While the measurement of neutralizing antibodies is considered a valuable tool in assessing protection against SARS-CoV-2, neutralization tests employ live-virus isolates and cell culture, requiring advanced laboratory biosafety levels. Including a large sample panel (over 700 samples), this study provides adapted cutoff values calculated for seven commercial immunoassays (including four surrogate neutralization assays and a protein-based microarray) that robustly correlate with specific titers of neutralizing antibodies.

This study demonstrates that the antigenic changes of the SARS-CoV-2 Omicron variant affect test results from commercial Spike- and RBD-specific antibody assays, significantly diminishing their sensitivities and diagnostic abilities to assess neutralizing antibodies.

Withdrawal from systemic opioids can induce long-term potentiation (LTP) at spinal C-fibre synapses (“opioid-withdrawal-LTP”). This is considered to be a cellular mechanism underlying opioid withdrawal-induced hyperalgesia, which is a major symptom of the opioid withdrawal syndrome. Opioids can activate glial cells leading to the release of proinflammatory mediators. These may influence synaptic plasticity and could thus contribute to opioid-withdrawal-LTP. Here, we report a sexual dimorphism in the mechanisms of morphine-withdrawal-LTP in adult rats. We recorded C-fibre-evoked field potentials in the spinal cord dorsal horn from deeply anaesthetised male and female rats. In both sexes, we induced a robust LTP through withdrawal from systemic morphine infusion (8 mg·kg−1 bolus, followed by a 1-hour infusion at a rate of 14 mg·kg−1·h−1). This paradigm also induced mechanical hypersensitivity of similar magnitude in both sexes. In male rats, systemic but not spinal application of (−)naloxone blocked the induction of morphine-withdrawal-LTP, suggesting the involvement of descending pronociceptive pathways. Furthermore, we showed that in male rats, the induction of morphine-withdrawal-LTP required the activation of spinal astrocytes and the release of the proinflammatory cytokines tumour necrosis factor and interleukin-1. In striking contrast, in female rats, the induction of morphine-withdrawal-LTP was independent of spinal glial cells. Instead, blocking µ-opioid receptors in the spinal cord was sufficient to prevent a facilitation of synaptic strength. Our study revealed fundamental sex differences in the mechanisms underlying morphine-withdrawal-LTP at C-fibre synapses: supraspinal and gliogenic mechanisms in males and a spinal, glial cell-independent mechanism in females.

The recently emerged Omicron variant is the most antigenically distinct SARS-CoV-2 variant of concern to date. As the heavily mutated spike protein enables escape from neutralizing antibodies, we studied the neutralizing activities of sera after Omicron BA.1 and BA.2 infections of naïve and vaccinated individuals. We show that primary BA.1 infections yielded reduced neutralizing antibody titers against wildtype (WT), Delta, and BA.2, while serum samples from individuals after BA.2 infection showed no cross-neutralization against the other variants. Fully vaccinated individuals were still able to neutralize both Omicron sub-lineages up to three months after vaccination, and Omicron-breakthrough infections showed equal cross-neutralizing activities against WT, Delta, BA.1, and BA.2. Our data demonstrate that Omicron variants are able to enhance cross-neutralizing antibodies in pre-immune individuals. Primary infections with one of the Omicron sub-lineages, however, induced variant-specific neutralizing antibodies. In particular, BA.2 infections generated a sub-lineage-specific response, emphasizing its antigenic distance.

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.

In 2022, Austria experienced a severe respiratory syncytial virus (RSV) epidemic with an earlier-than-usual start (Weeks 35/2021-45/2022) and increased numbers of pediatric patients in emergency departments. This surge came 2 years after a season with no cases detected as a result of coronavirus disease 2019 nonpharmaceutical interventions. We analyzed epidemiologic patterns and the phylodynamics of RSV based on approximately 30 800 respiratory specimens collected year-round over 10 years from ambulatory and hospitalized patients from 248 locations in Austria. Genomic surveillance and phylogenetic analysis of 186 RSV-A and 187 RSV-B partial glycoprotein sequences collected from 2018 to 2022 revealed that the 2022/2023 surge was driven by RSV-B in contrast to the surge in the 2021/2022 season that was driven by RSV-A. Whole-genome sequencing and phylodynamic analysis indicated that the RSV-B strain GB5.0.6a was the predominant genotype in the 2022/2023 season and emerged in late 2019. The results provide insight into RSV evolution and epidemiology that will be applicable to future monitoring efforts with the advent of novel vaccines and therapeutics.

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.

Background and MethodsThe SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Omicron (B.1.1.529) variant is the antigenically most distinct variant to date. As the heavily mutated spike protein enables neutralization escape, we studied serum-neutralizing activities of naïve and vaccinated individuals after Omicron BA.1 or BA.2 sub-lineage infections in live virus neutralization tests with Omicron BA.1, Omicron BA.2, wildtype (WT, B1.1), and Delta (B.1.617.2) strains. Serum samples obtained after WT infections and three-dose mRNA vaccinations with and without prior infection were included as controls.ResultsPrimary BA.1 infections yielded reduced neutralizing antibody levels against WT, Delta, and Omicron BA.2, while samples from BA.2-infected individuals showed almost no cross-neutralization against the other variants. Serum neutralization of Omicron BA.1 and BA.2 variants was detectable after three-dose mRNA vaccinations, but with reduced titers. Vaccination-breakthrough infections with either Omicron BA.1 or BA.2, however, generated equal cross-neutralizing antibody levels against all SARS-CoV-2 variants tested.ConclusionsOur study demonstrates that although Omicron variants are able to enhance cross-neutralizing antibody levels in pre-immune individuals, primary infections with BA.1 or BA.2 induced mostly variant-specific neutralizing antibodies, emphasizing the differently shaped humoral immunity induced by the two Omicron variants. These data thus contribute substantially to the understanding of antibody responses induced by primary Omicron infections or multiple exposures to different SARS-CoV-2 variants and are of particular importance for developing vaccination strategies in the light of future emerging variants.