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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.
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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.
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COVID-19 , Gammainfluenzavirus , Gripe Humana , Humanos , Adulto , Niño , Gripe Humana/epidemiología , Gammainfluenzavirus/genética , Austria/epidemiología , Vigilancia de Guardia , Estaciones del AñoRESUMEN
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.
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COVID-19 , Infecciones por Virus Sincitial Respiratorio , Virus Sincitiales Respiratorios , Niño , Humanos , Austria/epidemiología , COVID-19/epidemiología , Monitoreo Epidemiológico , Evolución Molecular , Técnicas de Genotipaje , Epidemiología Molecular , Filogenia , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitiales Respiratorios/clasificación , Virus Sincitiales Respiratorios/genética , Virus Sincitiales Respiratorios/aislamiento & purificación , Secuenciación Completa del GenomaRESUMEN
BackgroundTimely treatment with neuraminidase inhibitors (NAI) can reduce severe outcomes in influenza patients.AimWe 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.MethodsCase-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.ResultsOf 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)).ConclusionNAI 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.
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Gripe Humana , Oseltamivir , Humanos , Anciano , Oseltamivir/uso terapéutico , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Neuraminidasa , Mortalidad Hospitalaria , Antivirales/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Guanidinas/uso terapéutico , Zanamivir/uso terapéutico , Resultado del TratamientoRESUMEN
In nearly all picornaviruses the precursor of the smallest capsid protein VP4 undergoes co-translational N-terminal myristoylation by host cell N-myristoyltransferases (NMTs). Curtailing this modification by mutation of the myristoylation signal in poliovirus has been shown to result in severe assembly defects and very little, if any, progeny virus production. Avoiding possible pleiotropic effects of such mutations, we here used pharmacological abrogation of myristoylation with the NMT inhibitor DDD85646, a pyrazole sulfonamide originally developed against trypanosomal NMT. Infection of HeLa cells with coxsackievirus B3 in the presence of this drug decreased VP0 acylation at least 100-fold, resulting in a defect both early and late in virus morphogenesis, which diminishes the yield of viral progeny by about 90%. Virus particles still produced consisted mainly of provirions containing RNA and uncleaved VP0 and, to a substantially lesser extent, of mature virions with cleaved VP0. This indicates an important role of myristoylation in the viral maturation cleavage. By electron microscopy, these RNA-filled particles were indistinguishable from virus produced under control conditions. Nevertheless, their specific infectivity decreased by about five hundred fold. Since host cell-attachment was not markedly impaired, their defect must lie in the inability to transfer their genomic RNA into the cytosol, likely at the level of endosomal pore formation. Strikingly, neither parechoviruses nor kobuviruses are affected by DDD85646, which appears to correlate with their native capsid containing only unprocessed VP0. Individual knockout of the genes encoding the two human NMT isozymes in haploid HAP1 cells further demonstrated the pivotal role for HsNMT1, with little contribution by HsNMT2, in the virus replication cycle. Our results also indicate that inhibition of NMT can possibly be exploited for controlling the infection by a wide spectrum of picornaviruses.
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Aciltransferasas/metabolismo , Aminopiridinas/farmacología , Enterovirus/efectos de los fármacos , Enterovirus/fisiología , Sulfonamidas/farmacología , Ensamble de Virus/fisiología , Proteínas de la Cápside/metabolismo , Infecciones por Coxsackievirus/metabolismo , Células HeLa , Humanos , Virión/efectos de los fármacos , Virión/metabolismo , Ensamble de Virus/efectos de los fármacosRESUMEN
Natural killer (NK)-cell response against influenza viruses partly depends on expression of CD112, a ligand for NK-cell receptor CD226 (DNAM-1). We analyzed whether particular CD226 variants were associated with influenza disease severity. Comparison between 145 patients hospitalized with severe influenza at intensive care units (ICU) with 139 matched influenza-positive outpatients showed that presence of the rs763362 G allele (GG, AG) was associated with occurrence of severe influenza infections (P = .0076). Also, a higher frequency of rs727088 G and rs763361 T alleles was observed in the ICU group. Thus, CD226 variants may contribute to the severity of influenza virus disease.
