A5070543682- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Monoclonal and Polyclonal Antibodies Research
- Long-Term Effects of COVID-19
- vaccines and immunoinformatics approaches
- Animal Virus Infections Studies
- Bacterial Infections and Vaccines
- Granular flow and fluidized beds
- Transgenic Plants and Applications
- Viral Infections and Outbreaks Research
- COVID-19 epidemiological studies
- Mineral Processing and Grinding
- Iron and Steelmaking Processes
- Inhalation and Respiratory Drug Delivery
- Immunotherapy and Immune Responses
- Travel Writing and Literature
- Medical History and Research
- Cell death mechanisms and regulation
- interferon and immune responses
- Salmonella and Campylobacter epidemiology
- Microbial infections and disease research
- Viral gastroenteritis research and epidemiology
- COVID-19 diagnosis using AI
University Medical Center Freiburg
2021-2024
University of Freiburg
2021-2024
Institute of Medical Microbiology and Hygiene
2024
BOKU University
2020
The origin of SARS-CoV-2 variants concern remains unclear. Here, we test whether intra-host virus evolution during persistent infections could be a contributing factor by characterizing the long-term infection dynamics in an immunosuppressed kidney transplant recipient. Applying RT-qPCR and next-generation sequencing (NGS) sequential respiratory specimens, identify several mutations viral genome late infection. We demonstrate that isolate exhibiting similar to those found first identified...
Severity of COVID-19 shows an extraordinary correlation with increasing age. We generated a mouse model for severe and show that the age-dependent disease severity is caused by disruption timely well-coordinated innate adaptive immune response due to impaired interferon (IFN) immunity. Aggravated in aged mice was characterized diminished IFN-γ excessive virus replication. Accordingly, adult receptor-deficient phenocopied age-related severity, supplementation reversed increased susceptibility...
Broadly neutralizing antibodies are an important treatment for individuals with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2). Antibody-based therapeutics also essential pandemic preparedness against future Sarbecovirus outbreaks. Camelid-derived single domain (VHHs) exhibit potent antimicrobial activity and being developed as SARS-CoV-2–neutralizing antibody-like therapeutics. Here, we identified VHHs that neutralize both SARS-CoV-1...
In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. From December 2020 to June 2021 this lineage has been detected 31 countries. Phylogeographic analyses sequences obtained from national and international databases reveal a global spread through multiple introductions its inferred origin Western Africa. Variant is characterized mutational pattern spike gene that includes L18F, L452R N501Y amino...
Abstract Monoclonal antibodies (mAbs) directed against the spike of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are effective therapeutic options to combat infections in high-risk patients. Here, we report adaptation SARS-CoV-2 mAb cocktail REGN-COV a kidney transplant patient with hypogammaglobulinemia. Following treatment, did not clear infection. During viral persistence, acquired three novel mutations. Neutralization and mouse protection analyses demonstrate complete...
The ongoing COVID-19 pandemic and the emergence of new SARS-CoV-2 variants concern (VOCs) requires continued development effective therapeutics. Recently, we identified high-affinity neutralizing nanobodies (Nbs) specific for receptor-binding domain (RBD) SARS-CoV-2. Taking advantage detailed epitope mapping, generate two biparatopic Nbs (bipNbs) targeting a conserved outside different epitopes inside RBD:ACE2 interface. Both bipNbs bind all currently circulating VOCs with high affinities...
Coronavirus disease 2019 (COVID-19) mRNA vaccines that have contributed to controlling the SARS-CoV-2 pandemic induce specific serum antibodies, which correlate with protection. However, neutralizing capacity of antibodies for emerging variants is altered. Suboptimal antibody responses are observed in patients humoral immunodeficiency diseases, ongoing B cell depletion therapy, and aging. Common experimental mouse models altered compartments, such as or deficiency, do not fully recapitulate...
Abstract We have identified camelid single-domain antibodies (VHHs) that cross-neutralize SARS-CoV-1 and −2, such as VHH72, which binds to a unique highly conserved epitope in the viral receptor-binding domain (RBD) is difficult access for human antibodies. Here, we establish protein engineering path how stable, long-acting drug candidate can be generated out of VHH building block. When fused IgG1-Fc, prototype VHH72 molecule prophylactically protects hamsters from SARS-CoV-2. In addition,...
Abstract The recent emergence of SARS-CoV-2 variants showing increased transmissibility and immune escape is a matter global concern. Their origin remains unclear, but intra-host virus evolution during persistent infections could be contributing factor. Here, we studied the long-term infection in an immunosuppressed organ transplant recipient. Frequent respiratory specimens were tested for variant viral genomes by RT-qPCR, next-generation sequencing (NGS), isolation. Late infection, several...
Tracer experiments were conducted in a lab-scale cold flow model of 0.4 m by 0.2 cross section to investigate the solid mixing behavior bubbling fluidized beds under continuous particle exchange with and without immersed tube bundle heat exchangers. The superficial gas velocity, circulation rate, exchanger geometry varied thereby. An established inductance measurement setup detecting pulse-injected ferromagnetic tracer particles was used obtain residence time distribution continuously...
Abstract SARS-CoV-2 is a highly contagious respiratory virus and the causative agent for COVID-19. The severity of disease varies from mildly symptomatic to lethal shows an extraordinary correlation with increasing age, which represents major risk factor severe COVID-19 1 . However, precise pathomechanisms leading aggravated in elderly are currently unknown. Delayed insufficient antiviral immune responses early after infection as well dysregulated overshooting immunopathological processes...
Abstract The ongoing COVID-19 pandemic and the frequent emergence of new SARS-CoV-2 variants concern (VOCs), requires continued development fast effective therapeutics. Recently, we identified high-affinity neutralizing nanobodies (Nb) specific for receptor-binding domain (RBD) SARS-CoV-2, which are now being used as biparatopic Nbs (bipNbs) to investigate their potential future drug candidates. Following detailed in vitro characterization, chose NM1267 most promising candidate showing high...
Abstract In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. From December 2020 to June 2021 this lineage has been detected 31 countries. Phylogeographic analyses sequences obtained from national and international databases reveal a global spread through multiple introductions its inferred origin Western Africa. Variant is characterized mutational pattern spike gene that includes L18F, L452R...
1Peterhouse, Cambridge