There are a number of projects at University of Tübingen which focus on the Coronavirus SARS-CoV-2 and the infection it causes, COVID-19. Yet other research projects are looking at the economic and social effects of the Coronavirus crisis.
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Our immune system can efficiently fend off viral diseases. Two types of immune cells play an important role in this process: The T-cells, which firstly can directly destroy virus-infected cells and secondly enable the formation of efficient, virus-neutralizing antibodies by B-cells. These two cell types also play a crucial role in the immune defense against SARS-CoV-2 infection. Whereas antibody tests are already routinely performed, only little is known about the T-cell response against SARS-CoV-2 so far.
The research group of PD Dr. Juliane Walz at the Clinical Cooperation Unit Translational Immunology (KKE) of the University Hospital Tübingen and the Department of Immunology of the Interfaculty Institute for Cell Biology in Tübingen now succeeded in identifying the target structures (so-called T cell epitopes) for the T-cell response against SARS-CoV-2. For this work, now published in the renowned journal Nature Immunology, more than 180 volunteers were analyzed after convalescence from COVID-19. The T-cell epitopes identified in the study enabled the detection of SARS-CoV-2 T-cell responses in 100 percent of convalescent donors after infection. This was also true for patients in whom no antibody response could be detected.
Previous experience with two other corona viruses - SARS-CoV-1 and MERS-CoV-2 - as well as initial reports from convalescents’ after COVID-19 suggests that T-cell responses may also play a significant role in the defense against SARS-CoV-2, as is the case with all other viral infections. To characterize these SARS-CoV-2-directed T-cell responses the identification of the parts of the virus, so-called epitopes, which are recognized by the T-cells is fundamental. "These epitopes are not only important for the investigation and diagnosis of SARS-CoV-2 immunity, but may also represent the basis for the development of vaccines," says research group leader Juliane Walz.
In addition, the study, which was financed by the German Federal Ministry of Education and Research’s special funding line COVID-19, analyzed donor blood samples which were collected before the outbreak of the pandemic and thus had no contact with SARS-CoV-2. Strikingly, small amounts of SARS-CoV-2-directed T-cells, which recognize virus components, were identified in 81 percent of these unexposed donors. This could be due to previous contact of the donors with other human common cold corona viruses (HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV- HKU1) and sequence similarities of the SARS-CoV-2 T-cell epitopes with these HCoVs.
However, such cross-reactive T-cell detection is not equivalent to immunity against SARS-CoV-2: "The effect these preexisting cross-reactive SARS-CoV-2 T-cell responses in 81 percent of the population will be investigated further prospective studies," commented Juliane Walz.
Based on the findings of this study, the team of KKE (Medical Director: Prof. Dr. Helmut Salih) together with the Immunology (Director: Prof. Dr. Hans-Georg Rammensee) is currently developing a first clinical study, which will investigate a prophylactic vaccine against SARS-CoV-2, consisting of the here identified T-cell epitopes. This approach, which primarily aims at inducing T-cell responses against SARS-CoV-2, is further supported by first "long-term data" of Walz research group. First unpublished data of a follow-up study of the COVID-19 convalescent cohort - now six months after infection – still detects strong and even increasing T-cell responses against SARS-CoV-2, whereas the antibody responses, especially against the so-called spike protein, already showed a significant decrease.
Original title of the publication:
Nelde, A., Bilich, T., Heitmann, J.S. et al. SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition. Nat Immunol (2020).
The paper is available at the following URL: https://www.nature.com/articles/s41590-020-00808-x.
University Hospital Tübingen
KKE Translational Immunology
PD Dr. Juliane Walz
Otfried-Müller-Strasse 10, 72076 Tübingen
Phone: +49 (0)7071 29-88548
An international consortium involving the Institute of Tropical Medicine, Travel Medicine and Human Parasitology at the University of Tübingen and the Tübingen University Hospitals has received an EU Horizon 2020 Grant for the development and testing of a vaccine against COVID-19 in clinical trials. The consortium also includes the Department of Immunology and Microbiology at the University of Copenhagen (Denmark), the two companies AdaptVac and ExpreS2ion Biotechnologies (both in Denmark), the Department of Medical Microbiology at Leiden University Hospital (Netherlands) and the Laboratory of Virology at Wageningen University (Netherlands). The project partners are world leaders in their respective fields of research and cover all the relevant sub-areas of virus research and vaccine development necessary for the rapid clinical development of a vaccine against COVID-19.
