Superspreading events shaped the coronavirus disease 2019 (COVID-19) pandemic, and their rapid identification and containment are essential for disease control. Here, we provide a national-scale ...analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) superspreading during the first wave of infections in Austria, a country that played a major role in initial virus transmissions in Europe. Capitalizing on Austria's well-developed epidemiological surveillance system, we identified major SARS-CoV-2 clusters during the first wave of infections and performed deep whole-genome sequencing of more than 500 virus samples. Phylogenetic-epidemiological analysis enabled the reconstruction of superspreading events and charts a map of tourism-related viral spread originating from Austria in spring 2020. Moreover, we exploited epidemiologically well-defined clusters to quantify SARS-CoV-2 mutational dynamics, including the observation of low-frequency mutations that progressed to fixation within the infection chain. Time-resolved virus sequencing unveiled viral mutation dynamics within individuals with COVID-19, and epidemiologically validated infector-infectee pairs enabled us to determine an average transmission bottleneck size of 10
SARS-CoV-2 particles. In conclusion, this study illustrates the power of combining epidemiological analysis with deep viral genome sequencing to unravel the spread of SARS-CoV-2 and to gain fundamental insights into mutational dynamics and transmission properties.
Abstract
The kinetics of immunoglobulin G (IgG) avidity maturation during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection obtained from 217 participants of the Ischgl cohort, ...Austria, was studied 0.5–1.5 months (baseline) and 7–8 months (follow-up) after infection. The IgG avidity assay, using a modified IgG enzyme-linked immunosorbent assay (ELISA) and 5.5 M urea, revealed that old age does not diminish the increase in avidity, detected in all participants positive at both time points, from 18% to 42%. High avidity was associated with a marked residual neutralization capacity in 97.2.% of participants (211/217), which was even higher in the older age group, revealing an important role of avidity assays as easy and cheap surrogate tests for assessing the maturation of the immune system conveying potential protection against further SARS-CoV-2 infections without necessitating expensive and laborious neutralization assays.
Avidity and neutralization data from 217 SARS-CoV2–infected antibody-positive subjects revealed a strong immune response 7–8 months postinfection in >97% of subjects, not diminished in old age. Easy and cheap avidity assays may thus compensate for expensive neutralization assays.
Several studies have shown that SARS-CoV-2 BA.1 omicron is an immune escape variant. Meanwhile, however, omicron BA.2 and BA.5 became dominant in many countries and replaced BA.1. As both have ...several mutations compared to BA.1, we analyzed whether BA.2 and BA.5 show further immune escape relative to BA.1. Here, we characterized neutralization profiles against the BA.2 and BA.5 omicron sub-variants in plasma samples from individuals with different history of exposures to infection/vaccination and found that unvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and to BA.1. Consequently, our antigenic map including all Variants of Concern and BA.1, BA.2 and BA.5 omicron sub-variants, showed that all omicron sub-variants are distinct to pre-omicron variants, but that the three omicron variants are also antigenically distinct from each other. The antibody landscapes illustrate that cross-neutralizing antibodies against the current antigenic space, as described in our maps, are generated only after three or more exposures to antigenically close variants but also after two exposures to antigenically distant variants. Here, we describe the antigenic space inhabited by the relevant SARS-CoV-2 variants, the understanding of which will have important implications for further vaccine strain adaptations.
A general concern exists that cervical cancer screening using human papillomavirus (HPV) testing may lead to considerable overtreatment. We evaluated the trade‐off between benefits and overtreatment ...among different screening strategies differing by primary tests (cytology, p16/Ki‐67, HPV alone or in combinations), interval, age and diagnostic follow‐up algorithms. A Markov state‐transition model calibrated to the Austrian epidemiological context was used to predict cervical cancer cases, deaths, overtreatments and incremental harm–benefit ratios (IHBR) for each strategy. When considering the same screening interval, HPV‐based screening strategies were more effective compared to cytology or p16/Ki‐67 testing (e.g., relative reduction in cervical cancer with biennial screening: 67.7% for HPV + Pap cotesting, 57.3% for cytology and 65.5% for p16/Ki‐67), but were associated with increased overtreatment (e.g., 19.8% more conizations with biennial HPV + Papcotesting vs. biennial cytology). The IHBRs measured in unnecessary conizations per additional prevented cancer‐related death were 31 (quinquennial Pap + p16/Ki‐67‐triage), 49 (triennial Pap + p16/Ki‐67‐triage), 58 (triennial HPV + Pap cotesting), 66 (biennial HPV + Pap cotesting), 189 (annual Pap + p16/Ki‐67‐triage) and 401 (annual p16/Ki‐67 testing alone). The IHBRs increased significantly with increasing screening adherence rates and slightly with lower age at screening initiation, with a reduction in HPV incidence or with lower Pap‐test sensitivity. Depending on the accepted IHBR threshold, biennial or triennial HPV‐based screening in women as of age 30 and biennial cytology in younger women may be considered in opportunistic screening settings with low or moderate adherence such as in Austria. In organized settings with high screening adherence and in postvaccination settings with lower HPV prevalence, the interval may be prolonged.