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Antígenos de Diferenciación de Linfocitos T/genética , Gripe Humana/genética , Orthomyxoviridae , Polimorfismo de Nucleótido Simple/genética , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad , Hospitalización , Humanos , Lactante , Recién Nacido , Gripe Humana/virología , Unidades de Cuidados Intensivos , Células Asesinas Naturales/metabolismo , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250â000-500â000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999-2015. METHODS: We estimated country-specific influenza-associated respiratory excess mortality rates (EMR) for 33 countries using time series log-linear regression models with vital death records and influenza surveillance data. To extrapolate estimates to countries without data, we divided countries into three analytic divisions for three age groups (<65 years, 65-74 years, and ≥75 years) using WHO Global Health Estimate (GHE) respiratory infection mortality rates. We calculated mortality rate ratios (MRR) to account for differences in risk of influenza death across countries by comparing GHE respiratory infection mortality rates from countries without EMR estimates with those with estimates. To calculate death estimates for individual countries within each age-specific analytic division, we multiplied randomly selected mean annual EMRs by the country's MRR and population. Global 95% credible interval (CrI) estimates were obtained from the posterior distribution of the sum of country-specific estimates to represent the range of possible influenza-associated deaths in a season or year. We calculated influenza-associated deaths for children younger than 5 years for 92 countries with high rates of mortality due to respiratory infection using the same methods. FINDINGS: EMR-contributing countries represented 57% of the global population. The estimated mean annual influenza-associated respiratory EMR ranged from 0·1 to 6·4 per 100â000 individuals for people younger than 65 years, 2·9 to 44·0 per 100â000 individuals for people aged between 65 and 74 years, and 17·9 to 223·5 per 100â000 for people older than 75 years. We estimated that 291â243-645â832 seasonal influenza-associated respiratory deaths (4·0-8·8 per 100â000 individuals) occur annually. The highest mortality rates were estimated in sub-Saharan Africa (2·8-16·5 per 100â000 individuals), southeast Asia (3·5-9·2 per 100â000 individuals), and among people aged 75 years or older (51·3-99·4 per 100â000 individuals). For 92 countries, we estimated that among children younger than 5 years, 9243-105â690 influenza-associated respiratory deaths occur annually. INTERPRETATION: These global influenza-associated respiratory mortality estimates are higher than previously reported, suggesting that previous estimates might have underestimated disease burden. The contribution of non-respiratory causes of death to global influenza-associated mortality should be investigated. FUNDING: None.
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Salud Global/estadística & datos numéricos , Gripe Humana/mortalidad , Estaciones del Año , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Gripe Humana/complicaciones , Modelos Lineales , Masculino , Persona de Mediana Edad , Factores Socioeconómicos , Adulto JovenRESUMEN
Low responsiveness/nonresponsiveness is characterized by an insufficient immune response upon primary and/or booster vaccination and affects 1-10% of vaccinees. In the current study, we aimed to investigate whether nonresponsiveness is an Ag/vaccine-specific phenomenon and to clarify underlying immunological mechanisms. Nonresponders to tick-borne encephalitis (TBE) or hepatitis B Ag with a history of previous TBE vaccinations were booster vaccinated with TBE and influenza vaccine and compared with TBE high responders in terms of humoral and cellular immune response. Postboosters in TBE high responder existing TBE titers increased, and solid humoral responses to influenza vaccine were induced. In TBE nonresponders, low to undetectable prevaccination TBE titers remained low, whereas sufficient influenza Abs were induced. In both TBE groups, a positive correlation of humoral and cellular immune response was seen as high/low TBE titers were associated with sufficient/lack of Ag-specific T cell proliferation. Furthermore, responses to influenza were robust in terms of Abs and cytokine production. In contrast, in hepatitis B nonresponders, sufficient humoral responses to TBE and influenza Ags were induced despite lacking specific IL-2 and IFN-γ production. Importantly, these patients showed high IL-10 baseline levels in vitro. HLA-DR subtypes associated with hepatitis B nonresponsiveness were overrepresented in this group, and high IL-10 levels were linked to these subtypes. Whereas TBE and hepatitis B nonresponders had increased IL-10-producing FOXP3(+) T regulatory cells upon vaccination, only in hepatitis B nonresponders, showing elevated prevaccination IL-10 levels, a prominent population of B regulatory cells was detected. We conclude that immunological pathways of nonresponsiveness follow different patterns depending both on vaccine Ag and genetic predisposition of the vaccinee.