On 27 March 2020, Tübingen’s Institute of Tropical Medicine, working with the Bernhard Nocht Institute of Tropical Medicine, the University Medical Center Hamburg-Eppendorf and the Robert Bosch Hospital in Stuttgart, started clinical trials under the title "Randomized controlled trial of hydroxychloroquine versus placebo for the treatment of adult patients with acute coronavirus disease 2019 - COVID-19." The study aims to clinically test the effectiveness of hydroxychloroquine against the coronavirus SARS-CoV-2. Hydroxychloroquine has been used for many decades for treating and preventing autoimmune and infectious diseases; as yet, there is no proof of efficacy for COVID-19. The new study is supported by Germany’s Ministry of Education and Research (BMBF) and is a model of international cooperation, which is especially important in these times. In an example of this, the Vietnamese-German Center for Medical Research in Hanoi provided 6,000 swab tubes at short notice because these could not be obtained in Germany.
With the support of the Coalition for Epidemic Preparedness Innovations (CEPI), the Tübingen-based company CureVac AG is working on the development of a vaccine against the new coronavirus SARS-CoV-2. The Institute of Tropical Medicine, Travel Medicine and Human Parasitology at the University of Tübingen and the Tübingen University Hospitals will carry out the first clinical trials of the potential vaccine developed in this research project.
The biopharmaceutical company CureVac was established with sponsorship from the University of Tübingen and is a pioneer in the preclinical and clinical development of mRNA-based drugs and vaccines. CEPI is a public-private partnership for accelerating the development of vaccines against emerging infectious diseases and is co-funded by Germany’s Ministry of Education and Research.
The agreement builds on the existing partnership between CureVac and CEPI to develop a rapidly deployable vaccine platform. It includes up to 8.3 million US dollars in funding from CEPI for accelerated vaccine development, manufacturing and clinical trials.
The Tübingen bioinformatics specialists, assistant professor Dr. Andreas Dräger, Alina Renz and Lina Widerspick from the Department of Computer-Based Systems Biology of Infections were able to identify a potential drug target for the treatment of the infectious disease COVID-19. In flow balance analyses (FBA), switching off a human enzyme stopped the reproduction of the virus without impairing cell growth. For their approach they used an integrated computer model with the novel coronavirus 2019-nCOV and human alveolar macrophages. The drug target identified is the enzyme guanylate kinase (GK1). GK1 inhibitors have already been described in the literature; their potential for treating COVID-19 infections is now to be tested experimentally.
Tübingen immunologists Ralf Amann, Ferdinand Salomon and Melanie Müller of the Interfaculty Institute of Cell Biology (IFIZ) at the University of Tübingen are working with innovative platform technology to develop a vaccine against the Coronavirus SARS-CoV-2. They insert coronavirus antigens into a virus vector that is harmless to humans. Injection of this virus vector does not cause the disease in humans, but instead triggers an immune reaction that is intended to protect against severe illness in the event of a subsequent infection. Various antigens may be introduced into the virus vector. Such a vaccine could therefore also provide protection against mutations of SARS-CoV-2 as well as against other coronaviruses. Germany’s Economics Ministry has put up additional funding of 1.3 million euros for the project; and the Carl Zeiss Foundation has made a further 150,000 euros available. The three researchers founded Prime Vector Technologies GmbH in October 2019.
What role do children play in the spread of the Coronavirus? The Tübingen University Children’s Hospital - Department of Paediatrics is seeking the answer to that question with a new study - jointly with three other University medical centers, headed by Heidelberg. The initiative for the study came from State Premier Winfried Kretschmann; the state of Baden-Württemberg is to cover the cost of around 1.2 million euros.
With a jointly-conceived screening study, the Tübingen University Hospitals and the Medical Centers in Freiburg, Heidelberg and Ulm determine how many children and their parents are currently infected with SARS-CoV2; and how many have had contact with the Coronavirus and have developed corresponding antibodies to protect them against it as a result. A total of 2000 households, i.e. 2000 children and 2000 parents, were surveyed and examined for this study.
The study included healthy children aged 1-10 and a parent of each. It excluded children and parents who had had a past infection with SARS-CoV2 proven by a test. (Families of “index patients” (with SARS-CoV2) are to be addressed separately in a follow-up project.)
“The progression of a Coronavirus infection may be different in children than in adults. What role children play in the spread of Coronavirus would be highly relevant in the current debate surrounding the re-opening of child care facilities and schools. This study could lead to recommendations to help protect both children and adults,” says Professor Axel Franz, Director of the Center for Pediatric Clinical Studies at the University Children’s Hospital.