What's new?
While human papillomavirus (HPV)‐based testing is effective for cervical cancer detection, trade‐offs between benefits and harms, particularly overtreatment associated with HPV testing, remain poorly defined. This study, using model simulations, suggests that over the same screening interval, HPV testing is more effective than conventional Pap cytology and p16/Ki‐67 staining but carries a risk of overtreatment, particularly in settings with short screening intervals. Relative to annual cytology, HPV and Pap cotesting results in similar benefit but fewer unnecessary treatments. The findings indicate that harm‐benefit ratios for different screening methods vary depending on screening setting, interval, adherence, and HPV‐vaccination status.
Neutralizing antibodies are a major correlate of protection for many viruses including the novel coronavirus SARS-CoV-2. Thus, vaccine candidates should potently induce neutralizing antibodies to ...render effective protection from infection. A variety of in vitro assays for the detection of SARS-CoV-2 neutralizing antibodies has been described. However, validation of the different assays against each other is important to allow comparison of different studies. Here, we compared four different SARS-CoV-2 neutralization assays using the same set of patient samples. Two assays used replication competent SARS-CoV-2, a focus forming assay and a TCID
-based assay, while the other two assays used replication defective lentiviral or vesicular stomatitis virus (VSV)-based particles pseudotyped with SARS-CoV-2 spike. All assays were robust and produced highly reproducible neutralization titers. Titers of neutralizing antibodies correlated well between the different assays and with the titers of SARS-CoV-2 S-protein binding antibodies detected in an ELISA. Our study showed that commonly used SARS-CoV-2 neutralization assays are robust and that results obtained with different assays are comparable.
Human papillomavirus (HPV) is a sexually transmitted infection that causes cervical cancer, head and neck cancer, other urogenital cancers, and genital warts. In Austria, where HPV vaccination is ...free for children, the vaccination rate nevertheless remains insufficient for herd immunity against HPV. Using a cross-sectional survey of parents (N = 334) in the state of Tyrol, Austria, we examined parents' reasons for rejecting children's HPV vaccination and key predictors of vaccination intention for their children, including knowledge about HPV, attitude toward vaccination, sources of information about the HPV vaccine, socioeconomic factors, and HPV vaccination intention. Data analyzed using descriptive statistics and logistic regression modeling revealed an overall 81.9% acceptance rate of HPV vaccination. The most common reasons for vaccine hesitancy were a fear of side effects, a perceived lack of information, and the perception that children are too young to be vaccinated. A high level of knowledge about HPV was significantly associated with vaccine acceptance for female but not male children. Negative attitude toward vaccination was significantly related to lower vaccine acceptance, and parents who reported informing themselves about HPV vaccination from online sources were less likely to accept vaccination. Such results call for more educational measures to reduce misinformation about HPV vaccination and thereby reduce the fear of its side effects and promote early vaccination. More information is also needed to improve parents' attitude toward and their knowledge about vaccination, the dissemination of which should focus on the benefits of vaccines for children of both sexes.
Since emergence of the initial SARS-CoV-2 BA.1, BA.2 and BA.5 variants, Omicron has diversified substantially. Antigenic characterization of these new variants is important to analyze their potential ...immune escape from population immunity and implications for future vaccine composition. Here, we describe an antigenic map based on human single-exposure sera and live-virus isolates that includes a broad selection of recently emerged Omicron variants such as BA.2.75, BF.7, BQ, XBB and XBF variants. Recent Omicron variants clustered around BA.1 and BA.5 with some variants further extending the antigenic space. Based on this antigenic map we constructed antibody landscapes to describe neutralization profiles after booster immunization with bivalent mRNA vaccines based on ancestral virus and either BA.1 or BA.4/5. Immune escape of BA.2.75, BQ, XBB and XBF variants was also evident in bivalently boosted individuals, however, cross-neutralization was improved for those with hybrid immunity. Our results indicate that future vaccine updates are needed to induce cross-neutralizing antibodies against currently circulating variants.
To investigate the association between total serum cholesterol (TSC) and cancer incidence in the Metabolic syndrome and Cancer project (Me-Can).
