Pascal Crépey

Patient movement within and between hospitals creates a complex hospital network that facilitates the spread of antimicrobial-resistant bacteria and contributes to healthcare-associated infections. Yet most national-scale studies infer spread from aggregated hospital-to-hospital patient sharing, leaving patient-to-patient contact pathways and the role of routine patient mobility in shaping colonization risk poorly characterized. Using France's 2023-2024 national hospital-discharge data, we reconstructed a temporal patient-based network of 10.4 million patients across 1,408 acute-care hospitals, comprising 326.6 million overnight ward co-location interactions. We simulated colonization over 365 days on the observed day-by-day temporal network using a stochastic susceptible-colonized-susceptible model, with a mean colonization duration of 180 days. We used national carbapenemase-producing Enterobacterales (CPE) surveillance data to calibrate differences in transmission risk across clinical settings. Across 2,000 simulations initiated on randomly selected dates in 2023, we calculated patient-level colonization probabilities and summarized risk across patients' residential areas, wards, and hospitals. We further assessed hospital-level consistency between simulated risk and recorded CPE occurrence. Simulated risk was highly heterogeneous across patients and care settings. When mapped by place of residence, hospital-associated colonization risk showed strong spatial clustering in both urban and rural areas. Multivariable regression analyses identified patient- and hospital-level characteristics associated with heterogeneity in simulated colonization risk. Sensitivity analyses varying initial seeding and colonization duration showed that relative risk patterns remained highly stable. This nationwide framework shows how patient mobility and ward co-location patterns can reveal patterns of hospital-associated colonization risk and could support pathogen-specific surveillance and intervention evaluation.

Healthcare facilities are interconnected via patient transfers, facilitating pathogen spread. We systematically reviewed studies reconstructing patient-sharing networks. Following PRISMA 2020 guidelines and a preregistered protocol (CRD42024559127), we searched PubMed, Scopus and IEEE Xplore up to October 1, 2025. We included articles presenting networks of at least three healthcare facilities or units connected by observed patient transfers, excluding those restricted to specific patient groups. Seventy-nine articles were included from 5,721 screened, describing 50 distinct networks published across multiple disciplines. Overall confidence in study findings, assessed through a modified QuADS tool, was good (mean total score of 21/33), although precision in the description of underlying patient transfer data was often limited. Most networks were reconstructed in Europe and North America. The majority were restricted to hospitals, with nursing homes and other healthcare facilities rarely integrated, and 10 (20%) used temporal network approaches. While most articles reported descriptive statistics and network metrics, they focused mainly on density and degree (and its variants), with other metrics only rarely calculated. Only 27 (35%) articles developed mathematical models of pathogen transmission, including 12 that simulated public health interventions. Overall, this review highlights the value of patient-sharing networks to characterize healthcare connectivity and understand pathogen spread. Clearly articulating the methodological assumptions underlying network reconstruction and tailoring them to specific research questions is key to fully leveraging the reconstructed networks for public health purposes. In particular, including a broader range of facility types and more temporal modelling can help develop more realistic models of pathogen spread over these networks. This review was funded by the French National Research Agency (ANR 22-PAMR-0003).

Background: A French cohort study (2021/2022 influenza season) found the high‐dose influenza vaccine (HD) more effective than standard‐dose vaccines (SDs) in preventing influenza‐related hospitalizations in the elderly. The study continued to refine results and validate these findings. Methods: Data from community‐dwelling 65+ adults who received HD or SD during the 2022/2023 vaccination campaign were extracted from the National Health database. Hospitalizations were recorded from 14 days postvaccination until June 30, 2023. HD and SD recipients were matched using a propensity score. Associations between vaccines and hospitalizations were assessed by estimating incidence rate ratios and converting them to HD vs. SD vaccine relative effectiveness (rVE). Results: A total of 675,412 HD recipients were matched to 2,701,648 SD recipients. The rVE for influenza‐related hospitalizations was 27.4% [95% CI: 19.8; 34.3]. It ranged from 22.7% [9.8; 33.6] to 33.6% [21.2; 44.0] across age groups, indicating that HD consistently outperformed SDs in preventing influenza‐related hospitalizations, with the highest effect observed in 85+. Conclusions: Our study is the first to publish rVE data comparing HD and SDs in a real‐world setting in France for the 2022/2023 influenza season. Its findings reaffirm the benefit of HD vs. SDs. HD could help reduce the burden of severe respiratory infections in the elderly.

Background/Objectives: An influenza pandemic is likely to occur in the coming decades and will be associated with substantial healthcare and financial burdens. In this study, we evaluated the potential economic costs of different vaccination scenarios for the US population in the context of a moderate or severe influenza pandemic. Methods: Economic analysis was performed for initiation of pandemic vaccination from 3 months vs. 6 months in the US after declaration of a pandemic. We evaluated three vaccine effectiveness levels (high, moderate, low) and two pandemic severity levels (moderate and severe). Results: No vaccination would lead to total direct and indirect costs of $116 bn in a moderate pandemic and $823 bn in a severe pandemic. Initiation of vaccination at 3 months would result in cost savings versus no vaccination (excluding vaccine price) of $30–84 bn and $260–709 bn in a moderate and severe pandemic, respectively, whereas initiation of vaccination at 6 months would result in cost savings of $4–11 bn and $36–97 bn, respectively. Cost savings of $20 bn and $162 bn would occur in a moderate or severe pandemic, respectively, from use of a low effectiveness vaccine from 3 months instead of a high effectiveness vaccine from 6 months. Conclusions: Rapid initiation of vaccination would have a greater impact than increased vaccine effectiveness in reducing the economic impacts of an influenza pandemic.

