Since the outbreak of the pandemic, scientists at the German Center for Infection Research (DZIF) have been working at full speed to contain and treat the new infectious disease COVID-19. On this page, we bundle important developments and results for you in the following overarching topic areas:
- Prevention: Vaccine development
Information on the vector-based vaccine development at the DZIF
- Treatment: Emergency drugs
About antiviral drug development
- Understanding the virus
New insights into the virus and its infection mechanisms
- Clinical trials
Information on ongoing studies as well as on the results of clinical studies
- Diagnosis: Rapid and safe tests
Information on diagnostics
- Links on the topic
An overview of all news from DZIF research can be found here.
Prevention: Vaccine development
DZIF scientists in München, Marburg and Hamburg have been developed a vector vaccine based on genetic information of a SARS-CoV-2 surface protein which is inserted into a vector. Two vectors are being developed in parallel: A modified smallpox virus which has been rendered harmless (MVA) and the measles virus. The latter is currently being further developed by the Canvirex company.
The clinical trials for testing the MVA virus have not yet been fully completed. Interim analyses have shown promising results with 100 percent seroconversion in unvaccinated subjects and good immunological responses, even as a booster vaccine. Nevertheless, the current vaccine is not adapted to new virus variants and since there are already many established COVID-19 vaccines in registration, the development program for this vector vaccine is not being pursued at this time. However, promising other applications for the MVA platform are being pursued, such as the further development of a vaccine against the MERS virus.
Treatment: Emergency drugs
Finding new inhibitors against coronaviruses
In previous research, scientists around DZIF scientist Prof Thomas Schulz and Prof John Ziebuhr have succeeded in identifying 300 substances from a collection of around 60,000 small-molecule compounds that are able to inhibit the human coronavirus HCoV-229E. So far, eight of these substances have been shown to effectively inhibit also SARS-CoV-2. The DZIF is funding their further research with 440,000 €.
The DZIF is also involved in various other drug developments:
SARS-CoV-2 viruses can hide from recognition by the immune system when infecting cells, thereby delaying the onset of the immune response. In a mouse model, scientists around DZIF researcher Professor Gunther Hartmann from the University Hospital Bonn have demonstrated that stimulation of a special cellular virus-detecting immune receptor (RIG-I) can lead to early activation of the immune response and hence an overall faster reaction to viral infection. RIG-I was activated by systemic application of synthetic RNA.
A Munich research team with DZIF scientist Ulrike Protzer has developed a protein which has reliably prevented infection by the virus and its variants in cell culture tests. The scientists have combined the ACE2 protein with part of a human antibody protein, creating an active ingredient that blocks the virus's spike protein. In cell culture tests it was able to completely neutralise the virus and prevent infection.
A DZIF research group led by Professor Florian Klein at the University Hospital Cologne isolates antibodies from the blood of convalescents that render the SARS-CoV-2 virus harmless. They could be used as a drug against COVID-19—for prevention and therapy.
Together with the Helmholtz Centre for Infection Research (HZI), we have developed a concept to form a National Alliance for Pandemic Therapeutics (NA-PATH). With this, we want to specifically boost the research and development of widely effective therapeutics in order to be better prepared for future outbreaks due to viral pathogens with pandemic potential and to be able to quickly offer effective therapeutic options in the event of a crisis. Overcoming the current COVID-19 pandemic is made considerably more difficult by the lack of antiviral agents.
Prof. Rolf Hilgenfeld and his team at the University of Lübeck succeeded in elucidating the main protease’s precise structure, and consequently develops a first inhibitor termed RHCDS-13b into a drug.
MHH professor and DZIF scientist Thomas Pietschmann leads the German part of an international consortium of scientists. This research network is searching for substances that act against SARS-CoV-2 in the world's largest substance repurposing bank "ReFrame".
Infection biologists from the German Primate Center - Leibniz Institute for Primate Research in Göttingen, together with DZIF colleagues at Charité Universitätsmedizin Berlin, have investigated how the novel coronavirus SARS-CoV-2 penetrates cells. They have identified a cellular enzyme that is essential for viral entry into lung cells: the protease TMPRSS2. A clinically proven drug known to be active against TMPRSS2, Camostat Mesilate, was found to block SARS-CoV-2 infection and might constitute a novel treatment option.
Understanding the virus
Infection with common cold coronaviruses can trigger broad cross-immunity against SARS-CoV-2 proteins
Researchers at the University Medical Center Hamburg-Eppendorf have demonstrated cross-reactive immune responses to another SARS-CoV-2 protein besides the spike protein. The research team found a broad immune system T cell response to the RNA-dependent RNA polymerase of SARS-CoV-2 in blood samples from COVID-19 patients as well as from subjects who were never infected with SARS-CoV-2. The T cells of the never-infected probands presumably arose from previous infection with other common cold coronaviruses and cross-reacted with the SARS-CoV-2 RNA polymerase in the tests. The research may help advance the development of vaccines and therapies against corona- and other respiratory viruses.
