Evaluation of infectious virus titer is a challenge for respiratory syncytial virus (RSV) clinical trials because of the labile nature of RSV and rapid loss of infectivity without proper specimen handling. However, there has been no rigorous investigation into RSV stability in clinical specimens.
RSV stability was investigated by evaluating virus titers and defined as titer variation from baseline within three standard deviations of our titration assay. RSV stability in viral transport medium (VTM) at 4°C and the effect of freezing method on stability were evaluated using RSV-A2 stock. RSV stability in nasal aspirates collected in VTM at 4°C was estimated by regression analysis of virus titers measured at several time points. Stability of these specimens stored at −80°C for 10–15 months after freezing by the method, which maintained RSV-A2 stability, was also assessed.
Three standard deviations were calculated from our titration assay as 0.97 log10 50% tissue culture infectious dose (TCID50/mL), and RSV stability was defined as variation of virus titer from baseline within 1.0 log10TCID50/mL. RSV-A2 in VTM at 4°C was stable for at least 120 h. Freezing at −80°C negatively affected virus stability, whereas freezing in liquid nitrogen or a dry ice-ethanol bath did not. RSV in nasal aspirates was stable for 2 days at 4°C and for 10–15 months at −80°C after snap freezing.
RSV in nasal aspirates in VTM was estimated to be stable for 2 days at 4°C and for approximately 1 year at −80°C.
This retrospective study aimed to investigate the impact of the emergence of new variants and the epidemiological scenario on hospitalization rates of unvaccinated children (0–12 years) in Brazil. The study included 1614 children admitted to a hospital between March 2020 and December 2022 but 101 (6.3%) of them testing positive for COVID-19 via RT-PCR. The frequency of COVID-19 cases increased from 7.5% in 2020 to 9.3% in 2022 with the emergence of the Omicron variant. Children over 5 years old with comorbidities accounted for most cases (69% [70/101]). Sickle cell anemia was the most frequent comorbidity (20%), and influenza-like illness (36% [36/101]) and decompensation of underlying disease (33% [33/101]) were the main reasons for hospitalization. Coinfection was detected in 11% of cases, with respiratory syncytial virus (RSV) being the most common viral pathogen (71%). Hospital readmission occurred in 26% of cases, with a higher frequency in children over 5 years old. The death rate was 1.9%, with comorbidities such as cystic fibrosis and congenital heart disease as risk factors. These findings emphasize the need to prioritize vaccination with monovalent Omicron XBB for high-risk groups, including children over 5 years old with comorbidities, to mitigate the impact of new variants and reduce severe disease outcomes.
Though receptor binding specificity is well established as a contributor to host tropism and spillover potential of influenza A viruses, determining receptor binding preference of a specific virus still requires expensive and time-consuming laboratory analyses. In this study, we pilot a machine learning approach for prediction of binding preference.
We trained a convolutional neural network to predict the α2,6-linked sialic acid preference of influenza A viruses given the hemagglutinin amino acid sequence. The model was evaluated with an independent test dataset to assess the standard performance metrics, the impact of missing data in the test sequences, and the prediction performance on novel subtypes. Further, features found to be important to the generation of predictions were tested via targeted mutagenesis of H9 and H16 proteins expressed on pseudoviruses.
The final model developed in this study produced predictions on a test dataset correctly 94% of the time and an area under the receiver operating characteristic curve of 0.93. The model tolerated about 10% missing test data without compromising accurate prediction performance. Predictions on novel subtypes revealed that the model can extrapolate feature relationships between subtypes when generating binding predictions. Finally, evaluation of the features important for model predictions helped identify positions that alter the sialic acid conformation preference of hemagglutinin proteins in practice.
Ultimately, our results provide support to this in silico approach to hemagglutinin receptor binding preference prediction. This work emphasizes the need for ongoing research efforts to produce tools that may aid future pandemic risk assessment.
Surveillance programmes for influenza and other respiratory pathogens are important to generate vaccine effectiveness (VE) estimates and to inform vaccine composition. We aimed to explore the feasibility and acceptability of home-based testing.
