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International audience; Abstract Background Significant differences in COVID-19 incidence by gender, class and race/ethnicity are recorded in many countries in the world. Lockdown measures, shown to be effective in reducing the number of new cases, may not have been effective in the same way for all, failing to protect the most vulnerable populations. This survey aims to assess social inequalities in the trends in COVID-19 infections following lockdown. Methods A cross-sectional survey conducted among the general population in France in April 2020, during COVID-19 lockdown. Ten thousand one hundred one participants aged 18–64, from a national cohort who lived in the three metropolitan French regions most affected by the first wave of COVID-19. The main outcome was occurrence of possible COVID-19 symptoms, defined as the occurrence of sudden onset of cough, fever, dyspnea, ageusia and/or anosmia, that lasted more than 3 days in the 15 days before the survey. We used multinomial regression models to identify social and health factors related to possible COVID-19 before and during the lockdown. Results In all, 1304 (13.0%; 95% CI: 12.0–14.0%) reported cases of possible COVID-19. The effect of lockdown on the occurrence of possible COVID-19 was different across social hierarchies. The most privileged class individuals saw a significant decline in possible COVID-19 infections between the period prior to lockdown and during the lockdown (from 8.8 to 4.3%, P = 0.0001) while the decline was less pronounced among working class individuals (6.9% before lockdown and 5.5% during lockdown, P = 0.03). This differential effect of lockdown remained significant after adjusting for other factors including history of chronic disease. The odds of being infected during lockdown as opposed to the prior period increased by 57% among working class individuals (OR = 1.57; 95% CI: 1.00–2.48). The same was true for those engaged in in-person professional activities during lockdown (OR = 1.53; 95% CI: 1.03–2.29). Conclusions Lockdown was associated with social inequalities in the decline in COVID-19 infections, calling for the adoption of preventive policies to account for living and working conditions. Such adoptions are critical to reduce social inequalities related to COVID-19, as working-class individuals also have the highest COVID-19 related mortality, due to higher prevalence of comorbidities.

International audience; Objectives - In early January 2021 an outbreak of nosocomial cases of coronavirus disease 2019 (COVID-19) emerged in Western France; RT-PCR tests were repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole-genome sequencing (WGS) revealed a new variant, currently defining a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.616. In March, the WHO classified this as a 'variant under investigation' (VUI). We analysed the characteristics and outcomes of COVID-19 cases related to this new variant. Methods - Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled those inpatients with: (a) positive SARS-CoV-2 RT-PCR on a respiratory sample, (b) seroconversion with anti-SARS-CoV-2 IgG/IgM, or (c) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as B.1.616, a variant of concern (VOC), or unknown. Results - From 1st January to 24th March 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n = 39), VOC (n = 32), and unknown (n = 43). B.1.616-related cases were older than VOC-related cases (81 years, interquartile range (IQR) 73-88 versus 73 years, IQR 67-82, p < 0.05) and their first RT-PCR tests were rarely positive (6/39, 15% versus 31/32, 97%, p < 0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.0, 95%CI 1.5-10.9) and increased lethality (28-day mortality 18/39 (46%) for B.1.616 versus 5/32 (16%) for VOC, p = 0.006). Conclusion - We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, which is poorly detected by RT-PCR on nasopharyngeal samples and is associated with high lethality.

International audience; The current COVID-19 pandemic illustrates the importance of obtaining reliable methods for the rapid detection of SARS-CoV-2. A highly specific and sensitive diagnostic test able to differentiate the SARS-CoV-2 virus from common human coronaviruses is therefore needed. Coronavirus nucleoprotein (N) localizes to the cytoplasm and the nucleolus and is required for viral RNA synthesis. N is the most abundant coronavirus protein, so it is of utmost importance to develop specific antibodies for its detection. In this study, we developed a sandwich immunoassay to recognize the SARS-CoV-2 N protein. We immunized one alpaca with recombinant SARS-CoV-2 N and constructed a large single variable domain on heavy chain (VHH) antibody library. After phage display selection, seven VHHs recognizing the full N protein were identified by ELISA. These VHHs did not recognize the nucleoproteins of the four common human coronaviruses. Hydrogen Deuterium eXchange-Mass Spectrometry (HDX-MS) analysis also showed that these VHHs mainly targeted conformational epitopes in either the C-terminal or the N-terminal domains. All VHHs were able to recognize SARS-CoV-2 in infected cells or on infected hamster tissues. Moreover, the VHHs could detect the SARS variants B.1.17/alpha, B.1.351/beta, and P1/gamma. We propose that this sandwich immunoassay could be applied to specifically detect the SARS-CoV-2 N in human nasal swabs.

