Enterovirus D68 disease burden and epidemiology in hospital-admitted influenza-like illness, Valencia region of Spain, 2014-2020 influenza seasons.

Enterovirus D68 (EV-D68) is an emerging agent for which data on the susceptible adult population is scarce. We performed a 6-year analysis of respiratory samples from influenza-like illness (ILI) admitted during 2014-2020 in 4-10 hospitals in the Valencia Region, Spain. EV-D68 was identified in 68 (3.1%) among 2210 Enterovirus (EV)/Rhinovirus (HRV) positive samples. Phylogeny of 59 VP1 sequences showed isolates from 2014 clustering in B2 (6/12), B1 (5/12), and A2/D1 (1/12) subclades; those from 2015 (n = 1) and 2016 (n = 1) in B3 and A2/D1, respectively; and isolates from 2018 in A2/D3 (42/45), and B3 (3/45). B1 and B2 viruses were mainly detected in children (80% and 67%, respectively); B3 were equally distributed between children and adults; whereas A2/D1 and A2/D3 were observed only in adults. B3 viruses showed up to 16 amino acid changes at predicted antigenic sites. In conclusion, two EV-D68 epidemics linked to ILI hospitalized cases occurred in the Valencia Region in 2014 and 2018, with three fatal outcomes and one ICU admission. A2/D3 strains from 2018 were associated with severe respiratory infection in adults. Because of the significant impact of non-polio enteroviruses in ILI and the potential neurotropism, year-round surveillance in respiratory samples should be pursued.

Early estimates of nirsevimab immunoprophylaxis effectiveness against hospital admission for respiratory syncytial virus lower respiratory tract infections in infants, Spain, October 2023 to January 2024.

The monoclonal antibody nirsevimab was at least 70% effective in preventing hospitalisations in infants with lower respiratory tract infections (LRTI) positive for respiratory syncytial virus (RSV) in Spain (Oct 2023-Jan 2024), where a universal immunisation programme began late September (coverage range: 79-99%). High protection was confirmed by two methodological designs (screening and test-negative) in a multicentre active surveillance in nine hospitals in three regions. No protection against RSV-negative LRTI-hospitalisations was shown. These interim results could guide public-health decision-making.

Development of Photonic Multi-Sensing Systems Based on Molecular Gates Biorecognition and Plasmonic Sensors: The PHOTONGATE Project.

This paper presents the concept of a novel adaptable sensing solution currently being developed under the EU Commission-founded PHOTONGATE project. This concept will allow for the quantification of multiple analytes of the same or different nature (chemicals, metals, bacteria, etc.) in a single test with levels of sensitivity and selectivity at/or over those offered by current solutions. PHOTONGATE relies on two core technologies: a biochemical technology (molecular gates), which will confer the specificity and, therefore, the capability to be adaptable to the analyte of interest, and which, combined with porous substrates, will increase the sensitivity, and a photonic technology based on localized surface plasmonic resonance (LSPR) structures that serve as transducers for light interaction. Both technologies are in the micron range, facilitating the integration of multiple sensors within a small area (mm2). The concept will be developed for its application in health diagnosis and food safety sectors. It is thought of as an easy-to-use modular concept, which will consist of the sensing module, mainly of a microfluidics cartridge that will house the photonic sensor, and a platform for fluidic handling, optical interrogation, and signal processing. The platform will include a new optical concept, which is fully European Union Made, avoiding optical fibers and expensive optical components.

Role of age and birth month in infants hospitalized with RSV-confirmed disease in the Valencia Region, Spain.

BACKGROUND: RSV is the leading cause of hospital admissions in infants and the principal cause of bronchiolitis in young children. There is a lack of granular data on RSV-associated hospitalization per season using laboratory confirmed results. Our current study addresses this issue and intends to fill this gap. METHODS: The study was conducted from 2014 through 2018, in 4 to 10 hospitals in the Valencia Region, Spain. Infants included in this study were admitted in hospital through the Emergency Department with a respiratory complaint and tested by RT-PCR for RSV in a central laboratory. RESULTS: Incidence rates of RSV-associated hospitalization varied by season and hospital. Overall, the highest incidence rates were observed in 2017/2018. RSV-associated hospitalization was highest in infants below 3 months of age and in those born before or at the beginning of the RSV season. Almost 54% of total infants hospitalized with laboratory confirmed RSV were found to be born outside the season, from April to October. The RSV positivity rate by ICD-10 discharged codes varied by season and age with results from 48% to 57% among LRI (J09-J22). CONCLUSION: The study was instrumental in bringing forth the time unpredictability of RSV epidemics, the critical impact of age, and the comparable distribution of RSV-associated hospitalization in infants born on either side of the RSV season. These data could help in better characterization of the population that drives the healthcare burden and is crucial for the development of future immunization strategies, especially with upcoming vaccines in against RSV.