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Linfocitos B Reguladores/inmunología , Vacunas contra Hepatitis B/inmunología , Vacunas contra la Influenza/inmunología , Interleucina-10/inmunología , Linfocitos T Reguladores/inmunología , Vacunas Virales/inmunología , Adulto , Anticuerpos Antivirales/sangre , Encefalitis Transmitida por Garrapatas/inmunología , Encefalitis Transmitida por Garrapatas/prevención & control , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente , Predisposición Genética a la Enfermedad , Antígenos HLA-DR/genética , Hepatitis B/inmunología , Hepatitis B/prevención & control , Humanos , Inmunización Secundaria , MasculinoRESUMEN
During the influenza pandemic 2009 children and adults differed in the clinical course of the influenza disease. In following the question arose, if the case definitions used within the national and international organizations are an adequate tool for the clinical diagnosis of influenza in children as well as in adults. Therefore medical charts from 146 children and 229 adults were retrospectively analyzed. In addition, the initial viral loads of all 375 patients and the duration of virus shedding of a subset of 79 patients were also investigated. Children show a wider clinical spectrum including gastro enteric symptoms and also a different spectrum of laboratory parameters like elevated CRP-levels, leucocytosis, and higher viral loads. Further, children show significantly more often complications, for example, myositis that may be underdiagnosed. In patients receiving antiviral-therapy complications occurred significantly less often and the presence of symptoms was significantly shorter compared to the untreated group (2.3 days vs. 6.0 days). In summary, the differences in the clinical picture between children and adults should be taken into consideration for the clinical diagnosis of influenza and also for a future discussion on age specific influenza case definitions.
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Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/patología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Gripe Humana/complicaciones , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Carga Viral , Esparcimiento de Virus , Adulto JovenRESUMEN
Background: Respiratory syncytial virus (RSV) is one of the leading causes of hospitalisation, morbidity, and mortality due to respiratory infection in the first years of life. This longitudinal prospective study outlines the 2022/23 season's viral patterns in Austria after the epidemiological changes determined by public health measures. We aimed to highlight differences within the RSV subtypes and genotypes in 0-36-month-old children without chronic diseases in the outpatient setting. Methods: From November 2022 to March 2023 children younger than 36 months admitted to Vienna's largest paediatric primary healthcare centre with an acute respiratory infection were enrolled in this study. Nasal swabs and multiplex PCR panels detected 20 viruses including RSV subtypes and genotypes. Clinical presentation, features, and treatment of the participants were documented and analysed using the Modified Tal Score (MTS). Patients were scheduled for a telemedical follow-up one week after the initial appointment. Analysis was done using descriptive statistics, including Cramér V and binominal logarithmic regression. Results: Among the 345 samples from 329 children, RSV was the most common virus (31.9%), followed by influenza (17.5%) and rhinovirus infections (20.58%). Of the RSV positive samples, only 13 cases were RSV subtype A (11.8%), whereas 97 were of subtype B (87.3%); ON1 and BA9 were the only detectable RSV genotypes (ON1: BA9 = 1:9.25). RSV was the main predictor of hospitalisation (OR: 7.5, 95% CI: (1.46-38.40), and age had a significant but smaller effect (OR: 0.89, 95% CI: (0.81-0.99). Almost all patients' clinical status improved within the first days. Conclusion: RSV cases showed a rapid onset in late November 2022, and subtype B was predominant throughout the season. RSV infection was associated with higher hospitalisation rates, even after excluding high-risk patients (preterm and severe chronic diseases population).Further testing in the upcoming winter seasons will improve our knowledge of the dominant subtype and its association with disease severity, especially with the development of novel RSV vaccine candidates.
