SARS-CoV-2 / COVID-19

Since the end of 2019, a novel virus that can cause respiratory diseases and pneumonia has been spreading worldwide. The pathogen SARS-CoV-2 belongs to the coronavirus family and is closely related to the SARS virus, which caused a pandemic in 2002. Here we will keep you informed about current developments in research and provide answers to the most important questions.

The researchers at the HZI focus on the development of active substances and vaccines against the virus and want to decode the mechanisms of disease development and progression. We are also studying the dynamics of the spread of infection in the population. The HZI-developed app for disease control (SORMAS) is now also available for the current SARS-CoV-2 pandemic.

Below you will find a selection of the numerous HZI projects underway to research the novel coronavirus:

1. Basic research on the novel coronavirus

  • Dysregulation of neutrophils in severe COVID-19
    Scientists from the HZI, in cooperation with other centres of the Helmholtz Research Field Health and University Hospitals across Germany, determined changes in immune cell composition and activation in mild versus severe COVID-19 patients. Using single cell analysis at the proteomic and transcriptomic levels and ‘big data’ approaches, the scientists analysed the blood from COVID-19 patients in two different cohorts recruited in two centres. Severe cases of COVID-19 disease were identified to be associated with profound changes in immune cells. Particularly, dysfunctional neutrophils were detected, which might contribute to ineffective host immune response. The detailed insights into the systemic immune response to SARS-CoV-2 infection were gathered in a publication in Cell. This study suggests the possibility of specifically targeting altered immune cells in severe COVID-19 patients. 
    Original publication: Schulte-Schrepping et al. 2020 Cell. https://doi.org/10.1016/j.cell.2020.08.001

    Contact: Prof Yang Li, Department Computational Biology for Individualised Medicine at Centre for Individualised Infection Medicine (CiiM), Dr Antoine-Emmanuel Saliba, Research group Single-cell Analysis at the Helmholtz Institute for RNA-based Infection Research (HIRI) 

    Cooperation partners: German COVID-19 OMICS Initiative (DeCOI), Prof Schultze (University Bonn, DZNE), Prof Sander (Charité Berlin), Prof Sawatzki (Campus Virchow-Klinikum), Prof Nattermann (University Hospital Bonn, DZIF), Dr Anna Aschenbrenner (LIMES Institute at the University of Bonn)
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2. Digital tools for infection management

  • SORMAS: Digital Infection Management for Public Health Authorities 
    SORMAS is a specialised open-source software (Surveillance Outbreak Response Management and Analysis System), which has now been specially adapted to meet the needs of coping with the corona pandemic. The HZI has developed SORMAS together with its partners since the West African Ebola outbreak in 2015. SORMAS is now being used in Germany, Switzerland, France, Ghana, Nigeria and Fiji and covers a population of over 300 million people. The newly implemented coronavirus module mainly improves the digital management of quarantine and other infection control measures. At the same time, SORMAS generates real-time data for ongoing risk assessment at national and international level. SORMAS is available as open source software free of license and offers interfaces to various other digital systems.

    Further information can be found on these websites: 
    SORMAS-ÖGD-COVID-19: Contact Person Management in the Public Health Service (ÖGD): https://www.sormas-oegd.de/  
    SORMAS@DEMIS: Integrated and networked case and person management on COVID-19 for the Public Health Service: https://sormas-demis.de/
    SORMAS International: https://sormasorg.helmholtz-hzi.de/

    Contact: Prof Gérard Krause, Department of Epidemiology at the HZI

    Cooperation partners: Lower Saxony State Health Authorities, Public Health Authorities, Academy of Public Health Services, Robert Koch Institute, Symeda GmbH, Braunschweig, Netzlink Informationstechnik GmbH Braunschweig.
     
  • CORESMA - Effective collaboration with Big Data project on Covid-19
    The HZI coordinates the EU project CORESMA (Covid-19 Outbreak Response combining E-health, Serolomics, Modelling, Artificial Intelligence and Implementation Research). This project aims to close existing gaps between clinical, epidemiological and immunological information in order to better respond to the pandemic. European researchers from the Netherlands, Switzerland and Germany, as well as partners from China, Côte d'Ivoire and Nepal are working together to achieve this goal. They are collecting real-time clinical data via the SORMAS app developed by the HZI in 2014, with which outbreak data can be recorded locally and transmitted to health authorities. The focus here is on particularly endangered countries, including Ghana and Nigeria in addition to the Ivory Coast. In addition, existing cross- or partial immunity against SARS-CoV-2 is to be investigated in Germany and Nepal. The data collected will help to better assess the transmission of the virus and evaluate the effectiveness of measures against its spread.

