First star of ESCMID 2025: The VRS

To say that the Wien Center Mass is a congress center with space is an euphemism, as the Congress Center, a few strides from the Danube, is gigantic, with its spaces of conviviality, exchanges and those dedicated to pharmaceutical laboratories. You can even have photographed with festive accessories against the backdrop of the Vienna National Opera (document not supplied). Viewed, we have to approach the 10,000 delegates. The European Congress has become global and has been overweight with the crisis Covid A coronavirus disease, sometimes designated COVVID (according to the English acronym from Coronavirus DIEASE) is a disease caused by a coronavirus (VOC). The expression can refer to the following diseases: severe acute respiratory syndrome (SRAS) caused by the SARS-COV virus, the Middle East respiratory syndrome (seas) caused by the MERS-COV virus, 2019 coronavirus disease (COVVI-19) caused by the SARS-COV-2 virus. and the end of the too American Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Trump II will undoubtedly strengthen the American presence already important.

The VRS is one of the seasonal respiratory viruses-with the flu, the metapneumovirus, the SARS-COV-2-which weighs the most on the care system. In infants, but also in adults. In 60 to 90% of bronchiolitis in infants, the responsible infectious agent is the VRS. Each year almost 30% of children under 2 contracts bronchiolitis, or around 480,000 cases per year. And 2 to 3% of infants under 1 year old are hospitalized for more severe bronchiolitis.

In older people, the VRS may induce serious respiratory complications (acute respiratory distress syndrome, exacerbation of chronic cardiopulmonary or pneumonary disease requiring respiratory assistance in resuscitation) likely to lead to death. Each winter, 15,000 to 20,000 elderly people are hospitalized in France because of the VRS and several thousands die.

Pending antivirals (see below), two strategies aimed at limiting the devastating effects of the VRS are implemented during the VRS traffic season: immunization by a monoclonal antibody (ACMC, Nirsvimab/Befortus for the moment) or vaccination (two vaccines have obtained their AMM Marketing authorization. Administrative procedure which authorizes a pharmaceutical laboratory to market a molecule. European, Arexvy de GSK (reimbursed in the indications of the HAS and Abrysvo de Pfizer (not yet reimbursed) while waiting for the Moderna ARNM vaccine on approach). For the child to be born these two strategies are possible: vaccination of mothers during pregnancy or immunization by monoclonal antibodies of newborns and infants. This unprecedented alternative to infectious diseases is left to the choice of parents. This requires pedagogy efforts. For adults, HAS A in July 2024 determined the target population outside of pregnant women: people aged 75 and over and those over 65 with chronic respiratory or cardiac pathologies.

European Epidemiology of the VRS

To convince yourself of the overall interest in this respiratory virus at ESCMID 2025, you had to be at the EW 041 Hall 13 at 8:30 a.m., the first day of the congress itself that was full. Eeva BRUBERG (ECDC, WO 128) has drawn a view of European epidemiology 2020-2025 of the VRS and the burden of this infection in Europe: 245,244 admissions per year of children under 5, 1.8% of European children without risk factor (prematurity, immunodeficiency, trisomy 21) will be hospitalized the first year of life, 3 049 039 cases among those over 60 (underestimated) and 19,527 deaths in the hospital in this age group. With data updated at week 13 of 2025: 7% positivity in 20 countries. The comparative curves of winters-the peak of Vrs is located between Christmas and year-demonstrates a return to the pre-Pandemic area as observed in the winter of 2020-2021 with a co-circulation of the flu and the COVID-19 A coronavirus disease, sometimes designated COVVID (according to the English acronym from Coronavirus DIEASE) is a disease caused by a coronavirus (VOC). The expression can refer to the following diseases: severe acute respiratory syndrome (SRAS) caused by the SARS-COV virus, the Middle East respiratory syndrome (seas) caused by the MERS-COV virus, 2019 coronavirus disease (COVVI-19) caused by the SARS-COV-2 virus. (Figure1).

Under the weight of ACMC immunization, vaccination and barriers. In terms of ACMC Louis Bont (WO 129; Utrecht, Nederland) revealed the reference country in terms of VRS preventive coverage: Chile. Its national immunization program by the Norsevimab entered in 2024 coverage of 83-98% of children under the age of 4, the distribution of 93,373 doses resulting in a reduction of 86% of intensive care admission and 75% of hospitalizations with zero deaths versus 13 in 2023! This pediatrician also declined the possible second generation ACMC possible: Clesrovimab (MK 1654) a long promising Merck and Sustavumab (Regn22222) sea serpent in phase III as well as the thrust of direct antivirals that would close the vice against the VRS: Ziresovir (Arkbio) in phase III with good results, Sisunatovir (PFIZER) “Program completed” according to the oral presentation and ZELICAPAVIR (ENANANA) in phase II. Immunizing coverage in France by Nisevimab and socio-demographic data have been recently published as well as a major case/control study of its protective effects, a study that is owed to the Epiphare group. As well as HAS recommendations.

