Research and other activities on COVID-19 and SARS-CoV-2

It is becoming increasingly clear that the novel coronavirus SARS-CoV-2 often leads to inflammations in the body, which in turn lead to the damage observed in the lungs and other organs, during or after a COVID-19 infection. Therefore many PMI members, who are well-known inflammation experts, are also actively participating in tackling the coronavirus pandemic and its consequences. For example, they are conducting a study on possible long-term consequences of COVID-19, analyzing the spread of infections, working intensively on the analysis of viral and host genomes, and looking for possible therapeutic goals.  In addition, numerous members are active in research consortia, or advise politicians on the impact of the coronavirus.

The projects listed here can only represent a portion of the work.

 

Research projects

Immunological age and T-cell memory as risk factor for severe COVID-19 progression?

Immunological age and T-cell memory as risk factor for severe COVID-19 progression?

Many people had already had contact with other coronaviruses before the appearance of the novel coronavirus SARS-CoV-2, for example as a trigger for colds. Can this contact and the resulting T-cell memory make the immune system more resistant to SARS-CoV-2? Cluster members from Kiel and researchers from Cologne have investigated this question. They were indeed able to show that people who have not yet been infected with SARS-CoV-2 have T-cell memory cells that can also specifically recognize SARS-CoV-2. But these are not primarily caused by contact with cold viruses. Moreover, the quality of the immune response to the novel corona virus by these memory cells is apparently not suitable to ward off the infection. On the contrary, in people with a higher immunological age, i.e. with more T-memory cells, this could even lead to a more severe COVID-19 progression. The work is currently available as pre-print.

Participants and cooperations:

Several cluster members from the Institute of Immunology and the Institute of Clinical Molecular Biology (IKMB) at Kiel University (CAU) and University Medical Center Schleswig-Holstein (UKSH), Campus Kiel, are involved in the work, around Prof. Petra Bacher (first author), SH-Chair Junior Research Group Leader "Intestinal Immune Regulation", and Prof. Alexander Scheffold (senior author), Director of the Institute of Immunology, CAU & UKSH. The work was developed in cooperation with the research groups of Oliver Cornely and Philipp Köhler at University Hospital Cologne and Maria Vehreschild at University Hospital Frankfurt, as well as the research groups of Andre Franke and Philipp Rosenstiel at the Institute of Clinical Molecular Biology, CAU & UKSH.

More information:

Pre-print: Bacher et al.: Pre-existing T cell memory as a risk factor for severe COVID-19 in the elderly

Case report: Diabetes after COVID-19 disease

Case report: Diabetes after COVID-19 disease

The SARS-CoV-2 virus can also penetrate and damage the so-called beta cells in the pancreas, as a research team involving the Cluster of Excellence "Precision Medicine in Chronic Inflammation" has now observed for the first time. These cells are responsible for producing the insulin necessary for a healthy metabolism. Professor Matthias Laudes, Schleswig-Holstein Excellence-Chair for Endocrinology, Diabetology and Clinical Nutrition at the Kiel University (CAU), and his research team from the Clinic for Internal Medicine I of the University Medical Center Schleswig-Holstein (UKSH), Campus Kiel, together with researchers from Munich and Dresden, published the first case report of insulin deficiency diabetes after COVID-19 disease in Nature Metabolism.

Participants and cooperations:
First authors: Dr. Tim Hollstein, Clinic for Internal Medicine I, UKSH, Campus Kiel, and Prof. Dominik M. Schulte, SH-Chair Junior Research Group Leader, CAU. Senior Author: Prof. Matthias Laudes, SH-Chair for Endocrinology, Diabetology and Clinical Nutrition, CAU. The work was done in cooperation with Prof. Stefan Bornstein from the University Hospital Dresden and Prof. Anette-Gabriele Ziegler from HelmholtzZentrum München.

