Guillaume Lingas
A5015699146- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- SARS-CoV-2 detection and testing
- Respiratory viral infections research
- COVID-19 and healthcare impacts
- Diabetes and associated disorders
- COVID-19 and Mental Health
- Intensive Care Unit Cognitive Disorders
- Respiratory Support and Mechanisms
- Viral Infections and Outbreaks Research
- Sepsis Diagnosis and Treatment
- vaccines and immunoinformatics approaches
- interferon and immune responses
- Clinical Reasoning and Diagnostic Skills
- COVID-19 diagnosis using AI
- semigroups and automata theory
- COVID-19 epidemiological studies
- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Mosquito-borne diseases and control
- Machine Learning in Healthcare
- Inflammasome and immune disorders
- Computability, Logic, AI Algorithms
- Algorithms and Data Compression
Université Paris Cité
2020-2024
Inserm
2020-2024
Johns Hopkins Hospital
2024
Bicêtre Hospital
2023-2024
Assistance Publique – Hôpitaux de Paris
2023-2024
Université Paris-Saclay
2023-2024
Sorbonne Paris Cité
2024
Université Sorbonne Paris Nord
2024
Sorbonne Université
2024
Cohort (United Kingdom)
2022-2023
Significance A detailed characterization of viral load kinetics and its association with disease evolution is key to understand the virus pathogenesis, identify high-risk patients, design better treatment strategies. We here analyze mortality virological information collected in 655 hospitalized including 284 longitudinal measurements, we build a mathematical model dynamics survival. predict that peak occurs 1 d before symptom onset, on average, decline after slower older patients. Viral...
Despite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we use a Syrian hamster model assess efficacy favipiravir, understand its mechanism action and determine pharmacokinetics. When treatment is initiated before simultaneously infection, favipiravir has strong dose effect, leading reduction infectious titers lungs alleviation disease. Antiviral effect correlates with...
Memory B-cell and antibody responses to the SARS-CoV-2 spike protein contribute long-term immune protection against severe COVID-19, which can also be prevented by antibody-based interventions. Here, wide immunoprofiling in Wuhan COVID-19 convalescents combining serological, cellular, monoclonal explorations revealed humoral immunity coordination. Detailed characterization of a hundred memory antibodies uncovered diversity their repertoire antiviral functions. The latter were influenced...
Abstract Background The antiviral efficacy of remdesivir in COVID-19 hospitalized patients remains controversial. Objectives To estimate the effect blocking viral replication. Methods We analysed nasopharyngeal normalized loads from 665 included DisCoVeRy trial (NCT 04315948; EudraCT 2020-000936-23), randomized to either standard care (SoC) or SoC + remdesivir. used a mathematical model reconstruct kinetic profiles and Additional analyses were conducted stratified on time treatment...
Abstract Little is known on the association between clinical factors and coronavirus disease 2019 (COVID‐19) more than 15 days after diagnosis. We conducted a multicentric prospective cohort of COVID‐19 hospitalized patients to describe clinical, biological, virological characteristics at hospital admission over time, according mortality up Day 60 admission. For analysis risk survival, analyses assessing associations demographic or comorbidities were performed using Cox regression model....
Abstract The COVID-19 pandemic has exemplified that rigorous evaluation in large animal models is key for translation from promising vitro results to successful clinical implementation. Among the drugs have been largely tested trials but failed so far bring clear evidence of efficacy favipiravir, a nucleoside analogue with spectrum activity against several RNA viruses and small models. Here, we evaluate antiviral favipiravir Zika or SARS-CoV-2 virus cynomolgus macaques. In both models, high...
Lassa fever is an haemorrhagic caused by virus (LASV). There no vaccine approved against LASV and the only recommended antiviral treatment relies on ribavirin, despite limited evidence of efficacy. Recently, nucleotide analogue favipiravir showed a high efficacy, with 100% survival obtained in otherwise fully lethal non-human primate (NHP) model fever. However mechanism action drug not known absence pharmacokinetic data limits translation these results to human setting. Here we aimed better...
Abstract Despite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we used a Syrian hamster model assess efficacy favipiravir, understand its mechanism action and determine pharmacokinetics. When treatment was initiated before simultaneously infection, favipiravir had strong dose effect, leading dramatic reduction infectious titers lungs alleviation disease. Antiviral effect...