Retrospective screening for SARS-CoV-2 among influenza-like illness hospitalizations: 2018-2019 and 2019-2020 seasons, Valencia region, Spain.

On 9 March 2020, the World Health Organization (WHO) Global Influenza Programme (GIP) asked participant sites on the Global Influenza Hospital Surveillance Network (GIHSN) to contribute to data collection concerning severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We re-analysed 5833 viral RNA archived samples collected prospectively from hospital admissions for influenza-like illness (ILI) in the Valencia Region of Spain by the Valencia Hospital Surveillance Network for the Study of Influenza and Other Respiratory Viruses (VAHNSI) network (four hospitals, catchment area population 1 118 732) during the pre-pandemic 2018/2019 (n = 4010) and pandemic 2019/2020 (n = 1823) influenza seasons for the presence of SARS-CoV-2. We did not find evidence for community-acquired SARS-CoV-2 infection in hospital admissions for ILI in our region before early March 2020.

Re-emergence of enterovirus D68 in Europe after easing the COVID-19 lockdown, September 2021.

We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe.

Whole-Genome Analysis Surveillance of Influenza A Virus Resistance to Polymerase Complex Inhibitors in Eastern Spain from 2016 to 2019.

Molecular surveillance by whole-genome sequencing was used to monitor the susceptibility of circulating influenza A viruses to three polymerase complex inhibitors. A total of 12 resistance substitutions were found among 285 genomes analyzed, but none were associated with high levels of resistance. Natural resistance to these influenza A antivirals is currently uncommon.

Influenza Vaccine Effectiveness and Waning Effect in Hospitalized Older Adults. Valencia Region, Spain, 2018/2019 Season.

Influenza vaccination is annually recommended for specific populations at risk, such as older adults. We estimated the 2018/2019 influenza vaccine effectiveness (IVE) overall, by influenza subtype, type of vaccine, and by time elapsed since vaccination among subjects 65 years old or over in a multicenter prospective study in the Valencia Hospital Surveillance Network for the Study of Influenza and other Respiratory Viruses (VAHNSI, Spain). Information about potential confounders was obtained from clinical registries and/or by interviewing patients and vaccination details were only ascertained by registries. A test-negative design was performed in order to estimate IVE. As a result, IVE was estimated at 46% (95% confidence interval (CI): (16%, 66%)), 41% (95% CI: (-34%, 74%)), and 45% (95% CI: (7%, 67%)) against overall influenza, A(H1N1)pdm09 and A(H3N2), respectively. An intra-seasonal not relevant waning effect was detected. The IVE for the adjuvanted vaccine in ≥75 years old was 45% (2%, 69%) and for the non-adjuvanted vaccine in 65-74 years old was 59% (-16%, 86%). Thus, our data revealed moderate vaccine effectiveness against influenza A(H3N2) and not significant against A(H1N1)pdm09. Significant protection was conferred by the adjuvanted vaccine to patients ≥75 years old. Moreover, an intra-seasonal not relevant waning effect was detected, and a not significant IVE decreasing trend was observed over time.

Two Novel, Distantly Related Papillomaviruses Isolated from Healthy Skin of the Timor Deer (Rusa timorensis).

We report the complete genome sequences of Rusa timorensis papillomavirus 1 (RtimPV1) and Rusa timorensis papillomavirus 2 (RtimPV2), isolated from hair follicles of asymptomatic skin from the same Timor deer specimen. RtimPV1 and RtimPV2 are evolutionarily only distantly related. RtimPV1 lacks a canonical E2-binding site, and RtimPV2 does not carry an E6 gene.

Genome Sequences of Two Novel Papillomaviruses Isolated from Healthy Skin of Pudu puda and Cervus elaphus Deer.

We report the complete genome sequences of Pudu puda papillomavirus1 (PpudPV1) and Cervus elaphus papillomavirus2 (CelaPV2), isolated from healthy skin hair follicles of a Southern pudu and a red deer, respectively. PpudPV1 is basal to the DyokappaPVs, whereas CelaPV2 is basal to the XiPVs (Beta-XiPV crown group).

Assessing parallel gene histories in viral genomes.

