...the end of the pandemic is only possible when vaccines that are effective against circulating variants are distributed equitably across the world. ...for surveillance of the circulation of ...SARS-CoV-2 variants, sharing of variant-specific PCR primers could help to monitor their spread, particularly in resource-limited countries. ...a central repository of samples of sera and cells from individuals with past infection or past immunisation with available COVID-19 vaccines should be established for seroneutralisation and cellular immunity functional testing against newly discovered variants.
On Dec 31, 2019, China reported a cluster of cases of pneumonia in people at Wuhan, Hubei Province. The responsible pathogen is a novel coronavirus, named severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2). We report the relevant features of the first cases in Europe of confirmed infection, named coronavirus disease 2019 (COVID-19), with the first patient diagnosed with the disease on Jan 24, 2020.
In this case series, we followed five patients admitted to Bichat-Claude Bernard University Hospital (Paris, France) and Pellegrin University Hospital (Bordeaux, France) and diagnosed with COVID-19 by semi-quantitative RT-PCR on nasopharyngeal swabs. We assessed patterns of clinical disease and viral load from different samples (nasopharyngeal and blood, urine, and stool samples), which were obtained once daily for 3 days from hospital admission, and once every 2 or 3 days until patient discharge. All samples were refrigerated and shipped to laboratories in the National Reference Center for Respiratory Viruses (The Institut Pasteur, Paris, and Hospices Civils de Lyon, Lyon, France), where RNA extraction, real-time RT-PCR, and virus isolation and titration procedures were done.
The patients were three men (aged 31 years, 48 years, and 80 years) and two women (aged 30 years and 46 years), all of Chinese origin, who had travelled to France from China around mid-January, 2020. Three different clinical evolutions are described: (1) two paucisymptomatic women diagnosed within a day of exhibiting symptoms, with high nasopharyngeal titres of SARS-CoV-2 within the first 24 h of the illness onset (5·2 and 7·4 log10 copies per 1000 cells, respectively) and viral RNA detection in stools; (2) a two-step disease progression in two young men, with a secondary worsening around 10 days after disease onset despite a decreasing viral load in nasopharyngeal samples; and (3) an 80-year-old man with a rapid evolution towards multiple organ failure and a persistent high viral load in lower and upper respiratory tract with systemic virus dissemination and virus detection in plasma. The 80-year-old patient died on day 14 of illness (Feb 14, 2020); all other patients had recovered and been discharged by Feb 19, 2020.
We illustrated three different clinical and biological types of evolution in five patients infected with SARS-CoV-2 with detailed and comprehensive viral sampling strategy. We believe that these findings will contribute to a better understanding of the natural history of the disease and will contribute to advances in the implementation of more efficient infection control strategies.
REACTing (Research & Action Emerging Infectious Diseases).
Little quantitative information is available on the mixing patterns of children in school environments. Describing and understanding contacts between children at school would help quantify the ...transmission opportunities of respiratory infections and identify situations within schools where the risk of transmission is higher. We report on measurements carried out in a French school (6-12 years children), where we collected data on the time-resolved face-to-face proximity of children and teachers using a proximity-sensing infrastructure based on radio frequency identification devices.
Data on face-to-face interactions were collected on Thursday, October 1(st) and Friday, October 2(nd) 2009. We recorded 77,602 contact events between 242 individuals (232 children and 10 teachers). In this setting, each child has on average 323 contacts per day with 47 other children, leading to an average daily interaction time of 176 minutes. Most contacts are brief, but long contacts are also observed. Contacts occur mostly within each class, and each child spends on average three times more time in contact with classmates than with children of other classes. We describe the temporal evolution of the contact network and the trajectories followed by the children in the school, which constrain the contact patterns. We determine an exposure matrix aimed at informing mathematical models. This matrix exhibits a class and age structure which is very different from the homogeneous mixing hypothesis.
We report on important properties of the contact patterns between school children that are relevant for modeling the propagation of diseases and for evaluating control measures. We discuss public health implications related to the management of schools in case of epidemics and pandemics. Our results can help define a prioritization of control measures based on preventive measures, case isolation, classes and school closures, that could reduce the disruption to education during epidemics.
