Renal and circulatory effects of large volume plasma expansion in patients with hepatorenal syndrome type 1(◆)(◆) This work was financed by departmental funds. No grants were received. Wolfgang Huber is a member of the medical advisory board of Pulsion medical Systems, Munich, Germany.The other authors declare no conflict of interest.

Introduction. Hepatorenal syndrome type I (HRS I) may be a consequence of circulatory dysfunction in cirrhotic patients with portal hypertension. This uncontrolled interventional pilot study examines the hemodynamic and renal effects of large volume plasma expansion in HRS I.Material and methods. 14 cirrhotic patients (8 m, 6 f, age 60 (58-65) years) with HRS I received large volume plasma expansion with up to 400 mL of 20% human albumin solution per 12 over 48 h under hemodynamic monitoring by transpulmonary thermodilution. Creatinine clearances (ClCreat) were calculated for 12-h periods. Plasma expansion was withheld if criteria of volume overload [Extravascular lung Water Index (ELWI) > 9 mL/kg or Global End-Dias-tolic Volume Index (GEDI) > 820 mL/m2] were met. Paracentesis was performed according to clinical necessity and treatment continued for 48 h thereafter. Serum creatinine values were observed for 12 days.Results. Patients received 1.6 (1.5-2.0) g of albumin per kg bodyweight and day for 48 to 96 h. During the treatment period, GEDVI [724 (643-751) mL/m2 vs. 565 (488-719) mL/m2; p = 0.001], cardiac index (CI) [4.9 (4.1-6.15) L/min/m2 vs. 3.9 (3.4-5.0) L /min/m2; p = 0.033], urinary output [25 (17-69) mL/h vs. 17 (8-39) mL/h; p = 0.016) and ClCreat [20 (15-47) vs. 12 (6-17); p = 0.006] increased whereas systemic vascular resistance index (SVRI), plasma renin activity (PRA) and plasma aldosterone were significantly reduced. At 48 h there were two complete responses (serum creatinine < 133 umol/L) and on day 12, 8 patients had a complete response.Conclusion. HRS I may respond to large volume plasma expansion with or without paracentesis

Prior flavivirus immunity skews the yellow fever vaccine response to expand cross-reactive antibodies with increased risk of antibody dependent enhancement of Zika and dengue virus infection

Human pathogenic flaviviruses pose a significant health concern and vaccination is the most effective instrument to control their circulation. How pre-existing immunity to antigenically related viruses modulates immunization outcome remains poorly understood. In this study, we evaluated the effect of vaccination against tick-borne encephalitis virus (TBEV) on the epitope immunodominance and immunogenicity of the yellow fever 17D vaccine (YF17D) in a cohort of 250 human vaccinees. Following YF17D vaccination, all study participants seroconverted and generated protective neutralizing antibody titers. At day 28, TBEV pre-immunity did not affect the polyclonal neutralizing response which largely depended on the IgM fraction. We found that sera from TBEV-immunized individuals enhanced YF17D vaccine virus infection via antibody-dependent enhancement (ADE). Upon vaccination, individuals with TBEV pre-immunity had higher concentrations of cross-reactive IgG antibodies with limited neutralizing capacity against YF17D whereas vaccinees without prior flavivirus exposure showed a non-cross-reacting response. Using a set of recombinant YF17D envelope protein mutants displaying different epitopes, we identified quaternary epitopes as the primary target of neutralizing antibodies. Sequential immunizations redirected the IgG response towards the pan-flavivirus fusion loop epitope (FLE) with the potential to mediate enhancement of dengue and Zika virus infections whereas TBEV naïve individuals elicited an IgG response directed towards neutralizing epitopes without an enhancing effect. We propose that the YF17D vaccine effectively conceals the FLE and primes a neutralizing IgG response in individuals with no prior flavivirus exposure. In contrast, the response in TBEV-experienced recipients favors weakly-neutralizing, cross-reactive epitopes potentially increasing the risk of severe dengue and Zika disease due to ADE