Original publication and more information:

  • Tim Hollstein* Dominik M. Schulte*, Juliane Schulz, Andreas Glück, Anette G. Ziegler, Ezio Bonifacio, Mareike Wendorff, Andre Franke, Stefan Schreiber, Stefan R. Bornstein und Matthias Laudes: Autoantibody-negative Insulin-dependent Diabetes Mellitus after SARS-CoV-2 infection: a case report. Nat Metab (2020). DOI: 10.1038/s42255-020-00281-8  *these authours contributed equally.
  •  
  • press release: Diabetes as a consequence of COVID-19
COVIDOM: Statistically representative study of COVID-19 secondary complications

COVIDOM: Statistically representative study of COVID-19 secondary complications

Although COVID-19 mostly affects the respiratory tract or the lungs, during the acute stage it already also affects many other organ systems. In light of the severity of the attack on the organs in some cases, it can be expected that there might also be long-term damage to these organs. A clinical research team at Kiel University (CAU), the University of Lübeck (UzL) and the University Medical Center Schleswig-Holstein (UKSH), under the leadership of cluster spokesperson Prof. Stefan Schreiber, would like to investigate these consequences in a new study on patients infected with SARS-CoV-2 in Schleswig-Holstein.

Participants and cooperations:
COVIDOM is being carried out at the University Medical Center Schleswig-Holstein (UKSH) as well as at Kiel University and the University of Lübeck. The UKSH plays a leading role. Prof. Stefan Schreiber is heading the study. He is the Director of the Department of Internal Medicine I at the UKSH, Campus Kiel, and the Director of the Institute of Clinical Molecular Biology (IKMB), CAU and UKSH.

More information:
Study website covidom.de

ELISA study: Lübeck longitudinal study on infections with SARS-CoV-2

ELISA study: Lübeck longitudinal study on infections with SARS-CoV-2

The large-scale study "ELISA" provides information about the actual spread of the novel coronavirus. In particular, it should investigate to what extent the measures for curbing the virus and their relaxation affect the further spread of SARS-CoV-2. Key activities include the generation of health data as well as testing for current and past SARS-CoV-2 infections in selected groups.

Participants and cooperations:

Prof. Dr. Christine Klein (PMI), Prof. Dr. Katalinic, Prof. Dr. Jan Rupp (PMI) (scientific director of the study)

The study is a collaboration between the University of Lübeck, the University Medical Center Schleswig-Holstein in the framework of the COVID-19 Research Initiative Schleswig-Holstein, and the local health authorities in Lübeck.

The study includes scientists from the University of Lübeck and Kiel University, the University Medical Center Schleswig-Holstein and the Research Center Borstel - Leibniz Lung Center (FZB, Borstel).

COVit – a dietary intervention trial in early-disease COVID-19 patients to investigate the effect of nicotinamide supplementation on the disease course

COVit – a dietary intervention trial in early-disease COVID-19 patients to investigate the effect of nicotinamide supplementation on the disease course

Based on the literature, it seems likely that supplementation with nicotinamide (a form of vitamin B3) can support the treatment of COVID-19. In the COVit study, two groups of 650 patients at an early stage of their COVID-19 disease take either 1,000 mg/day of vitamin B3 or (in the control group) 245 mg of silica daily for 4 weeks. The study investigates whether progression to severe disease occurs less frequently in the vitamin B3 group. Patients register online and receive telephone support, so that patients in domestic quarantine are also able also participate. In addition to the initial consultation and control calls after 2 and 4 weeks, the further course of the disease is investigated after 6 weeks and 6 months. Patients at the UKSH in Kiel can also provide biosamples (serum and stool) for molecular analyses. The study should show whether vitamin B3 supplementation can ameliorate the disease course of COVID-19.

Participants and cooperations:

The COVit trial is headed by Prof. Dr. Stefan Schreiber and Prof. Dr. Matthias Laudes and conducted by the Department of Internal Medicine I of the UKSH (Campus Kiel) together with the Competence Network Intestinal Diseases and the Institute of Epidemiology of Kiel University (Prof. Dr. Wolfgang Lieb).

Genetic association study on risk genes for severe progression of COVID-19

Genetic association study on risk genes for severe progression of COVID-19

Why do some people become seriously ill with COVID-19 while others hardly show any symptoms? In the world's first large-scale genetic study, scientists at the University Medical Center Schleswig-Holstein (UKSH) and Kiel University (CAU), in cooperation with a working group from Norway, have found gene variants which significantly impact the progression of the disease – one of them affects the gene for the blood group attribute. The work was published in the New England Journal of Medicine and has gained significant media attention world-wide.

