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PURPOSE: Asymptomatic pharyngeal gonorrhoea could play an important role in transmission and should be screened for in persons at risk. We investigated the sensitivity of oral gargle samples to detect N. gonorrhoea and describe the frequency of infection by anatomical site. METHODS: From June 2021 to July 2022 persons diagnosed with gonorrhoea in the STI/HIV department were asked to provide self-collected specimens for single-site testing by NAAT from throat (by gargling and swabbing), anorectum, and first-void urine. RESULTS: 104 episodes of gonorrhoea were analysed in 88 individuals. The median age was 33 years, 85 persons (96.5%) were male. The pharynx was the most common site of infection (71 cases, 68.2%); in 26 persons (25.0%) it was the only site of infection. Anorectal infection was detected in 65 cases (62.5%) and urogenital infection in 25 cases (24.0%). In 46 cases (44.2%) infection was detected in more than one anatomical site. Gargling was less sensitive than throat swabbing to detect pharyngeal infection (85.9% versus 97.2%, p = .038), but was preferred by patients. Only 4 of 71 pharyngeal infections (5.6%) were symptomatic; anorectal and urogenital infections were symptomatic in 12.3% and 76.0% of cases, respectively. Culture recovery of N.gonorrhoeae was only possible in 15.8% of throat swabs, but was successful in 61.9% of anorectal and 84.2% of urogenital samples. CONCLUSIONS: Asymptomatic pharyngeal gonorrhoea is common. Gargle samples should be used only as alternative specimens with inferior sensitivity compared to throat swab samples.
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BACKGROUND: Hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury in children. HUS is known as an acute disease followed by complete recovery, but patients may present with kidney abnormalities after long periods of time. This study evaluates the long-term outcome of Shiga toxin-producing Escherichia coli-associated HUS (STEC-HUS) in pediatric patients, 10 years after the acute phase of disease to identify risk factors for long-term sequelae. METHODS: Over a 6-year period, 619 patients under 18 years of age with HUS (490 STEC-positive, 79%) were registered in Austria and Germany. Long-term follow-up data of 138 STEC-HUS-patients were available after 10 years for analysis. RESULTS: A total of 66% (n = 91, 95% CI 0.57-0.73) of patients fully recovered showing no sequelae after 10 years. An additional 34% (n = 47, 95% CI 0.27-0.43) presented either with decreased glomerular filtration rate (24%), proteinuria (23%), hypertension (17%), or neurological symptoms (3%). Thirty had sequelae 1 year after STEC-HUS, and the rest presented abnormalities unprecedented at the 2-year (n = 2), 3-year (n = 3), 5-year (n = 3), or 10-year (n = 9) follow-up. A total of 17 patients (36.2%) without kidney abnormalities at the 1-year follow-up presented with either proteinuria, hypertension, or decreased eGFR in subsequent follow-up visits. Patients needing extracorporeal treatments during the acute phase were at higher risk of presenting symptoms after 10 years (p < 0.05). CONCLUSIONS: Patients with STEC-HUS should undergo regular follow-up, for a minimum of 10 years following their index presentation, due to the risk of long-term sequelae of their disease. An initial critical illness, marked by need of kidney replacement therapy or plasma treatment may help predict poor long-term outcome.
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Infecções por Escherichia coli , Síndrome Hemolítico-Urêmica , Escherichia coli Shiga Toxigênica , Humanos , Síndrome Hemolítico-Urêmica/microbiologia , Síndrome Hemolítico-Urêmica/terapia , Síndrome Hemolítico-Urêmica/complicações , Síndrome Hemolítico-Urêmica/epidemiologia , Escherichia coli Shiga Toxigênica/isolamento & purificação , Masculino , Feminino , Criança , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/diagnóstico , Pré-Escolar , Seguimentos , Adolescente , Lactente , Alemanha/epidemiologia , Fatores de Risco , Taxa de Filtração Glomerular , Áustria/epidemiologia , Fatores de Tempo , Proteinúria/etiologia , Proteinúria/microbiologia , Proteinúria/diagnósticoRESUMO
The global dissemination of SARS-CoV-2 resulted in the emergence of several variants, including Alpha, Alpha + E484K, Beta, and Omicron. Our research integrated the study of eukaryotic translation factors and fundamental components in general protein synthesis with the analysis of SARS-CoV-2 variants and vaccination status. Utilizing statistical methods, we successfully differentiated between variants in infected individuals and, to a lesser extent, between vaccinated and non-vaccinated infected individuals, relying on the expression profiles of translation factors. Additionally, our investigation identified common causal relationships among the translation factors, shedding light on the interplay between SARS-CoV-2 variants and the host's translation machinery.