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BACKGROUND: By March, 2023, 54 countries, areas, and territories (hereafter CAT) in the WHO European Region had reported more than 2·2 million COVID-19-related deaths to the WHO Regional Office for Europe. Here, we estimated how many lives were directly saved by vaccinating adults in the WHO European Region from December, 2020, to March, 2023. METHODS: In this retrospective surveillance study, we estimated the number of lives directly saved by age group, vaccine dose, and circulating variant-of-concern (VOC) period, regionally and nationally, using weekly data on COVID-19 mortality and infection, COVID-19 vaccination uptake, and SARS-CoV-2 virus characterisations by lineage downloaded from The European Surveillance System on June 11, 2023, as well as vaccine effectiveness data from the literature. We included data for six age groups (25-49 years, 50-59 years, ≥60 years, 60-69 years, 70-79 years, and ≥80 years). To be included in the analysis, CAT needed to have reported both COVID-19 vaccination and mortality data for at least one of the four older age groups. Only CAT that reported weekly data for both COVID-19 vaccination and mortality by age group for 90% of study weeks or more in the full study period were included. We calculated the percentage reduction in the number of expected and reported deaths. FINDINGS: Between December, 2020, and March, 2023, in 34 of 54 CAT included in the analysis, COVID-19 vaccines reduced deaths by 59% overall (CAT range 17-82%), representing approximately 1·6 million lives saved (range 1·5-1·7 million) in those aged 25 years or older: 96% of lives saved were aged 60 years or older and 52% were aged 80 years or older; first boosters saved 51% of lives, and 60% were saved during the Omicron period. INTERPRETATION: Over nearly 2·5 years, most lives saved by COVID-19 vaccination were in older adults by first booster dose and during the Omicron period, reinforcing the importance of up-to-date vaccination among the most at-risk individuals. Further modelling work should evaluate indirect effects of vaccination and public health and social measures. FUNDING: US Centers for Disease Control and Prevention.
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OBJECTIVE: To investigate the immunogenicity and safety of BNT162b2 booster vaccination with and without a tetravalent influenza vaccine. METHODS: A prospective, open-label cohort study on immunogenicity and safety of COVID-19 booster vaccination with or without a tetravalent influenza vaccine was performed. Eight hundred thirty-eight health care workers were included in the following study arms: BNT162b2 booster-only, influenza-vaccine-only or combination of both. Levels of antibodies against SARS-CoV-2 spike receptor binding domain, and haemagglutinin inhibition tested for four different influenza strains (A(H1N1)pdm09, A(H3N2), B/Victoria, B/Yamagata) were measured at the time of vaccination and 4 weeks later. RESULTS: After 4 weeks, median (interquartile range) levels of antibodies against the receptor binding domain of the viral spike (S) protein and relative change from baseline were high in individuals who received BNTb162b2 booster vaccination only (absolute: 16 600 [10 980-24 360] vs. 12 630 [8198-18 750] BAU/mL [p < 0.0001]; relative increase: 49% [23.6-95.3] vs. 40% [21.9-80.6] [p 0.048]; booster-only n = 521 vs. combination-arm n = 229 respectively). Results were confirmed after matching for sex, age, body mass index, baseline antibody levels and vaccine compound received for primary immunization (absolute: 13 930 [10 610-22 760] vs. 12 520 [8710-17 940]; [p 0.031]; relative increase: 55.7% [27.8-98.5] vs. 42.2% [22.9-74.5]; p 0.045). Adverse events were almost identical in the booster-only and the combination-arm, but numerically low in the influenza arm (525/536 [97.9%] vs. 235/240 [97.9%] vs. 26/33 [78.8 %]). DISCUSSION: Although no safety concerns occurred, our study provides evidence on reduced immunogenicity of a BNT162b2 booster vaccination in combination with a tetravalent influenza vaccine. Further studies investigating new influenza variants as well as potential differences vaccine effectiveness are needed.
