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As countries in Europe implement strategies to control the COVID-19 pandemic, different options are chosen regarding schools. Through a stochastic age-structured transmission model calibrated to the observed epidemic in Île-de-France in the first wave, we explored scenarios of partial, progressive, or full school reopening. Given the uncertainty on children’s role, we found that reopening schools after lockdown may increase COVID-19 cases, yet protocols exist to keep the epidemic controlled. Under a scenario with stable epidemic activity if schools were closed, reopening pre-schools and primary schools would lead to up to 76% [67, 84]% occupation of ICU beds if no other school level reopened, or if middle and high schools reopened later. Immediately reopening all school levels may overwhelm the ICU system. Priority should be given to pre- and primary schools allowing younger children to resume learning and development, whereas full attendance in middle and high schools is not recommended for stable or increasing epidemic activity. Large-scale test and trace is required to keep the epidemic under control. Ex-post assessment shows that progressive reopening of schools, limited attendance, and strong adoption of preventive measures contributed to a decreasing epidemic after lifting the first lockdown. The role of children in the spread of COVID-19 is not fully understood, and the circumstances under which schools should be opened are therefore debated. Here, the authors demonstrate protocols by which schools in France can be safely opened without overwhelming the healthcare system.

Dès les premières semaines de l’épidémie de la Covid-19, en France, plusieurs voix se sont levées pour dire que l’heure n’était pas à la réflexion éthique, mais à l’action, en soulignant néanmoins l’importance d’un retour d’expérience à l’issue de l’urgence. Dans cette visée, le Centre d’éthique clinique de l’AP-HP a proposé, dès la fin du 1er confinement national, à des soignants, comme à des patients ou à des proches, de revenir, s’ils le souhaitaient, sur les questionnements ou les difficultés éthiques rencontrées pendant cette période (ce qu’il a appelé des « relectures éthiques »). Entre mai et septembre 2020, 31 professionnels y ont participé, 1 seul patient (médecin à la retraite) a été rencontré et aucun proche. Cet article souhaite partager la façon dont ces professionnels sont revenus, dans l’après-coup, sur les premiers mois de la crise. Plus d’une année plus tard, à l’heure où ce qui était « inhabituel » commence par devenir « ordinaire », et le « retour à la vie normale » semble à l’horizon, il n’est pas inutile de rappeler leurs réactions, leurs interrogations et leurs malaises. Au croisement des entretiens, c’est un questionnement quant à ce que soigner veut dire aujourd’hui et au rôle de la médecine en contexte de crise que l’on voit émerger. From the beginning of the Covid-19 pandemic in France, many argued that now was the time for action, not ethics, while acknowledging the need for feedback once the crisis had passed. To this end, the Parisian clinical ethics’ center suggested that health professionals, patients, and families come back on difficulties or questions they might have had during the first national lockdown once it was over. We called it ethical debriefs. Between May and September 2021, 31 professionals agreed to participate, but only 1 patient (a retired physician) and no proxy was met. The aim of this article is to share how these health professionals revisited the first months of the crisis. Indeed today, more than one year since Covid started and as what was once unusual is becoming common practice, it is useful not to forget how they reacted, what their questions were and where did their ethical difficulties lie at that time. Now that coming back to normal might be conceivable, all these interviews highlight the importance of a questioning on what caring for patients means nowadays, as well as on the definition of role of medicine in a context of crisis.

AbstractBluetongue virus (BTV) is an arbovirus transmitted by blood-feeding midges to a wide range of wild and domestic ruminants. In this report, we showed that BTV, through its virulence non-structural protein NS3 (BTV-NS3), is able to activate the MAPK/ERK pathway. In response to growth factors, the MAPK/ERK pathway activates cell survival, differentiation, proliferation and protein translation but can also lead to the production of several inflammatory cytokines. By combining immunoprecipitation of BTV-NS3 and mass spectrometry analysis from both BTV-infected and NS3-transfected cells, we identified the serine/threonine-protein kinase B-Raf (BRAF), a crucial player of the MAPK/ERK pathway, as a new cellular interactor of BTV-NS3. BRAF silencing led to a significant decrease of the MAPK/ERK activation by BTV supporting a model where BTV-NS3 interacts with BRAF to activate this signaling cascade. Furthermore, the intrinsic ability of BTV-NS3 to bind BRAF and activate the MAPK/ERK pathway is conserved throughout multiple serotypes/strains but appears to be specific to BTV compared to other members ofOrbivirusgenus. Inhibition of MAPK/ERK pathway with U0126 reduced viral titers, suggesting that BTV manipulates this pathway for its own replication. Therefore, the activation of the MAPK/ERK pathway by BTV-NS3 could benefit to BTV replication by promoting its own viral protein synthesis but could also explain the deleterious inflammation associated with tissue damages as already observed in severe cases of BT disease. Altogether, our data provide molecular mechanisms to explain the role of BTV-NS3 as a virulence factor and determinant of pathogenesis.ImportanceBluetongue Virus (BTV) is responsible of the non-contagious arthropod-borne disease Bluetongue (BT) transmitted to ruminants by blood-feeding midges. Despite the fact that BTV has been extensively studied, we still have little understanding of the molecular determinants of BTV virulence. In this report, we found that the virulence protein NS3 interacts with BRAF, a key component of the MAPK/ERK pathway. In response to growth factors, this pathway promotes cell survival, increases protein translation but also contributes to the production of inflammatory cytokines. We showed that BTV-NS3 enhances the MAPK/ERK pathway and this activation is BRAF-dependent. Our results demonstrate, at the molecular level, how a single virulence factor has evolved to target a cellular function to ensure its viral replication. On the other hand, our findings could also explain the deleterious inflammation associated with tissue damages as already observed in severe cases of BT disease.

