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Achieving sufficient worldwide vaccination coverage against SARS-CoV-2 will require additional approaches to currently approved viral vector and mRNA vaccines. Subunit vaccines may have distinct advantages when immunizing vulnerable individuals, children and pregnant women. Here, we present a new generation of subunit vaccines targeting viral antigens to CD40-expressing antigen-presenting cells. We demonstrate that targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to CD40 (αCD40.RBD) induces significant levels of specific T and B cells, with long-term memory phenotypes, in a humanized mouse model. Additionally, we demonstrate that a single dose of the αCD40.RBD vaccine, injected without adjuvant, is sufficient to boost a rapid increase in neutralizing antibodies in convalescent non-human primates (NHPs) exposed six months previously to SARS-CoV-2. Vaccine-elicited antibodies cross-neutralize different SARS-CoV-2 variants, including D614G, B1.1.7 and to a lesser extent B1.351. Such vaccination significantly improves protection against a new high-dose virulent challenge versus that in non-vaccinated convalescent animals. In this study, Marlin et al. provide insights into the potential use of subunit vaccines that induce a high level of protection against SARS-CoV-2 in animal models.

ObjectivesSleep is important for human health and well-being. No previous study has assessed whether the COVID-19 pandemic impacts sleep and daytime function across the globe.MethodsThis large-scale international survey used a harmonised questionnaire. Fourteen countries participated during the period of May–August 2020. Sleep and daytime problems (poor sleep quality, sleep onset and maintenance problems, nightmares, hypnotic use, fatigue and excessive sleepiness) occurring ‘before’ and ‘during’ the pandemic were investigated. In total, 25 484 people participated and 22 151 (86.9%) responded to the key parameters and were included. Effects of COVID-19, confinement and financial suffering were considered. In the fully adjusted logistic regression models, results (weighted and stratified by country) were adjusted for gender, age, marital status, educational level, ethnicity, presence of sleep problems before COVID-19 and severity of the COVID-19 pandemic in each country at the time of the survey.ResultsThe responders were mostly women (64%) with a mean age 41.8 (SD 15.9) years (median 39, range 18–95). Altogether, 3.0% reported having had COVID-19; 42.2% reported having been in confinement; and 55.9% had suffered financially. All sleep and daytime problems worsened during the pandemic by about 10% or more. Also, some participants reported improvements in sleep and daytime function. For example, sleep quality worsened in about 20% of subjects and improved in about 5%. COVID-19 was particularly associated with poor sleep quality, early morning awakening and daytime sleepiness. Confinement was associated with poor sleep quality, problems falling asleep and decreased use of hypnotics. Financial suffering was associated with all sleep and daytime problems, including nightmares and fatigue, even in the fully adjusted logistic regression models.ConclusionsSleep problems, fatigue and excessive sleepiness increased significantly worldwide during the first phase of the COVID-19 pandemic. Problems were associated with confinement and especially with financial suffering.

Cholesterol has been shown to affect the extent of coronavirus binding and fusion to cellular membranes. The severity of Covid-19 infection is also known to be correlated with lipid disorders. Furthermore, the levels of both serum cholesterol and high-density lipoprotein (HDL) decrease with Covid-19 severity, with normal levels resuming once the infection has passed. Here we demonstrate that the SARS-CoV-2 spike (S) protein interferes with the function of lipoproteins, and that this is dependent on cholesterol. In particular, the ability of HDL to exchange lipids from model cellular membranes is altered when co-incubated with the spike protein. Additionally, the S protein removes lipids and cholesterol from model membranes. We propose that the S protein affects HDL function by removing lipids from it and remodelling its composition/structure. Graphical abstract

Acute flaccid myelitis; Enterovirus D68; Surveillance Mielitis flàcida aguda; Enterovirus D68; Vigilància Mielitis flácida aguda; Enterovirus D68; Vigilancia We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe.

