Project 09

Metabolic and immunologic influences of post-acute infection syndromes (PAISs)

• Principial Investigators:
  • TUD: Stefan. R. Bornstein & Nicole Töpfner
  • UZH: elix Beuschlein & Zsuzanna Varga Milo Puhan & Irene Alma Abela
• Students:
  • TUD: Rupali Mohanty (1st year-PhD student), Katharina Winkler (Dr. med. student) 

  • UZH: Hannah Moll (2nd year-PhD student)

Background: Post infection sequelae have been described for multiple bacterial and viral 
infectious diseases with a notably clinical overlap of symptoms and disease courses. Besides Long/Post COVID syndrome, MIS-C (Multisystem Inflammatory Syndrome in Children) and ME-CFS (Myalgic encephalomyelitis/chronic fatigue syndrome) follow SARS-CoV-2 infection. Striking similarities exist with ME-CFS following EBV-infection, fatigue following HIV infection, neuropsychiatric and cardiac disorders following streptococci infection and, exertional dyspnoe following influenza, RSV and other viral infections in children and adults.We have recently formed an interdisciplinary group consisting of experts in SARS-CoV-2, HIV, streptococci and other infections that aims to systematically investigate post infection syndromes incl. Long/Post COVID. This group has succeeded so far to: a) assess the prevalence and disease course of Post-COVID syndrome both in Switzerland and Germany with the use of the population-based Zurich Coronavirus Cohort Study and of health care data from nearly half of the German population , b) demonstrate morphorheological changes of blood cells after SARS-CoV-2-infection, c) evaluated the risk of autoimmune diseases following COVID-19 in children and adolescence, d) develop and validate a prediction model for Long COVID based on 
an immunoglobulin signature with total IgM and IgG3 levels combined with socio-epidemiological factors to predict the risk of Long COVID .
Several important questions remain though open. First of all, the role of the antibodies that we identified in patients after SARS-CoV-2 infection remain unclear regarding the development or progression of the disease . Moreover, the risk factors for developing Long/Post COVID or other post viral syndromes in patients with metabolic and endocrine diseases have only partially been identified. Furthermore, there is a significant correlation of the above-named neurotransmitter receptors with immunoglobulin levels, T-cell activation, and other autoantibodies such as ANA or TPO suggesting a multifaceted activation of the immune system. In view of therapeutic options, the first evidence gained from our centre showed that in patients who reported a significant improvement after two cycles of extracorporeal therapeutic apheresis, there was a significant reduction in neurotransmitter antibodies, lipids and inflammatory markers. 

Aims: 1) We aim to assess the risk of paediatric and adult patients with metabolic and endocrine diseases to develop post viral sequela such as Long/Post COVID and conversely evaluate the risk of post infection syndromes to induce and/or exponentiate a metabolic and endocrine disease. 2) Furthermore, we aim to assess whether and in which extent patients with post infection syndromes, such as Long/Post COVID, develop autoantibodies, T cell priming as well as changes in morphorheological blood cell signatures to identify how these effects may regulate immune system activity. 3) We aim to evaluate in a prospective clinical study whether extracorporeal apheresis affects immune system activity by decreasing autoantibodies, change T cell activity and/or influence blood 
cell rheology to induce a significant improvement of all or a special subset of patients with Long/Post COVID as an exemplary treatment option for patients with post viral symptoms.

Added value through the collaboration between Dresden & Zurich: The Clinic of Internal Medicine III in the Dresden under the direction of Prof. Bornstein has extensive experience in extracorporeal apheresis. Töpfner group has great experience in the field of infectious diseases, and Bornstein group in metabolism/metabolic-related stress and SARS-CoV-2 research. Prof. Puhan is an experienced epidemiologist and PI of the Zurich 
Coronavirus Cohort Study and Corona Immunitas that is prominently contributing to the Long Covid Global Burden of Disease, PRECIOUS and CoVICIS collaborations. Dr. Abela is a talented young virologist with expertise in HIV, SARS-CoV-2 and CMV infectious diseases. Combining these areas of expertise will provide a major opportunity for understanding post infections syndromes from mechanistically, clinical and population perspectives and pave the way for potential treatments of post infection syndromes.

Synergies: We will collaborate with project 4, assess the virome profile in our cohorts of post-infection syndromes, and correlate our findings with immune profile of these patients and in relation to their metabolic/endocrine state. Additionally, we will interact with project 6 and assess infection susceptibility in in vitro models of primary differentiated human airway cells from patients with post-COVID and post-acute infection syndromes and in relation to their metabolic state.