Welcome to the RESIST study area!
On these pages we would like to inform you about our RESIST cohort, which aims to better understand individual susceptibility to infections in order to be able to treat them more effectively. We also present you an overview of the other cohorts – constantly growing groups of people with the same disease – whose data we are using for our research. Many of these cohorts were established for other independent projects but can be accessed by the RESIST research programme and some were initiated in preparation of the RESIST research proposal.
In addition to the RESIST cohort, there are other cohorts – groups of people who, for example, have a particular disease (such as hepatitis B) or who have received a particular treatment (as in the PRIMAL study). RESIST researchers help to establish the cohorts. They generate the patients’ data and analyze it to improve our understanding of the infection diseases and their long-term treatment.
Patients with cystic fibrosis (CF) suffer from chronic respiratory tract infections, which drastically affect the severity of the disease. In order to find better prognosis options and therapies for that patients, scientists from the Hannover Medical School (MHH) together with CF centres in Berlin, Lübeck, Gießen and Heidelberg establish a cohort of patients suffering from cystic fibrosis. Their clinical data is stored in a registry and the biosamples collected in Hannover including DNA, RNA and serum are stored at the Hannover Unified Biobank (HUB). The aim is to find and validate biomarkers for lung infections and to characterize genetic information of the microorganisms that persist in the respiratory tract. The RESIST project C3 uses data from this cohort, among others.
Contact: Professor Dr. Burkhard Tümmler
The German Registry for Primary Immunodeficiencies (PID-NET Registry) collects clinical and genetic data of children and adults with primary immunodeficiencies (PID), who suffer from different forms of infectious diseases and in this context often from autoimmunity. The collected data can be used to conduct studies to better understand and treat primary immunodeficiencies.
37 German centres participate in the PID-NET-Registry. To the largest subcohorts belong these at the Centre for Chronic Immunodeficiency (CCI) in Freiburg and at Hannover Medical School (MHH). Collected data contains in addition to phenotypic, epidemiological and socio-economic parameters, in most cases also genetic information. Corresponding samples – serum, cells and DNA – are collected in the FREEZE Biobank in Freiburg and in the Hannover Unified Biobank (HUB).
The PID-NET Registry was established in 2009, initially funded by the Federal Ministry of Education and Research and since 2018 supported by changing sponsors such as the Care-for-Rare Foundation and ProImmun e.V. The aim is to recruit as many patients as possible. Researcher of the RESIST project A2 have access to the information from this registry.
Contact: Professor Dr. Bodo Grimbacher, Centre for Chronic Immunodeficiency at the University Hospital of Freiburg
Healing of a chronic viral hepatitis B infection that can lead to scarring of the liver tissue and liver cancer is so far possible only in very few cases. Interestingly this phenomenon was also observed in patients, who interrupted a therapy with nucleoside or nucleotide analogues (NUCs) in a structured manner. Which mechanisms lead to cure and are there biomarkers that can indicate the cure? In order to clarify these questions and in long-term to develop better therapies, the Hannover Medical School (MHH) has been continuously recruiting patients with HBV infection to a cohort since 2011. This hepatitis B cohort is part of the German Centre for Infection Research (DZIF). Researchers of the RESIST project B8 have access on data from patients whose NUC therapy was interrupted.
Contact: Professor Cornberg
Almost all people with chronic hepatitis C can be cured. However, the treatment costs are high and the cure does not protect against re-infection. And it is also known that, at least in the short term, the immune system is not completely recovered from the effects caused by the viruses. Therefore, a vaccine is still needed to protect against the infection of hepatitis C virus (HCV).
For development of a vaccine against HCV, a cohort, in which data and biosamples from patients with chronic hepatitis C virus infection are continuously sampled, has been established at the Hannover Medical School (MHH) since 2014. The aim of this cohort, which is also funded by the German Center for Infection Research (DZIF), is to investigate immune reactions during the HCV infection and to clarify the question of whether the cure of HCV restores the immune system in the long term.
Contact: Professor Cornberg
Some patients with atopic dermatitis suffer from recurrent severe forms of skin infections caused by the herpes simplex virus 1 (HSV1). Such Eczema herpeticum (EH) and other severe herpes infections can lead to life-threatening complications such as encephalitis.
Which genetic and immunological factors lead to severe courses of disease in some people with otherwise harmless herpes infections of the skin? In order to investigate this question, a HSV Cohort has been established at Hannover Medical School (MHH) since 2017. A total of 150 affected persons will be included. People with diagnosed atopic dermatitis who do not suffer from herpes infections will serve as control.