    Contact: Prof Gérard Krause, Department of Epidemiology at the HZI

    Cooperation partners: Dr Nicole Schneiderhan-Marra (NMI Natural and Medical Sciences Institute at the University of Tübingen), Prof Mirjam Kretzschmar (Dutch National Institute for Public Health and the Environment, RIVM), Prof Kaspar Wyss (Swiss Tropical and Public Health Institute, Swiss TPH)
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3. Diagnostics / Diagnostic tools

  • MULTICOV-AB: a multiplex-based coronavirus antibody test
    The detection of an immune response mediated by specific antibodies is an essential indicator of whether immune protection against SARS-CoV-2 already exists. Due to the often unsatisfactory precision of commercially available test systems and the question of the role of cross-immunity to other endemic coronaviruses, there is a need to develop a test procedure that can test against antibodies and against different coronaviruses at the same time. In a comparative study with four commercially available antibody tests, MultiCoV-Ab has shown the highest sensitivity and specificity. This method is already being used in the MuSPAD antibody study and provides valuable evidence for future vaccination strategies. As prevalence increases, reliable antibody detection will also play a relevant role in identifying those individuals who are already immune and therefore are expected to have a low risk of infection or disease. This will play an increasing role, especially in medical and nursing professions, but also in many other occupational groups, and visitors from very old or immunocompromised people. People with this test result would then no longer be subject to travel or activity restrictions. Negative effects of non-pharmaceutical measures such as contact barriers could thus be significantly reduced. 

    MultiCoV-Ab is already being used in the MuSPAD antibody study in Germany. The use in Colombia and Nepal is in preparation.

    Contact: Prof Gérard Krause, Dr Monika Strengert, both Department of Epidemiology at the HZI

    Cooperation partners: NMI Natural and Medical Sciences Institute at the University of Tübingen
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4. Vaccine development/drug research/drug screening

  • Testing and development of inhibitor applied by inhalation against the novel coronavirus
    Medical researchers around the world are looking for ways to prevent the proliferation of the novel coronavirus with the help of active substances. A team from the University of Lübeck and the HZI has found a promising approach. The basis for this is the analysis of the three-dimensional structure of functional viral proteins. Using the high-intensity X-ray light from the synchrotron source BESSY II at the Helmholtz-Zentrum Berlin (HZB), researchers were able to decipher the three-dimensional architecture of the viral main protease of SARS-CoV-2. This enzyme is involved in the replication of the viruses. Using the crystal structure, the University of Lübeck (Prof Hilgenfeld) was able to transform a previously developed lead compound into a potent inhibitor.

    Dr Katharina Rox, DZIF scientist at the HZI in Braunschweig, tested larger amounts of the inhibitor in healthy mice and observed no adverse effects. The compound reaches the best concentrations at the target sites when applied under the skin or by inhalation. In further work, the compounds will be optimized medicinal-chemically and characterized with regard to their pharmacokinetic properties.

    Contact: Dr Katharina Rox, Head of Pharmacokinetics/Pharmacodynamics Unit at DZIF, Department of Chemical Biology at the HZI, Prof Mark Brönstrup (Department of Chemical Biology)

    Cooperation partners: University of Lübeck

    Original publication: Linlin Zhang, Daizong Lin, Xinyuanyuan Sun, Ute Curth, Christian Drosten, Lucie Sauerhering, Stephan Becker, Katharina Rox, Rolf Hilgenfeld, Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors, Science 2020, DOI: 2010.1126/science.abb3405
     
  • Proof of concept studies of a SARS-CoV-2 vaccine with recombinant spike protein
    Since the beginning of the SARS-CoV-2 outbreak, many research groups have been trying to develop a prophylactic vaccine. The HZI approach is based on a so-called subunit vaccine that can induce protective immunity and has a good safety profile for immunocompromised individuals. Ideally, it is administered via the mucous membranes. It is also comparatively easy to produce in sufficient quantities to meet the needs of the current pandemic. In this respect, the spike (S) protein is a promising vaccine antigen, as it has already been shown for SARS-CoV and MERS-CoV that the stimulation of neutralizing antibodies against the S protein prevents infection. The project aims to provide proof-of-concept for an intranasal S-based vaccine with c-di-AMP as adjuvant. The scientists want to prove that the vaccine stimulates virus-neutralizing humoral immune responses and can protect vaccinated mice against SARS-CoV-2. They will also use silico algorithms to generate synthetic S-variants with optimized sequences that are able to stimulate immune responses against different SARS-CoV variants and possibly also cross-reactively against SARS and MERS. This would potentially lead to a situation where large parts of the population would also be protected against future coronaviruses. The project includes the development of the vaccine candidate and preclinical testing.