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COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Humanos , Anticuerpos Antivirales , Vacuna BNT162 , Estudios de Cohortes , COVID-19/etiología , Subtipo H3N2 del Virus de la Influenza A , Vacunas contra la Influenza/efectos adversos , Gripe Humana/prevención & control , Estudios Prospectivos , SARS-CoV-2 , Vacunación/efectos adversos , Vacunas de Productos InactivadosRESUMEN
Influenza epidemics lead to an increase in hospitalizations and deaths. Up to now the overall impact of attributable deaths due to seasonal and pandemic influenza viruses in Austria has not been investigated in detail. Therefore we compared the number and age distribution of influenza associated deaths during ten influenza epidemic seasons to those observed during the pandemic influenza A(H1N1)2009 season. A Poisson model, relating age and daily deaths to week of influenza season using national mortality and viral surveillance data adjusted for the confounding effect of co-circulating Respiratory Syncytial Virus was used. We estimated an average of 316 influenza associated deaths per seasonal influenza epidemic (1999/2000-2008/2009) and 264 for the pandemic influenza season 2009/2010 in the area of Vienna, Austria. Comparing the mortality data for seasonal and pandemic influenza viruses in different age groups revealed a statistically significant increase in mortality for pandemic A(H1N1)2009 influenza virus in the age groups below 34 years of age and a significant decrease in mortality in those above 55 years. Our data adjusted for co-circulating RSV confirm the different mortality pattern of seasonal and pandemic influenza A(H1N1)2009 virus in different age groups.
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Causas de Muerte , Gripe Humana/mortalidad , Pandemias/estadística & datos numéricos , Estaciones del Año , Adolescente , Adulto , Austria/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Subtipo H1N1 del Virus de la Influenza A , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Análisis de Supervivencia , Adulto JovenRESUMEN
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-CoV2 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 COVID19. 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 COVID19 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.
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COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiología , Hospitalización , Humanos , Atención Primaria de Salud , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2 , Resultado del TratamientoRESUMEN
BACKGROUND. The nonstructural protein NS1 of influenza virus counteracts the interferon-mediated immune response of the host. By deleting the open reading frame of NS1, we have generated a novel type of influenza vaccine. We studied the safety and immunogenicity of an influenza strain lacking the NS1 gene (DeltaNS1-H1N1) in healthy volunteers. METHODS. Healthy seronegative adult volunteers were randomized to receive either a single intranasal dose of the DeltaNS1-H1N1 A/New Caledonia vaccine at 1 of 5 dose levels (6.4, 6.7, 7.0, 7.4, and 7.7 log(10) median tissue culture infective dose) (n = 36 recipients) or placebo (n = 12 recipients). RESULTS. Intranasal vaccination with the replication-deficient DeltaNS1-H1N1 vaccine was well tolerated. Rhinitis-like symptoms and headache were the most common adverse events identified during the 28-day observation period. Adverse events were similarly distributed between the treatment and placebo groups. Vaccine-specific local and serum antibodies were induced in a dose-dependent manner. In the highest dose group, vaccine-specific antibodies were detected in 10 of 12 volunteers. Importantly, the vaccine also induced neutralizing antibodies against heterologous drift variants. CONCLUSIONS. We show that vaccination with an influenza virus strain lacking the viral interferon antagonist NS1 induces statistically significant levels of strain-specific and cross-neutralizing antibodies despite the highly attenuated replication-deficient phenotype. Further studies are warranted to determine whether these results translate into protection from influenza virus infection. TRIAL REGISTRATION. ClinicalTrials.gov identifier: NCT00724997 .
