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Researchers gather around

Researchers gather around COVID-19

text ANNICA HULTH photo MIKAEL WALLERSTEDT

“Scientists are a fantastic resource and many are keen to help,” says Siv Andersson, Professor of Molecular Evolution and co-director of national research centre SciLifeLab, who has been involved in allocating funds to 67 different projects across Sweden related to the coronavirus and COVID-19.

The Coronavirus D

DURING SPRING 2020, SciLifeLab redirected its organisation to focus on the new coronavirus and COVID-19. As Siv Andersson tells us, the need for urgent action was already apparent in March, when she was invited to a board meeting of the Knut and Alice Wallenberg Foundation to give a presentation on the current state of knowledge about the coronavirus:

“The board was considering whether to intervene in the emergency. A week later, the Foundation returned with an offer, stating that it was prepared to fund coronavirus testing via SciLifeLab.”

A laboratory was set up relatively quickly at Karolinska Institutet under the direction of Lars Engstrand to test for infection in real time.

THE WALLENBERG FOUNDATION invested a total of SEK 50 million to be distributed to various research projects. There was considerable interest among researchers, as Andersson explains:

“We received almost 300 applications to a call that was only open for six days. In the first phase, we primarily approved grants for the development of technology and testing methods, including antibody tests.”

After the first decision on grants was reached on 8 April, the management group examined the applications in more detail, dividing them into a dozen or so fields and appointing experts to examine applications Johan Lennerstrand, Associate in their own field. In the end, a total of 67 apProfessor of Clini- plications were grantcal Microbiology. ed, a quarter of which came from Uppsala University and a quarter from Karolinska Institutet. The remainder were from universities across Sweden.

ACCORDING TO ANDERSSON, the enormous interest can in part be explained by the fact that many researchers were able to adjust their research to focus on the coronavirus:

“This might be anything from developing new methods for tracing the virus or testing for antibodies to studies of viral sequence evolution or the immune system, or drug development research and how to trace the spread of the virus in the environment from water treatment plants.

“Then we have biobanks, where we have particularly invested in Huddinge as well as other universities that collect samples we believe will prove valuable for many years to come.”

SciLifeLab is also in the process of constructing a COVID-19 portal through which research data can be disseminated and channelled to a European data portal.

MANY PAPERS HAVE already been published thanks to an accelerated working method, making results available to other researchers.

“This is the only way to work in such a crisis. That said, it does mean that the research is not quality assured, rather we are in the midst of the research process. As a researcher, one is only too aware that this may be somewhat confusing to the public. What is fact and what is a research conclusion that may not be one hundred per cent reviewed and critiqued?” says Andersson.

As a member of the Management Group at SciLifeLab, Professor Andersson has found herself at the centre of events – her days filled with meetings, discussions and coordination.

“It has certainly been different and unlike anything else I have done in my 40 years as a researcher. We have adopted a completely different way of working, while at the same time we have been under intense media scrutiny.”

ONE OF THE RESEARCH groups that redirected its efforts during spring 2019 is the Zoonosis Science Center (ZSC) at the Uppsala Biomedical Centre, under the leadership of Professor of Virology Åke Lund-

During the spring, funds were allocated to 67 different projects across Sweden related to the coronavirus and COVID-19.

kvist, where intensive research is underway to develop effective drugs to combat the new coronavirus, SARS-CoV-2.

“We want to develop antiviral drugs that attack various targets in the virus. There will be a need for multiple effective drugs, ideally ones that can be easily taken in tablet form,” says Johan Lennerstrand, Associate Professor of Clinical Microbiology at the Department of Medical Sciences, whose research group has focused on developing an inhibitor for a unique enzyme, the virus’s main protease, found in the virus but not in human cells.

“Such protease inhibitors have previously proven successful in the treatment of HIV and Hepatitis C,” says Lennerstrand, who has spent 20 years of his career researching HIV drugs and the past 10 years researching drugs to combat Hepatitis C.

WITH THE ASSISTANCE of colleagues at Oxford University and Karolinska Institutet, the group has been able to obtain SARS-

CoV-2 in pure form. Initially, the research is being conducted on SciLifeLab’s Drug Discovery and Development Platform, where they can utilise virtual screening in combination with the vast substance libraries held at SciLifeLab.

Lennerstrand is confident that they will find several interesting matches between the enzyme and various substances. They will then carry on working with the most promising results in collaboration with Anja Sandström, a researcher at the Department of Medicinal Chemistry, who has a wealth of experience in developing protease inhibitors against Hepatitis C and HIV.

“Once we have identified a few initial candidates using chemical synthesis we will test for toxicity, partly using enzymatic tests and partly in our biosafety laboratory here at ZSC,” explains Lennerstrand. “Perhaps we can contribute one piece to the puzzle together with many other researchers doing the same thing internationally. We are developing points of departure for drugs.” ONE IMPORTANT ISSUE for researchers is to map the spread of infection in Sweden. This is the aim of the COVID Symptom Study project, which is simultaneously studying risk factors for serious illness.

The project, which is based on a mobile app to which users log in each day to state whether they have any symptoms, is being run in a collaboration between Lund University and Uppsala University. The app was launched on 29 April and by the end of August it had gathered data from over 188,500 adult volunteers in Sweden.

