Since the beginning of the SARS-CoV-2 pandemic in 2020, DRFZ researchers have used their expertise in epidemiology, rheumatology, immunology and cell and molecular biology to elucidate the pathogenesis of COVID-19, and in particular, the specific challenges of SARS-CoV-2 infection in patients with rheumatic diseases.
Patients with rheumatic diseases were considered a high-risk group for SARS-CoV-2 infection, which resulted in a very unsettling phase for both patients and doctors early on in the pandemic. Rapid presentation of research results from the Epidemiology and Health Services Research Programme Area, in collaboration with national and international collaborators, were crucially important in promptly developing differentiated recommendations for the treatment and advising of patients with inflammatory rheumatic diseases.
The influence of the pandemic still resonates at the DRFZ: Andreas Radbruch was co-organiser of the EFIS (European Federation of Immunological Societies) Symposium ‘The Reaction to SARS-CoV-2: an Immunological Retrospective’, which took place on 4.4.2025 in Berlin. Moreover, the DRFZ is part of the Leibniz Lab ‘Pandemic Preparedness’, which addresses the most urgent questions about how to deal with future pandemics.
The commitment of the scientists in Programme Area 2, Epidemiology and Health Services Research, to research in national, European and global COVID-19 registers resulted, among others, in:
Strangfeld, A., et al., Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry. Annals of the Rheumatic Diseases, 2021. 80(7): p. 930-942. https://doi.org/10.1136/annrheumdis-2020-219498
Hasseli, R., et al., Older age, comorbidity, glucocorticoid use and disease activity are risk factors for COVID-19 hospitalisation in patients with inflammatory rheumatic and musculoskeletal diseases. Rmd Open, 2021. 7(1). https://doi.org/10.1136/rmdopen-2020-001464
Gianfrancesco, M., et al., Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Annals of the Rheumatic Diseases, 2020. 79(7): p. 859-866. https://doi.org/10.1136/annrheumdis-2020-217871
Bermas, B.L., et al., COVID-19 in Pregnant Women With Rheumatic Disease: Data From the COVID-19 Global Rheumatology Alliance. Journal of Rheumatology, 2022. 49(1): p. 110-114. https://doi.org/10.3899/jrheum.210480
Maguire, S., et al., Obstetric outcomes in women with rheumatic disease and COVID-19 in the context of vaccination status. Rheumatology, 2023. 62(4): p. 1621-1626. https://doi.org/10.1093/rheumatology/keac534
Machado, P.M., et al., Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry. Annals of the Rheumatic Diseases, 2022. 81(5): p. 695-709. https://doi.org/10.1136/annrheumdis-2021-221490
Lawson-Tovey, S., et al., SARS-CoV-2 vaccine safety in adolescents with inflammatory rheumatic and musculoskeletal diseases and adults with juvenile idiopathic arthritis: data from the EULAR COVAX physician-reported registry. Rmd Open, 2022. 8(2). https://doi.org/10.1136/rmdopen-2022-002322
Liew, J., et al., SARS-CoV-2 breakthrough infections among vaccinated individuals with rheumatic disease: results from the COVID-19 Global Rheumatology Alliance provider registry. Rmd Open, 2022. 8(1). https://doi.org/10.1136/rmdopen-2021-002187
Lawson-Tovey, S., et al., SARS-CoV-2 infection after vaccination in patients with inflammatory rheumatic and musculoskeletal diseases. Annals of the Rheumatic Diseases, 2022. 81(1): p. 145-150. https://doi.org/10.1136/annrheumdis-2021-221217
The immunological expertise of the DRFZ’s experimental programme areas was instrumental in uncovering an immune evasion mechanism of SARS-CoV-2. This mechanism leads to dysfunctional innate and adaptive immune responses in severe COVID-19, leading to autoreactivity, chronic inflammation and finally fibrosis.
Additionally, the DRFZ affiliated teams identified functional biomarkers predictive of vaccine responses in immunosuppressed patients with rheumatic diseases, critical for guiding vaccination strategies in patients with rheumatic diseases.
Experimental research from the DRFZ resulted in publications with high societal and scientific impact. Examples of these results include:
Ferreira-Gomes, M., et al., SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself. Nature Communications, 2021. 12(1). https://doi.org/10.1038/s41467-021-22210-3
Witkowski, M., et al., Untimely TGFβ responses in COVID-19 limit antiviral functions of NK cells. Nature, 2021. 600(7888): p. 295-+. https://doi.org/10.1038/s41586-021-04142-6
Frischbutter, S., et al., Serum TGF-β as a predictive biomarker for severe disease and fatality of COVID-19. European Journal of Immunology, 2023. 53(10). https://doi.org/10.1002/eji.202350433
Mothes, R., et al., Distinct tissue niches direct lung immunopathology via CCL18 and CCL21 in severe COVID-19. Nature Communications, 2023. 14(1). https://doi.org/10.1038/s41467-023-36333-2
Bondareva, M., et al., Cross-regulation of antibody responses against the SARS-CoV-2 Spike protein and commensal microbiota via molecular mimicry. Cell Host & Microbe, 2023. 31(11): p. 1866-+. https://doi.org/10.1016/j.chom.2023.10.007
Bondareva, M., et al., Induction of cross-reactive, mucosal anti-SARS-CoV-2 antibody responses in rheumatoid arthritis patients after 3rd dose of COVID-19 vaccination. Journal of Autoimmunity, 2022. 133. https://doi.org/10.1016/j.jaut.2022.102918
Stefanski, A.L., et al., B Cell Characteristics at Baseline Predict Vaccination Response in RTX Treated Patients. Front Immunol, 2022. 13: p. 822885. https://doi.org/10.3389/fimmu.2022.822885
Akbil, B., et al., Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies. Journal of Clinical Immunology, 2022. 42(6): p. 1111-1129. https://doi.org/10.1007/s10875-022-01252-2
Stefanski, A.L., et al., Persistent but atypical germinal center reaction among 3<SUP>rd</SUP> SARS-CoV-2 vaccination after rituximab exposure. Frontiers in Immunology, 2022. 13. https://doi.org/10.3389/fimmu.2022.943476
Romero-Olmedo, A.J., et al., Dynamics of humoral and T-cell immunity after three BNT162b2 vaccinations in adults older than 80 years. Lancet Infectious Diseases, 2022. 22(5): p. 588-589. https://doi.org/10.1016/s1473-3099(22)00219-5
Romero-Olmedo, A.J., et al., Induction of robust cellular and humoral immunity against SARS-CoV-2 after a third dose of BNT162b2 vaccine in previously unresponsive older adults. Nature Microbiology, 2022. 7(2): p. 195-+. https://doi.org/10.1038/s41564-021-01046-z