Abstract Background The composition of the digestive microbiota may be associated with outcome and infections in patients admitted to intensive care unit (ICU). dominance by opportunistic pathogens (such as Enterococcus ) has been death. However, whether this association remains all throughout hospitalization are lacking. Methods We performed a single-center observational prospective cohort study critically ill severe SARS-CoV-2 infection. Oropharyngeal rectal swabs were collected at...
Following a severe COVID-19 infection, proportion of individuals develop prolonged symptoms. We investigated the immunological dysfunction that underlies persistence symptoms months after resolution acute COVID-19.We analyzed cytokines, cell phenotypes, SARS-CoV-2 spike-specific and neutralizing antibodies, whole blood gene expression profiles in convalescent patients 1, 3, 6 following hospital discharge.We observed persistent abnormalities until month marked by (i) high serum levels...
Abstract Background The antiviral efficacy of Evusheld (AZD7442) in patients hospitalized for SARS-CoV-2 is unknown. Methods We analysed the evolution both nasopharyngeal viral load and serum neutralization activity against variant infection 199 (109 treated with Evusheld, 90 placebo) infected virus included randomized, double-blind, trial DisCoVeRy (NCT04315948). Using a mechanistic mathematical model, we reconstructed trajectories kinetics how they are modulated by increase during...
To better understand plausible SARS-CoV-2 transmission through fomites, a physiological model was designed to analyze the decay rate of infectivity. We focused on non-porous materials present in high-touch surfaces or used as containment barrier surfaces, namely glass, acrylic photo-activated coated stainless steel and aluminium. survival depended material considered, with half-lives aluminium equal 6.9, 4.1, 3.5 2.3 h, respectively. This study highlights potential utility coatings fight...
Abstract Background While anti-SARS-CoV-2 antibody kinetics have been well described in large populations of vaccinated individuals, we still poorly understand how they evolve during a natural infection and this impacts viral clearance. Methods For that purpose, analyzed the both load neutralizing levels prospective cohort individuals acute by Alpha variant. Results Using mathematical model, show progressive increase antibodies leads to shortening half-life infected cells infectious...
The role of antiviral treatment in coronavirus disease 2019 hospitalized patients is controversial. To address this question, we analyzed simultaneously nasopharyngeal viral load and the National Early Warning Score 2 (NEWS-2) using an effect compartment model to relate dynamics evolution clinical severity. applied 664 included DisCoVeRy trial (NCT04315948; EudraCT 2020-000936-23) randomly assigned either standard care (SoC) or SoC + remdesivir. Then use simulate impact treatments on time...
Therapeutic monoclonal antibodies have been successful in protecting vulnerable populations against SARS-CoV-2. However, their effectiveness has hampered by the emergence of new variants. To adapt therapeutic landscape, health authorities based recommendations mostly on vitro neutralization tests. these do not provide a reliable understanding changes dose-effect relationship and how they may translate into clinical efficacy. Taking example EvusheldTM (AZD7442), we aimed to investigate vivo...
Although anti‐severe acute respiratory syndrome‐coronavirus 2 antibody kinetics have been described in large populations of vaccinated individuals, we still poorly understand how they evolve during a natural infection and this impacts viral clearance. For that purpose, analyzed the both load neutralizing levels prospective cohort individuals with alpha variant. Using mathematical model, show progressive increase antibodies leads to shortening half‐life infected cells infectious particles. We...
Abstract The presence of free severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) nucleocapsid‐antigen in sera (N‐antigenemia) has been shown COVID‐19 patients. However, the link between quantitative levels N‐antigenemia and disease severity is not entirely understood. To assess dynamics clinical association N‐antigen with patients, we analyzed data from patients included French COVID cohort, at least one sample January September 2020. We assessed anti‐N IgG titers, patient outcomes...
Abstract The efficacy of pre-exposure prophylaxis by the Tixagevimab/Cilgavimab cocktail (AZD7442) was evaluated in hamsters against a clinical BA.1 strain SARS-CoV-2 variant Omicron. AZD7442 retains inhibitory activity Omicron despite substantial loss efficacy. We estimate that virus requires about 20-times more antibodies plasma than ancestral B.1 (G614) to achieve similar drug reducing lung infectious titers.
Abstract Despite several clinical studies, the antiviral efficacy of remdesivir in COVID-19 hospitalized patients remains controversial. We analyzed nasopharyngeal normalized viral loads collected 29 days following randomization from 665 included DisCoVeRy trial, allocated to either standard care (SoC, N=329) or SoC + for 10 (N=336). used a mathematical model reconstruct kinetic profiles and estimate reducing production. To identify factors associated with kinetics, additional analyses were...