The researchers expect their findings to include indications of whether there are differences in the infection rate depending on the ages of the children; whether children and parents infect each other, and to what extent the parents’ accommodation situation and profession play a role. Particularly important is any difference between children who had continued contact with other children in emergency child care and those who were solely in the care of their immediate family. The idea, procedure, and evaluation of the study is a joint effort at four locations; the first results from it are to be publicized as soon as possible due to the current situation.
Link to study:
Professor Axel Franz
Center for Pediatric Clinical Studies (CPCS) at the Tübingen University Children’s Hospital - Department of Paediatrics
E-Mail: cpcs @med.uni-tuebingen.de
How does the new Coronavirus (SARS-CoV-2) alter its genetic information? Which other infections occur in patients with COVID-19? Are there genetic risk factors which promote infections? Many genome researchers are pooling their expertise and sequencing infrastructure so as to make a scientific contribution to managing the COVID-19 pandemic. These activities are now being brought together officially in the German COVID-19 OMICS initiative (DeCOI), to accelerate research in the field. Researchers at more than 22 institutions are active in DeCOI - and that number is growing.
The central coordination is in the hands of Professor Joachim Schultze at the University of Bonn. Participants at the University of Tübingen include Professor Oliver Kohlbacher of the Interfaculty Institute for Biomedical Informatics (IBMI) and Dr. Sven Nahnsen at the Quantitative Biology Center (QBiC). At the University Hospitals Professor Olaf Rieß and Professor Stephan Ossowski, both of the Institute of Medical Genetics and Applied Genomics, and Professor July Frick of the Institute of Medical Microbiology and Hygiene are all members of the initiative.
The SARS-CoV-2 genome is being sequenced at many locations around the world in order to identify changes in the virus’s genetic code. The more these virus genomes are sequenced, the better researchers can understand its variations. With the analysis of related structures in individual viruses, scientists can draw conclusions about their origins and about different forms of the virus in the population.
All areas of genome research produce vast data sets which are analyzed using powerful computers. “Only by making proper connections between the clinical data and the genomic data can we make the biggest possible contribution to understanding COVID-19,” says Oliver Kohlbacher. The DeCOI alliance aims to answer many of the key questions faster by working together. DeCOI will work closely also with other initiatives to establish worldwide solid information to help deal with the crisis.
What do experts in the fields of virology, microbiology, hygiene, tropical medicine, immunology and internal medicine/ intensive care say about the current risks and measures regarding the Covid-19 pandemic? How certain/ reliable is the current state of knowledge? Researchers at the University Hospitals in Tübingen and Hamburg-Eppendorf launched a survey aimed at finding out.
The doctors and scientists surveyed supported the maintaining of social distancing rules and the ban on public gatherings - this was shown by the interim results from the survey. The answers of 178 respondents were evaluated and compared with the responses of 197 persons questioned in a first round of the survey. Experts with degrees in virology, microbiology, hygiene, tropical medicine, immunology, internal medicine and intensive care took part in the anonymous online survey. The results may be seen as a reflection of opinion in Germany at the current time.
The survey was conducted by a team headed by Professor Michael Schindler (Virology, Tübingen) and Professor Steffen Moritz (Psychiatry, Hamburg) and was sponsored by the Gesellschaft für Virologie (GfV), Deutsche Gesellschaft für Hygiene und Mikrobiologie (DGHM), and the Deutsche Gesellschaft für Innere Medizin (DGIM).
Initial results of an interim evaluation
The current survey shows that more than 70 percent of the respondents approved of, and even favored, the 2-meter distance rule and the ban on public gatherings as potential measures for monitoring and containing SARS-CoV-2. By contrast, only a small proportion viewed closing schools and kindergartens as an important measure (less than 5 percent). The responses regarding the usefulness of covering the mouth and nose were ambivalent, however.
Approval of the measures brought in by the German government has fallen and is currently at just 50.1 percent; in the first round of the survey in March, approval was 80.7 percent.
The role of the media is increasingly seen as critical - only 59 percent saw the media as neutral (79.7 percent in the first round of the survey). The experts’ estimation of the virus’s course and severity had changed little or not at all. On average, they assume that up to 50 percent of the population will be infected with the Coronavirus. The experts are assuming that around 5 percent of patients will have to be treated in intensive care, with one percent dying of the virus.