Participants and cooperations:

Prof. Andre Franke (senior author), Director at the Institute of Clinical Molecular Biology (IKMB) at the CAU and the UKSH, Dr. Frauke Degenhardt (first author) and Prof. David Ellinghaus (first author), also from the IKMB, were all involved. Prof. Andre Franke led the research work together with the Norwegian specialist in internal medicine Prof. Tom Karlsen.

Original publication and more detailed information:

David Ellinghaus & Frauke Degenhardt et al.: Genomewide Association Study of Severe Covid-19 with Respiratory Failure. NEJM (2020). DOI: 10.1056/NEJMoa2020283

COVID-19: First large-scale genome-wide study on risk genes (press release on the study)

Molecular genetic epidemiology of SARS-CoV-2

Molecular genetic epidemiology of SARS-CoV-2

A group of international researchers in the fields of genetics and archaeology from Kiel and Cambridge, with the participation of the PMI member Dr. Michael Forster, has succeeded in tracing the origin and spread of the novel coronavirus (SARS-CoV-2), through the application of phylogenetic network analysis. The results published in the renowned scientific journal PNAS show that in the first phase of the outbreak in Europe and America, mainly other SARS-CoV-2 types (A, C) spread, instead of the type B predominant in Wuhan at that time. After independent validation by the working group led by Andrew Rambaut (Edinburgh), the classification of the virus types A and B is now also used in the official database GISAID.

Participants and cooperations:

Scientists Dr. Michael Forster, Institute of Clinical Molecular Biology (IKMB) at Kiel University (CAU) and the University Medical Center Schleswig-Holstein (UKSH), Campus Kiel, and the team led by Dr. Peter Forster from the McDonald Institute for Archaeological Research at the University of Cambridge.

Original publication:

Peter Forster, Lucy Forster, Colin Renfrew, Michael Forster (2020): Phylogenetic network analysis of SARS-CoV-2 genomes. Proceedings of the National Academy of Sciences First published 08.04.2020. DOI: 10.1073/pnas.2004999117

Identification of putative drugs against coronavirus infections by applying a pharmacovigilance analysis tool

Identification of putative drugs against coronavirus infections by applying a pharmacovigilance analysis tool

Pharmacovigilance data are primarily used to identify adverse drug reactions. However, scanning for associations of drugs and adverse events that occur less frequently than expected provides hypotheses for drug-repurposing, i.e. a known drug could be therapeutically beneficial for a new indication like the coronavirus disease (COVID-19). Drugs associated with viral respiratory tract infections and/or influenza were extracted from the U.S. FAERS pharmacovigilance data using the pharmacovigilance tool OpenVigil2.1-MedDRA17, filtered for significant inverse associations, checked for plausibility, and grouped by their anatomical-therapeutic-chemical (ATC) classification.

Participants and cooperation:

Böhm R, Bulin C, Waetzig V, Herdegen T, Cascorbi I, Institute of experimental und clinical pharmacology, Kiel University
Klein HJ, Institute for informatics, Kiel University

Lipid metabolism intervention as a host-targeted treatment for coronavirus infections

Lipid metabolism intervention as a host-targeted treatment for coronavirus infections

The researchers have the goal of blocking the multiplication of coronaviruses through intervention in the biochemical processes of the host cells. They have been able to prove that inhibitors of the enzyme phospholipase A2α significantly reduce the reproduction of coronaviruses by disrupting the formation of the replicative cell organelles.

Participants and cooperation:

PD Dominik Schwudke, Bioanalytical Chemistry, Research Center Borstel (FZB)
Cooperation with Prof. John Ziebuhr, Medical Virology, Giessen University (JLU), and Dr. Christin Müller (DZIF - Cooperation)

Original publication:

Müller C, Hardt M, Schwudke D, Neuman BW, Pleschka S, Ziebuhr J.: Inhibition of Cytosolic Phospholipase A2α Impairs an Early Step of Coronavirus Replication in Cell Culture. J. of Virol. 2018 Jan 30;92(4):e01463-17. DOI: 10.1128/JVI.01463-17.