“Progress in the effectiveness of vaccines against respiratory infections”

Same crowd hall 9 at 11 a.m. for the LB 001 session: «Advances in vaccine effectiveness for respiratory infections» With Jean-Paul Stahl (France) as co-chair. The opportunity to abandon the VRS for a while to return to the coronavirus with Frances Priddy (Cambridge, USA l 0001) and the development of Moderna Arnm vaccines against JN.1 and KP-2 variants of SARS-COV-2. Good results in terms of neutralizing immunogenicity but the decrease in antibodies of antibodies against the following variants, KP.3.1.1, XEC and LP 8.1, still suggests the exhaust capacities of these variants. Daniel Jenkin (Oxford Vaccine Group, L0004) took us to the very forgotten coronavirus, the seas responsible for the respiratory syndrome from the Middle East with high mortality, with the development of a promising Chadox1 vaccine with a good immune response. Even in people who have already been exposed to the same vector (adenovirus) used in many vaccines including that against the covid developed precisely by the University of Oxford. Hoping that the destiny of this VRS vaccine is better than its equivalent against COVID, particularly in terms of stability in the vaccine protein.

It is in this context of triple response (ACMC, vaccine then an antiviral day) that the central question of the selection pressure and the output of the resistant VRS variants, notably in particular in Norsevimab arises. The nirsevimab indeed targets a specific antigen site (the epitope Ø) on a protein located on the surface of the Vrs involved in the viral multiplication – the fusion protein f— and thus blocks the virus. There is a theoretical risk of emergence of VRS variants with mutations in resistance to neutralization by nirsevimab, even in the absence of selection pressure by the antibody. The VRS is, in fact, like any virus virus a variable virus and this risk could increase with the generalized preventive use of the nirsvimab. As was the case for the covid virus.

The Polyres study

This is why the oral presentation of Pr Slim Fourati, responsible for the virology unit- respiratory virus at the Henri Mondor CHU, Inserm National Institute of Medical Research. U955, was found in the top 10 oral communications of April 12 in Vienna. Works on the “molecular characterization of VRS infections in elderly patients during the 2023/2024 season” and the fruit of a collaboration AP-HP Assistance Publique-Hôpitaux de Paris. Inserm, Paris-Est-Créteil University (UPEC) Institut Pasteur and benefiting from financing from the Anrs-MI within the framework of the Emergen consortium. The Polyres study is its name presents the characteristics of the syncytial respiratory virus after treatment with the Nirsvimab in an observational study taking place in real life during the winter season 2023-2024 as already published in October 2024 and extended in the winter of 2024-2025. During clinical trials of phase IIB/III, only 48 VRS having infected children under treatment with the Nirsvimab had been studied and exhaust mutations had been found in two of them. In this study conducted between September 2023 and March 2024, 695 infants aged under a year infected with the VRS and coming from 31 French hospitals were included: 346 cases receiving Nirsvimab and 349 cases not exposed.

The sequencing of the complete genome of the VRS revealed the co-circulation of several lines of VRS-A and VRS-B in infections not exposed to Nirsvimab and in cases occurring in the presentations. The VRS-A was in the majority this season and was found in 87 % of infected children (n = 472) and the VRS-B in 13 % of cases. The teams analyzed the characteristics of the VRS-A and VRS present in the nasopharyngeal samples taken as part of the usual care of children. The complete sequence of the viral genome has been determined to search in particular mutations in the link site (the Ø site) of the Nirsvimab (genotypic analysis). The capacity of the Norsevimab to inhibit the multiplication of viruses in cell culture has also been studied (phenotypic analysis). The analysis of 472 VRS-A (half of which from treated children) revealed no mutation of resistance to the Norsevimab in the Ø site of protein F. In cases which occurred in children exposed (Breakthrough), all VRS-A isolates remain sensitive to Nirsvimab. For the VRS-B, the team identified two variants (2/24) highly resistant to norsevimab: (i) carrying a resistance mutation F: N208D and a double mutation F: i64m + F: K65E never described. The fusion inhibition tests made it possible to identify these two mutational profiles in the Vrs-B inducing resistance to the inhibition of the fusion by the nirsvimab which suggests a high level of resistance to the nirsvimab. The team identified the molecular mechanism (in 3D) of this very rare resistance but asking questions. During the 2024-2025 season approximately 800 infants were recruited. The sequencing and phenotypic analysis are in progress. It was specified.

This study remains the largest concerning virological analyzes of chess to Nirsvimab to date. For Slim Fourati, “the weak prevalence Number of people affected by an infection or other disease given in a determined population. Norsevimab resistance mutations in treated patients is reassuring. However, some VRS-B from treated patients analyzed to date have exhaust mutations, which invites caution and highlights the importance of active molecular surveillance in the context of a future use of Nirsévimab on a global scale. “