Tübingen University Hospitals
Institute of Medical Virology and Epidemiology of Viral Diseases
Professor Dr. Michael Schindler
For the majority of the population, the current Covid-19 pandemic is a big challenge and a burden. It has been empirically shown that measures such as quarantine and social distancing have manifold negative consequences on mental health - such as depression, anxiety and sleep disorders. At the same time, studies show the preventative effects of exercise and social support with regard to mental health problems.
In this context, Sebastian Wolf (Institute of Psychology and Institute of Sports Science) and Professor Gorden Sudeck (Institute of Sports Science), are investigating the protective effects of regular physical activities and social support on various parameters such as anxiety, depression and sleep disorders as a result of the Covid-19 pandemic. Their longitudinal study will look at the influence of changes to these factors at three points in time. A further goal is to create an empirical basis for the quick development of online modules to promote exercise and social support.
The study is conducted via an online questionnaire. Data is to be collected in: April, Mai/June and at the end of the pandemic.
In an international research project, Tübingen-based economist Professor Gernot Müller has surveyed 200 households in the USA every day since 10 March 2020 about their expectations and fears in the face of the coronavirus crisis. The project involves researchers from the Universities of Tübingen and Bonn in Germany, and Brandeis in the United States. Households are asked what effects they expect the coronavirus pandemic to have on GDP in the US, and on their personal income. They are also asked about their inflation expectations. At the same time, the researchers are monitoring whether the pandemic is influencing behavior - for example, whether households are savings more. A model analysis is then used to quantify the impact of these expectations on economic development in the United States.
What are the effects of the Coronavirus pandemic on high-performance sport? Researchers at the Sports Medicine section of the Tübingen University Hospitals are exploring that question, headed by Professor Dr. Christof Burgstahler. They have developed an online survey which is being publicized by four major German sports association and the state of Baden-Württemberg’s sports governing body.
The survey has been available since 21 April for athletes to fill out anonymously. More than 600 sportsmen and 600 sportswomen did so in the first eight days alone. The respondents included 278 professional sportspersons, 471 top German athletes, and 564 top state athletes. 406 members of a national team are also in the group.
The initial results show that infection rates are not higher in high-performance sports. Nearly 97 percent of the respondents said in their first assessment that the crisis was having only a mild effect on their playing of their sport. The proportion of athletes who are worried about their health (33 percent) or sporting future (53 percent) was also large. Only 14 percent said they were concerned about their financial situation.
The survey was additionally launched in Austria at the start of May. The Tübingen Sports Medicine researchers will know next week if the results are similar there.
How are people with anxiety and depression managing their day-to-day lives amid the Coronavirus pandemic? How do those affected by eating or compulsive disorders, acoustic or optical hallucinations, or panic attacks deal with the pandemic? And how do those with mental illnesses generally fare in comparison with the rest of the population? This and other questions are being explored by the University of Tübingen working group in Clinical Psychology and Psychotherapy, headed by Professor Dr. Jennifer Svaldi in cooperation with the Universities of Münster and Osnabrück. More than 2000 people with and without mental disorders have voluntarily taken part in the online study.
Professor Dr. Jennifer Svaldi
Department of Psychology
Clinical Psychology and Psychotherapy
Countries around the world have taken drastic measures to contain the COVID-19 pandemic. They include the temporary closure of schools, kindergartens, sportsgrounds, playgrounds and social institutions, as well as a shift to forms of online learning within the framework of homeschooling.
In a collaboration between Professor Dr. Sascha Neumann of the University of Tübingen Institute of Education (IfE) and the University of Luxembourg, an international study was launched on 07 May 2020 to investigate the effects of these measures on the wellbeing of children and teenagers, depending on their families’ socio-economic situation. The study’s goal is to obtain data on the short- and middle-term consequences for kids and young people which arise from the measures to contain the pandemic and which should be considered in future political decision-making. It is also expected that teachers and parents will be able to harness the results as key data forming the basis of appropriate responses to the social consequences for children and teenagers.
The study - COVID KIDS - Understanding the influence of COVID-19 on children’s and adolescents’ school experience and subjective well-being - is based on an online survey in five different languages (German, English, French, Luxemburgish, Portuguese), which was conducted in several countries. The survey directly addresses children and teenagers between the ages of 6 and 16.
All interested children and teenagers are invited to take part in the anonymous survey!
Link to survey:
Professor Dr. Sascha Neumann
Institute of Education
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