German version

Focus I: Impact of the innate immune system

Whereas most patients exposed to SARS-CoV2 exhibit control of the viral replication and just mild symptoms, some COVID-19 patients experience severe complications characterized by hyperinflammation. Exactly how SARS-CoV-2 spike protein (S-protein) or mRNA vaccines stimulate innate immune cells to form antigen-specific adaptive immunity has long been unknown. Our recent publications (Theobald et al., EMBO MM 2021; Theobald et al., EMBO MM 2022) show that both SARS-CoV-2 infection and SARS-CoV2 mRNA vaccination activate a protein complex involved in the initiation of inflammatory responses (NLRP3 inflammasome) in human macrophages. In addition, we identified the spleen tyrosine kinase SYK as a regulatory node that modulates spike protein-specific T-cell responses. Moreover, vaccine-triggered priming of macrophages can be enhanced by repeated antigen exposure, which is a rationale for prime-boost concepts in which inflammasomes are activated to enhance immune signaling and crosstalk.  In further studies, we would like to systematically determine the influence of the innate immune system on the quality and strength of long-lived antiviral immunity. These data will be important for the development of future vaccines and vaccination regimens against SARS-CoV-2 and other viral pathogens.

Focus II: Post-COVID syndrome

Post-COVID syndrome (PCS) encompasses multiple symptoms that may affect all organ systems (e.g., morbid fatigue and dyspnea, headache, chest and joint pain, cough, neurologic symptoms, depression, exercise intolerance, and activity limitations) observed in a substantial number of patients following SARS-CoV-2 infection. These multiple organ manifestations of SARS-CoV-2-related disorders are caused by the broad tropism of the virus, which is defined by the distribution of the viral receptor. Entry of SARS-CoV-2 begins with binding to the angiotensin-converting enzyme 2 (ACE2) receptor, which is present in many tissues in the human body. There is growing evidence that dysregulation of the innate and adaptive immune systems contributes to PCS. It is also possible that persisting viral components lead to chronic inflammation, which may eventually lead to PCS.

As part of our research consortium, we aim to unravel the precise nature and underlying triggers for these immune disorders. Therefore, we will utilize our large, well defined PCS patient cohort and state-of-the-art methods to detect long-lived reprogramming of blood- and tissue-associated immune cells. In addition, we will investigate the role of gut-associated lymphoid tissue (GALT) as a potential SARS-CoV-2 reservoir in PCS. Our findings will comprehensively improve our understanding of this novel disease to identify therapeutic approaches for PCS. In addition, we aim to define much-needed biomarkers required for the prevention, prediction and detection of PCS. This project is part of a BMBF funded consortium (AG Lehmann/ Rybniker) in cooperation with the Institute of Biochemistry of the University of Cologne (Henning Walczak) and the Max Planck Institute for Biology of Aging (Peter Tessarz). The work will be carried out in close cooperation with the interdisciplinary post-COVID consultation

Focus III: Evaluation of clinical parameters for SARS-CoV-2 immunity

Our laboratories are part of a scientific network for the determination and utilization of SARS-CoV-2 immunity (COVIM) within the nationwide Network University Medicine (NUM). The aim is to investigate the type and duration of protective immunity after infection or vaccination against SARS-CoV-2 and to systematically pool and evaluate these clinical data. To this end, the Germany-wide collaborative project COVIM was designed to pool the expertise and data of many scientists from different disciplines, such as immunology, virology, clinical infectiology, pneumology and microbiology. The project will thus explore which groups of people are immunologically protected from SARS-CoV-2 infection, by what means and for how long.