    Contact:Prof Carlos A. Guzmán, Department of Vaccinology and Applied Microbiology at the HZI

    Cooperation partners: Prof Luka Cicin-Sain, Dr Joop van den Heuvel, Prof Alice McHardy, Prof Ulrich Kalinke
     
  • Repurposing of an active substance against SARS-CoV-2
    Prof Thomas Pietschmann, researcher in the Excellence Cluster RESIST and at TWINCORE Hannover, is heading the German branch of an international research network, which is investigating whether approved drugs are effective against the coronavirus SARS-CoV-2. The "ReFrame" drug collection of Scripps Research (USA) contains around 14,000 approved drugs as well as active compounds for which extensive safety data are already available with regard to their use in humans. This so-called repurposing - the use of a proven active compound for new indications - shortens the drug's development phase.

    In a first step, the scientists in Hanover use high-throughput processes to search for active ingredients that inhibit the replication of viruses. For these candidates, the mode of action, the effect on lung cells and the optimal dose are analysed. Based on these results, drug candidates from the ReFrame database are to be rapidly transferred into clinical studies.

    Contact: Prof Thomas Pietschmann, TWINCORE Hanover

    Cooperation partners: MHH (Prof Schulz, Institute of Virology), University of Bern, Scripps Research, German Centre for Infection Research (DZIF), HZI Department of Chemical Biology (Prof Brönstrup)
     
  • SCORE: Swift Coronavirus therapeutics response
    The HZI is also involved in the EU project SCORE. The aim of the project is the development of antivirals against COVID-19 and future coronavirus outbreaks. Thereby, different screens are deployed to find compounds (re-purposed or new ones). The role of the HZI is the pharmacological characterization of hit and lead compounds. HZI will conduct ADME assays as well as pharmacokinetic (PK) studies to select the appropriate candidate and inform for dosing regimens for efficacy studies. The screening hits are currently validated and HZI is waiting for compounds to be tested. The next steps after successful hit validation are in vitro characterization of compounds via ADME-assays before performing PK studies.

    Contact: Katharina Rox, Department Chemical Biology, DZIF PK/PD unit

    Cooperation partners: Eric Snijder (LUMC), Johan Neyts (KU Leuven), Bruno Canard (Aix-Marseille University), Frank van Kuppeveld (Utrecht University), Volker Thiel (Uni Bern), Rolf Hilgenfeld (Uni Lübeck), Marnix van Loock (Janssen Pharmaceutica)
     
  • MEMUMAB Pipeline
    Monoclonal antibodies (mAb) represent a promising approach for the therapy of various diseases. Also in the context of the global SARS-CoV-2 pandemic, mAbs are being developed for both a preventive and therapeutic approach to COVID-19 diseases. Our analyses of SARS-CoV-2 specific memory B cells from the blood of convalescent COVID-19 patients showed that the proportion of spike and receptor binding domain (RBD)-specific memory B cells varies in different patients. To analyse which SARS-CoV-2 specific antibodies are produced by different patients, the MEMUMBAB pipeline was established. Spike-labelled memory B-cells are isolated from the blood of convalescent COVID-19 patients, RNA is isolated from SARS-CoV-2 specific memory B-cells at the single cell level and the variable regions of the heavy and light antibody chains are sequenced. Based on the sequence information, DNA fragments of the variable regions are then synthesised and cloned into lentiviral IgG expression vectors. After stable transduction of a cell line containing the heavy and light antibody chains, supernatants are collected to study antibody properties. In particular, the SARS-CoV-2 binding and neutralisation properties of the antibodies are determined from the supernatants. In this way, monoclonal antibodies with promising properties can be identified and, if necessary, brought into clinical development. The developed method is potentially applicable for all infectious diseases and is therefore also of importance for future outbreaks of infectious diseases.