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Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Vacunas Atenuadas/inmunología , Proteínas no Estructurales Virales/genética , Adulto , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/aislamiento & purificación , Relación Dosis-Respuesta Inmunológica , Método Doble Ciego , Eliminación de Gen , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/efectos adversos , Líquido del Lavado Nasal/inmunología , Líquido del Lavado Nasal/virología , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/efectos adversos , Esparcimiento de VirusRESUMEN
BACKGROUND: Since the worldwide spread of SARS-CoV-2, different European countries reacted with temporary national lockdowns with the aim to limit the virus transmission in the population. Also Austria started a lockdown of public life in March 2020. OBJECTIVES: In this study we investigated whether the circulation of different respiratory virus infections in Austria, as assessed by the established respiratory virus surveillance system, is affected by these measures as well and may reflect the success of the lockdown in limiting respiratory virus transmission. STUDY DESIGN: Sentinel data obtained for influenza virus, respiratory syncytial virus, human metapneumovirus and rhinovirus cases were analyzed and compared between the season 2019/2020 and the five previous seasons. RESULTS: We observed a rapid and statistically significant reduction of cumulative cases for all these viruses within short time after the lockdown in March 2020, compared to previous seasons (each p < 0.001). Also, sentinel screening for SARS-CoV-2 infections was performed and a decrease of SARS-CoV-2 was seen after the lockdown. While for the seasonally occurring viruses as influenza, respiratory syncytial virus or human metapneumovirus the lockdown led to the end of the annual epidemics, a re-increase of rhinovirus infections was observed after liberalization of numerous lockdown measures. CONCLUSIONS: Our data provide evidence that occurrence of different respiratory virus infections reflect not only the efficiency of lockdown measures taken against SARS-CoV-2 but it shows also the effects of lockdown releases on the transmission of respiratory viruses.
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COVID-19/epidemiología , COVID-19/prevención & control , Control de Enfermedades Transmisibles , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/prevención & control , Austria/epidemiología , COVID-19/transmisión , Epidemias , Humanos , Gripe Humana/virología , Metapneumovirus/aislamiento & purificación , Orthomyxoviridae/aislamiento & purificación , Vigilancia en Salud Pública , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Infecciones del Sistema Respiratorio/transmisión , Infecciones del Sistema Respiratorio/virología , Estudios Retrospectivos , Rhinovirus/aislamiento & purificación , SARS-CoV-2/aislamiento & purificación , Estaciones del Año , Virosis/epidemiología , Virosis/prevención & control , Virosis/transmisión , Virosis/virologíaRESUMEN
BACKGROUND: Testing for COVID-19 with quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) may result in delayed detection of disease. Antigen detection via lateral flow testing (LFT) is faster and amenable to population-wide testing strategies. Our study assesses the diagnostic accuracy of LFT compared to RT-PCR on the same primarycare patients in Austria. METHODS: Patients with mild to moderate flu-like symptoms attending a general practice network in an Austrian district (October 22 to November 30, 2020) received clinical assessment including LFT. All suspected COVID-19 cases obtained additional RT-PCR and were divided into two groups: Group 1 (true reactive): suspected cases with reactive LFT and positive RT-PCR; and Group 2 (false non-reactive): suspected cases with a non-reactive LFT but positive RT-PCR. FINDINGS: Of the 2,562 symptomatic patients, 1,037 were suspected of COVID-19 and 826 (79.7%) patients tested RT-PCR positive. Among patients with positive RT-PCR, 788/826 tested LFT reactive (Group 1) and 38 (4.6%) non-reactive (Group 2). Overall sensitivity was 95.4% (95%CI: [94%,96.8%]), specificity 89.1% (95%CI: [86.3%, 91.9%]), positive predictive value 97.3% (95%CI:[95.9%, 98.7%]) and negative predictive value 82.5% (95%CI:[79.8%, 85.2%]). Reactive LFT and positive RT-PCR were positively correlated (r = 0.968,95CI=[0.952,0.985] and κ = 0.823 , 95%CI=[0.773,0.866]). Reactive LFT was negatively correlated with Ct-value ( r = -0.2999, p < 0.001) and pre-test symptom duration (r = -0.1299,p = 0.0043) while Ct-value was positively correlated with pre-test symptom duration (r = 0.3733),p < 0.001). INTERPRETATION: We show that LFT is an accurate alternative to RT-PCR testing in primary care. We note the importance of administering LFT properly, here combined with clinical assessment in symptomatic patients. FUNDING: Thomas Czypionka received funding from the European Union's Horizon 2020 Research and Innovation Programe under the grant agreement No 101016233 (PERISCOPE). No further funding was available for this study.
