Monika Redlberger-Fritz

Background: Vaccination programmes initiated in the early 1970s reduced the incidence of measles in Austria, which resulted in the interruption of endemic measles virus (MeV) circulation and the achievement of elimination status in 2018. However, large outbreaks occurred in 2023 and 2024. Aim: By assessing MeV-specific IgG antibody levels, we analysed if immunity recently declined due to the COVID-19 pandemic, vaccine-induced immunity waned over long term or immunity gaps already pre-existed in the population. Methods: We determined anti-MeV antibody levels in a retrospective dataset of 56,360 diagnostic samples (from 50,754 individuals) collected 2010–2024 and correlated antibody cutoffs to titres from a live-virus neutralisation test. Results: Individuals born before 1970 (n = 15,007) had antibody levels > 3,000 IU/L, persisting into higher age, and < 2% (n = 300) of them were seronegative. In contrast, individuals born after 1990 (n = 12,778) displayed seronegativity rates of 13–20% and lower median antibody concentrations in seropositive individuals (449–773 IU/L). In these individuals, antibody levels decreased noticeably between the ages of 2 and 10 years but remained stable between those aged 10 and 30 years. There was no significant difference in seronegativity rates at the age of 12–24 months in children born 2016–2019 and 2020–2022 (the years of the COVID-19 pandemic). Conclusion: In Austria, there are significant immunity gaps in individuals born after 1970, which pre-existed before the COVID-19 pandemic. Thus, young and middle-aged populations not immune against measles should be vaccinated to counteract a further decline of immunity at the population level and prevent outbreaks whenever MeV is imported.

Zoonotic viruses may be neglected as etiologies of meningoencephalitis in humans. We performed retrospective testing of cerebrospinal fluid from encephalitis cases in biobank material for three zoonotic or potentially zoonotic viruses: rustrela virus (Rubivirus strelense, Matonaviridae); Tahyna virus (Orthobunyavirus tahynaense, Peribunyaviridae); and lymphocytic choriomeningitis virus (“LCMV”, Mammarenavirus choriomeningitidis, Arenaviridae). The cohort consisted of 443 samples, received for routine diagnostic testing year-round between January 2019 and February 2023, and were negative for herpes simplex viruses, varicella zoster virus, and enteroviruses. Using published RT-qPCR protocols, we did not detect rustrela virus or Tahyna virus in any sample. Using a herein described RT-qPCR protocol, we detected LCMV in one sample. Partial genetic sequencing of the virus suggested that the virus was locally acquired. Our study provides information about the incidence of these viruses in humans in Austria when encephalitis is suspected.

Background and objectives: Viral respiratory infections significantly affect young children, particularly extremely premature infants, resulting in high hospitalization rates and increased health‐care burdens. Nasal epithelial cells, the primary defense against respiratory infections, are vital for understanding nasal immune responses and serve as a promising target for uncovering underlying molecular and cellular mechanisms.Methods: Using a trans‐well pseudostratified nasal epithelial cell system, we examined age‐dependent developmental differences and antiviral responses to influenza A and respiratory syncytial virus through systems biology approaches.Results: Our studies revealed differences in innate‐receptor repertoires, distinct developmental pathways, and differentially connected antiviral network circuits between neonatal and adult nasal epithelial cells. Consensus network analysis identified unique and shared cellular‐viral networks, emphasizing highly relevant virus‐specific pathways, independent of viral replication kinetics.Conclusion: This research highlights the importance of nasal epithelial cells in innate antiviral immune responses and offers crucial insights that allow for a deeper understanding of age‐related differences in nasal epithelial cell immunity following respiratory virus infections.

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.

Background: Timely treatment with neuraminidase inhibitors (NAI) can reduce severe outcomes in influenza patients. Aim: We assessed the impact of antiviral treatment on in-hospital deaths of laboratory-confirmed influenza patients in 11 European Union countries from 2010/11 to 2019/20. Methods: Case-based surveillance data from hospitalised patients with known age, sex, outcome, ward, vaccination status, timing of antiviral treatment, and hospitalisation were obtained. A mixed effect logistic regression model using country as random intercept was applied to estimate the adjusted odds ratio (aOR) for in-hospital death in patients treated with NAIs vs not treated. Results: Of 19,937 patients, 31% received NAIs within 48 hours of hospital admission. Older age (60–79 years aOR 3.0, 95% CI: 2.4–3.8; 80 years 8.3 (6.6–10.5)) and intensive care unit admission (3.8, 95% CI: 3.4–4.2) increased risk of dying, while early hospital admission after symptom onset decreased risk (aOR 0.91, 95% CI: 0.90–0.93). NAI treatment initiation within 48 hours and up to 7 days reduced risk of dying (0–48 hours aOR 0.51, 95% CI: 0.45–0.59; 3–4 days 0.59 (0.51–0.67); 5–7 days 0.64 (0.56–0.74)), in particular in patients 40 years and older (e.g. treatment within 48 hours: 40–59 years aOR 0.43, 95% CI: 0.28–0.66; 60–79 years 0.50 (0.39–0.63); ≥80 years 0.51 (0.42–0.63)). Conclusion: NAI treatment given within 48 hours and possibly up to 7 days after symptom onset reduced risk of in-hospital death. NAI treatment should be considered in older patients to prevent severe outcomes.

