👤 Klaus F Rabe

Post-COVID syndrome (PCS) is an important sequela of COVID-19, characterised by symptom persistence for >3 months, post-acute symptom development, and worsening of pre-existing comorbidities. The causes and public health impact of PCS are still unclear, not least for the lack of efficient means to assess the presence and severity of PCS. COVIDOM is a population-based cohort study of polymerase chain reaction (PCR) confirmed cases of SARS-CoV-2 infection, recruited through public health authorities in three German regions (Kiel, Berlin, Würzburg) between November 15, 2020 and September 29, 2021. Main inclusion criteria were (i) a PCR confirmed SARS-CoV-2 infection and (ii) a period of at least 6 months between the infection and the visit to the COVIDOM study site. Other inclusion criteria were written informed consent and age ≥18 years. Key exclusion criterion was an acute reinfection with SARS-CoV-2. Study site visits included standardised interviews, in-depth examination, and biomaterial procurement. In sub-cohort Kiel-I, a PCS (severity) score was developed based upon 12 long-term symptom complexes. Two validation sub-cohorts (Würzburg/Berlin, Kiel-II) were used for PCS score replication and identification of clinically meaningful predictors. This study is registered at clinicaltrials.gov (NCT04679584) and at the German Registry for Clinical Studies (DRKS, DRKS00023742). In Kiel-I ( PCS severity can be quantified by an easy-to-use symptom-based score reflecting acute phase disease burden and general psychological predisposition. The PCS score thus holds promise to facilitate the clinical diagnosis of PCS, scientific studies of its natural course, and the development of therapeutic interventions. The COVIDOM study is funded by the Network University Medicine (NUM) as part of the National Pandemic Cohort Network (NAPKON). Show less

Effector functions of IgG Abs are regulated by their Fc N-glycosylation pattern. IgG Fc glycans that lack galactose and terminal sialic acid residues correlate with the severity of inflammatory (auto)immune disorders and have also been linked to protection against viral infection and discussed in the context of vaccine-induced protection. In contrast, sialylated IgG Abs have shown immunosuppressive effects. We sought to investigate IgG glycosylation programming during the germinal center (GC) reaction following immunization of mice with a foreign protein antigen and different adjuvants. Mice were analyzed for GC T-cell, B-cell, and plasma cell responses, as well as for antigen-specific serum IgG subclass titers and Fc glycosylation patterns. Different adjuvants induce distinct IgG This study's findings regarding adjuvant-dependent GC responses and IgG glycosylation programming may aid in the development of novel vaccination strategies to induce IgG Abs with both high affinity and defined Fc glycosylation patterns in the GC. Show less

The establishment of axon-dendrite polarity is fundamental for radial migration of neurons during cortex development of mammals. We demonstrate that the E3 ubiquitin ligases WW-Containing Proteins 1 and 2 (Wwp1 and Wwp2) are indispensable for proper polarization of developing neurons. We show that knockout of Wwp1 and Wwp2 results in defects in axon-dendrite polarity in pyramidal neurons, and their aberrant laminar cortical distribution. Knockout of miR-140, encoded in Wwp2 intron, engenders phenotypic changes analogous to those upon Wwp1 and Wwp2 deletion. Intriguingly, transcription of the Wwp1 and Wwp2/miR-140 loci in neurons is induced by the transcription factor Sox9. Finally, we provide evidence that miR-140 supervises the establishment of axon-dendrite polarity through repression of Fyn kinase mRNA. Our data delineate a novel regulatory pathway that involves Sox9-[Wwp1/Wwp2/miR-140]-Fyn required for axon specification, acquisition of pyramidal morphology, and proper laminar distribution of cortical neurons. Show less