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Background Therapies for refractory cytomegalovirus infections (with or without resistance [R/R]) in transplant recipients are limited by toxicities. Maribavir has multimodal anti-cytomegalovirus activity through the inhibition of UL97 protein kinase. Methods In this phase 3, open-label study, hematopoietic-cell and solid-organ transplant recipients with R/R cytomegalovirus were randomized 2:1 to maribavir 400 mg twice daily or investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for 8 weeks, with 12 weeks of follow-up. The primary endpoint was confirmed cytomegalovirus clearance at end of week 8. The key secondary endpoint was achievement of cytomegalovirus clearance and symptom control at end of week 8, maintained through week 16. Results 352 patients were randomized (235 maribavir; 117 IAT). Significantly more patients in the maribavir versus IAT group achieved the primary endpoint (55.7% vs 23.9%; adjusted difference [95% confidence interval (CI)]: 32.8% [22.80–42.74]; P Conclusions Maribavir was superior to IAT for cytomegalovirus viremia clearance and viremia clearance plus symptom control maintained post-therapy in transplant recipients with R/R cytomegalovirus. Maribavir had fewer treatment discontinuations due to TEAEs than IAT. Clinical Trials Registration. NCT02931539 (SOLSTICE).

International audience; We are presenting the application of an optical and computational pipeline FAMOUS for revealing the presence of free viral particles named "virions". The idea of such a protocol is to give rise to images of virions in their environment with a soft solution for recording the native image, contrary to the standard solution of imaging virions with electron microscopy (EM) for visualizing viral particles. The final aim of the current work is to observe free viral particles of SARS-CoV-2, the virions responsible for the worldwide pandemic of Covid-19. But such particles have diameters between 80 and 120 nm, a dimension smaller than the resolution limit of optical-only microscopy solutions. We have chosen to start with the biggest free virions, cytomegalovirus (CMV), a virus from the herpesvirus family also named "Human Herpes Virus 5". Two kinds of cultures were involved: a fluorescent culture (BAD) and a label-free one (VHLE), both being collected from infected cell culture. VHLE virions were first observed after secondary immunostaining and concentrated with magnetic nanoparticles and then without labelling. The optical protocol rests on a standard solution of multiphoton microscopy combined with a computational strategy based on the point-spread-function (PSF) recordings, its mathematical modeling and the restauration of the image resting on the PSF model. A test with free viral particles of SARS-CoV-2 is led, delivering an optical visualization of the free-viral particles. The visualization of objects aggregates obtained in both situations confirm the relevance of the pipeline FAMOUS for imaging free virions.

The complexity of the COVID-19 pandemic reveals important methodological debates and challenges with regard to the articulation of different research disciplines. The current COVID-19 societal research highlights the need for a holistic study of the COVID-19 pandemic issues based on a multidisciplinary research approach. The multidisciplinary approach appears to be essential to seize the invisible enemy of SARS-CoV-2 virus and related “domino effect” of consequences. In this article, we propose concrete avenues of reflection, drawn on innovative approaches of collective intelligence and co-design. Indeed, these approaches allow to initiate a logic of cross-fertilization of different disciplines by positioning the object of the study at the center of concerns of each of these disciplines. It is from this cross-fertilization that the CoviZion project will be able to evolve from a multidisciplinary device to an interdisciplinary or even transdisciplinary device allowing a 360-degree reading of the complex and unprecedented societal situation that is the COVID-19 crisis. This transdisciplinary approach is essential and has important implications, such as providing tools for better efficiency in the sanitary crisis management, particularly through public health policies., La complexité de la pandémie de COVID-19 révèle d’importants débats méthodologiques et des défis quant à l’articulation de différentes approches de recherche. La recherche sociétale actuelle concernant la COVID-19 met en évidence la nécessité d'une étude holistique de la situation de la pandémie de COVID-19, fondée sur une approche de recherche multidisciplinaire. L'approche multidisciplinaire apparaît indispensable pour saisir l'ennemi invisible qu’est le virus SARS-COV-2 et ses conséquences sociétales à « l’effet domino ». Dans cet article, nous proposons des pistes de réflexion concrètes qui s’appuient sur les approches méthodologiques de l’intelligence collective et de co-design. En effet, celles-ci permettent d’engager une logique de fertilisation croisée des disciplines en positionnant l’objet d’étude au centre des préoccupations de chacune des disciplines convoquées. C’est à partir de cette fertilisation croisée que le projet CoviZion pourra évoluer en passant d’un dispositif multidisciplinaire à un dispositif interdisciplinaire voire transdisciplinaire permettant une lecture à 360 degrés de la situation sociétale complexe et inédite qu’est la crise COVID-19. Cette approche transdisciplinaire est essentielle et connaît des implications importantes, notamment celle de fournir des outils permettant une meilleure efficacité dans la gestion des crises sanitaires par les politiques de santé publiques particulièrement.

International audience; We demonstrate the interest of multiphoton microscopy (MPM) for imaging bacteria without any labelling process. Six families of bacteria are tested: Escherichia coli, Staphylococcus epidermidis, Proteus vulgaris, Pseudomonas fluorescens, Bacillus subtilis and Clostridium perfringens. For each of these bacteria, the image of a cell is recorded through a multiphoton microscope thus revealing the 3D shape of these bacteria. For the first time, the images of such bacteria are recorded without any labelling solution. A protocol of controlling the image produced is led thanks to a standard staining protocol with carboxy fluorescein diacetate (CFDA) for E. Coli and Staphylococcus epidermidis. Similar object shapes with or without labelling are produced, thus validating the label-free images generated by MPM. Then, the two-photon excitation spectra are measured for each of these bacteriaand the emission spectra delivered by E. Coli and Bacillus subtilis are shown. The origin of the two-photon fluorescence (TPF) emission of the bacteria thanks to the nonlinear imaging solution is discussed regarding to the TPF excitation and emission spectra of metabolic indicators.

International audience; The 21st century extreme situations, such as the global COVID-19 breakdown elicited by the invisible SARS-CoV-2 virus, represent major collective upheavals for people and societies. Indeed, to date, the global COVID-19 Coronavirus pandemic has caused more than 336 790 193 confirmed cases and 5 560 718 deaths (World Health Organization: Coronavirus COVID-19 Dashboard, January 20, 2022). Thus, the complexity of the COVID-19 pandemic requires a pluri-disciplinary research approach in order to investigate these extraordinary circumstances. The pluri-disciplinary research program CoviZion conducted currently in France is based on innovative collaboration between hard and soft sciences that allows to construct a holistic overview of the COVID-19 pandemic and its impact on the population. Specifically, the SARS-CoV-2 virus of 120 nm in diameter, at the origin of the COVID-19 Coronavirus disease, is investigated by innovative methods from the field of virology, physics, computational sciences and multiphoton microscopy that allow imaging the biological representation of the virus. Further, the socially constructed representations of SARS-CoV-2 virus were investigated by mixed methods research design. The main latest results of CoviZion demonstrated that laypeople, aged from 18 to 84 years, perceive SARS-CoV-2 as a dangerous and worldwide killing virus that elicits negative emotions (fear, anxiety, sadness) and aversive reactions (uncertainty, stress, loneliness, tiredness, depression). Moreover, discourse analyses of older participants’ storytelling demonstrated that the unknown and invisible virus remains a source of various fears, fascinations and fantasies. In particular, the “war metaphor” and martial rhetoric that emerged in older participants’ storytelling resonate in line with the COVID-19 mass media and political storytelling in France. These findings contribute not only to an improved knowledge of the impact of COVID-19 pandemic on the population, but also to an improved crisis management effectiveness of current and future pandemic breakdowns.