In an optimum One Health approach, because southeast Asian bat species harbour coronaviruses similar to SARS-CoV-2, coronavirus surveillance14 should have been triggered with regular biobanking from ...reservoirs, surveillance of transmission to potentially susceptible animals or to humans in contact with those animals, and an analysis of the environmental factors favouring transmission (ie, analysis of ecosystems and factors associated with carriage; figure). The omicron (B.1.1.529) variant is speculated to have possibly emerged after reverse zoonosis (figure).19 This understanding of potential evolutionary processes through reverse virus zoonosis and their consequences is part of the One Health strategy that needs to be addressed for each emergence (eg, monkeypox virus; appendix p 2). The panel published a new inclusive definition of One Health, encouraging intersectoral, but also interdisciplinary and multistakeholder approaches.21,22 Several One Health operationalisation plans have also been developed, such as the One Health Joint Plan of Action developed by the Quadripartite Agreement, working together for the health of humans, animals, plants and the environment,23 and the One Health operational framework proposed by The World Bank.24 However, although declarations and action plans provided by each stakeholder in their own sector are a prerequisite for any change, they are not enough. Conversely, this global understanding is more advanced in the ecology and animal health sectors, although One Health activities are poorly funded and mostly theoretical.
We detected highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus in a domestic cat that lived near a duck farm infected by a closely related virus in France during December 2022. Enhanced ...surveillance of symptomatic domestic carnivores in contact with infected birds is recommended to prevent further spread to mammals and humans.
We aimed to describe direct medical costs of annual RSV-associated hospitalisation in the first year of life.
Retrospective cohort study in Lyon, France (2012–2016). A case was defined as a ...laboratory confirmed RSV-infection with hospitalisation in the first year of life. Hospital costs were estimated based on the French version of Diagnosis Related Groups.
Overall, 350 cases in 21,930 children were identified. Incidence of RSV-associated hospitalisation in the first year of life per 1000 births was 14.5 (95% CI 13.4–15.6). Related direct medical annual costs were 364,269 €, mostly attributed to children born during the RSV season (231,959 €) and children born premature (108,673 €).
Medical costs for RSV-associated hospitalisation of newborns are higher for children born premature or born during the RSV season. Prioritised targeting of those groups may facilitate a cost-efficient strategy for the national prevention program.
In response to the current pandemic caused by the novel SARS-CoV-2, identifying and validating effective therapeutic strategies is more than ever necessary. We evaluated the in vitro antiviral ...activities of a shortlist of compounds, known for their cellular broad-spectrum activities, together with drugs that are currently under evaluation in clinical trials for COVID-19 patients. We report the antiviral effect of remdesivir, lopinavir, chloroquine, umifenovir, berberine and cyclosporine A in Vero E6 cells model of SARS-CoV-2 infection, with estimated 50% inhibitory concentrations of 0.99, 5.2, 1.38, 3.5, 10.6 and 3 μM, respectively. Virus-directed plus host-directed drug combinations were also investigated. We report a strong antagonism between remdesivir and berberine, in contrast with remdesivir/diltiazem, for which we describe high levels of synergy, with mean Loewe synergy scores of 12 and peak values above 50. Combination of host-directed drugs with direct acting antivirals underscore further validation in more physiological models, yet they open up interesting avenues for the treatment of COVID-19.
•In the context of SARS-CoV-2 pandemic, identifying and validating effective therapeutic strategies is more than ever necessary.•Several compounds including drugs currently under clinical evaluation were evaluated in vitro for their antiviral activities.•We report antiviral effects of remdesivir, lopinavir, chloroquine, umifenovir, berberine and cyclosporine A in Vero E6 cells.•We report strong antagonism for remdesivir/berberine and high level of synergy for remdesivir/diltiazem drug combinations.•Combinations of host-directed drugs with direct acting antivirals open interesting avenues for the treatment of COVID-19.
Schools were closed extensively in 2020–21 to counter SARS-CoV-2 spread, impacting students' education and wellbeing. With highly contagious variants expanding in Europe, safe options to maintain ...schools open are urgently needed. By estimating school-specific transmissibility, our study evaluates costs and benefits of different protocols for SARS-CoV-2 control at school.
We developed an agent-based model of SARS-CoV-2 transmission in schools. We used empirical contact data in a primary and a secondary school and data from pilot screenings in 683 schools during the alpha variant (B.1.1.7) wave in March–June, 2021, in France. We fitted the model to observed school prevalence to estimate the school-specific effective reproductive number for the alpha (Ralpha) and delta (B.1.617.2; Rdelta) variants and performed a cost–benefit analysis examining different intervention protocols.