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Introduction: 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. Methods: 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. Results: 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. Conclusion: 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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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Carga Viral , Nasofaringe , Manejo de Espécimes/métodos , RNA Viral/genética , RNA Viral/análiseRESUMO
We analyzed neutralizing antibodies in samples from ancestral + BA.1 and ancestral + BA.4/5 boosted individuals, collected around 5.5 months after booster. Titers of neutralizing antibodies generally decreased compared to a time point early after the bivalent booster immunization. This was more pronounced for individuals without infection history and for recently emerged Omicron variants.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Anticorpos Amplamente Neutralizantes , COVID-19/prevenção & controle , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos AntiviraisRESUMO
PURPOSE: If not eliminated by the immune system and persisting over years, oropharyngeal high-risk HPV infection can lead to cancer development in the oropharynx. HPV infection is very commonly found in the genital region and can serve as an HPV reservoir. In this study, we investigate whether women with a genital HPV infection are at a higher risk of harboring an undetected oropharyngeal HPV infection via genital-oropharyngeal transmission. METHODS: Women presenting for routine gynecological checkups were included in this study. All participants received an HPV brush test from the genital region as well as from the oropharynx. Additionally, probable risk factors for an HPV infection were assessed in a structured questionnaire. RESULTS: 142 women were included in this study. The rate of oropharyngeal HPV infection was low with 2/142 (1,4%) women positive for a low-risk HPV genotype. In the genital brush test, 54/142 (38%) women were tested HPV positive of which 41/142 (29%) were positive for a high-risk HPV genotype. CONCLUSIONS: The rate of an oropharyngeal HPV detection in our population was low with 2/142 women harboring a low-risk HPV infection.
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Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Feminino , Masculino , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Fatores de Risco , Genitália , Papillomaviridae/genéticaRESUMO
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.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/prevenção & controle , Anticorpos , Anticorpos Amplamente Neutralizantes , Vacinas CombinadasRESUMO
Introduction: The rapid evolution of SARS-CoV-2 has posed a challenge to long-lasting immunity against the novel virus. Apart from neutralizing function, binding antibodies induced by vaccination or infection play an important role in containing the infection. Methods: To determine the proportion of wild-type (WT)-generated antibodies recognizant of more recent variants, plasma samples from either SARS-CoV-2 WT-infected (n = 336) or double-mRNA (Comirnaty)-vaccinated individuals (n = 354, age and sex matched to the convalescent group) were analyzed for binding antibody capacity against the S1 protein of the BA.1 omicron variant. Results: Overall, 38.59% (95% CI, 37.01- 40.20) of WT-generated antibodies recognized Omicron BA.1 S1 protein [28.83% (95% CI, 26.73-30.91) after infection and 43.46% (95% CI, 41.61-45.31) after vaccination; p < 0.001]. Although the proportion of WT-generated binding and neutralizing antibodies also binding to BA.1 is substantially reduced, the avidity of the remaining antibodies against the Omicron variant was non-inferior to that of the ancestral virus: Omicron: 39.7% (95% CI: 38.1-41.3) as compared to the avidity to WT: 27.0% (95% CI, 25.5-28.4), respectively (p < 0.001). Furthermore, we noticed a modestly yet statistically significant higher avidity toward the Omicron epitopes among the vaccinated group (42.2%; 95% CI, 40.51-43.94) as compared to the convalescent counterparts (36.4%; 95% CI, 33.42-38.76) (p = 0.003), even after adjusting for antibody concentration. Discussion: Our results suggest that an aspect of functional immunity against the novel strain was considerably retained after WT contact, speculatively counteracting the impact of immune evasion toward neutralization of the strain. Higher antibody levels and cross-binding capacity among vaccinated individuals suggest an advantage of repeated exposure in generating robust immunity.