The DZIF is researching the virus in several projects:
Effective drugs against viral diseases like COVID-19 are urgently needed now and in the future. The DZIF scientist and bioinformatician Andreas Dräger and his team from the University of Tübingen are working on a computer-based method that can help to accelerate the time-consuming identification and development of antiviral agents. Using a novel analysis technique that applies to any virus and host cell type, the research team around Dräger has created a model to detect additional host cell targets that allow inhibiting SARS-CoV-2 replication.
In a case study, DZIF scientists at the University Medical Center Hamburg-Eppendorf investigated the T-cell response of a cancer patient, who was suffering from prolonged COVID-19. No B cells were detectable in the patient’s peripheral blood, entailing that she had no possibility of forming SARS-CoV-2 antibodies. SARS-CoV-2 virus particles were detectable in the patient for nearly three months after infection with the virus. The study provides clues as to how the development of a specific immune response in patients might be influenced by therapies for cancer or autoimmune diseases.
Infection with SARS-CoV-2 leaves some people almost unaffected, while others develop life-threatening COVID-19 symptoms. A team of scientists has now discovered that severe courses of the disease are not only marked by strong immune activation and inflammatory reactions, but also by a dysfunctional endothelium, in other words, the vascular system: If this barrier between blood flow and tissue is damaged, the patient’s condition deteriorates.
A new study from Munich shows that the immune system develops a high-quality antibody response after a total of three encounters with the viral spike protein of SARS-CoV-2. These antibodies can also efficiently neutralise the omicron variant. In this regard, a breakthrough infection with SARS-CoV-2 after two vaccinations achieves the same protective effect as an additional booster vaccination. For the study, researchers from Helmholtz Munich, LMU and TUM followed the immunity of vaccinated and recovered individuals over two years. It was led by DZIF scientist Prof. Ulrike Protzer.
Cell culture studies show SARS-CoV-2 variant Omicron evades antibodies generated after infection and vaccination and is resistant to several therapeutic antibodies. In contrast, antibodies induced upon triple immunization with BioNTech-Pfizer or heterologous vaccination with Oxford-AstraZeneca/ BioNTech-Pfizer inhibited the Omicron spike with increased efficiency. Therefore, booster and heterologous vaccination could provide stronger protection against the Omicron variant.
SARS-CoV-2 coronavirus enters the body via the respiratory tract and lungs and airways are the obvious center of the disease symptoms. However, it was shown early on that many other organs and the blood vessels are also affected. Neurological symptoms can occur in both the acute and late phases of COVID-19 disease. These include frequently occurring impaired taste perception or, for example, epileptic seizures and states of confusion. Investigation results show that the coronavirus can indeed enter the cell via the ACE2 receptor formed by some endothelial cells and trigger a characteristic pathology that can be recognised under the microscope. A central finding is that endothelial cells and blood-brain barrier are destroyed in this way.
After infection with SARS-CoV-2, some infected individuals respond with an exaggerated immune response to the virus. Severe inflammation of the lungs and other organs can be the result. Researchers at the University Hospital of Cologne and the DZIF are investigating the effect of the viral spike protein on the innate immune system, which is strongly associated with severity of disease. The research team has been able to show that certain white blood cells (macrophages, also known as phagocytes) are massively stimulated by the viral spike protein to produce the pro-inflammatory signalling molecule interleukin 1. Macrophages belong primarily to the innate immune system, which is distinguished from the acquired immune system.
For more than a year, the group around Tübingen’s DZIF scientist Andreas Dräger has worked on a computer model that identifies weaknesses of the virus and, thus, potential attack points. Previously, the researchers have already identified a human enzyme as such a promising target. Their latest study confirms this result. Furthermore, the bioinformaticians show new attack points and demonstrate that they also apply to the new mutants.
DZIF scientists Prof. Rolf Hilgenfeld and Dr Albrecht von Brunn discovered how SARS viruses enhance the production of viral proteins in infected cells, so that many new copies of the virus can be generated. Other coronaviruses apart from SARS-CoV and SARS-CoV-2 do not use this mechanism, thereby providing a possible explanation for the much higher pathogenicity of the SARS viruses.
What exactly happens when the corona virus SARS-CoV-2 infects a cell? In an article published in Nature, a team from the Technical University of Munich (TUM) and the Max Planck Institute of Biochemistry and paints a comprehensive picture of the viral infection process. For the first time, the interaction between the coronavirus and a cell is documented at five distinct proteomics levels during viral infection. The result is a freely accessible dataset that provides information on which cellular proteins the viral proteins bind to and the effects of these interactions on the cell.
How protective is a COVID-19 combination vaccine?