“While registering symptoms using the app is a cost-effective method of monitoring the development of the disease, it needs to be combined with other data sources. Based on the symptoms the users report, we calculate the percentage of sick residents in each postcode in Sweden,” explains Professor Tove Fall of the Department of Medical Sciences, who is leading the research at Uppsala University.

The Coronavirus

We hope that the results will contribute to an even better use of symptom data; for example, in the government’s efforts to check new major outbreaks.

THE APP WAS developed in the United Kingdom by ZOE Global Ltd in collaboration with researchers at King’s College London and Guy’s and St Tove Fall, Professor Thomas’s Hospitals in at the Department London. In addition to of Medical Sciences. the United Kingdom and Sweden, the app has also been launched in the United States. During July, the app was used by a combined total of over four million people in the three countries.

Data collection will continue for as long as COVID-19 infections are reported in Sweden.

“We hope that the results will contribute to an even better use of symptom data; for example, in the government’s efforts to check new major outbreaks. Through the research project we will also learn more about when symptom registration data is likely to work well or less well, which will be of immense help in future COVID-19 research, as well as when we want to study other types of diseases,” says Fall.

MENTAL HEALTH IN different countries is also currently being surveyed. Professor Karin Brocki of Uppsala University’s Department of Psychology is studying the psychological effects of the pandemic. Her initial findings show higher levels of mental illness in the Karin Brocki, Professor at the Swedish population during the COVID-19 Department of pandemic compared Psychology. to public health data

“It has certainly been different and unlike anything else I have done in my 40 years as a researcher,” says Siv Andersson, Co-Director of SciLifeLab.

collected in 2018 and similar studies prior to the pandemic; this despite Sweden adopting a more liberal approach and lighter restrictions to prevent the spread of infection than many other countries.

“We identified clinically significant levels of depression (30%), anxiety (24%) and sleep disorders (38%), figures that are comparable with the levels of mental illness reported in psychological studies conducted in China and Italy during the pandemic,” says Brocki.

“While there are certainly differences in methodological aspects, phases of the pandemic and recruitment strategies, we can see that the mental health of a significant percentage of people in all surveyed countries appears to have been adversely affected.”

Over 1,500 people between the ages of 18 and 88 participated in the online survey so that researchers can map which groups are most affected.

“One interesting factor is psychological flexibility – the ability to cope with whatever your current circumstances might be. Our results demonstrate that this is a protective factor but that low psychological flexibility is also a vulnerability factor for mental illness. This is an attribute that can be trained and that responds to cognitive behavioural therapy (CBT),” says Brocki.

Another study is looking at how children and their families are being affected by the COVID-19 pandemic and the resulting restrictions. This is an international collaboration initiated by Cambridge University in England. The study will be conducted in a total of seven countries: the United Kingdom, Sweden, Italy, China, Australia, New Zealand and the United States.

AS CO-DIRECTOR OF SciLifeLab, Siv Andersson has been closely following the intensive events of recent months. She finds

it interesting to see how during the crisis the role of researchers has evolved into active and truly beneficial involvement; for example, performing tests. It was far from obvious that researchers would be involved in mass testing and initially this was questioned.

“It can be very difficult to cross boundaries. Scientists are a fantastic resource and many of them are keen to help; however, at first society was not really prepared to utilise that resource.”

She has even been asked whether there is a need for so much research in Sweden when so much is being conducted in other countries.

“My usual response is that, if we are to critically evaluate and question the research conducted in other countries, we need to have researchers who are sufficiently conversant to understand it.” 

They are developing methods for assessing immunity

ULF LANDEGREN, Professor of Molecular Medicine at Uppsala University, whose research group is developing a new method for large-scale analysis of coronavirus immunity and evaluation of potential vaccines.

What’s going on in the laboratory? “We are developing a variation on one of our established tools for identifying target proteins. The project is one of several life science initiatives currently being coordinated by SciLifeLab in order to improve the effectiveness of the fight against the coronavirus.” What benefits will your work have for healthcare? “Society is faced with an enormous challenge and research into the coronavirus is being conducted all over the world, making it a challenge to contribute anything unique. That said, we are hoping to do our bit by creating a new method for large-scale analysis of who is carrying antibodies and is therefore immune to the virus, while simultaneously measuring other immune responses that might have an impact on the prognosis for individual patients. Should we succeed with our specific approach of beginning with self-testing by patients at home, the tests may prove indicative of the kind of care patients need.” When will you be able to present a result? “This is a prioritised assignment and we have now begun analysing patient samples on a smaller scale. To a certain extent, the project has been impacted by the difficulties inherent in operating during the pandemic. As always in research, it is therefore difficult to predict an approximate timeframe.” Do you see a risk that the ongoing crisis will drive researchers to rush their work? “Right now there is an enormous demand for available data and clearly some papers are being published without undergoing the usual scientific scrutiny. That said, we are in an extreme situation in which the shortest possible route from research to publication is likely to benefit society. Such haste carries the risk that many people will be simultaneously attacking identical issues in an uncoordinated manner, which makes SciLifeLab’s coordinating role crucial to the work we are conducting in Sweden.”

Ulf Landegren, Professor of Molecular Medicine at Uppsala University.

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