The Second ENCORE European conference in October 2021 in Paris, France, has gathered two communities, the Risk Perception and Behaviour Survey of Surveyors (Risk-SoS) and the H2020-DRS01 Cluster on risk perception and adaptive behaviour (a grouping of several Horizon Europe – Disaster Resilient Societies projects, most notably RESILOC, BUILDERS, ENGAGE, LINKS, CORE and Risk PACC). During the Covid-19 pandemic lockdowns in 2020 and 2021 the monthly Risk-SoS webinars have been keeping the risk perception and adaptive behaviour research community together with panels on the role of theories in research on hazards adaptation, resilience and vulnerability. Topics were on risk perception and behaviour across challenges and time, across disciplines and methods, as well as panel and longitudinal approaches, and workshops on theories and methods to advance the design of a collective surveying approach with potentially common questions and answers’ scales to foster comparability. The Risk-SoS webinars have also been discussing the results of the Survey of Surveyors and sustaining the collective effort to build a harmonised approach for risk perception and adaptive behaviour assessment. In an hybrid format, the Second ENCORE conference has gathered 25 researchers and experts from 10 countries (Austria, Belgium, France, Germany, the Netherlands, Poland, Spain, Sweden, Switzerland and the United Kingdom) at the Ministry of Research in Paris, France.

Abstract COVID‐19 vaccines already in use or in clinical development may have reduced efficacy against emerging SARS‐CoV‐2 variants. In addition, although the neurotropism of SARS‐CoV‐2 is well established, the vaccine strategies currently developed have not taken into account protection of the central nervous system. Here, we generated a transgenic mouse strain expressing the human angiotensin‐converting enzyme 2, and displaying unprecedented brain permissiveness to SARS‐CoV‐2 replication, in addition to high permissiveness levels in the lung. Using this stringent transgenic model, we demonstrated that a non‐integrative lentiviral vector, encoding for the spike glycoprotein of the ancestral SARS‐CoV‐2, used in intramuscular prime and intranasal boost elicits sterilizing protection of lung and brain against both the ancestral virus, and the Gamma (P.1) variant of concern, which carries multiple vaccine escape mutations. Beyond induction of strong neutralizing antibodies, the mechanism underlying this broad protection spectrum involves a robust protective T‐cell immunity, unaffected by the recent mutations accumulated in the emerging SARS‐CoV‐2 variants. A lentiviral vector‐based vaccine, used in prime and intranasal boost, induces strong B‐ and T‐cell immunity. This vaccine candidate protects against both pulmonary and neurological COVID‐19 caused by either ancestral or emerging SARS‐CoV‐2.

International audience; Background: Lymphopenia and the neutrophil/lymphocyte ratio may have prognostic value in COVID-19 severity.Objective: We investigated neutrophil subsets and functions in blood and bronchoalveolar lavage (BAL) of COVID-19 patients on the basis of patients’ clinical characteristics.Methods: We used a multiparametric cytometry profiling based to mature and immature neutrophil markers in 146 critical or severe COVID-19 patients.Results: The Discovery study (38 patients, first pandemic wave) showed that 80% of Intensive Care Unit (ICU) patients develop strong myelemia with CD10−CD64+ immature neutrophils (ImNs). Cellular profiling revealed three distinct neutrophil subsets expressing either the lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), the interleukin-3 receptor alpha (CD123), or programmed death-ligand 1 (PD-L1) overrepresented in ICU patients compared to non-ICU patients. The proportion of LOX-1- or CD123-expressing ImNs is positively correlated with clinical severity, cytokine storm (IL-1β, IL-6, IL-8, TNFα), acute respiratory distress syndrome (ARDS), and thrombosis. BALs of patients with ARDS were highly enriched in LOX-1-expressing ImN subsets and in antimicrobial neutrophil factors. A validation study (118 patients, second pandemic wave) confirmed and strengthened the association of the proportion of ImN subsets with disease severity, invasive ventilation, and death. Only high proportions of LOX-1-expressing ImNs remained strongly associated with a high risk of severe thrombosis independently of the plasma antimicrobial neutrophil factors, suggesting an independent association of ImN markers with their functions.Conclusion: LOX-1-expressing ImNs may help identifying COVID-19 patients at high risk of severity and thrombosis complications.