Relevance of aging-related cellular changes as key factors for the severity of COVID-19

In this project, metabolic computer models are created of virus-infected cells, to determine which cellular changes related to aging determine the relationship between age and the severity of COVID-19. Using the sequencing data of individual cells, the researchers were able to show that the cells of older patients are less able to produce viruses. Based on this, they developed the hypothesis that SARS-CoV-2 counteracts this limitation of the viral replication ability in old age by recruiting specific immune cells, which activate cellular programs that promote viral replication, but thereby cause major damage to the lung tissue. Building on this, the research team wants to use computer models of infected cells in this project to identify specific enzymes which are highly important for viral replication, and inhibiting which offers a starting point for new treatment approaches, especially for severe progression of COVID-19.

Participants and cooperations:

Prof. Christoph Kaleta, Institute of Experimental Medicine/Medical Systems Biology, CAU In cooperation with Dr. Andreas Dräger & Alina Renz (University of Tübingen), Prof. Nathan Lewis & Dr. Chintan Joshi (University of California, San Diego).

Influence of different vaccination strategies on the quality of the antibodies

Influence of different vaccination strategies on the quality of the antibodies

Adjuvants, which are added to vaccines to boost the immune response, can influence the immune response and also the quantity and type of antibodies to a much greater extent than has long been assumed. Researchers including the participation of the PMI Cluster have investigated how these co-stimulators or different adjuvants in vaccines affect the immune response and the quality (IgG subclasses and their Fc glycosylation) and quantity of IgG antibodies.

Participants and cooperations:

Prof. Marc Ehlers, Institute of Nutritional Medicine, University of Lübeck

Original publication:

Bartsch et al. J Allergy and Clinical Immunol 2020. DOI: /10.1016/j.jaci.2020.04.059

Participation in initiatives

Deutsche COVID-19 OMICS Initiative (DeCOI)

Many genome researchers in Germany have joined forces in the Deutsche COVID-19 OMICS Initiative (DeCOI), in order to accelerate research. The DeCOI network is currently analyzing the genome of SARS-CoV-2, in order to characterize changes in the genetic code of the virus. In addition, the DeCOI scientists are also analyzing the genomes of COVID-19 patients. This is based on the suspicion that there are also genetic risk factors which could affect the chances of infection or the severity of the disease.

In the framework of DeCOI, the Kiel research team from the IKMB is investigating misdirected cellular programs, which cause the strong immune response in some COVID-19 patients, the "cytokine storm" of inflammation. In doing so, they perform so-called single cell sequencing, by which the activation states of tens of thousands of cells can be determined in parallel by sequencing. These analyses can, for example, provide information about the activity and function of individual immune cells. This procedure is also used in the framework of clinical trials to understand the impact of new drugs against SARS-CoV-2 on the immune system.

Participants in the Cluster:

Prof. Philip Rosenstiel, Institute of Clinical Molecular Biology (IKMB), CAU and UKSH

More information:

Website of the initiative https://decoi.eu/

COVID-19 Host Genetics Initiative (COVID19hg)

COVID-19 Host Genetics Initiative (COVID19hg)

Researchers in the field of human genetics worldwide have joined forces in the "COVID-19 Host Genetics Initiative" in order to generate, share and analyze data, and thereby identify the genetic determinants of susceptibility, severity and outcomes of COVID-19. Such findings could help to create hypotheses for the reorientation of medicines, identify people with an unusually high or low risk, and contribute to the global knowledge about the biology of SARS-CoV-2 infections and diseases.

Participants in the Cluster:

Institute of Clinical Molecular Biology (IKMB), CAU and UKSH

More information:

Website COVID19hg.org

Public communication

Representation and communication of models on the coronavirus pandemic for the general public

Representation and communication of models on the coronavirus pandemic for the general public

The Department Evolutionary Theory at the Max Planck Institute for Evolutionary Biology in Plön (MPI-EB) works with mathematical models. For the general public, they have visualized up-to-date developments, regional differences and an analysis of the effect of the lockdown measures on a dedicated website.

Participants:

Prof. Arne Traulsen, Department Evolutionary Theory, Max Planck Institute for Evolutionary Biology in Plön.

More information:

Website with visualizations

Ethical aspects of vaccine research

Ethical aspects of vaccine research

How does one distribute a vaccine fairly? Is it okay to make money from a vaccine? When is it okay if immune people enjoy advantages? The bioethicist and cluster member Prof. Christoph Rehmann-Sutter discusses these and similar questions for the general public in press interviews.

Participants:

Prof. Christoph Rehmann-Sutter, Institute for Medical History and Science Research (IMGWF)
University of Lübeck.