Patients with heart failure (HF) who contract SARS-CoV-2 infection are at a higher risk of cardiovascular and non-cardiovascular morbidity and mortality. Regardless of therapeutic attempts in COVID-19, vaccination remains the most promising global approach at present for controlling this disease. There are several concerns and misconceptions regarding the clinical indications, optimal mode of delivery, safety and efficacy of COVID-19 vaccines for patients with HF. This document provides guidance to all healthcare professionals regarding the implementation of a COVID-19 vaccination scheme in patients with HF. COVID-19 vaccination is indicated in all patients with HF, including those who are immunocompromised (e.g. after heart transplantation receiving immunosuppressive therapy) and with frailty syndrome. It is preferable to vaccinate against COVID-19 patients with HF in an optimal clinical state, which would include clinical stability, adequate hydration and nutrition, optimized treatment of HF and other comorbidities (including iron deficiency), but corrective measures should not be allowed to delay vaccination. Patients with HF who have been vaccinated against COVID-19 need to continue precautionary measures, including the use of facemasks, hand hygiene and social distancing. Knowledge on strategies preventing SARS-CoV-2 infection (including the COVID-19 vaccination) should be included in the comprehensive educational programmes delivered to patients with HF. This article is protected by copyright. All rights reserved. [Abstract copyright: This article is protected by copyright. All rights reserved.]

International audience; The influenza D virus (IDV) was first identified and characterized in 2011. Considering the virus' zoonotic potential, its genome nature (segmented RNA virus), its worldwide circulation in livestock and its role in bovine respiratory disease, an increased interest is given to IDV. However, few data are available on drivers of emergence of IDV. We first listed fifty possible drivers of emergence of IDV in ruminants and swine. As recently carried out for COVID-19 in pets (Transboundary and Emerging Diseases, 2020), a scoring system was developed per driver and scientific experts (N = 28) were elicited to (a) allocate a score to each driver, (b) weight the drivers' scores within each domain and (c) weight the different domains among themselves. An overall weighted score was calculated per driver, and drivers were ranked in decreasing order. Drivers with comparable likelihoods to play a role in the emergence of IDV in ruminants and swine in Europe were grouped using a regression tree analysis. Finally, the robustness of the expert elicitation was verified. Eight drivers were ranked with the highest probability to play a key role in the emergence of IDV: current species specificity of the causing agent of the disease; influence of (il)legal movements of live animals (ruminants, swine) from neighbouring/European Union member states and from third countries for the disease to (re-)emerge in a given country; detection of emergence; current knowledge of the pathogen; vaccine availability; animal density; and transport vehicles of live animals. As there is still limited scientific knowledge on the topic, expert elicitation of knowledge and multi-criteria decision analysis, in addition to clustering and sensitivity analyses, are very important to prioritize future studies, starting from the top eight drivers. The present methodology could be applied to other emerging animal diseases.