RESUMEN
In a gilt producing farm in Lower Austria, respiratory diseases occurred over the previous years in self-reared gilts after being introduced into the sow herd. In addition, fertility disorders in terms of late abortions and re-breeders were observed in the fall of 2019. Nasal swabs of 3 gilts with respiratory signs and fever were tested positive for influenza A virus (IAV) subtype H1avN1 by PCR. However, examination of serum samples from these animals at 2 different time points did not detect antibodies using the standard hemagglutination inhibition (HI) test of the laboratory. Examination of additional age groups likewise failed to detect H1avN1 antibody titers. In consequence to the extension of the diagnostic panel of the HI test by 7 additional H1avN1 test antigens, a clear seroconversion of the PCR positive sows against 2 different H1avN1 isolates could be measured. In addition, high antibody titers against these 2 H1avN1 strains were also detectable in the majority of the remaining age groups tested. Following the administration of the trivalent influenza vaccine, which has been approved throughout Europe, a significant improvement of the clinical presentation in the herd was achieved. The present case report illustrates that direct and indirect pathogen detection should be used in combination for targeted influenza diagnostics. In addition, it was shown that the continuous adaptation of test antigens to the isolates circulating in the field would be extremely crucial for the significance of the HI test.
Asunto(s)
Vacunas contra la Influenza , Gripe Humana , Infecciones por Orthomyxoviridae , Enfermedades de los Porcinos , Animales , Anticuerpos Antivirales , Femenino , Humanos , Infecciones por Orthomyxoviridae/diagnóstico , Infecciones por Orthomyxoviridae/veterinaria , Embarazo , Sus scrofa , Porcinos , Enfermedades de los Porcinos/diagnósticoRESUMEN
Respiratory syncytial virus (RSV) testing is generally available in most care centres, but it is rarely performed because clinicians' seldom suspect RSV to be the underlying pathogen in adults with respiratory disease. Here, we evaluate the impact of broad combined influenza/RSV testing on the clinical practice. Overall, 103 patients were tested positively for RSV. Our study indicates that positively tested patients were mostly of advanced age and suffered from chronic diseases. Mortality was significant in our cohort and higher in patients with advanced age. Further, we report a significant increase in detected RSV cases but also in detection rate. Together, these findings suggest that implementation of a combined influenza/RSV testing led to a significant increase in detection rate, supported clinicians establishing the correct diagnosis and allowed a safe and controlled handling of RSV patients.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio/mortalidad , Virus Sincitiales Respiratorios , Adulto , Anciano , Austria/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Estudios RetrospectivosRESUMEN
Influenza vaccine effectiveness (IVE) assessment is increasingly stratified by vaccine type or brand, such as done by the European network of DRIVE. In 2019/2020, eleven influenza vaccines were licensed in Europe. If more than one vaccine type is recommended or if more than one vaccine brand is available for a specific risk group, it is not clear which factors affect the choice of a specific vaccine (type or brand) by a health practitioner for individual patients. This is important for IVE assessment. A survey tailored to the 2019/20 local vaccine recommendations was conducted among GPs in four European countries (Austria, Italy, Spain, UK) to understand how influenza vaccine is offered to recommended risk groups and, if GPs have a choice between 2 or more vaccines, what factors influence their vaccine choice for patients. Overall, 360 GPs participated. In Austria, Italy and Spain GPs indicated that influenza vaccines are commonly offered when patients present for consultation, whereas in the UK all GPs indicated that all relevant patients are contacted by letter. In Austria and Italy, roughly 80% of GPs had only one vaccine type available for patients <65y. The use of any specific vaccine type in this age group is mostly determined by the availability of specific vaccine type(s) at the clinic. GPs frequently reported availability of more than one vaccine type for patients ≥65y in Austria (45%), Italy (70%) and Spain (79%). In this group, patient characteristics played a role in choice of vaccine, notably older age and presence of (multiple) comorbidities. Knowing that a non-patient related factor usually determines the vaccine type a patient receives in settings where more than one vaccine type is recommended for risk groups <65y, simplifies IVE assessment in this age group. However, patient characteristics need careful consideration when assessing IVE in those ≥65y.