Day of Immunology – DRFZ vs SARS-CoV-2

Radbruch Lab: Our studies have shown that SARS-CoV-2-reactive memory CD4+ T cells can be found in individuals with no previous history of infection with SARS-CoV-2. These cells do not express IL-21 and TGF-ß, unlike in patients with severe Covid-19 disease, which is associated with a TGF-ß-dominated chronic immune response (see AG Mashreghi). Presently, we are conducting research to further characterize SARS-CoV-2 reactive T cells. © Jacqueline Hirscher

Strangfeld group: The set-up of the Global/European COVID-19 database (including the German C19-Register) has been a great success. Currently, data are available from over 16,000 patients with rheumatic diseases (RMD) and COVID-19 including >200 children.
Our analyses showed that risk factors for a severe course of COVID-19 or COVID-19 related death in patients with RMD are similar to those in the general population: older age >65 years, male sex and comorbidities. As an additional risk factor specific to RMD patients, we identified a high level of inflammatory disease activity. This finding highlights the enormous importance of adequate disease control in RMD patients, especially during the pandemic. The treatment required to achieve remission or at least low disease activity should therefore be continued and, if necessary, be intensified. © Jacqueline Hirscher

Minden group: Current data from the National Pediatric Rheumatology Database suggest that children with rheumatic diseases have a mild disease course of COVID-19, even under various immunosuppressive drugs. The SARS-CoV-2 infection does not seem to have a relevant influence on the underlying disease activity. © Jacqueline Hirscher

Kruglov lab: We study the interplay between Sars-Cov-2, immune system and microbiota in the induction of severe COVID disease. Severe Covid-19 is characterized by a significant dysbiosis with the depletion of potentially beneficial bacteria and outgrowth of opportunistic ones. Thus, we believe that restoring the microbiota could be a way of ameliorating disease course once infected with Sars-Cov-2. We are currently developing strategies for the selection of bacteria that may have such beneficial role. © Jacqueline Hirscher

Chang lab: To gain further understanding on the impact of the gut bacteria on the immune reaction against the SARS-Cov-2 virus, we analyse stool samples of different age groups and correlate the composition of the gut flora with the executed immune response after the vaccination in cooperation with AG Mei. © Jacqueline Hirscher

Mei lab: With the help of mass cytometry, we want to understand the immune response in SARS-CoV2 infection and determine what goes wrong when the infection takes a severe course. In this context, mass cytometry enables a detailed analysis of the cells of the immune system, because this method can be used to determine the properties of large quantities of single immune cells from the blood with high precision. The mass cytometry lab at DRFZ has contributed to important single cell studies that have revealed characteristics of the innate and adaptive immune system in COVID-19 disease.
Currently, the imprinting of additional cell types in COVID-19 and vaccination against coronavirus are being investigated in collaboration with various research groups across Germany. Furthermore, we are pursuing the prediction of severe COVID-19 courses with the aim of being able to timely identify and treat patients with a high risk of a severe course. © Jacqueline Hirscher

Mashreghi lab: To better understand the immune reaction occurring in severe cases of COVID-19, we analyzsed plasmablasts from patients requiring intensive care hospitalization at different time points after their ICU (intensive care unit) admission. We observed that through time in the intensive care, the early interferon-driven response induced by SARS-CoV-2 changes into a chronic TGF-β-dominated adaptive immune response. Notably, this response is no longer directed against SARS-CoV-2, as no protective TGF-β-induced antibodies (IgA2) could be found in circulation and no IgA2 plasmablasts migrate to the lungs of severe patients. © Jacqueline Hirscher

Diefenbach lab: We analyze NK cell responses during severe COVID-19 and patients who readily control SARS-CoV-2. Particularly, we test various NK cell effector functions and the signals controlling the functional programs. Goal is to uncover the regulatory pathways driving NK cell dysfunction during COVID-19 that may also be targets for future therapeutic approaches. © Jacqueline Hirscher

Hauser lab: We are using multiplex microscopy techniques in combination with spatially resolved transcriptome analyses, to analyze inflammatory changes in lung tissue in autopsy material from patients with severe COVID-19. In this way, immune cell infiltrates have been characterized in detail, and a spatial relationship between specific immune cell types and fibrotic changes in the lung could be established. © Jacqueline Hirscher

Niesner lab: In collaboration with Dr. Helena Radbruch (Neuropathology, Charité) and AG Hauser, we currently investigate the effect of serum from patients with mild vs. severe COVID19 cases on the functionality of immature vs. mature neutrophils in an organotypic model of human lung. Thereby, we focus on the capacity of the different neutrophil populations to keep the balance between activating NOX2(phox) and undergoing NETosis/pyroptosis – often observed in the lung of succumbed COVID19 patients. © Jacqueline Hirscher