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COVID-19 , Humanos , COVID-19/prevenção & controle , Anticorpos Amplamente Neutralizantes , SARS-CoV-2 , Anticorpos Neutralizantes , RNA Mensageiro , VacinaçãoRESUMO
BACKGROUND: Correlates of protection could help to assess the extent to which a person is protected from SARS-CoV-2 infection after vaccination (so-called breakthrough infection). We aimed to clarify associations of antibody and T-cell responses after vaccination against COVID-19 with risk of a SARS-CoV-2 breakthrough infection and whether measurement of these responses enhances risk prediction. METHODS: We did an open-label, phase 4 trial in two community centres in the Schwaz district of the Federal State of Tyrol, Austria, before the emergence of the omicron (B.1.1.529) variant of SARS-CoV-2. We included individuals (aged ≥16 years) a mean of 35 days (range 27-43) after they had received a second dose of the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. We quantified associations between immunological parameters and breakthrough infection and assessed whether information on these parameters improves risk discrimination. The study is registered with the European Union Drug Regulating Authorities Clinical Trials Database, 2021-002030-16. FINDINGS: 2760 individuals (1682 [60·9%] female, 1078 [39·1%] male, mean age 47·4 years [SD 14·5]) were enrolled into this study between May 15 and May 21, 2021, 712 (25·8%) of whom had a previous SARS-CoV-2 infection. Over a median follow-up of 5·9 months, 68 (2·5%) participants had a breakthrough infection. In models adjusted for age, sex, and previous infection, hazard ratios for breakthrough infection for having twice the immunological parameter level at baseline were 0·72 (95% CI 0·60-0·86) for anti-spike IgG, 0·80 (0·70-0·92) for neutralising antibodies in a surrogate virus neutralisation assay, 0·84 (0·58-1·21) for T-cell response after stimulation with a CD4 peptide pool, and 0·77 (0·54-1·08) for T-cell response after stimulation with a combined CD4 and CD8 peptide pool. For neutralising antibodies measured in a nested case-control sample using a pseudotyped virus neutralisation assay, the corresponding odds ratio was 0·78 (0·62-1·00). Among participants with previous infection, the corresponding hazard ratio was 0·73 (0·61-0·88) for anti-nucleocapsid Ig. Addition of anti-spike IgG information to a model containing information on age and sex improved the C-index by 0·085 (0·027-0·143). INTERPRETATION: In contrast to T-cell response, higher levels of binding and neutralising antibodies were associated with a reduced risk of breakthrough SARS-CoV-2 infection. The assessment of anti-spike IgG enhances the prediction of incident breakthrough SARS-CoV-2 infection and could therefore be a suitable correlate of protection in practice. Our phase 4 trial measured both humoral and cellular immunity and had a 6-month follow-up period; however, the longer-term protection against emerging variants of SARS-CoV-2 remains unclear. FUNDING: None.
