Welcome to the RESIST study area!
On these pages we would like to inform you about our senior individuals 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.
Cohort Overview
In addition to the senior individuals 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.
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. So far, more than 110 patients have been included in the cohort (as of 5/2024). 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 Dr. Thomas Werfel
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. Patients are recruited in particular at the MHH Clinics for Dermatology and Neurology during their hospitalisation. 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 around 150 patients were included in the Zoster cohort (8/2024). Researchers of the RESIST projects A3, B5, B7 use the data of this cohort for further analysis.
Contact: Professor Dr. Thomas Werfel
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. So far, 300 participants have been included in the study (as of May 2024).
Contact: Prof. Anna-Maria Dittrich
Sepsis is a major risk for premature and newborn babies. It is associated with high mortality and serious secondary diseases. The misdirected development of interactions between the immune system and bacterial colonisation has been identified as the cause. Preliminary work has shown that the alarmins S100A8/A9 are crucial for the postnatal interaction of the immune system and microbiome. They are present in high concentrations in breast milk.
The ‘PROSPER’ consortium is investigating the effectiveness and safety of S100A8/A9 as a dietary supplement for the intervention of neonatal sepsis and for the development of healthy intestinal flora in preterm infants. Teams from the University Hospital of Würzburg, the MHH and the Max Delbrück Center, and the University Hospital of Münster are working together on this. Biological samples from the established preterm infant cohorts ‘PRIMAL’, ‘IPOP’ and ‘IRON’ are being used for extensive investigations. 425 patients have already been included in the cohort (as of 8/2024).
Contact (in the RESIST team): Professor Viemann
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), among others.
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. More than 4,800 patients have been admitted to date. There are currently around 2,800 patients in the MHH and CCI sub-cohorts (as of 8/2024). Researcher of the RESIST project A2 have access to the information from this registry.
Contact: Professor Dr. Bodo Grimbacher
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. To date, around 130 patients have been included in the cohort (8/2024).
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. Prof. 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.
Curing a chronic hepatitis B virus infection, which can lead to scarring of the liver tissue and liver cell cancer, has only been successful in very few people to date. One approach to achieving this is the structured and closely monitored interruption of therapy with nucleoside or nucleotide analogues (NUCs).
But which mechanisms lead to healing and which biomarkers can indicate this healing? In order to clarify these questions and ultimately develop better therapies, patients with HBV infection have been continuously enrolled in a cohort at Hannover Medical School (MHH) since 2011. Biomaterials are collected from the patients and virological and immunological parameters are examined. This hepatitis B cohort is part of the German Centre for Infection Research (DZIF). So far, this cohort comprises data from around 850 patients, 30 of whom have interrupted NUC therapy in a structured manner (as of 8/2024). The researchers of the RESIST project B8 are using the data from these patients.
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. So far, more than 1,300 patients have been included in the cohort. (Status: 5/2024)
Contact: Professor Dr. Markus Cornberg
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.
Around 190 patients were included in the “Rheuma-VOR” cohort (8/2024). 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 Rheumatology and Immunology. Email: Hoeper.Kirsten@mh-hannover.de
How does the immune system react – also in the long term – to a SARS-CoV-2 infection or vaccination? These are the central questions of the COVID-19 Contact (CoCo) Study. It provides valuable information on the spread of infection and the quality and duration of the antibody response after infection or vaccination.
The study started in March 2020, with more than 200 voluntarily participating employees of the MHH and affiliated institutions having their blood taken weekly and analysed for antibodies (anti-SARS-CoV2 IgG). The participants also answered questions that included respiratory symptoms. Blood samples were later taken at intervals depending on the situation.
Since the beginning of 2021, the CoCo study has been investigating the immune response after various COVID-19 vaccinations. So far, more than 1,300 participants have been included in the study. Status: May 2024
Further information can be found here: www.cocostudie.de
Contact: Prof. Dr. Georg Behrens
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. So far, around 300 children have been included in the study (8/2024).
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 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.
Contact: Professor Dr. Thorsten Witte