people on the planet, and the composition of the cells with different receptors changes throughout our life. It’s a dynamic, complex system that can only be understood statistically.
There are many things we don’t understand about [immunity]
We know this system works. We fight infections. But there are many things we don’t understand about it. For example, we’re hearing recently that different individuals show different reactions to COVID-19. Why is this? What makes a good immune system? What makes a bad immune system? Even if we are generally considered healthy, we’re not the same. This is clearer now more than ever.
In my ERC grant, my team and I study the co-evolution of viruses and the immune system. On the one hand, if we encounter a pathogen, the immune system will change to control it as best as it can. On the other hand, you can think of the spread of the virus as a pinball machine. We all put pressure on it by trying to fight it, so the virus evolves rapidly to try and find a way to move to a new host. They shape each other.
Basic science is important
I think this is a moment when everyone is realising that basic science is important. My group’s research is not directly in the battlefield, we will not find the immediate solution in a day or a month. But perhaps we can help answer basic questions like why are we seeing so many different responses to the virus and can we help people in some way? And, as the situation evolves, how will the virus coevolve to stay in the population? At the moment we don’t have a framework to think about these problems, but this is what me and the people I work with are trying to achieve.'