Biosamples of all persons are analysed in the laboratory and epidemiological and socioeconomic parameters are recorded, as well as the severity of the disease, IgE antibody levels and specificities for allergens. The data are included in analysis of RESIST projects A4, B5 and B6.
Contact: Professor Werfel
In the cohort of the Clinical Research Group 250 (KFO 250) at Hannover Medical School (MHH), data and biosamples of more than 1,500 people suffering from connective tissue diseases, rheumatoid arthritis, spondyloarthritis or autoimmune hepatitis were collected from 2010 to 2018. Such rheumatological diseases affect up to five percent of the population and can be triggered by infections. They require immunosuppressive treatment, which is associated with increased infection rates by various pathogens. The KFO 250 cohort includes, for example, data on the duration and manifestation of the disease, on therapy and possible complications as well as biosamples such as DNA and blood, which are stored in the Hannover Unified Biobank (HUB). The establishment of the cohort was financially supported by the ”Deutsche Forschungsgemeinschaft” (DFG). Researcher of RESIST project A2 have access to data and biomaterial from this cohort.
Being able to recognise rheumatism patients more quickly and to treat them in a more targeted manner – that is what “Rheuma-VOR” wants. This network exists since 2017 and is funded as an innovation fund project by the Federal Joint Committee (Gemeinsamer Bundesausschus). The aim is to establish structures and treatment options for people with chronic inflammatory diseases such as rheumatoid arthritis, spondylarthritis or psoriasis-arthritis in three federal states of Germany. The initiative promotes research in the field of care for rheumatism patients, which takes place, for example, in the RESIST project B2. The biosamples are stored in the Hannover Unified Biobank (HUB). More information on “Rheuma-Vor” can be found on the homepage of the “Rheuma-Vor” network.
Contact at the Hannover Medical School (MHH) is Dr. Kirsten Hoeper from the Department of Immunology and Rheumatology. Email: Hoeper.Kirsten@mh-hannover.de
A consortium of scientists and physicians from the MHH and the Helmholtz Centre for Infection Research is involved in establishing this cohort of COVID-19 patients. Patients with an acute SARS-CoV2 infection are included in the cohort during a stay at the MHH or the KRH Klinikum Siloah and are invited for follow-up examinations at regular intervals after the infection has subsided. The collection of biomaterial and data at different points in time of the infection enables the longitudinal study of the course of the disease. In total, up to 1,000 patient visits with different severities of disease progression or control subjects will be included in the COVID-19 cohort. The biomaterial collection includes blood, live blood cells, plasma, serum, saliva, urine and bronchioalveolar lavage (BAL). The biospecimens are processed and stored in the Hannover Unified Biobank (HUB) of the MHH.
A uniform core data set is recorded for all biospecimens, which is currently being supplemented by the extensive follow-up recording of further clinical patient data. In order to better understand the pathophysiology of the disease and to detect biomarkers for the severity, intensive molecular characterisation is planned for the cohort and has already been partially implemented. Whole genome, transcriptome and epigenome data sets have already been generated for about one third of the patients enrolled so far. The collected biospecimens and data are already being used in about 25 research projects and can be applied for further COVID-19 research projects through the Use and Access Committee of the COVID-19 Biobank.
The establishment of the cohort is financed by a grant from the Lower Saxony Ministry of Science and Culture (MWK).
Contact: Prof. Dr. Thomas Illig
This COVID-19 cohort is being established as part of the National Pandemic Cohort Network (NAPKON) of the National University Medicine Research Network (NUM) for current and future pandemic response in Germany. The project aims to establish a harmonised, expandable and interoperable National Pandemic Cohort Network (NAPKON) to support both the fight against the current COVID-19 pandemic and its consequences as well as future pandemics of any origin and other clinical trials. The NAPKON cohort is made up of three sub-cohorts of the High Resolution Platform (HAP), the Cross-Sectoral Platform (SÜP) and the Population-based Platform (POP).
The coordination group of the NAPKON biospecimen core, with Prof. Dr. Thomas Illig and other coordinators, has developed an overall cohort concept for this purpose, on the basis of which all necessary biospecimens and data will be collected throughout Germany using uniform specifications and brought together in the joint research data platform. Within the framework of this platform, an in-depth clinical, molecular and immunological phenotyping of patients with COVID-19 beyond the acute disease phase as well as a follow-up with a structured investigation programme is carried out. In total, over 5000 patients have been enrolled in NAPKON to date. The MHH is including COVID-19 patients for the high-resolution platform (HAP) of the NAPKON COVID-19 cohort.