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.

Sentinel surveillance of influenza‐like illnesses revealed an increase in the cases of influenza C virus in children and adults in Austria, 2022, compared to previous years, following one season (2020/2021), wherein no influenza C virus was detected. Whole‐genome sequencing revealed no obvious genetic basis for the increase. We propose that the reemergence is explained by waning immunity from lack of community exposure due to restrictions intended to limit severe acute respiratory syndrome coronavirus 2 spread in prior seasons, pending further investigation.

Summary: Objective: To increase knowledge of discrete symptoms shall help to avoid misinterpretation of test results and to gain better understanding of associations between early symptoms and severe disease to provide additional criteria for targeted early interventions.Design: Retrospective observational study.Setting: Austrian GP practices in the year 2020, patients above 18 years were included.Participants: We recruited 25 practices which included 295 participants with a positive SARS-CoV‑2 test.Main outcome measures: Data collection comprised basic demographic data, risk factors and the recording of symptoms at several points in time in the course of the illness. Descriptive analyses for possible associations between demographics and symptoms were conducted by means of cross tabulation. Group differences (hospitalized yes/no) were assessed using Fisher’s exact test. The significance level was set to 0.05; due to the observational character of the study, no adjustment for multiplicity was performed.Results: Only one third of patients report symptoms generally understood to be typical for COVID‑19. Most patients presented with unspecific complaints. We found symptoms indicating complicated disease, depending on when they appear. The number of symptoms may be a predictor for the need of hospital care. More than 50% of patients still experience symptoms 14 days after onset.Conclusion: Unspecific symptoms are valuable indicators in the detection of early COVID‑19 disease that practitioners and the general public should be aware of also in the interpretation of low sensitivity tests. Monitoring patients using the indicators we identified may help to identify patients who are likely to profit from early intervention.

Background: Research indicates that timely treatment with neuraminidase inhibitors (NAI) reduces severe outcomes in influenza-infected patients. Our aim was to analyse case-based data on NAI treatment in hospitalised laboratory-confirmed influenza patients in EU countries from 2010/11 to 2019/20 to assess this. Methods: Propensity weighted adjusted robust Poisson regression models were used to estimate the incidence rate ratio (IRR) for in-hospital death in patients treated with NAIs versus not treated, adjusted for age, sex, virus (sub)type, timing of hospitalisation and treatment, hospital unit, and spatial clustering Findings: NAI were mostly (83%) given within two days after hospital admission. Our results support the role of early treatment within 48 hours (incidence risk ration (IRR) 0·63; 95% confidence interval (CI) 0·56-0·70), even administered later than 48 hours and up to seven days, to reduce the risk of in-hospital death. Older age and intensive care unit admission (IRR 2·69; 95%CI 2·49-2·91) increased the risk of dying, while early hospital admission after onset of symptoms decreased the risk (IRR 0·94; 95%CI 0·92-0·95). Age-stratified analysis showed that NAI treatment reduced the risk in people 40 years and older. Among hospitalised patients with underlying conditions and clinical complications, antiviral treatment reduced risk to die when given within 48 hours after onset of symptoms compared to later (IRR 0·79; 95%CI 0·66-0·94). Interpretation: NAI treatment given up to seven days after symptom onset reduced the risk of in-hospital death. NAI treatment should be considered particularly in age-group ≥ 40 to prevent severe outcomes. Funding Information: Internal funds of ECDC. Declaration of Interests: None declared. Ethics Approval Statement: Not required.

Background: Efficacy of vaccines and disease activity linked to immunization are major concerns among people with multiple sclerosis (pwMS).Objective: To assess antibody responses to seasonal influenza antigens and vaccine-associated neuroaxonal damage utilizing serum neurofilament light chain (sNfL) in pwMS receiving dimethyl fumarate (DMF).Methods: In this prospective study, the 2020/2021 seasonal tetravalent influenza vaccine was administered to 20 pwMS treated with DMF and 15 healthy controls (HCs). The primary endpoints were responder rate of strain-specific antibody production (seroconversion or significant (4-fold) increase in influenza-antibody titers for ≥2/4 strains) at 30 days post-vaccination and changes in sNfL levels.Results: All patients treated with DMF fulfilled the responder criteria for immunization compared with 53% of the controls. However, higher proportions of HCs already had influenza-antibody titers ≥1:40 at baseline (53% vs. 41%, p = 0.174). sNfL levels were comparable among both groups at baseline and did not increase 34 days after vaccination. In addition, no clinical or radiological disease reactivation was found.Conclusion: DMF-treated patients mount an adequate humoral immune response to influenza vaccines. Within the limits of the small cohort investigated, our data suggest that influenza immunization is not associated with clinical or subclinical disease reactivation.