Up until now, there were no data available to indicate to what extent the human organism would react to a combined vaccination from AstraZeneca and an mRNA vaccine and start to form antibodies. A team of researchers has now proven that the antibody response is much stronger with the combination vaccine than with two doses of the AstraZeneca vaccine. The immune response to combination vaccines has proven to be just as good as the antibody response after two vaccinations with the mRNA vaccine from BioNTech/Pfizer.
The DZIF is involved in further clinical trials:
DZIF researchers from the Charité – Universitätsmedizin Berlin and the University of Bonn were able to identify four substances which inhibit SARS-CoV-2 replication in the host cell. The most pronounced antiviral effect was associated with niclosamide, which the researchers had shown to be effective against the MERS coronavirus during an earlier study. A phase II trial will test the safety, tolerability, and efficacy of niclosamide combined with camostat (another licenced drug) in patients recently diagnosed with COVID-19. Anyone interested in participating in the study can obtain more information from the Charité Research Organisation at +49 30 450 539 210 or email@example.com.
What started as a preliminary evaluation of laboratory data in 2020 has since evolved into the largest-ever investigation of viral load levels in patients with SARS-CoV-2. A team of researchers from the German Center for Infection Research and Charité – Universitätsmedizin Berlin have now analyzed the PCR samples of more than 25,000 persons with COVID-19. Working under the leadership of Prof. Dr. Christian Drosten, the team determined the viral loads of each individual sample and used their results to estimate levels of infectiousness. No notable differences in viral load levels were recorded among SARS-CoV-2-positive individuals aged between 20 and 65 years. Viral loads were found to be lowest in very young children (0 to 5 years).
A central participant registry is created at the DZIF; those interested can register there. Supported by the German Ministry of Education and Research (BMBF), the DZIF Clinical Trial Unit at the University Hospital Cologne is setting up a platform across Germany and Europe that provides an overview of experienced clinical trial sites for testing vaccines against the new coronavirus.
In order to attain an overview of all clinical trials taking place in Germany and to provide an effective network for the researchers, the Clinical Trial Unit of the DZIF at Cologne University has, for the first time, created a registry for all clinical trial activities taking place in Germany - involving now SARS-CoV-2/COVID 19. For the first time, not only DZIF study activities are presented here: In order to provide a comprehensive overview in the current pandemic situation of planned and already active COVID-19 studies in Germany, the Clinical Trial Unit is cooperating with researchers from various German Centers for Health Research and other networks.
The need for vaccine studies continues to be high, as many questions remain unanswered about the safety, efficacy and possibly necessary adaptation of vaccines to emerging virus variants. In order to coordinate these studies, the European Union is funding the creation of the new VACCELERATE vaccine research network. To date, 26 partner institutions from 21 European countries are participating in the network. VACCELERATE will be the pandemic preparedness network that will establish a structure for the quick and effective development and testing of vaccine candidates across Europe, also beyond Corona.
Following the example of the LEOSS case registry, which has been collecting and evaluating clinical data of COVID-19 patients throughout Europe since March 2020, the German Center for Infection Research is now establishing the "LEOSS.sero-survey" platform. This platform allows for the timely comparison and cross-analysis of different antibody studies on immunity or seroprevalence in the population. The project is led by scientists at the Helmholtz Centre for Infection Research (HZI) and is implemented in cooperation with the Helmholtz Federated IT Services (HIFIS).
The DZIF and the German Society of Infectious Diseases (DGI) have set up a European case registry which is to collect clinical data of patients with SARS-CoV-2 infection. A special feature of this new registry is that all the data collected will be made available to the scientific community for use in joint analyses. LEOSS is multilingual and is to be implemented across the entire EU. By mid-January 21, 6000 patient data had already been recorded.
Diagnosis: Rapid and safe tests
DZIF experts at Charité support Colombian SARS-CoV-2 diagnostic efforts
Colombia currently houses several million refugees and migrants. The success of the country’s pandemic control measures will depend on the careful monitoring of infection levels, including within this particularly vulnerable population. Experts from Charité – Universitätsmedizin Berlin and DZIF will support the efforts of local health care authorities by delivering SARS-CoV-2 tests and training laboratory staff to use them. A particular emphasis will be placed on monitoring the Mu variant, which has spread widely throughout Colombia. The research team plans to develop a new PCR test that can simultaneously detect virus variants that are particularly relevant for Colombia, such as beta, delta and lambda, in addition to Mu.
Researchers develop first diagnostic test for novel coronavirus in China
Shortly after the outbreak in China in January 2020, DZIF scientists at Charité – Universitätsmedizin Berlin developed the first test for SARS-CoV-2. Using the virus’s genetic information, Prof. Christian Drosten and his team succeeded in developing a test based on the PCR (polymerase chain reaction) technique. The test is currently being used worldwide. Now the aim is to refine the test methods as well as to develop and validate new tests which can be used to determine immune responses in the human body. “We will only be able to develop a vaccine once we know what happens inside the patient’s body,” Drosten explains.