Longitudinal viscosity of blood plasma for rapid COVID-19 prognostics (preprint)

Blood Plasma Viscosity (PV) is an established biomarker for numerous diseases. While PV colloquially refers to the shear viscosity, there is a second viscosity component--the bulk viscosity--that describes the irreversible fluid compressibility on short time scales. The bulk viscosity is acutely sensitive to solid-like suspensions, and obtainable via the longitudinal viscosity from acoustic attenuation measurements. Whether it has diagnostic value remains unexplored yet may be pertinent given the association of diverse pathologies with the formation of plasma suspensions, such as fibrin-microstructures in COVID-19 and long-COVID. Here we show that the longitudinal PV measured using Brillouin Light Scattering (BLS) can serve as a proxy for the shear PV of blood plasma, and exhibits a temperature dependence consistent with increased suspension concentrations in severe COVID-patient plasma. Our results open a new avenue for PV diagnostics based on the longitudinal PV, and show that BLS can provide a means for its clinical implementation.

Bivalent COVID-19 mRNA booster vaccination (BA.1 or BA.4/BA.5) increases neutralization of matched Omicron variants (preprint)

We report SARS-CoV-2 neutralizing antibody titers in sera of triple-vaccinated individuals who received a booster dose of an original monovalent or a bivalent BA.1- or BA.4/BA.5-adapted vaccine, or had a breakthrough infection with Omicron variants BA.1, BA.2 or BA.4/BA.5. A bivalent BA.4/BA.5 booster or Omicron-breakthrough infection induced increased Omicron-neutralization titers compared with the monovalent booster. The XBB.1.5 variant effectively evaded neutralizing-antibody responses elicited by current vaccines and/or infection with previous variants.

The respiratory syncytial virus surge in Austria, 2022, was caused by lineages present before the COVID-19 pandemic (preprint)

In 2022, Austria experienced a severe respiratory syncytial virus (RSV) epidemic with an earlier-than-usual start and increased numbers of paediatric patients in emergency departments. Nationwide multiyear genomic surveillance revealed that the surge was driven by RSV-B, however genotypes consisted of multiple lineages that were circulating prior to the pandemic.

The Systemic Renin-Angiotensin System in COVID-19 (preprint)

Introduction: SARS-CoV-2 gains cell entry via angiotensin-converting enzyme (ACE) 2, a membrane-bound enzyme of the “alternative” (alt) renin-angiotensin system (RAS). ACE2 counteracts angiotensin II by converting it to potentially protective angiotensin 1–7.Methods Using mass spectrometry, we assessed key metabolites of the classical RAS (angiotensins I–II) and alt-RAS (angiotensins 1–7 and 1–5) pathways as well as ACE and ACE2 concentrations in 159 patients hospitalized with COVID-19, stratified by disease severity (severe, n = 76; non-severe: n = 83). Plasma renin activity (PRA-S) was calculated as the sum of RAS metabolites. We estimated ACE activity using the angiotensin II:I ratio (ACE-S) and estimated systemic alt-RAS activation using the ratio of alt-RAS axis metabolites to PRA-S (ALT-S). We applied mixed linear models to assess how PRA-S and ACE/ACE2 concentrations affected ALT-S, ACE-S, and angiotensins II and 1–7.Results Median angiotensin I and II levels were higher with severe versus non-severe COVID-19 (both p < 0.05), demonstrating activation of classical RAS. The difference disappeared with analysis limited to patients not taking a RAS inhibitor. ALT-S in severe COVID-19 increased with time (days 1–6: 0.12; days 11–16: 0.22) and correlated with ACE2 concentration (r = 0.831). ACE-S was lower in severe versus non-severe COVID-19 (p < 0.001), but ACE concentrations were similar between groups and weakly correlated with ACE-S (r = 0.232). ACE2 and ACE-S trajectories in severe COVID-19, however, did not differ between survivors and non-survivors. Overall RAS alteration in severe COVID-19 resembled severity of disease-matched patients with influenza. In mixed linear models, renin activity most strongly predicted angiotensin II and 1–7 levels. ACE2 also predicted angiotensin 1–7 levels and ALT-S. No single factor or the combined model, however, could fully explain ACE-S. ACE2 and ACE-S trajectories in severe COVID-19 did not differ between survivors and non-survivors.Conclusions Angiotensin II was elevated in severe COVID-19 but markedly influenced by RAS inhibitors and driven by overall RAS activation. ACE-S was significantly lower with severe COVID-19 and did not correlate with ACE concentrations. A shift to the alt-RAS axis because of increased ACE2 could partially explain the relative reduction in angiotensin II levels.

Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial (preprint)

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID-19 vaccination. In this blinded randomized clinical trial (EudraCT 2021-002348-57) we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non-seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV-19 (Oxford-AstraZeneca). Patients were stratified according to the presence of peripheral B-cells. The primary efficacy endpoint was the difference in the SARS-CoV-2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week four. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at weeks one and four. Seroconversion rates at week four were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccine (p=0.6). Overall, 27% of patients seroconverted; specific T-cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. No serious adverse events, related to immunization, were observed. This enhanced humoral and/or cellular immune response supports an additional booster vaccination in non-seroconverted patients irrespective of a heterologous or homologous vaccination regimen.