Me-Can consists of seven cohorts from Norway, Austria, ...and Sweden including 289,273 male and 288,057 female participants prospectively followed up for cancer incidence (n = 38,978) with a mean follow-up of 11.7 years. Cox regression models with age as the underlying time metric were used to estimate hazard ratios (HR) and their 95% confidence intervals (CI) for quintiles of cholesterol levels and per 1 mmol/l, adjusting for age at first measurement, body mass index (BMI), and smoking status. Estimates were corrected for regression dilution bias. Furthermore, we performed lag time analyses, excluding different times of follow-up, in order to check for reverse causation.
In men, compared with the 1st quintile, TSC concentrations in the 5th quintile were borderline significantly associated with decreasing risk of total cancer (HR = 0.94; 95%CI: 0.88, 1.00). Significant inverse associations were observed for cancers of the liver/intrahepatic bile duct (HR = 0.14; 95%CI: 0.07, 0.29), pancreas cancer (HR = 0.52, 95% CI: 0.33, 0.81), non-melanoma of skin (HR = 0.67; 95%CI: 0.46, 0.95), and cancers of the lymph-/hematopoietic tissue (HR = 0.68, 95%CI: 0.54, 0.87). In women, hazard ratios for the 5th quintile were associated with decreasing risk of total cancer (HR = 0.86, 95%CI: 0.79, 0.93) and for cancers of the gallbladder (HR = 0.23, 95%CI: 0.08, 0.62), breast (HR = 0.70, 95%CI: 0.61, 0.81), melanoma of skin (HR = 0.61, 95%CI: 0.42, 0.88), and cancers of the lymph-/hematopoietic tissue (HR = 0.61, 95%CI: 0.44, 0.83).
TSC was negatively associated with risk of cancer overall in females and risk of cancer at several sites in both males and females. In lag time analyses some associations persisted, suggesting that for these cancer sites reverse causation did not apply.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Initial studies have indicated diabetes and obesity to be risk factors for hepatocellular carcinoma; but the association between other metabolic risk factors and primary liver cancer (PLC) has not ...been investigated. The metabolic syndrome and cancer project (Me‐Can) includes cohorts from Norway, Austria and Sweden with data on 578,700 subjects. We used Cox proportional hazard models to calculate relative risks (RRs) of PLC by body mass index (BMI), blood pressure and plasma levels of glucose, cholesterol and triglycerides as continuous standardized variables (z‐score with mean = 0 and standard deviation (SD) = 1) and their standardized sum of metabolic syndrome (MetS) z‐score. RRs were corrected for random error in measurements. During an average follow‐up of 12.0 years (SD = 7.8), 266 PLCs were diagnosed among cohort members. RR of liver cancer per unit increment of z‐score adjusted for age, smoking status and BMI and stratified by birth year, sex and sub‐cohorts, was for BMI 1.39 (95% confidence interval (CI) 1.24–1.58), mid blood pressure 2.08 (0.95–4.73), blood glucose 2.13 (1.55–2.94) cholesterol 0.62 (0.51–0.76) and serum triglycerides 0.85 (0.65–1.10). The RR per one unit increment of the MetS z‐score was 1.35 (1.12–1.61). BMI, glucose and a composite MetS score were positively and cholesterol negatively associated with risk of liver cancer.
SARS-CoV-2 is known to infect respiratory tissue cells. However, less is known about infection of ocular tissue and potential infectivity of lacrimal fluid. With this study, we want to compare viral ...loads in eye and nasopharyngeal swabs and analyze these for infectious virus.
Between May 2020 and April 2021 ocular and nasopharyngeal swabs were collected from 28 SARS-CoV-2 infected patients treated on the corona virus disease 2019 (COVID-19)-ward of the University Hospital of Innsbruck, Austria. Samples with PCR detectable SARS-CoV-2 were analyzed via whole genome sequencing and an attempt was made to isolate infectious virus.
At the time point of sample collection, 22 individuals were still PCR positive in nasopharyngeal samples and in 6 of these patients one or both ocular samples were additionally positive. CT-values in eyes were generally higher compared to corresponding nasopharyngeal samples and we observed a tendency for lower CT-values, i.e. increased viral load, in nasopharyngeal swabs of individuals with at least one infected eye, compared to those where ocular samples were PCR negative. Ocular and nasopharyngeal sequences from the same patient were assigned to the same variant, either the D614G or the Alpha variant. Infectious virus was successfully isolated from 9 nasopharyngeal swabs, however only from one of the seven PCR positive ocular samples.
We could detect SARS-CoV-2 in eyes of some of the infected patients albeit at lower levels compared to nasopharyngeal swabs. However, our results also indicate that lacrimal fluid might be infectious in patients with high viral load.
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