There is uncertainty about the seroprevalence of anti-SARS-CoV-2 antibodies in the general population of Austria and about the waning of antibodies over time. We conducted a seroepidemiological study between June 2020 and September 2021, enrolling blood donors aged 18–70 years across Tyrol, Austria (participation rate: 84.0%). We analyzed serum samples for antibodies against the spike or the nucleocapsid proteins of SARS-CoV-2. We performed a total of 47,363 samples taken from 35,193 individuals (median age, 43.1 years (IQR: 29.3–53.7); 45.3% women; 10.0% with prior SARS-CoV-2 infection). Seroprevalence increased from 3.4% (95% CI: 2.8–4.2%) in June 2020 to 82.7% (95% CI: 81.4–83.8%) in September 2021, largely due to vaccination. Anti-spike IgG seroprevalence was 99.6% (95% CI: 99.4–99.7%) among fully vaccinated individuals, 90.4% (95% CI: 88.8–91.7%) among unvaccinated individuals with prior infection and 11.5% (95% CI: 10.8–12.3%) among unvaccinated individuals without known prior infection. Anti-spike IgG levels were reduced by 44.0% (95% CI: 34.9–51.7%) at 5–6 months compared with 0–3 months after infection. In fully vaccinated individuals, they decreased by 31.7% (95% CI: 29.4–33.9%) per month. In conclusion, seroprevalence in Tyrol increased to 82.7% in September 2021, with the bulk of seropositivity stemming from vaccination. Antibody levels substantially and gradually declined after vaccination or infection.

Summary Background Seroepidemiological studies provide important insight into the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2) in our society. We aimed to determine seropositivity of SARS-CoV‑2 antibodies and its cross-sectional correlates in a large cohort of blood donors. Methods In this observational cohort study, we tested healthy blood donors residing in Tyrol, Austria, for SARS-CoV‑2 antibodies using the Abbott SARS-CoV‑2 IgG chemiluminescent microparticle immunoassay. We estimated 95% confidence intervals (95% CI) of seroprevalences using bootstrapping and tested for differences by participant characteristics using logistic regression. Findings Between 8 June and 4 September 2020, we screened 5345 healthy individuals at local blood donor sessions (mean age 42.7 years, SD 13.5 years, 46.7% female). Overall seroprevalence was 3.1% (95% CI 2.7–3.6%, 165 cases), which is 5.1-fold higher (95% CI 4.5–6.0%) than the case number identified by the health authorities in the state-wide testing program (0.6%; 4536 out of 757,634). Seroprevalence was higher in the district Landeck (16.6%, P < 0.001) and in individuals aged < 25 years (4.7%, P = 0.043), but did not differ by gender, blood types, or medication intake. The odds ratio for seropositivity was 2.51 for participants who had travelled to Ischgl (1.49–4.21, P = 0.001), 1.39 who had travelled to other federal states (1.00–1.93, P = 0.052), and 2.41 who had travelled abroad (1.61–3.63, P < 0.001). Compared to participants who had a suspected/confirmed SARS-CoV‑2 infection but were seronegative, seropositive participants more frequently reported loss of smell (odds ratio = 2.49, 1.32–4.68, P = 0.005) and taste (odds ratio = 2.76, 1.54–4.92, P = 0.001). Conclusion In summer 2020, SARS-CoV‑2 seroprevalence in Tyrolean blood donors was 3.1%. Our study revealed regional variation and associations with young age, travel history and specific symptoms.