We estimated Ralpha to be 1·40 (95% CI 1·35–1·45) in the primary school and 1·46 (1·41–1·51) in the secondary school during the spring wave, higher than the time-varying reproductive number estimated from community surveillance. Considering the delta variant and vaccination coverage in Europe as of mid-September, 2021, we estimated Rdelta to be 1·66 (1·60–1·71) in primary schools and 1·10 (1·06–1·14) in secondary schools. Under these conditions, weekly testing of 75% of unvaccinated students (PCR tests on saliva samples in primary schools and lateral flow tests in secondary schools), in addition to symptom-based testing, would reduce cases by 34% (95% CI 32–36) in primary schools and 36% (35–39) in secondary schools compared with symptom-based testing alone. Insufficient adherence was recorded in pilot screening (median ≤53%). Regular testing would also reduce student-days lost up to 80% compared with reactive class closures. Moderate vaccination coverage in students would still benefit from regular testing for additional control—ie, weekly testing 75% of unvaccinated students would reduce cases compared with symptom-based testing only, by 23% in primary schools when 50% of children are vaccinated.
The COVID-19 pandemic will probably continue to pose a risk to the safe and normal functioning of schools. Extending vaccination coverage in students, complemented by regular testing with good adherence, are essential steps to keep schools open when highly transmissible variants are circulating.
EU Framework Programme for Research and Innovation Horizon 2020, Horizon Europe Framework Programme, Agence Nationale de la Recherche, ANRS–Maladies Infectieuses Émergentes.
In the current COVID-19 pandemic context, proposing and validating effective treatments represents a major challenge. However, the scarcity of biologically relevant pre-clinical models of SARS-CoV-2 ...infection imposes a significant barrier for scientific and medical progress, including the rapid transition of potentially effective treatments to the clinical setting. We use reconstituted human airway epithelia to isolate and then characterize the viral infection kinetics, tissue-level remodeling of the cellular ultrastructure, and transcriptional early immune signatures induced by SARS-CoV-2 in a physiologically relevant model. Our results emphasize distinctive transcriptional immune signatures between nasal and bronchial HAE, both in terms of kinetics and intensity, hence suggesting putative intrinsic differences in the early response to SARS-CoV-2 infection. Most important, we provide evidence in human-derived tissues on the antiviral efficacy of remdesivir monotherapy and explore the potential of the remdesivir-diltiazem combination as an option worthy of further investigation to respond to the still-unmet COVID-19 medical need.
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We use reconstituted human airway epithelia to characterize SARS-CoV-2 infection kineticsSARS-CoV-2 induces characteristic remodeling of the respiratory epithelium cellular ultrastructureSARS-CoV-2 induces differential early immune responses in nasal and bronchial HAEWe evaluate the antiviral activity of remdesivir and remdesivir-diltiazem in both Vero E6 and HAE models
Pizzorno et al. report the characterization of SARS-CoV-2 infection, tissue-level remodeling of cellular ultrastructure, and transcriptional immune signatures using a model of reconstituted human airway epithelia. This model was advantageously used to evaluate the antiviral activity of remdesivir or a combination of remdesivir-diltiazem against SARS-CoV-2.
There is an urgent need for specific antiviral treatments directed against SARS-CoV-2 to prevent the most severe forms of COVID-19. By drug repurposing, affordable therapeutics could be supplied ...worldwide in the present pandemic context. Targeting the nucleoprotein N of the SARS-CoV-2 coronavirus could be a strategy to impede viral replication and possibly other essential functions associated with viral N. The antiviral properties of naproxen, a non-steroidal anti-inflammatory drug (NSAID) that was previously demonstrated to be active against Influenza A virus, were evaluated against SARS-CoV-2. Intrinsic fluorescence spectroscopy, fluorescence anisotropy, and dynamic light scattering assays demonstrated naproxen binding to the nucleoprotein of SARS-Cov-2 as predicted by molecular modeling. Naproxen impeded recombinant N oligomerization and inhibited viral replication in infected cells. In VeroE6 cells and reconstituted human primary respiratory epithelium models of SARS-CoV-2 infection, naproxen specifically inhibited viral replication and protected the bronchial epithelia against SARS-CoV-2-induced damage. No inhibition of viral replication was observed with paracetamol or the COX-2 inhibitor celecoxib. Thus, among the NSAID tested, only naproxen combined antiviral and anti-inflammatory properties. Naproxen addition to the standard of care could be beneficial in a clinical setting, as tested in an ongoing clinical study.
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