The Canada Research Chairs program provided funding for the core writing team. Field research funding was provided by A.G. Leventis Foundation; Agence Nationale de la Recherche, [grant number ANR-18-32–0010CE-01 (JCJC PEPPER)]; Agencia Estatal de Investigaci; Agência Regional para o Desenvolvimento da Investigação Tecnologia e Inovação (ARDITI), [grant number M1420-09-5369-FSE-000002]; Alan Peterson; ArcticNet; Arkadaşlar; Army Corp of Engineers; Artificial Reef Program; Australia's Integrated Marine Observing System (IMOS), National Collaborative; Research Infrastructure Strategy (NCRIS), University of Tasmania; Australian Institute of Marine Science; Australian Research Council, [grant number LP140100222]; Bai Xian Asia Institute; Batubay Özkan; BC Hydro Fish and Wildlife Compensation Program; Ben-Gurion University of the Negev; Bertarelli Foundation; Bertarelli Programme in Marine Science; Bilge Bahar; Bill and Melinda Gates Foundation; Biology Society of South Australia; Boston University; Burak Över; California State Assembly member Patrick O'Donnell; California State University Council on Ocean Affairs, Science & Technology; California State University Long Beach; Canada Foundation for Innovation (Major Science Initiative Fund and funding to Oceans Network Canada), [grant number MSI 30199 for ONC]; Cape Eleuthera Foundation; Centre National d'Etudes Spatiales; Centre National de la Recherche Scientifique; Charles Darwin Foundation, [grant number 2398]; Colombian Institute for the Development of Science and Technology (COLCIENCIAS), [grant number 811–2018]; Colombian Ministry of Environment and Sustainable Development, [grant number 0041–2020]; Columbia Basin Trust; Commission for Environmental Cooperation; Cornell Lab of Ornithology; Cultural practices and environmental certification of beaches, Universidad de la Costa, Colombia, [grant number INV.1106–01–002-15, 2020–21]; Department of Conservation New Zealand; Direction de l'Environnement de Polynésie Française; Disney Conservation Fund; DSI-NRF Centre of; Excellence at the FitzPatrick Institute of African Ornithology; Ecology Project International; Emin Özgür; Environment and Climate Change Canada; European Community: RTD programme - Species Support to Policies; European Community's Seventh Framework Programme; European Union; European Union's Horizon 2020 research and innovation programme, Marie Skłodowska-Curie, [grant number 798091, 794938]; Faruk Eczacıbaşı; Faruk Yalçın Zoo; Field research funding was provided by King Abdullah University of Science and Technology; Fish and Wildlife Compensation Program; Fisheries and Oceans Canada; Florida Fish and Wildlife Conservation Commission, [grant numbers FWC-12164, FWC-14026, FWC-19050]; Fondo Europeo de Desarrollo Regional; Fonds québécois de la recherche nature et technologies; Foundation Segré; Fundação para a Ciência e a Tecnologia (FCT Portugal); Galapagos National Park Directorate research, [grant number PC-41-20]; Gordon and Betty Moore Foundation, [grant number GBMF9881 and GBMF 8072]; Government of Tristan da Cunha; Habitat; Conservation Trust Foundation; Holsworth Wildlife Research Endowment; Institute of Biology of the Southern Seas, Sevastopol, Russia; Instituto de Investigación de Recursos Biológicos Alexander von Humboldt; Instituto Nacional de Pesquisas Espaciais (INPE), Brazil; Israeli Academy of Science's Adams Fellowship; King Family Trust; Labex, CORAIL, France; Liber Ero Fellowship; LIFE (European Union), [grant number LIFE16 NAT/BG/000874]; María de Maeztu Program for Units of Excellence in R&D; Ministry of Science and Innovation, FEDER, SPASIMM,; Spain, [grant number FIS2016–80067-P (AEI/FEDER, UE)]; MOE-Korea, [grant number 2020002990006]; Mohamed bin Zayed Species Conservation Fund; Montreal Space for Life; National Aeronautics and Space Administration (NASA) Earth and Space Science Fellowship Program; National Geographic Society, [grant numbers NGS-82515R-20]; National Natural Science Fund of China; National Oceanic and Atmospheric Administration; National Parks Board, Singapore; National Science and Technology Major Project of China; National Science Foundation, [grant number DEB-1832016]; Natural Environment Research Council of the UK; Natural Sciences and Engineering Research Council of Canada (NSERC), Alliance COVID-19 grant program, [grant numbers ALLRP 550721–20, RGPIN-2014-06229 (year: 2014), RGPIN-2016-05772 (year: 2016)]; Neiser Foundation; Nekton Foundation; Network of Centre of Excellence of Canada: ArcticNet; North Family Foundation; Ocean Tracking Network; Ömer Külahçıoğlu; Oregon State University; Parks Canada Agency (Lake Louise, Yoho, and Kootenay Field Unit); Pew Charitable Trusts; Porsim Kanaf partnership; President's International Fellowship Initiative for postdoctoral researchers Chinese Academy of Sciences, [grant number 2019 PB0143]; Red Sea Research Center; Regional Government of the Azores, [grant number M3.1a/F/025/2015]; Regione Toscana; Rotary Club of Rhinebeck; Save our Seas Foundation; Science & Technology (CSU COAST); Science City Davos, Naturforschende Gesellschaft Davos; Seha İşmen; Sentinelle Nord program from the Canada First Research Excellence Fund; Servizio Foreste e Fauna (Provincia Autonoma di Trento); Sigrid Rausing Trust; Simon Fraser University; Sitka Foundation; Sivil Toplum Geliştirme Merkezi Derneği; South African National Parks (SANParks); South Australian Department for Environment and Water; Southern California Tuna Club (SCTC); Spanish Ministry for the Ecological Transition and the Demographic Challenge; Spanish Ministry of Economy and Competitiveness; Spanish Ministry of Science and Innovation; State of California; Sternlicht Family Foundation; Suna Reyent; Sunshine Coast Regional Council; Tarea Vida, CEMZOC, Universidad de Oriente, Cuba, [grant number 10523, 2020]; Teck Coal; The Hamilton Waterfront Trust; The Ian Potter Foundation, Coastwest, Western Australian State NRM; The Red Sea Development Company; The Wanderlust Fund; The Whitley Fund; Trans-Anatolian Natural Gas Pipeline; Tula Foundation (Hakai Institute); University of Arizona; University of Pisa; US Fish and Wildlife Service; US Geological Survey; Valencian Regional Government; Vermont Center for Ecostudies; Victorian Fisheries Authority; VMRC Fishing License Fund; and Wildlife Warriors Worldwide The global lockdown to mitigate COVID-19 pandemic health risks has altered human interactions with nature. Here, we report immediate impacts of changes in human activities on wildlife and environmental threats during the early lockdown months of 2020, based on 877 qualitative reports and 332 quantitative assessments from 89 different studies. Hundreds of reports of unusual species observations from around the world suggest that animals quickly responded to the reductions in human presence. However, negative effects of lockdown on conservation also emerged, as confinement resulted in some park officials being unable to perform conservation, restoration and enforcement tasks, resulting in local increases in illegal activities such as hunting. Overall, there is a complex mixture of positive and negative effects of the pandemic lockdown on nature, all of which have the potential to lead to cascading responses which in turn impact wildlife and nature conservation. While the net effect of the lockdown will need to be assessed over years as data becomes available and persistent effects emerge, immediate responses were detected across the world. Thus initial qualitative and quantitative data arising from this serendipitous global quasi-experimental perturbation highlights the dual role that humans play in threatening and protecting species and ecosystems. Pathways to favorably tilt this delicate balance include reducing impacts and increasing conservation effectiveness 18 pages, 5 figures, supplementary data https://doi.org/10.1016/j.biocon.2021.109175.-- The data supporting the findings of this study are available in the Supplementary Materials (Appendix 3–5, Table A3-A5). Raw datasets (where available) and results summary tables for each analysis of human mobility and empirical datasets are deposited in a github repository: https://github.com/rjcommand/PAN-Environment With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S Peer reviewed