Because a large proportion of the Austrian population has been infected with SARS-CoV-2 during high incidence periods in winter 2021/2022, up-to-date estimates of seroprevalence of anti-SARS-CoV-2 antibodies are required to inform upcoming public health policies. We quantified anti-Spike IgG antibody levels in 22,607 individuals that donated blood between October 2021 and April 2022 across Tyrol, Austria (participation rate: 96.0%). Median age of participants was 45.3 years (IQR: 30.9–55.1); 41.9% were female. From October 2021 to April 2022, seropositivity increased from 84.9% (95% CI: 83.8–86.0%) to 95.8% (94.9–96.4%), and the geometric mean anti-Spike IgG levels among seropositive participants increased from 283 (95% CI: 271–296) to 1437 (1360–1518) BAU/mL. The percentages of participants in categories with undetectable levels and detectable levels at <500, 500–<1000, 1000–<2000, 2000–<3000, and ≥3000 BAU/mL were 15%, 54%, 15%, 10%, 3%, and 3% in October 2021 vs. 4%, 18%, 17%, 18%, 11%, and 32% in April 2022. Of 2711 participants that had repeat measurements taken a median 4.2 months apart, 61.8% moved to a higher, 13.9% to a lower, and 24.4% remained in the same category. Among seropositive participants, antibody levels were 16.8-fold in vaccinated individuals compared to unvaccinated individuals (95% CI: 14.2–19.9; p-value < 0.001). In conclusion, anti-SARS-CoV-2 seroprevalence in terms of seropositivity and average antibody levels has increased markedly during the winter 2021/2022 SARS-CoV-2 waves in Tyrol, Austria.

Oncolytic viruses (OVs) can eradicate tumor cells and elicit antitumor immunity. VSV-GP, a chimeric vesicular stomatitis virus (VSV) with the glycoprotein (GP) of the lymphocytic choriomeningitis virus, is a promising new OV candidate. However, the interaction of VSV-GP with host immune cells is not fully understood. Dendritic cells (DCs) are essential for inducing efficient antitumor immunity. Thus, we aimed to investigate the interaction of VSV-GP with different murine and human DCs subsets in direct comparison to the less cytopathic variant VSV-dM51-GP and wild type VSV. Immature murine bone marrow-derived DCs (BMDCs) were equally infected and killed by VSV and VSV-GP. Human monocyte-derived DCs (moDCs) were more permissive to VSV. Interestingly, VSV-dM51-GP induced maturation instead of killing in both BMDCs and moDCs as well as a pronounced release of pro-inflammatory cytokines. Importantly, matured BMDCs and moDCs were no longer susceptible to VSV-GP infection. Mouse splenic conventional DC type 1 (cDC1) could be infected ex vivo by VSV and VSV-GP to a higher extent than cDC2. Systemic infection of mice with VSV-GP and VSV-dM51-GP resulted in strong activation of cDCs despite low infection rates in spleen and tumor tissue. Human blood cDC1 were equally infected by VSV and VSV-GP, whereas cDC2 showed preferential infection with VSV. Our study demonstrated differential DC infection, activation, and cytokine production after the treatment with VSV and VSV-GP variants among species and subsets, which should be taken into account when investigating immunological mechanisms of oncolytic virotherapy in mouse models and human clinical trials.

Naïve T cells remain in an actively maintained state of quiescence until activation by antigenic signals, upon which they start proliferation and generation of effector cells to initiate a functional immune response. Metabolic reprogramming is essential to meet the biosynthetic demands of the differentiation process, and failure to do so can promote the development of hypofunctional exhausted T cells. Here we used13C metabolomics and transcriptomics to study the metabolic dynamics of CD8+T cells in their complete course of differentiation from naïve over stem-like memory to effector cells. The quiescence of naïve T cells was evident in a profound suppression of glucose oxidation and a decreased expression ofENO1, downstream of which no glycolytic flux was detectable. Moreover, TCA cycle activity was low in naïve T cells and associated with a downregulation of SDH subunits. Upon stimulation and exit from quiescence, the initiation of cell growth and proliferation was accompanied by differential expression of T cell regulatory genes and metabolic reprogramming towards aerobic glycolysis with high rates of nutrient uptake, respiration and lactate production. High flux in anabolic pathways imposed a strain on NADH homeostasis, which coincided with engagement of the proline cycle for mitochondrial redox shuttling. With acquisition of effector functions, cells increasingly relied on glycolysis as opposed to oxidative phosphorylation, which paradoxically was not linked to changes in mitochondrial abundance. We further investigated the metabolic phenotype of exhausted T cells, finding that decreased effector function concurred with a reduction in mitochondrial metabolism, glycolysis and amino acid import, and an upregulation of suppressive and quiescence-associated genes, includingTXNIPandKLF2. Thus, these results identify multiple features critical for the metabolic reprogramming that supports quiescence, proliferation and effector function of CD8+T cells during differentiation. Further, an impairment of the same processes in exhaustion suggests that targeting these control points may be useful for both modulation of differentiation and prevention of exhaustion.