We modeled the impact of initiating one-dose influenza vaccination at 3 months vs 6 months after declaration of a pandemic over a 1-year timeframe in the US population. Three vaccine effectiveness (VE) and two pandemic severity levels were considered, using an epidemic curve based on typical seasonal influenza epidemics. Vaccination from 3 months with a high, moderate, or low effectiveness vaccine would prevent ~95%, 84%, or 38% deaths post-vaccination, respectively, compared with 21%, 18%, and 8%, respectively following vaccination at 6 months, irrespective of pandemic severity. While the pandemic curve would not be flattened from vaccination from 6 months, a moderate/high effectiveness vaccine could flatten the curve if administered from 3 months. Overall, speed of initiating a vaccination campaign is more important than VE in reducing the health impacts of an influenza pandemic. Preparedness strategies may be able to minimize future pandemic impacts by prioritizing rapid vaccine roll-out.

Background A French retrospective observational cohort study conducted during the 2021/22 influenza season found that the high-dose influenza vaccine (HD) was more effective than standard-dose vaccines (SDs) in preventing influenza-related hospitalizations in the elderly. The study continued during the 2022/23 season to obtain more accurate results and validate the findings during a different influenza season. Material and methods Data from community-dwelling 65+ adults vaccinated with HD or SD during the 2022/23 vaccination campaign were extracted from the National Health database. Hospitalizations were recorded from 14 days after vaccination until 30 June 2023. HD and SD recipients were matched using a propensity score with an exact constraint on age, sex, vaccination week, and geographical region. Associations between vaccines and hospitalizations (influenza or non-influenza related) were assessed by estimating incidence rate ratios and converting them to HD vs SD vaccine relative effectiveness (rVE). Results 675,412 HD recipients were matched to 2,701,648 SD recipients. The HD vs SD rVE for influenza-related hospitalizations was 27.39% [95%CI: 19.79;34.27]. It ranged from 22.65% [9.84;33.64] to 33.55% [21.19;43.98] across age groups, indicating that HD resulted in consistently better protection than SDs against influenza-related hospitalizations in all age groups, with the highest effect observed in 85+. Conclusion Our study is the first to publish rVE data comparing HD and SD in France, for the 2022/23 influenza season. Its findings reaffirm the benefit of HD vs SD in reducing influenza-related hospitalizations in a real-world setting. HD could help reduce the burden of severe respiratory infections in the elderly. Registration number: Not applicable. Take-home message In France, during the 2022/23 influenza season, the high-dose vaccine has reduced influenza-related hospitalizations by 27.4% compared to standard-dose vaccines among community-dwelling 65+ adults, with a clinical benefit observed across all age groups.

Background: Self-amplifying mRNA vaccines have the potential to increase the magnitude and duration of protection against COVID-19 by boosting neutralizing antibody titers and cellular responses. Methods: In this study, we used the immunogenicity data from a phase 3 randomized trial comparing the immunogenicity of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, with BNT162b2 mRNA COVID-19 vaccine to estimate the relative vaccine efficacy (rVE) of the two vaccines over time in younger (<60 years) and older (≥60 years) adults. Results: By day 181 post-vaccination, the rVE against symptomatic and severe Wuhan-Hu-1 disease was 9.2–11.0% and 1.2–1.5%, respectively, across age groups whereas the rVE against symptomatic and severe Omicron BA.4/5 disease was 26.8–48.0% and 5.2–9.3%, respectively, across age groups. Sensitivity analysis showed that varying the threshold titer for 50% protection against severe disease up to 10% of convalescent sera revealed incremental benefits of ARCT-154 over BNT162b2, with an rVE of up to 28.0% against Omicron BA.4/5 in adults aged ≥60 year. Conclusions: Overall, the results of this study indicate that ARCT-154 elicits broader and more durable immunogenicity against SARS-CoV-2, translating to enhanced disease protection, particularly for older adults against Omicron BA.4/5.

Seasonal influenza outbreaks in France cause a surge in patients, exacerbating the overburdened healthcare system each winter. Older adults are particularly vulnerable to serious events related to influenza. Quadrivalent influenza high dose (QIV HD) vaccines have been developed to offer better clinical protection in older adults, who often exhibit suboptimal immune response to quadrivalent influenza standard dose vaccines (QIV SD). This study aims to evaluate the public health impact and cost-effectiveness of administering HD versus SD vaccines to individuals aged 65+ in France. Using a static model and decision-tree approach, the study analyzed health outcomes such as influenza cases, GP (general practitioner) visits, hospitalizations, and mortality; relative vaccine efficacy (rVE) estimates were derived from a pivotal randomized-controlled trial and a meta-analysis comparing HD to SD vaccines. Two approaches were implemented to model hospitalizations (conditional on influenza or not), and analyses on bed occupancy were performed. Results showed that using QIV HD instead of QIV SD during an average influenza season in France led to the prevention of 57,209 additional cases of influenza, 13,704 GP visits, and 764 influenza-related deaths. Moreover, switching to QIV HD resulted in additional 1,728 to 15,970 hospitalizations avoided and 15,124 to 138,367 reduced days of hospitalization depending on the hospitalization approach used. The cost-utility analysis showed a cost per quality-adjusted life year (QALY) gained ranging from 24,020 €/QALY to 5,036 €/QALY. Switching to QIV HD in older adults showed to be cost-effective, with even greater public health benefits at higher coverage rate, regardless the season severity.

In July 2023, the Center of Excellence in Respiratory Pathogens organized a two-day workshop on infectious diseases modelling and the lessons learnt from the Covid-19 pandemic. This report summarizes the rich discussions that occurred during the workshop.