International audience; We conducted a pilot study to evaluate the potential and feasibility of back-support exoskeletons to help the caregivers in the Intensive Care Unit (ICU) of the University Hospital of Nancy (France) executing Prone Positioning (PP) maneuvers on patients suffering from severe COVID-19-related Acute Respiratory Distress Syndrome. After comparing four commercial exoskeletons, the Laevo passive exoskeleton was selected and used in the ICU in April 2020. The first volunteers using the Laevo reported very positive feedback and reduction of effort, confirmed by EMG and ECG analysis. Laevo has been since used to physically assist during PP in the ICU of the Hospital of Nancy, following the recrudescence of COVID-19, with an overall positive feedback.

Abstract The devastating pandemic due to SARS‐CoV‐2 and the emergence of antigenic variants that jeopardize the efficacy of current vaccines create an urgent need for a comprehensive understanding of the pathophysiology of COVID‐19, including the contribution of inflammation to disease. It also warrants for the search of immunomodulatory drugs that could improve disease outcome. Here, we show that standard doses of ivermectin (IVM), an anti‐parasitic drug with potential immunomodulatory activities through the cholinergic anti‐inflammatory pathway, prevent clinical deterioration, reduce olfactory deficit, and limit the inflammation of the upper and lower respiratory tracts in SARS‐CoV‐2‐infected hamsters. Whereas it has no effect on viral load in the airways of infected animals, transcriptomic analyses of infected lungs reveal that IVM dampens type I interferon responses and modulates several other inflammatory pathways. In particular, IVM dramatically reduces the Il‐6/Il‐10 ratio in lung tissue and promotes macrophage M2 polarization, which might account for the more favorable clinical presentation of IVM‐treated animals. Altogether, this study supports the use of immunomodulatory drugs such as IVM, to improve the clinical condition of SARS‐CoV‐2‐infected patients. COVID‐19, caused by SARS‐CoV‐2, induces airways and pulmonary symptoms, and in severe cases can lead to respiratory distress and death. This study shows that the modulation of the host's inflammatory response using ivermectin as a repurposed drug, independently of the viral load, strongly diminished the clinical score and severity of the disease (including anosmia) observed in SARS‐CoV‐2‐infected golden hamsters. This study brings the proof‐of‐concept that a chemical therapy using ivermectin can preserve the clinical condition by modulating the inflammatory response, even without antiviral activity.

Abstract Background Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. Methods We developed a multiplex serological test for measuring antibodies to 5 SARS-CoV-2 antigens and the spike proteins of seasonal coronaviruses. We measured antibody responses in cohorts of hospitalized patients and healthcare workers followed for up to 11 months after symptoms. A mathematical model of antibody kinetics was used to quantify the duration of antibody responses. Antibody response data were used to train algorithms for estimating time since infection. Results One year after symptoms, we estimate that 36% (95% range, 11%–94%) of anti-Spike immunoglobulin G (IgG) remains, 31% (95% range, 9%–89%) anti-RBD IgG remains, and 7% (1%–31%) of anti-nucleocapsid IgG remains. The multiplex assay classified previous infections into time intervals of 0–3 months, 3–6 months, and 6–12 months. This method was validated using data from a seroprevalence survey in France, demonstrating that historical SARS-CoV-2 transmission can be reconstructed using samples from a single survey. Conclusions In addition to diagnosing previous SARS-CoV-2 infection, multiplex serological assays can estimate the time since infection, which can be used to reconstruct past epidemics. Longitudinal follow-up of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reveals differences in the duration of antibodies to multiple antigens. Mathematical models of antibody waning and statistical algorithms can estimate an individual’s time since SARS-CoV-2 infection, and previous transmission waves in a population.

International audience; Here, we introduce ITEXT-BIO, an intelligent process for biomedical domain terminology extraction from textual documents and subsequent analysis. The proposed methodology consists of two complementary approaches, including free and driven term extraction. The first is based on term extraction with statistical measures, while the second considers morphosyntactic variation rules to extract term variants from the corpus. The combination of two term extraction and analysis strategies is the keystone of ITEXT-BIO. These include combined intra-corpus strategies that enable term extraction and analysis either from a single corpus (intra), or from corpora (inter). We assessed the two approaches, the corpus or corpora to be analysed and the type of statistical measures used. Our experimental findings revealed that the proposed methodology could be used: (1) to efficiently extract representative, discriminant and new terms from a given corpus or corpora, and (2) to provide quantitative and qualitative analyses on these terms regarding the study domain.