ABSTRACTClinical manifestations of COVID-19 caused by the novel coronavirus SARS-CoV-2 are associated with age. While children are largely spared from severe respiratory disease, they can present with a SARS-CoV-2-associated multisystem inflammatory syndrome (MIS-C) similar to Kawasaki’s disease. Here, we show distinct antibody (Ab) responses in children with MIS-C compared to adults with severe COVID-19 causing acute respiratory distress syndrome (ARDS), and those who recovered from mild disease. There was a reduced breadth and specificity of anti-SARS-CoV-2-specific antibodies in MIS-C patients compared to the COVID patient groups; MIS-C predominantly generated IgG Abs specific for the Spike (S) protein but not for the nucleocapsid (N) protein, while the COVID-19 cohorts had anti-S IgG, IgM and IgA Abs, as well as anti-N IgG Abs. Moreover, MIS-C patients had reduced neutralizing activity compared to both COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children and adults who develop severe disease, with implications for optimizing treatments based on symptom and age.

On both sides of the Atlantic, in Anglo-Saxon countries, the issue of excess mortality due to Covid-19 among members of minorities has emerged as a central social justice issue. Outside the Anglo-Saxon countries, where race and ethnicity are generally recorded, it is difficult to address this issue. However, in France, data for the period up to the end of confinement, mentioning country of birth and place of death, from "état-civil" files, allow comparisons to be made on the determinants of the severity of Covid-19 integrating ethnicity. Regression analyses based on the difference in death counts between the spring of 2020 and the same period of previous years, show that the interweaving of health status, household size and ethnicity accurately reflects the disparities between departmental mortality rates due to Covid-19. People born in Black Africa clearly appear to be in a worse position than those born in the Maghreb, in Asian and European countries, not to mention the natives, in terms of risk of death.

The ongoing COVID-19 outbreak has expanded rapidly throughout China. Major behavioral, clinical, and state interventions are underway currently to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, have affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was well explained by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases are still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China have substantially mitigated the spread of COVID-19. One sentence summary: The spread of COVID-19 in China was driven by human mobility early on and mitigated substantially by drastic control measures implemented since the end of January.

It is now recognized that aerosol transport contributes to the transmission of the SARS-CoV-2 virus. Here we improve existing social distancing guidelines for airborne pathogens, which are typically given in terms of distance with vague statements (if any) about contact times. Also, estimates of inhalation of virus in a contaminated space usually assume a well-mixed environment, which is realistic for some, but not all, situations. In particular, we consider a local casual interaction of an infected individual and a susceptible individual, both maskless, account for the air flow and aerosol transport characteristics of speaking and breathing, and propose social distancing guidelines that involve both space and contact time, based on a conservative model of the interactions.

AbstractBackgroundCOVID-19 is spreading rapidly in nursing homes (NHs). It is urgent to evaluate the effect of infection prevention and control (IPC) measures to reduce COVID spreading.MethodsWe analysed COVID-19 outbreaks in 12 NH using rRT-PCR for SARS-CoV-2. We estimated secondary attack risks (SARs) and identified cofactors associated with the proportion of infected residents.ResultsThe SAR was below 5%, suggesting a high efficiency of IPC measures. Mask-wearing or establishment of COVID-19 zones for infected residents were associated with lower SAR.ConclusionsWearing masks and isolating potentially infected residents appear to limit SARS-CoV-2 spread in nursing homes.