    Contact: Prof Ulrich Kalinke, Experimental Infection Research, TWINCORE Centre for Experimental and Clinical Infection Research
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5. Modelling

  • Mathematical modelling provides new insights for risk assessment of the coronavirus pandemic
    Scientists at the HZI and Forschungszentrum Jülich simulated the effect of various conditions on the development of the SARS-CoV-2 epidemic in Germany. Their results suggest that the restrictions on social life are effective and that a further slowing of the spread is possible. The HZI scientists around the physicist Prof Michael Meyer-Hermann described a method to evaluate the effects and the situation on a daily basis, thus providing decision makers in politics with a basis for assessing the situation. A decisive variable in the description of the spread of an infectious pathogen is the reproduction number. The basic reproduction number indicates how many people an infected person infects on average. It is an important indicator of how quickly an epidemic spreads. Daily updated values for the SARS-CoV-2 reproduction number can be found at http://secir.theoretical-biology.de.

    The modelling significantly contributed to the Helmholtz position paper on the epidemiological situation from 14 April 2020.

    Contact: Prof Michael Meyer-Hermann, HZI Department of Systems Immunology at BRICS (Braunschweig Integrated Centre of Systems Biology)

    Cooperation partners: Forschungszentrum Jülich (Prof Wolfgang Marquardt), Department of Epidemiology at the HZI
    In addition, a joint study with the ifo Institute, which calculates the health and economic scenarios for easing pandemic-related restrictions, was published on 13 May 2020.
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6. Epidemiology & Transmission

  • Nationwide antibody study on the spread of SARS-CoV-2 infections (MuSPAD)
    The Multilocal and Serial Prevalence Study on Antibodies against SARS-2 Coronavirus in Germany (MuSPAD) is one of the most comprehensive and largest antibody studies in Germany. The actual seroprevalence of COVID-19 in the population is crucial to establish vaccination strategies against COVID-19, to quantify a possible under-coverage of infected persons, to better identify risk groups and to better understand the temporal and geographical spread of the pandemic

    The main objective of this study is to determine the proportion of the population that has antibodies in their blood against SARS-CoV-2 and is therefore likely to have been infected with the virus. This will be done for each participating county, also in comparison to the other counties. In addition, different age groups and self-reported symptoms of SARS-CoV-2 infection will be analysed. Another part of this study is to follow the course of the infection over a year, as well as to determine the antibody concentration in the blood of actually positively reported COVID-19 patients several times, in order to gain insight into how long a person is immune to the virus. People are to be tested in up to eight districts throughout Germany, with up to 50,000 people aged 18 years and older able to take part in the study within one year. After four months, the antibodies of the people in the participating districts will be tested again in order to observe the spread of the virus, also with regard to changes in the measures, and to document the progress of the "infestation" of the population. The HZI has already examined up to 3000 test persons in five cities, in November and December in Magdeburg (1st round) and Freiburg (2nd round). In MuSPAD, the MultiCov-Ab antibody test developed by the HZI and NMI (Natural and Medical Sciences Institute at the University of Tübingen) is also being used.

    Contact: Prof Gérard Krause, Department of Epidemiology at HZI
     
  • SARS-CoV-2 outbreak investigation in the meat industry: role of aerosol transmission
    In this project, we studied a SARS-CoV-2 outbreak in a meat plant in Germany. Our results suggest climate conditions and airflow as factors that can promote efficient spread of SARS-CoV-2 via distances of more than several meters and provide insights into possible requirements for pandemic mitigation strategies in industrial workplace settings. The results have been peer-reviewed and were published in the journal EMBO Molecular Medicine.

    Contact: Prof Melanie Brinkmann, Research group Viral Immune Modulation at the HZI

    Cooperation partners: Prof Adam Grundhoff (Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology), Prof Nicole Fischer (University Medical Center Hamburg-Eppendorf)
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Coronavirus

The coronaviruses are a family of viruses that includes a series of very different pathogens. These viruses usually infect mammals, rodents, and birds, but only few coronaviruses adapted to humans. They did this with great success: About one third of all typical "common colds" and some cases of diarrhoea as well are caused by these RNA Viruses, which are the largest of their kind. [more]

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With your donation to the HZI you directly support innovative coronavirus research projects that contribute to solutions for the containment of the virus and the identification of possible therapies. [more]

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