In three out of nine provinces in South Africa, we established a self-referral system for individuals aged ≥ 18 years with respiratory symptoms of ≤ 10 days duration. Following consent, swab collection material was delivered to participants who also completed a questionnaire including self-reported vaccination status. Swabs were tested by PCR for influenza, respiratory syncytial virus (RSV) and SARS-CoV-2. A test-negative methodology was used to estimate influenza VE.
Of 1456 samples collected between 19 November 2021 and 3 September 2022, 73 (5%) tested positive for influenza, 38 (3%) tested positive for RSV and 394 (27%) for SARS-CoV-2. We subtyped 55% (40/73) of the influenza positive specimens; 16/40 (40%) were influenza A(H1N1)pdm09; 10/40 (25%)A(H3N2)) and all 14/40(35%) influenza B were B/Victoria. Only 20% (279/1451) of participants reported influenza-like illness case definition symptoms of fever and cough. Influenza vaccine coverage was 11% (157/1454). The overall influenza VE was 26% (95% confidence interval: −73%, 69%). Of the completed acceptability questionnaires, 123/127 (97%) participants would make use of the service again; 90% (1306) were recruited via the COVID-19 testing centre (call in, social media, webpage), and 7% (99/1306) through CoughWatchSA.
Home-based swabbing was feasible and acceptable. We were able to calculate an influenza VE, although a larger sample size and verification of vaccine status may improve the VE estimates in the future.
Rapid and safe neutralization assays are required for highly pathogenic avian influenza viruses, including a clade 2.3.4.4b H5N1 subtype recently found in cows. Here, we report a neutralization assay using luminescent virus-like particles. This assay has lower biosafety requirements and provides a larger dynamic range than conventional methods. We applied this technique to evaluate the cross-reactivity of neutralizing antibodies induced by clade 2.3.4.4b candidate vaccine viruses (CVVs) with the cow-derived H5N1 virus. Our findings indicate that these CVVs share antigenic characteristics with the cow-derived H5N1 virus, suggesting the potential efficacy of vaccines developed using these CVVs.
Live attenuated influenza vaccine (LAIV) is recommended in Ireland for all children aged 2–17 years. Quadrivalent influenza vaccine (QIV) is recommended for all others eligible for vaccination, including those ≥ 18 years with underlying medical conditions and all aged ≥ 65 years. We aimed to estimate influenza vaccine effectiveness (IVE) against acute respiratory infection (ARI) presentations to primary care due to influenza over two influenza seasons in Ireland, to inform vaccination recommendations and communication campaigns.
We undertook a test-negative case control study within the Irish sentinel general practice surveillance network as part of the Vaccine Effectiveness Burden and Impact Studies (VEBIS) network. We compared influenza vaccination status among influenza PCR positive cases with influenza PCR negative controls, both with ARI presentations, of all ages. We estimated IVE using logistic regression adjusting for age, onset time, medical conditions and sex.
In 2022/2023, there were 288 cases and 765 controls. In 2023/2024, there were 567 cases and 1832 controls. In 2022/2023, overall IVE was 42% (95% CI 9 to 64) and 50% (95% CI −30 to 83) in 2- to 17-year-olds. Overall IVE in 2023/2024 was 35% (95% CI 15 to 51) and 68% (95% CI 30 to 87) in 2- to 17-year-olds.
Influenza vaccination reduced the risk of influenza among ARI patients presenting to general practice, demonstrating the benefits of vaccination, particularly among children. Promotion of the seasonal influenza vaccine to recommended groups, should remain a public health priority. Targeted vaccination campaigns for children promoting LAIV should emphasise the effectiveness of LAIV in children.
Monitoring how the incidence of influenza infections changes over time is important for quantifying the transmission dynamics and clinical severity of influenza. Infection incidence is difficult to measure directly, and hence, other quantities which are more amenable to surveillance are used to monitor trends in infection levels, with the implicit assumption that they correlate with infection incidence.
Here, we demonstrate, through mathematical reasoning using fundamental mathematical principles, the relationship between the incidence of influenza infections and three commonly reported surveillance indicators: (1) the rate per unit time of influenza-like illness reported through sentinel healthcare sites, (2) the rate per unit time of laboratory-confirmed influenza infections and (3) the proportion of laboratory tests positive for influenza (‘test-positive proportion’).
