Denis Malvy

BackgroundUrbanization imposes severe anthropogenic pressures on ecosystems, yet its systemic impacts on the structural cohesion of environmental microbiomes and the co-occurrence of antimicrobial resistance (AMR) remain poorly understood.MethodsWe combined Illumina NextSeq metabarcoding (16S/ITS2) with in vitro AMR screening of cultivable isolates across aquatic and solid matrices in Nouvelle-Aquitaine (France). Random Forest models (RFM), co-occurrence and bipartite network inferences were deployed to quantify localized ecological drivers and evaluate network resilience via percolation simulations.ResultsWhile urbanization categorical diversity indices did not significantly differ between urban and natural habitats (p > 0.05), RFM revealed that microbial richness is driven by distinct, continuous local gradients. Urbanization triggered severe structural fragmentation of microbial networks, marked by a collapse in edge density, higher modularity, and eradication of critical connectors. Percolation analysis confirmed this fragility, showing accelerated network collapse under targeted attacks in urban settings. Conversely, the bipartite networks focusing on the environmental resistome revealed an interesting paradox: whilst urbanization fragmented global networks, it significantly densified the bipartite network of antibiotic multidrug resistance. This resistome, structured around nodes of cefalexin, amoxicillin, and fosfomycin, exhibited increased structural stability, a doubling of inter-domain connectivity (bacterial-fungal), and an increase in positive correlation (39.7% vs 24.4%).Discussion and ConclusionThis study reveals that urbanization induces a trade-off between the overall cohesion of microbial ecosystems and the stability of specialized AMR-networks. It highlights the major interest of integrating high-resolution network analysis into One Health surveillance of AMR, to accurately predict and intercept the AMR spread in anthropized landscapes.

The One Health framework endorsed by the quadripartite (World Health Organization, World Organisation for Animal Health, Food and Agriculture Organization, and United Nations Environment Program) is defined, in part, as an “integrated, unifying approach that aims to sustainably balance and optimize the health of people, animals, and ecosystems,” and it explicitly refers to the health of plants as part of the whole interrelated system to consider. Although the ultimate issue is the planet's habitability for humans, the definition introduces a shift in perspective—human health is no longer the sole priority but must be balanced and optimized alongside the health of animals, plants, and ecosystems. This raises some practical and ethical questions. Drawing on case studies and the framework of the IPBES (Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services) on the values of nature, this study explores the implications of a global approach to health, with the ethical and practical questions that it raises.

The aim of this study was to describe the outcomes of targeted COVID-19 treatments in immunocompromised patients with asymptomatic or mild COVID-19 during the period of expansion of the different Omicron subvariants in France. A retrospective monocentric observational study was performed. All immunocompromised patients aged 18 or more, with asymptomatic SARS-CoV-2 infection or mild COVID-19, and who had received a targeted treatment with sotrovimab, tixagevimab/cilgavimab, nirmatrelvir/ritonavir or remdesivir at the Bordeaux University Hospital from 1st January 2022 to 31st December 2022 were eligible. The primary outcomes of interest was defined as a composite of either (i) progression to moderate (WHO-Clinical Progression Scale at 4 or 5) or severe COVID-19 (WHO-CPS ≥ 6), or (ii) the occurrence of COVID-19-related death. The secondary outcomes of interest were the components of the primary outcome. Outcomes were collected until day 30 after targeted treatment administration or at discharge for patients still hospitalised in relation with COVID-19 at day 30. 223 immunocompromised patients received targeted treatment for asymptomatic SARS-CoV-2 infection or mild COVID-19: 114 received sotrovimab, 50 tixagevimab/cilgavimab, 49 nirmatrelvir/ritonavir, and 10 remdesivir. Among 223 treated patients, 10 (4.5%) progressed to moderate or severe disease: three patients (1.3%) progressed to moderate COVID-19 and 7 (3.1%) patients progressed to severe disease. Among them, 4 (1.8%) died of COVID-19. More than 95% of immunocompromised patients with asymptomatic SARS-CoV-2 infection or mild COVID-19 treated by targeted therapies during the Omicron subvariants era did not progress to moderate or severe disease.

Patient experiences and perspectives on trial participation and follow-up may influence their compliance with research procedures or negatively impact their well-being. We aimed to explore the acceptability and feasibility of home-based and hospital-based follow-up modalities among COVID-19 patients enrolled in the ANTICOV ANRS COV33 Coverage-Africa trial in Burkina Faso and Guinea. The trial (2021–2022) evaluated the efficacy of treatments to prevent clinical worsening among COVID-19 patients with mild to moderate symptoms. Patients were either based at home or hospitalized, as per national recommendations, and followed-up through face-to-face visits and phone calls. We conducted a mixed-methods sub-study administering a questionnaire to all consenting participants and individually interviewing purposively selected participants. We performed descriptive analyses of Likert scale questions for the questionnaires and thematic analysis for the interviews. We conducted framework analysis and interpretation. Of the 400 trial patients, 220 completed the questionnaire (n = 182 in Burkina Faso, n = 38 in Guinea) and 24 were interviewed (n = 16 and n = 8, respectively). Participants were mostly followed-up at home in Burkina Faso; all patients from Guinea were first hospitalized, then followed-up at home. Over 90% of participants were satisfied with follow-up. Home follow-up was considered acceptable if (i) participants perceived they were not severely ill, (ii) it was combined with telemedicine, and (iii) the risk of stigma could be avoided. Hospital-based follow-up was viewed as a way to prevent contamination of family members, but could be badly experienced when mandatory and conflicting with family responsibilities and commitments. Phone calls were seen as reassuring and as a way to ensure continuity of care. These overall positive findings support the development of home-based follow-up for mildly ill patients in West-Africa, provided that both emotional and cognitive factors at individual, familial/inter-relational, healthcare and national levels be addressed when planning the implementation of a trial, or developing any public health strategy.

The COVID-19 pandemic has exemplified that rigorous evaluation in large animal models is key for translation from promising in vitro results to successful clinical implementation. Among the drugs that have been largely tested in clinical trials but failed so far to bring clear evidence of clinical efficacy is favipiravir, a nucleoside analogue with large spectrum activity against several RNA viruses in vitro and in small animal models. Here, we evaluate the antiviral activity of favipiravir against Zika or SARS-CoV-2 virus in cynomolgus macaques. In both models, high doses of favipiravir are initiated before infection and viral kinetics are evaluated during 7 to 15 days after infection. Favipiravir leads to a statistically significant reduction in plasma Zika viral load compared to untreated animals. However, favipiravir has no effects on SARS-CoV-2 viral kinetics, and 4 treated animals have to be euthanized due to rapid clinical deterioration, suggesting a potential role of favipiravir in disease worsening in SARS-CoV-2 infected animals. To summarize, favipiravir has an antiviral activity against Zika virus but not against SARS-CoV-2 infection in the cynomolgus macaque model. Our results support the clinical evaluation of favipiravir against Zika virus but they advocate against its use against SARS-CoV-2 infection.