The collected biospecimens include blood, live blood cells, plasma, serum, saliva, urine, various swabs and bronchioalveolar lavage (BAL). The NAPKON biospecimens from the MHH are processed and stored in the Hannover Unified Biobank (HUB). The biosamples from the other NAPKON sites are also stored locally. The data collected includes epidemiological and demographic parameters, medical history and potential risk factors, documentation of routine medical procedures and clinical course, including different patterns of organ involvement, quality of care, morbidity and quality of life. Serial biosampling and data collection enables in-depth molecular, immunological and virological phenotyping through single-cell and bulk multiomics analyses. In addition to extensive central analysis of biosamples and data within NAPKON, samples and data can also be requested for further research projects via a central Use and Access Committee.
The establishment of the NAPKON cohorts is financed by a grant from the Federal Ministry of Education and Research (BMBF).
Contact: Prof. Dr. Thomas Illig
The composition of the human intestinal flora (microbiome) can be very important for health. It is believed that disturbance of intestinal colonisation (dysbiosis) in early life can be associated with long-term health problems. Premature babies are particularly susceptible to disturbance of early intestinal colonisation, as premature birth is often accompanied by medically necessary measures such as caesarean section or the administration of antibiotics.
The PRIMAL study examines in 600 premature babies born in the 28th to 33rd week of pregnancy whether the early administration of probiotics (dietary supplements from lactic acid and Bifidus bacteria) can prevent intestinal dysbiosis. The study started in 2018, is funded by the Federal Ministry of Education and Research (BMBF) and is being carried out at 19 Centres for Paediatric and Adolescent Medicine in Germany. Within the framework of RESIST and the Hanover Cohort of the PRIMAL study the influence of the intestinal microbiome on the shaping of the human immune defense is investigated and also whether probiotics show a positive effect in this regard. The acronym PRIMAL stands for: “Priming Immunity at the beginning of Life”.
You can find more information on the PRIMAL study’s website.
Contact (in the RESIST team): Professor Viemann
Primary sclerosing cholangitis (PSC) is an autoimmune disease of the liver that affects the bile duct system and for which there is no curative therapy available yet. Many patients finally need a liver transplant. In order to gain a better understanding of the disease mechanisms and for better treatment of patients, a PSC cohort was established at Hannover Medical School (MHH) in 2017 and patients are continuously recruited. Human Biosamples are collected, for example bile and stool samples, as well as disease data. These data is also used by the team of the RESIST project B11. PD Dr. Heidrich is the corresponding contact person. Establishment of the cohort was financed by funds of the support program for young medical scientists “Young Academy of the MHH” and the Integrated Research and Treatment Centre for Transplantation IFB-Tx.
The respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in young children globally. The infection can be severe and lead to death, especially for infants. To find out the genetic and cellular factors playing a central role in immunedefences against RSV and thus improve RSV treatment, a RSV cohort (IRIS) of 150 infants aged less than two years was established in 2015. The cohort is located at the Hannover Medical School (MHH) and will be continuously expanded.
Basic epidemiological and socioeconomic as well as various clinical parameters will be recorded. In addition, biosamples are stored in the Hannover Unified Biobank (HUB, link). First genetic determinants with functional relevance and cellular molecules have already been identified. The RESIST project A1 uses data from this cohort.
The cohort was established by the Helmholtz Initiative Personalized Medicine (Helmholtz iMed) and is financially supported by the State of Lower Saxony (INDIRA project).
Contact: Professor Dr. Gesine Hansen and Professor Dr. Thomas Pietschmann
In some people, varicella zoster viruses (VZV) are able to reactivate – in other words, the virus become active again after having attacked the body initially long time ago (often with the clinical picture chickenpox) and then survived in the nerve cells. In the majority of cases, this reactivation causes shingles and in five to 20 percent of affected individuals, a post-herpetic neuralgia (PHN) associated with nerve pain follows. Other complications rarely occur when viral particles spread through skin or blood and cause damage in other areas, or when there is tissue loss with deep wounds in the affected tissue segments.
In order to identify genetic factors that contribute to the development of such a disease, but also to find new biomarkers that can be used to predict the manifestation of the virus in the body as well as complications and secondary diseases, a Zoster Cohort has been in development at Hannover Medical School (MHH) since 2017. The patients are recruited in particular in the MHH clinics for dermatology and for neurology. This cohort will also help to understand why older people in particular, but also subgroups of younger patients, are more susceptible to VZV reactivation with or without complications. The long-term goal for the analysis of disease data and biomaterials is to improve the treatment of affected people. A total of 150 patients will be recruited in the Zoster cohort of the MHH. Researchers of the RESIST project A3, B5, B7 will use the data of this cohort for further analysis.
Contact: Professor Werfel