Our analysis suggests that none of these ubiquitously reported surveillance indicators are a reliable tool for monitoring influenza incidence. In particular, we highlight how these surveillance indicators can be heavily biassed by the following: the dynamics of circulating pathogens (other than influenza) with similar symptom profiles, changes in testing rates and differences in infection rates, symptom rates and healthcare-seeking behaviour between age-groups and through time. We make six practical recommendations to improve the monitoring of influenza infection incidence. The implementation of our recommendations would enable the construction of more interpretable surveillance indicator(s) for influenza from which underlying patterns of infection incidence could be readily monitored.
The implementation of all (or a subset) of our recommendations would greatly improve understanding of the transmission dynamics, infection burden and clinical severity of influenza, improving our ability to respond effectively to seasonal epidemics and future pandemics.
Respiratory syncytial virus (RSV) is a major cause of hospital admission in adults over 65, leading to severe complications and death. However, the disease burden in primary care for older adults in Europe is poorly understood. This pilot study aims to test a study protocol for evaluating the clinical burden of RSV in older adults in primary care settings in Italy.
In the 2022–23 winter season, we designed a study on RSV burden in individuals over 65 with acute respiratory infections (ARIs) in Liguria, Apulia, and Tuscany, Italy. Recruited patients underwent nasopharyngeal swabs for RSV confirmation and provided epidemiological and clinical data. RSV-positive patients completed follow-up questionnaires after 14 and 30 days regarding their clinical conditions, healthcare utilization, and socio-economic impact.
We enrolled 152 patients with ARIs; 33 (21.7%) tested positive for RSV. The median disease duration was 14 days, with 3% hospitalized. Among RSV-positive patients, 87% received drug treatment, 52% of whom received antibiotics. After diagnosis, 74% required further GP consultations within 2 weeks. Additionally, 48% incurred extra costs. On day 30, 21% reported health complications or deterioration.
Our pilot study highlights the need for an ARIs surveillance system for older adults in primary care. This is crucial for defining vaccination strategies to reduce the disease burden on these patients and the healthcare system. Moreover, these data are essential for assessing costs and parameters for cost-effectiveness models, facilitating informed decisions in public health planning and resource allocation.
Respiratory syncytial virus (RSV) and influenza virus are major viral etiologies of pediatric lower respiratory tract infection, but comparative data on inpatient burden are lacking.
Using a large-scale health claims database in Japan, we identified patients under 5 years of age with a confirmed RSV or influenza diagnosis as an outpatient or inpatient between 2011 and 2022. Hospitalization rate, inpatient characteristics, various in-hospital outcomes/complications, and healthcare resource utilization were described.
A total of 176,911 RSV-confirmed outpatients, 153,383 influenza-confirmed outpatients, 90,413 RSV-confirmed hospitalizations, and 11,186 influenza-confirmed hospitalizations were identified. Among outpatients, 24.7% of RSV infection and 2.8% of influenza cases required hospitalization within 1 week. There was no co-morbidities/prematurity for 95.0% of RSV hospitalizations and 96.5% of influenza hospitalizations. Proportions of in-hospital outcomes/complications were (RSV infection vs. influenza): oxygen use 47.6% vs. 14.8%, mechanical ventilation 2.1% vs. 0.7%, pneumonia 33.6% vs. 12.8%, otitis media 7.7% vs. 2.3%, febrile seizure 1.5% vs. 34.4%, encephalitis/encephalopathy 0.1% vs. 0.5%, myocarditis < 0.1% vs. 0.6%, antibiotics prescription 48.0% vs. 24.4%. The mean inpatient stay was 6.1 vs. 4.3 days at direct medical costs of 435,744 vs. 315,809 JPY/patient. These trends held true in age-stratified data. In-hospital death occurred in 31 RSV infection and 6 influenza cases.
Although both infections resulted in substantial burden, RSV infection led to more frequent hospitalizations, worse in-hospital outcomes, longer inpatient stays, higher medical costs, and more frequent antibiotics prescription compared to influenza. Most RSV hospitalizations occurred among healthy term children, emphasizing the need for prevention measures in all children.
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