On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID-19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV-ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC-CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug-induced CV-ADRs from COVID-19 effects, we restricted analyses to patients with COVID-19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08-3.29), bradycardia (aOR: 2.09, 95% CI: 1.24-3.53), and hypotension (aOR: 1.67, 95% CI: 1.03-2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC-CMs in time- and dose-dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin. Funding Agencies|Yonsei University College of Medicine for 2021 [2021-32-0049] Funding Source: Medline

International audience; The etiopathogenesis of critical COVID-19 remains unknown. Indeed given major confounding factors (age and comorbidities), true drivers of this condition have remained elusive. Here, we employ an unprecedented multi-omics analysis, combined with artificial intelligence, in a young patient cohort where major comorbidities have been excluded at the onset. Here, we established a three-tier cohort of individuals younger than 50 years without major comorbidities. These included 47 “critical” (in the ICU under mechanical ventilation) and 25 “non-critical” (in a non-critical care ward) COVID-19 patients as well as 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cells proteomics, cytokine profiling and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing and structural causal modeling led to key findings. Critical patients were characterized by exacerbated inflammation, perturbed lymphoid/myeloid compartments, coagulation and viral cell biology. Within a unique gene signature that differentiated critical from non-critical patients, several driver genes promoted critical COVID-19 among which the upregulated metalloprotease ADAM9 was key. This gene signature was supported in a second independent cohort of 81 critical and 73 recovered COVID-19 patients, as were ADAM9 transcripts, soluble form and proteolytic activity. Ex vivo ADAM9 inhibition affected SARS-CoV-2 uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, COVID-19 cohort, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. The key driver, ADAM9, interfered with SARS-CoV-2 biology. A repositioning strategy for anti-ADAM9 therapeutic is feasible.

Abstract Background Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk. Objectives We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI). Methods Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry. Results We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient. Conclusions We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.