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Vacinas contra COVID-19 , COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Neutralizantes , Áustria/epidemiologia , Vacina BNT162 , Infecções Irruptivas , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Imunidade Celular , Imunoglobulina G , SARS-CoV-2RESUMO
Background: The role of respiratory viruses in chronic otitis media with effusion (COME) in children is not clearly defined. In our study we aimed to investigate the detection of respiratory viruses in middle ear effusions (MEE) as well as the association with local bacteria, respiratory viruses in the nasopharynx and cellular immune response of children with COME. Methods: This 2017-2019 cross-sectional study included 69 children aged 2-6 undergoing myringotomy for COME. MEE and nasopharyngeal swabs were analyzed via PCR and CT-values for the genome and loads of typical respiratory viruses. Immune cell populations and exhaustion markers in MEE related to respiratory virus detection were studied via FACS. Clinical data including the BMI was correlated. Results: Respiratory viruses were detected in MEE of 44 children (64%). Rhinovirus (43%), Parainfluenzavirus (26%) and Bocavirus (10%) were detected most frequently. Average Ct values were 33.6 and 33.5 in MEE and nasopharynx, respectively. Higher detection rates correlated with elevated BMI. Monocytes were elevated in MEE (9.5 ± 7.3%/blood leucocytes). Exhaustion markers were elevated on CD4+ and CD8+ T cells and monocytes in MEE. Conclusion: Respiratory viruses are associated with pediatric COME. Elevated BMI was associated with increased rates of virus associated COME. Changes in cell proportions of innate immunity and expression of exhaustion markers may be related to chronic viral infection.
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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.
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COVID-19 , Humanos , Anticorpos Amplamente Neutralizantes , SARS-CoV-2/genética , Aclimatação , Anticorpos Antivirais , Anticorpos NeutralizantesRESUMO
Complementing the adult seroprevalence data collected at the time of the rapid SARS-CoV-2 mass vaccination in the district of Schwaz in 2021, we set out to establish the seroprevalence of SARS-CoV-2 among the pediatric population of the district. A total of 369 children, mean age 9.9 (SD 3.4), participated in the study, answering a structured questionnaire on the history of SARS-CoV-2 infection, household contacts, symptoms and history of vaccination. We determined binding and neutralizing antibody levels using plasma samples provided. We estimated the overall prevalence of SARS-CoV-2 infection in the general pediatric population at the time of the study using the census data from Statistik Austria and daily reports of officially confirmed cases. Excluding study participants who reported a history of PCR-confirmed infection, the age-standardized seroprevalence of previously unknown SARS-CoV-2 infection among the general pediatric population of the district was 27% (95% CI: 26.1-27.8). Adding this to the officially documented cases, the true overall prevalence was 32.8% (95% CI: 31.9-33.6) in contrast to the officially documented 8.0% (95% CI: 7.5-8.5) by June 2021. This translated into a proportion of 75.7% (95% CI: 74.4-77.0) of cases being officially undocumented, suggesting a high extent of silent SARS-CoV-2 infections in the pediatric population and possibly silent transmission.
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COVID-19 , Adulto , Criança , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Soroepidemiológicos , Prevalência , Anticorpos Antivirais , Imunoglobulina G , Anticorpos NeutralizantesRESUMO
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.
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Infecções por Papillomavirus , Vacinas contra Papillomavirus , Criança , Masculino , Feminino , Humanos , Infecções por Papillomavirus/prevenção & controle , Estudos Transversais , Aceitação pelo Paciente de Cuidados de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Vacinação , Pais , Inquéritos e Questionários , Papillomavirus HumanoRESUMO
In order to curb the rapid dissemination of the B.1.351 variant of SARS-CoV-2 in the district of Schwaz and beyond, the EU allocated additional vaccine doses at the beginning of March 2021 to implement a rapid mass vaccination of the population (16+). The aim of our study was to determine the seroprevalence of SARS-CoV-2 among the adult population in the district of Schwaz at the time of the implementation. Data on previous history of infections, symptoms and immunization status were collected using a structured questionnaire. Blood samples were used to determine SARS-CoV-2 specific anti-spike, anti-nucleocapsid and neutralizing antibodies. We recruited 2,474 individuals with a median age (IQR) of 42 (31-54) years. Using the official data on distribution of age and sex, we found a standardized prevalence of undocumented infections at 15.0% (95% CI: 13.2-16.7). Taken together with the officially documented infections, we estimated that 24.0% (95% CI: 22.5-25.6) of the adult population had prior SARS-CoV-2 infection. Hence, the proportion of undocumented infections identified by our study was 55.8% (95% CI: 52.7-58.5). With a vaccination coverage of 10% among the adults population at that time, we imply that a minimum of two-thirds of the target popuation was susceptible to the circulating threat when this unique campaign started.