BACKGROUND: The increasing abundance of sequence data has exacerbated a long known problem: gene trees and species trees for the same terminal taxa are often incongruent. Indeed, genes within a genome have not all followed the same evolutionary path due to events such as incomplete lineage sorting, horizontal gene transfer, gene duplication and deletion, or recombination. Considering conflicts between gene trees as an obstacle, numerous methods have been developed to deal with these incongruences and to reconstruct consensus evolutionary histories of species despite the heterogeneity in the history of their genes. However, inconsistencies can also be seen as a source of information about the specific evolutionary processes that have shaped genomes. RESULTS: The goal of the approach here proposed is to exploit this conflicting information: we have compiled eleven variables describing phylogenetic relationships and evolutionary pressures and submitted them to dimensionality reduction techniques to identify genes with similar evolutionary histories. To illustrate the applicability of the method, we have chosen two viral datasets, namely papillomaviruses and Turnip mosaic virus (TuMV) isolates, largely dissimilar in genome, evolutionary distance and biology. Our method pinpoints viral genes with common evolutionary patterns. In the case of papillomaviruses, gene clusters match well our knowledge on viral biology and life cycle, illustrating the potential of our approach. For the less known TuMV, our results trigger new hypotheses about viral evolution and gene interaction. CONCLUSIONS: The approach here presented allows turning phylogenetic inconsistencies into evolutionary information, detecting gene assemblies with similar histories, and could be a powerful tool for comparative pathogenomics.

The First Papillomavirus Isolated from Vulpes vulpes (VvulPV1) Is Basal to the Gammapapillomavirus Genus.

We report the complete genomic sequence of Vulpes vulpes papillomavirus type 1 (VvulPV1), isolated from the hair follicles of a red fox. VvulPV1 does not cluster with other carnivoran papillomaviruses, and is instead a sister taxon to the Gammapapillomavirus genus, thus sustaining the scenario of a biphasic evolution of papillomaviruses.

A novel papillomavirus isolated from a nasal neoplasia in an Italian free-ranging chamois (Rupicapra r. rupicapra).

Most amniotes are the hosts of many, distantly related papillomaviruses (PVs). Infection by PVs can be asymptomatic, or lead instead to benign or malignant lesions. However, PVs infecting animals and associated with malignancies are still largely understudied. In the present study, we communicate the complete genome of a novel PV found in a nasal neoplasia of a free-ranging alpine chamois (Rupicapra r. rupicapra) in an Italian national park. Long-PCR and cloning approaches followed for Sanger sequencing were used to identify the first PV found in chamois. The genome of the novel virus - RrupPV1 - of 7256 bp in length, presents the classical PV structure, and lacks the interE2-L2 region that hosts the E5 gene in AlphaPVs and in DeltaPVs. The nucleotide identity percentage of the L1 ORF, places RrupPV1 together with OaPV3 in the same genus. The latter is a PV isolated from a squamous cell carcinoma in sheep in Sardinia. Full-genome phylogenetic reconstructions suggest that these two viruses are sister taxa, and that both of them are very distantly related to any other known PV. Many cetartiodactyl species are infected by non-monophyletic PVs. Our results exemplify further the multiple links between the infection by certain, distantly related PVs and the development of diverse cancers in animals and highlight the need of a systematic search of oncogenic and non-oncogenic animal PVs.

Novel animal papillomavirus sequences and accurate phylogenetic placement.

All amniotes are probably infected by specific papillomaviruses (PVs), but knowledge about PV diversity remains sparse. An insufficient taxon sampling, and a focus on humans as hosts, may perturb phylogenetic analyses leading to wrong conclusions about PV evolution. We performed a systematic approach to explore the diversity of PVs combining rolling circle amplification with the use of "universal" primers to search for the presence of novel PV sequences in animal samples. We communicate 12 sequences putatively corresponding to novel PVs gained from 10 host species in eight mammal families: Bovidae, Canidae, Cervidae, Equidae, Hominidae, Phocoenidae, Procyonidae and Pteropodidae. The phylogenetic position of the new sequences was inferred with an evolutionary placement algorithm under a Maximum Likelihood framework using a pre-computed, well-resolved tree constructed with the E1-E2-L1 gene sequences as a backbone. The new sequences were phylogenetically diverse and could be respectively placed with confidence within all four PV crown groups. The prevailing presence of sequences from the crown groups Alpha+Omikron-PVs and Beta+Xi-PVs may correspond to an increased viral diversity in these taxa, or rather reflect a combination of anthropocentric bias and preferential amplification from commonly used "universal" primers. Our results combined with literature data support the view that the number and diversity of animal PVs is overwhelmingly large.