Prior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection

Abstract The yellow fever 17D vaccine (YF17D) is highly effective but is frequently administered to individuals with pre-existing cross-reactive immunity, potentially impacting their immune responses. Here, we investigate the impact of pre-existing flavivirus immunity induced by the tick-borne encephalitis virus (TBEV) vaccine on the response to YF17D vaccination in 250 individuals up to 28 days post-vaccination (pv) and 22 individuals sampled one-year pv. Our findings indicate that previous TBEV vaccination does not affect the early IgM-driven neutralizing response to YF17D. However, pre-vaccination sera enhance YF17D virus infection in vitro via antibody-dependent enhancement (ADE). Following YF17D vaccination, TBEV-pre-vaccinated individuals develop high amounts of cross-reactive IgG antibodies with poor neutralizing capacity. In contrast, TBEV-unvaccinated individuals elicit a non-cross-reacting neutralizing response. Using YF17D envelope protein mutants displaying different epitopes, we identify quaternary dimeric epitopes as the primary target of neutralizing antibodies. Additionally, TBEV-pre-vaccination skews the IgG response towards the pan-flavivirus fusion loop epitope (FLE), capable of mediating ADE of dengue and Zika virus infections in vitro. Together, we propose that YF17D vaccination conceals the FLE in individuals without prior flavivirus exposure but favors a cross-reactive IgG response in TBEV-pre-vaccinated recipients directed to the FLE with potential to enhance dengue virus infection

Spatially resolved qualified sewage spot sampling to track SARS-CoV-2 dynamics in Munich - One year of experience

Rubio-Acero R, Beyerl J, Muenchhoff M, et al. Spatially resolved qualified sewage spot sampling to track SARS-CoV-2 dynamics in Munich - One year of experience. Science of The Total Environment. 2021;797: 149031

The representative COVID-19 cohort Munich (KoCo19): from the beginning of the pandemic to the Delta virus variant

Le Gleut R, Plank M, Pütz P, et al. The representative COVID-19 cohort Munich (KoCo19): from the beginning of the pandemic to the Delta virus variant. BMC Infectious Diseases. 2023;23(1): 466.**Background** Population-based serological studies allow to estimate prevalence of SARS-CoV-2 infections despite a substantial number of mild or asymptomatic disease courses. This became even more relevant for decision making after vaccination started. The KoCo19 cohort tracks the pandemic progress in the Munich general population for over two years, setting it apart in Europe. **Methods** Recruitment occurred during the initial pandemic wave, including 5313 participants above 13 years from private households in Munich. Four follow-ups were held at crucial times of the pandemic, with response rates of at least 70%. Participants filled questionnaires on socio-demographics and potential risk factors of infection. From Follow-up 2, information on SARS-CoV-2 vaccination was added. SARS-CoV-2 antibody status was measured using the Roche Elecsys® Anti-SARS-CoV-2 anti-N assay (indicating previous infection) and the Roche Elecsys® Anti-SARS-CoV-2 anti-S assay (indicating previous infection and/or vaccination). This allowed us to distinguish between sources of acquired antibodies. **Results** The SARS-CoV-2 estimated cumulative sero-prevalence increased from 1.6% (1.1-2.1%) in May 2020 to 14.5% (12.7-16.2%) in November 2021. Underreporting with respect to official numbers fluctuated with testing policies and capacities, becoming a factor of more than two during the second half of 2021. Simultaneously, the vaccination campaign against the SARS-CoV-2 virus increased the percentage of the Munich population having antibodies, with 86.8% (85.5-87.9%) having developed anti-S and/or anti-N in November 2021. Incidence rates for infections after (BTI) and without previous vaccination (INS) differed (ratio INS/BTI of 2.1, 0.7-3.6). However, the prevalence of infections was higher in the non-vaccinated population than in the vaccinated one. Considering the whole follow-up time, being born outside Germany, working in a high-risk job and living area per inhabitant were identified as risk factors for infection, while other socio-demographic and health-related variables were not. Although we obtained significant within-household clustering of SARS-CoV-2 cases, no further geospatial clustering was found. **Conclusions** Vaccination increased the coverage of the Munich population presenting SARS-CoV-2 antibodies, but breakthrough infections contribute to community spread. As underreporting stays relevant over time, infections can go undetected, so non-pharmaceutical measures are crucial, particularly for highly contagious strains like Omicron