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COVID-19 , Vacinas Virais , Adulto , Anticorpos Neutralizantes , COVID-19/epidemiologia , COVID-19/prevenção & controle , Surtos de Doenças , Humanos , Vacinação em Massa , SARS-CoV-2 , Estudos SoroepidemiológicosRESUMO
We investigated antibody titers and avidity after heterologous versus homologous coronavirus disease 2019 vaccination over 6 months after the second dose. We found a significantly higher avidity in regimens including at least 1 dose of the adenoviral vector vaccine ChAdOx1-S compared with 2 doses of the mRNA vaccine BNT162b2.
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Afinidade de Anticorpos , Vacina BNT162 , COVID-19 , ChAdOx1 nCoV-19 , Humanos , Adenoviridae , Vacina BNT162/imunologia , COVID-19/prevenção & controle , Cinética , Glicoproteína da Espícula de Coronavírus/genética , Vacinação , ChAdOx1 nCoV-19/imunologiaRESUMO
In response to a large outbreak of the SARS-CoV-2 Beta (B.1.351) variant in the district Schwaz, Austria, a rapid mass vaccination campaign with BNT162b2 was carried out in spring 2021, immunizing more than 70% of the adult population within one week. Subsequent analysis revealed that the mass vaccination was associated with a significant reduction in new SARS-CoV-2 infections compared to control districts. Here, we aimed to evaluate both SARS-CoV-2-specific T- and B-cell responses at 35 ± 8 and 215 ± 7 days after the second dose in 600 study subjects who participated at both time points. Overall, a robust antibody and T-cell response was measured at day 35, which waned over time. Nevertheless, all persons preserved seropositivity and T cell response could still be detected in about half of the participants at day 215. Further, antibody response correlated negatively with age; however, in persons who experienced SARS-CoV-2 infection prior to study enrolment, the serum levels of both S- and N-specific antibodies surprisingly increased with age. In contrast, there was no correlation of T cell response with age. We could not detect any sex-related difference in the immune responses. SARS-CoV-2 infections prior to study enrolment or incident infections before day 215 resulted in higher antibody levels and T cell responses at day 215 compared to study participants with no history of infection. Collectively, our data support that vaccination with BNT162b2 against COVID-19 provides a durable immune response and emphasize the usefulness of vaccination even after a natural infection.
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COVID-19 , SARS-CoV-2 , Adulto , Anticorpos Antivirais , Formação de Anticorpos , Áustria , Vacina BNT162 , COVID-19/prevenção & controle , Seguimentos , Humanos , Vacinação em Massa , VacinaçãoRESUMO
BACKGROUND: Several COVID-19 vaccines have been approved. The mRNA vaccine from Pfizer/BioNTech (Comirnaty, BNT162b2; BNT) and the vector vaccine from AstraZeneca (Vaxzevria, ChAdOx1; AZ) have been widely used. mRNA vaccines induce high antibody and T cell responses, also to SARS-CoV-2 variants, but are costlier and less stable than the slightly less effective vector vaccines. For vector vaccines, heterologous vaccination schedules have generally proven more effective than homologous schedules. METHODS: In the HEVACC three-arm, single-blinded, adaptive design study (ClinicalTrials.gov Identifier: NCT04907331), participants between 18 and 65 years with no prior history of SARS-CoV-2 infection and a first dose of AZ or BNT were included. The AZ/AZ and the AZ/BNT arms were randomized (in a 1:1 ratio stratified by sex and trial site) and single-blinded, the third arm (BNT/BNT) was observational. We compared the reactogenicity between the study arms and hypothesized that immunogenicity was higher for the heterologous AZ/BNT compared to the homologous AZ/AZ regimen using neutralizing antibody titers as primary endpoint. FINDINGS: This interim analysis was conducted after 234 participants had been randomized and 254 immunized (N=109 AZ/AZ, N=115 AZ/BNZ, N=30 BNT/BNT). Heterologous AZ/BNT vaccination was well tolerated without study-related severe adverse events. Neutralizing antibody titers on day 30 were statistically significant higher in the AZ/BNT and the BNT/BNT groups than in the AZ/AZ group, for B.1.617.2 (Delta) AZ/AZ median reciprocal titer 75.9 (99.9% CI 58.0 - 132.5), AZ/BNT 571.5 (99.9% CI 396.6 - 733.1), and BNT/BNT 404.5 (99.9% CI 68.3 - 1024). Similarly, the frequency and multifunctionality of spike-specific T cell responses was comparable between the AZ/BNT and the BNT/BNT groups, but lower in the AZ/AZ vaccinees. INTERPRETATION: This study clearly shows the immunogenicity and safety of heterologous AZ/BNT vaccination and encourages further studies on heterologous vaccination schedules. FUNDING: This work was supported by the Medical University of Innsbruck, and partially funded by NIAID contracts No. 75N9301900065, 75N93021C00016, and 75N93019C00051.
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COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Imunidade , Vacinação , Vacinas Sintéticas , Vacinas de mRNARESUMO
BACKGROUND: In early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria initiated the spread of SARS-CoV-2 throughout Austria and Northern Europe. METHODS: Between April 21st and 27th 2020, a cross-sectional epidemiologic study targeting the full population of Ischgl (n = 1867), of which 79% could be included (n = 1473, incl. 214 children), was performed. For each individual, the study involved a SARS-CoV-2 PCR, antibody testing and structured questionnaires. A mathematical model was used to help understand the influence of the determined seroprevalence on virus transmission. RESULTS: The seroprevalence was 42.4% (95% confidence interval (CI) 39.8-44.7). Individuals under 18 showed a significantly lower seroprevalence of 27.1% (95% CI 21.3-33.6) than adults (45%; 95% CI 42.2-47.7; OR of 0.455, 95% CI 0.356-0.682, p < 0.001). Of the seropositive individuals, 83.7% had not been diagnosed to have had SARS-CoV-2 infection previously. The clinical course was generally mild. Over the previous two months, two COVID-19-related deaths had been recorded, corresponding to an infection fatality rate of 0.25% (95% CI 0.03-0.91). Only 8 (0.5 %) individuals were newly diagnosed to be infected with SARS-CoV-2 during this study. CONCLUSIONS: Ischgl was hit early and hard by SARS-CoV-2 leading to a high local seroprevalence of 42.4%, which was lower in individuals below the age of 18 than in adults. Mathematical modeling suggests that a drastic decline of newly infected individuals in Ischgl by the end of April occurred due to the dual impact from the non-pharmacological interventions and a high immunization of the Ischgl population.
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BACKGROUND: Short-term antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown previously. The further development remains to be determined. METHODS: We prospectively followed 29 coronavirus disease 2019 cases, mean age 44⯱ 13.2 years. Except for one participant in whom rheumatoid arthritis existed, all other cases were previously healthy. We determined anti-viral binding antibodies at 2-10 weeks, 3 months, 6 months, and 12 months after disease onset as well as neutralizing antibodies (NAb) against wild type at 6 and 12 months and the B.1.1.7 and B.1.351 variants at month 12. Three binding antibody assays were used, targeting the nucleocapsid protein (NCP), the S1 subunit of the spike protein, and the receptor binding domain (RBD). RESULTS: Antibodies to the RBD persisted for 12 months in all cases with increasing concentrations, whereas antibodies to S1 dropped below cut-off point in 7 participants and NCP antibodies were above cut-off point in only 5 subjects at month 12. The NAb against wild type were detected in all but 2 samples at 12 months of follow-up but clearly less frequently when targeting the variants. In 5 participants who were vaccinated against COVID-19 there was a strong increase of antibodies against S1 and RBD as well as an increase of NAb titres against wild type and the variants. CONCLUSION: There was a persisting antibody response against SARS-CoV2 up to 12 months after COVID-19 with declining concentrations except for RBD and a strong increase of all antibody concentrations after vaccination.